What is Phenobarbital

Phenobarbital is a barbiturate that is widely used as a sedative and an antiseizure medication to control seizures. Phenobarbital is also used to relieve anxiety. Phenobarbital is also used to prevent withdrawal symptoms in people who are dependent (‘addicted’; feel a need to continue taking the medication) on another barbiturate medication and are going to stop taking the medication. Phenobarbital was introduced into clinical medicine in 1911 but was never subjected to critical controlled studies to demonstrate safety and efficacy. For these reasons, phenobarbital is now considered of unproven benefit in controlling seizures. Neverthess, it is commonly used for prevention and management of partial and generalized seizures, usually as an adjunctive agent in combination with other anticonvulsants. Phenobarbital is also used for sedation and insomnia although its use for these conditions is now uncommon. Phenobarbital is also used in fixed combinations with other antispasmotics or anticholinergic agents and used for gastrointestinal complaints, including irritable bowel syndrome.

Phenobarbital is available only with your doctor’s prescription.

Phenobarbital works by slowing activity in the brain. Phenobarbital is believed to act as a nonselective depressant. Phenobarbital also has anticonvulsant activity and is believed to act by suppressing spread of seizure activity by enhancing the effect of gamma aminobutyric acid (GABA), raising the seizure threshold.

Phenobarbital comes as a tablet and an elixir (liquid) to take by mouth. The typical starting dose in treating seizures in adults is 60 to 100 mg in three divided doses daily. Oral formulations of tablets or capsules of 15, 16, 30, 60, 90 and 100 mg are available in multiple generic forms. Parenteral formations and oral elixirs for pediatric use are also available.

Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take phenobarbital exactly as directed.

If you take phenobarbital for a long time, it may not control your symptoms as well as it did at the beginning of your treatment. Talk to your doctor about how you are feeling during your treatment.

Phenobarbital can be habit-forming. Do not take a larger dose, take it more often, or take it for a longer time than prescribed by your doctor.

Do not stop taking phenobarbital without talking to your doctor. If you suddenly stop taking phenobarbital, you may experience withdrawal symptoms such as anxiety, muscle twitching, uncontrollable shaking of a part of the body, weakness, dizziness, changes in vision, nausea, vomiting, seizures, confusion,difficulty falling asleep or staying asleep, or dizziness or fainting when getting up from a lying position. Your doctor will probably decrease your dose gradually.

Phenobarbital frequent side effects include drowsiness, sedation, hypotension, and skin rash.

Phenobarbital administration

Phenobarbital is given through a variety of routes. These include ¹⁾:

• Intramuscular (IM)
• Oral
• Intravenous (IV)

When phenobarbital is given intravenously, it should be for emergency cases. Other routes of administration should be accessed first and checked for any indurations. Studies have shown that an induration at a site of infusion results in a decreased bioavailability of phenobarbital ²⁾. Another study has shown rectal administration of phenobarbital to be effective, with a relative bioavailability reaching 90% ³⁾.

Phenobarbital mechanism of action

Phenobarbital works by increasing the amount of time chloride channels are open which in turn depresses the central nervous system. This is done by acting on GABA-A receptor subunits. When phenobarbital binds to these receptors, the chloride ion gates open and stay open allowing a steady flow of these ions into neuronal cells ⁴⁾. This action hyperpolarizes the cell’s membrane, thereby increasing the threshold for the action potential. This is the reasoning as to why this drug is effective in the treatment of seizures. As per the metabolism and clearance of the drug, phenobarbital is a water-soluble agent metabolized by the liver and expelled mainly through the kidneys ⁵⁾. It is important to remember clearance rates vary with patients and their specific presentations. For instance, terminally ill cancer patients on phenobarbital may need dose adjustments due to reduced clearance of this drug ⁶⁾. Cytochrome p450 is induced by phenobarbital, and so careful consideration must be made when given concurrently with other medications. For instance, an epileptic woman who takes oral contraceptive pills and phenobarbital must be fully aware of the possible interaction between the medications. Phenobarbital, an antiepileptic drug, is known to induce the liver’s cytochrome p450 enzyme. Inducing this enzyme speeds up the metabolism of estrogens and progestins. Thus, a woman taking both anti-epileptic medication and oral contraceptive pills can have an unexpected pregnancy due to the decreased efficacy of her oral contraceptive pills ⁷⁾. This is why it is crucial to educate the patient about potential risks.

Phenobarbital special precautions

Before taking phenobarbital:

• tell your doctor and pharmacist if you are allergic to phenobarbital; other barbiturates such as amobarbital (Amytal), butabarbital (Butisol), pentobarbital, and secobarbital (Seconal); any other medications, or any of the ingredients in phenobarbital tablets or liquid. Ask your doctor or pharmacist for a list of the ingredients.
• tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: anticoagulants (‘blood thinners’) such as warfarin (Coumadin); disulfiram (Antabuse); doxycycline (Vibramycin); griseofulvin (Fulvicin); hormone replacement therapy (HRT); monoamine oxidase (MAO) inhibitors such as isocarboxazid (Marplan), phenelzine (Nardil), seligiline (Eldepryl, Emsam, Zelapar) , or tranylcypromine (Parnate); medications for anxiety, depression, pain, asthma, colds, or allergies; certain medications for seizures such as phenytoin (Dilantin) and valproate (Depakene); oral steroids such as dexamethasone (Decadron, Dexone), methylprednisolone (Medrol), and prednisone (Deltasone);sedatives; sleeping pills; and tranquilizers. Your doctor may need to change the doses of your medications or monitor you more carefully for side effects.
• tell your doctor if you have or have ever had porphyria (condition in which certain natural substances build up in the body and may cause stomach pain, changes in thinking and behavior, and other symptoms); any condition that causes shortness of breath or difficulty breathing; or liver disease. Your doctor will probably tell you not to take phenobarbital.
• tell your doctor if you drink or have ever drunk large amounts of alcohol, used street drugs, or overused prescription medications; if you have pain now or have any condition that causes you ongoing pain; if you have ever thought about harming or killing yourself or planned or tried to do so; and if you have or have ever had depression, any condition that affects your adrenal gland (small gland next to the kidney that produces important natural substances), or kidney disease.
• tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. If you become pregnant while taking phenobarbital, call your doctor. Phenobarbital may harm the fetus.
• talk to your doctor about the risks and benefits of taking phenobarbital if you are 65 years of age or older. Older adults should not usually take phenobarbital because it is not as safe or effective as other medications that can be used to treat the same condition.
• you should know that phenobarbital may decrease the effectiveness of hormonal contraceptives (birth control pills, patches, rings, injections, implants, or intrauterine devices). Talk to your doctor about methods of birth control that will work for you while you are taking phenobarbital. Tell your doctor if you have a missed period or think you may be pregnant while you are taking phenobarbital.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking phenobarbital.
• you should know that this medication may make you drowsy. Do not drive a car or operate machinery until you know how this medication affects you.
• avoid drinking alcohol during your treatment with phenobarbital. Alcohol can make the side effects of phenobarbital worse.

Phenobarbital in pregnancy

Phenobarbital should be used during pregnancy only if the benefit outweighs the risk to the fetus.

Pregnancy category D/B: manufacturer dependent

• US FDA pregnancy category D: There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.
• US FDA pregnancy category B: Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.

If phenobarbital is used during pregnancy, or if the patient becomes pregnant while taking phenobarbital, the patient should be apprised of the potential harm to the fetus.

Supplementation with folic acid is recommended before conception and during pregnancy; vitamin K supplementation in women and neonates may be necessary.

If used during pregnancy, monitor the newborn for acute withdrawal syndrome symptoms for up to 14 days after birth.

If used during labor, monitor the newborn for respiratory depression and have resuscitation equipment available.

Human studies suggest that phenobarbital is connected to fetal abnormalities. Fetal blood levels approached maternal levels with parenteral administration. This drug crosses the placental barrier and distributes in fetal tissues, including the placenta, liver, and brain. Use during the first and third trimesters may be associated with an increased risk of teratogenicity and withdrawal symptoms in the newborn, respectively.

Phenobarbital in breastfeeding

Not recommended. Phenobarbital is excreted into human milk.

Comments:

• Breastfed infants should be monitored for sedation, weight gain, and developmental milestones, especially in younger infants who are exclusively breastfed or during concomitant use with psychotropic drug combinations.
• If toxicity is a concern, infant serum concentration of phenobarbital should be obtained.

Excretion of phenobarbital into breastmilk is highly variable. Breastfed infants showed increased sedation and suckling difficulties compared to infants that were not exposed to phenobarbital. Reports of infantile spasms and withdrawal symptoms in infants occurred after abrupt discontinuation. Since phenobarbital is excreted in breastmilk, methemoglobinemia is another potential risk.

Phenobarbital contraindications

A person with underlying obstructive lung disease will have a higher risk of complications ⁸⁾. The respiratory drive depression associated with barbiturate toxicity compounded with an already compromised respiratory system can contribute to complications ⁹⁾. It was also found that drug interaction from combined oral theophylline medication and phenobarbital, negatively impacted theophylline blood levels compared to plain oral theophylline pills ¹⁰⁾. Phenobarbital has been shown to decrease levels of steroids and theophylline via the cytochrome p450 liver metabolism system ¹¹⁾. Therefore, persons receiving combined oral treatment for their lung condition can experience issues regarding subtherapeutic blood levels of theophylline and or corticosteroids.

It is imperative not to drink alcohol while taking phenobarbital because there is a danger of severe respiratory depression when both are in one’s system. When taken simultaneously, both drug’s individual effects on GABA-A add to the other ¹²⁾. This can cause a life-threatening scenario.

When taking a prescription of a barbiturate such as phenobarbital, one may go into withdrawal if they were to stop taking it suddenly. Tapering of the drug must be implemented.

Phenobarbital uses

Phenobarbital is a medicine used to treat epilepsy, anxiety, and insomnia. Phenobarbital is even recommended as an agent to treat status epilepticus ¹³⁾. A study performed in China comparing valproic acid to phenobarbital for the treatment of status epilepticus, showed intravenous phenobarbital to have better clinical outcomes in the study population compared to valproic acid ¹⁴⁾. Although proven effective for status epilepticus, phenobarbital has widely been replaced with other drugs that offer less harmful side effects ¹⁵⁾. Phenobarbital can also be used to relieve insomnia ¹⁶⁾ and apprehensiveness, although addiction is a point of concern when phenobarbital is used for insomnia. This drug can also be used for benzodiazepine and alcohol withdrawal treatment ¹⁷⁾, due to its anti-seizure properties and sedative effect. The syndrome resulting from alcohol withdrawal has a better clinical outcome when treated with benzodiazepines according to significant evidence-based studies ¹⁸⁾. Long-acting agents such as phenobarbital are not the preferred option for surgical induction; short-acting barbiturates are commonly used for this purpose ¹⁹⁾. Phenobarbital’s involvement in severe brain injury management is to reduce intracranial pressure by suppressing cerebral metabolism, but phenobarbital’s adverse effect of hypotension negatively impacts the brain’s supply of oxygen thus offsetting any clinical benefit ²⁰⁾.

Phenobarbital monitoring

The range of phenobarbital deemed effective without causing issues to an individual is between 10 To 40 mcg/mL. Once blood levels increase above 40 mcg/mL, the patient is in a lethal range and at substantial risk ²¹⁾.

Phenobarbital dosage

Adult dose for Sedation

Uses: Daytime sedation; preoperative sedation

Daytime Sedation:

• 30 to 120 mg orally, IM, or IV in 2 or 3 divided doses
• Maximum dose: 400 mg during a 24-hour period

Preoperative Sedation:

• Parenteral: 100 to 200 mg IM 60 to 90 minutes before surgery

Comments:

• Frequency of administration should be determined by the patient response.
• Parenteral administration should be reserved for situations in which oral administration is impossible/impractical.

Adult dose for Insomnia

Uses: Bedtime hypnosis; hypnosis

Oral:

• Recommended dose: 100 to 200 mg orally once a day
• Maximum dose: 400 mg during a 24-hour period

Parenteral:

• Recommended dose: 100 to 320 mg IM or IV once a day
• Maximum dose: 400 mg during a 24-hour period

Comments:

• Phenobarbital may begin to lose effectiveness for inducing and maintaining sleep after 2 weeks.

Adult dose for Seizures

Uses: Treatment of generalized and partial seizures; treatment/prophylaxis of febrile seizures

Acute Convulsions

• Parenteral: 20 to 320 mg IM or IV every 6 hours as necessary

Anticonvulsant

• Oral: 60 to 200 mg orally per day

Comments:

• Maintenance doses should be determined by clinical laboratory reference values.
• Prevention of febrile seizures may not influence the development of epilepsy.

Pediatric dose for Seizures

Uses: Anticonvulsant used for the treatment of generalized and partial seizures, treatment/prophylaxis of febrile seizures, and treatment of status epilepticus.

Anticonvulsant:

• Oral:
  • Initial dose: 15 to 20 mg/kg orally
  • Recommended dose: 3 to 6 mg/kg orally
• Parenteral: 4 to 6 mg/kg/day for 7 to 10 days or 5 to 15 mg/kg/day IM or IV

Status epilepticus:

• Parenteral:
  • Initial dose: 15 to 20 mg/kg IV over 10 to 15 minutes

Comments:

• Loading doses of 15 to 20 mg/kg are predicted to produce blood levels of approximately 20 mcg/mL after administration.
• Maintenance doses should be determined by clinical laboratory reference values.
• Prevention of febrile seizures may not influence the development of epilepsy.

Pediatric dose for Sedation

Use: Preoperative sedation

• Parenteral: 1 to 3 mg/kg IM or IV

Renal Dose Adjustments

• Dose adjustments may be required; however, no specific guidelines have been suggested. Caution recommended.

Liver Dose Adjustments

• Mild to moderate liver impairment: Dose adjustments may be required; however, no specific guidelines have been suggested. Caution recommended.
• Marked/severe liver impairment: Contraindicated

What should I do if I forget a dose?

Take the missed dose as soon as you remember it. However, if it is almost time for your next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Phenobarbital side effects

Phenobarbital may cause side effects. Call your doctor if any of the following symptoms are severe or do not go away:

• drowsiness
• headache
• dizziness
• excitement or increased activity (especially in children)
• nausea
• vomiting

Some side effects can be serious. If you experience any of the following symptoms, call your doctor immediately:

• slowed breathing or difficulty breathing
• swelling of the eyes, lips, or cheeks
• rash
• blistering or peeling skin
• fever
• confusion

Phenobarbital overdose

Phenobarbital overdose occurs when someone takes too much of phenobarbital. Your local poison center can be reached directly by calling the national toll-free Poison Help hotline (1-800-222-1222) from anywhere in the United States. This hotline number will let you talk to experts in poisoning. They will give you further instructions.

This is a free and confidential service. All local poison control centers in the United States use this national number. You should call if you have any questions about poisoning or poison prevention. It does NOT need to be an emergency. You can call for any reason, 24 hours a day, 7 days a week.

Take the pill container with you to the hospital, if possible.

Phenobarbital overdose symptoms

Symptoms of phenobarbital overdose may include the following:

• uncontrollable movements of the eyes
• loss of coordination
• drowsiness
• slowed breathing
• drop in body temperature
• blisters

Heart and blood vessels:

• Heart failure
• Low blood pressure
• Weak pulse

Kidneys and bladder:

• Kidney failure (possible)

Lungs:

• Difficulty breathing
• Slowed or stopped breathing
• Pneumonia (possible)

Nervous system:

• Coma
• Confusion
• Decreased energy
• Delirium (confusion and agitation)
• Headache
• Sleepiness
• Slurred speech
• Unsteady gait

Skin:

• Large blisters
• Rash

What to expect at the Emergency Room

Your health care provider will measure and monitor your vital signs, including temperature, pulse, breathing rate, and blood pressure. Blood tests will be done to check the phenobarbital level.

Symptoms will be treated as appropriate. You may receive:

• Activated charcoal
• Airway support, including oxygen, breathing tube through the mouth (intubation), and ventilator (breathing machine)
• Blood and urine tests
• Chest x-ray
• EKG (electrocardiogram, or heart tracing)
• Fluids through the vein (intravenous or IV)
• Laxative
• Medicines to treat symptoms

This list may not be all-inclusive.

Phenobarbital overdose prognosis

How well the person does depends on the severity of the phenobarbital overdose and how quickly treatment is received. If there has been prolonged coma and shock (damage to multiple internal organs), a more serious outcome is possible.

Individuals suffering from barbiturate overdose typically do well if they receive prompt medical treatment and are otherwise healthy ²²⁾. Individuals with other significant health conditions, such as heart and pulmonary disease, may have a more complicated clinical course. For example, an individual with coronary artery atherosclerosis and/or cardiomegaly (an enlarged heart) will be already prone to suffering a myocardial infarction. Respiratory depression or hypotension from a depressant drug (like a barbiturate) will further decrease the amount of oxygen reaching the heart. An individual with a chronic obstructive pulmonary disease (COPD) or another pulmonary disease will have an increased risk for complications since respiratory drive is compromised with barbiturate toxicity.

Phenobarbital toxicity

Phenobarbital toxicity is noticeable at 1 gram via oral route, although this amount varies depending on the individual. Doses above 2 grams have caused deaths, but a deadly dose usually spans from 40 to 80 mcg/mL according to the following article ²³⁾.

Toxicity from phenobarbital varies, but common symptoms include the following ²⁴⁾:

• Cognitive impairment
• Decreased heart rate
• Incoordination
• Nausea
• Muscle weakness
• Polydipsia (excessive thirst)
• Below normal urine output
• Decreased body temperature
• Mydriasis (dilated pupils)

Deaths have resulted from marked respiratory depression, hypotension, and coma ²⁵⁾.

Treatment of phenobarbital toxicity is supportive ²⁶⁾. The first step in treatment, as with any overdose, is assessing the patient’s airway, breathing, and circulation. With significant sedation and respiratory depression, maintenance of airway function through endotracheal intubation and mechanical ventilation may become necessary, correction of bradycardia and hypotension with IV fluids and vasopressors, if necessary. After properly assessing and correcting the patient’s airway, breathing, and circulation; it is imperative to remove the drug from the body. This can be done via gastric irrigation, forced alkaline diuresis or dialysis ²⁷⁾. Early treatment with activated charcoal may be useful and can be given via nasogastric tube. For now, an explicit treatment does not exist ²⁸⁾.

Patients will likely need to be admitted or observed. During recovery, the patient should receive counseling about the dangers of barbiturate misuse. Long-term barbiturate use can cause tolerance and physical dependence. Therefore, withdrawal symptoms can occur with abrupt discontinuation ²⁹⁾.

Other options for managing phenobarbital toxicity include forced alkaline diuresis and hemodialysis for severe cases. Bemegride (Megimide) is a central nervous system stimulant that increases respiration and can be used as a treatment for depressant toxicity. It is, however, an emetic which raises the concern of emesis and aspiration.

Management of long-term use involves restoring central nervous system (CNS) inhibitory tone. Abrupt cessation can lead to severe symptoms of withdrawal; therefore, discontinuance of barbiturates should be a gradual taper using medications that demonstrate cross-tolerance, with the first line being benzodiazepines.

Phenobarbital toxicity complications

Complications include hypotension, coma, and respiratory depression. It is important to maintain the respiratory and cardiovascular status, as failure to do so can result in hypoxic brain injury and death. Rarely, phenobarbital has been associated with Steven-Johnson syndrome, a medical emergency that results in blisters (especially mucous membranes), fever, and widespread pain.

Long-term abuse has been associated with depression, loss of appetite, achiness, and rarely liver damage. As previously discussed, withdrawal symptoms can be severe, and the patient should be monitored carefully and treated accordingly.

Lidocaine

Lidocaine is a commonly used local anesthetic (numbing medication) for pain control during minor surgery or invasive procedures such as biopsies, small excisions or dental work. Lidocaine works by blocking nerve signals in your body or blocking thenerve signals at the nerve endings in your skin. Lidocaine is chemically referred to as aminoethylamides or amide local anesthetic. Lidocaine is usually given as a single injection locally into a lesion or the area of incision, but can be given as infusions for hours or for several days by epidural or wound-based catheters. Lidocaine infusion can also be used for postoperative pain management. Lidocaine has an excellent tolerance and safety. Lidocaine injection is to be given only by or under the direct supervision of your doctor.

Local anesthetics have been shown to be effective and are used widely in preventing or reducing pain from minor surgery, incisions, biopsies, dental and obstetrical procedures and pain from wounds.

Lidocaine was approved for use as a local anesthetic in the 1948 originally under the commercial name Xylocaine, ropivacaine in 1990 (Naropin), and bupivacaine in 1990 (Marcaine). Other less commonly used amide anesthetics include articaine (Septocaine: 2000), mepivacaine (Carbocaine: 1960), and prilocaine (Citanest: 1965). A liposomal and longer acting preparation of bupivacaine was approved for use in controlling postsurgical pain in 2011 (Exparel). Side effects of the local anesthetics are usually dose related and occur mostly as a result of systemic administration or exposure. They include neurological symptoms such as drowsiness, tinnitus, dizziness and twitching as well as gastrointestinal effects such as nausea, vomiting and constipation. Cardiovascular depression can also occur and ventricular arrhythmias, especially with higher doses.

Lidocaine Patch

Lidocaine patches are used to relieve the pain of post-herpetic neuralgia, the burning, stabbing pains, or aches that may last for months or years after a shingles infection. Lidocaine patch is to be applied to the skin only once a day as needed for pain. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Use lidocaine patches exactly as directed.

Your doctor will tell you how many lidocaine patches you may use at one time and the length of time you may wear the patches. Never apply more than three patches at one time, and never wear patches for more than 12 hours per day. Using too many patches or leaving patches on for too long may cause serious side effects.

To apply the lidocaine patches, follow these steps:

1. Look at the skin that you plan to cover with a lidocaine patch. If the skin is broken or blistered, do not apply a patch to that area.
2. Use scissors to remove the outer seal from the package. Then pull apart the zipper seal.
3. Remove up to three patches from the package and press the zipper seal tightly together. The remaining patches may dry out if the zipper seal is not tightly closed.
4. Cut patch(es) to the size and shape that will cover your most painful area.
5. Peel the transparent liner off the back of the patch(es).
6. Press the patch(es) firmly onto your skin. If you are applying a patch to your face, be careful not to let it touch your eyes. If you do get lidocaine in your eye, wash it with plenty of water or saline solution.
7. Wash your hands after handling lidocaine patches.
8. Do not reuse lidocaine patches. After you are finished using a patch, remove it and dispose of it out of reach of children and pets. Used patches contain enough medication to seriously harm a child or pet.

What is lidocaine used for?

Lidocaine is commonly used local anesthetic, often in combination with epinephrine, for pain control during minor surgery or invasive procedures such as biopsies, small excisions or dental work. Lidocaine injection is used to numb an area of your body to help reduce pain or discomfort caused by invasive medical procedures such as surgery, needle punctures, or insertion of a catheter or breathing tube. Lidocaine injection is sometimes used to treat irregular heart rhythms that may signal a possible heart attack. Lidocaine injection is also given in an epidural (spinal block) to reduce the discomfort of contractions during labor.

Lidocaine is usually given as a single injection locally into a lesion or the area of incision, but can be given as infusions for hours or for several days by epidural or wound-based catheters. Lidocaine infusion can also be used for postoperative pain management. Lidocaine has an excellent tolerance and safety. Lidocaine has variable duration of action, and short acting versions are often given with epinephrine, which acts as a vasopressor and extends its duration of action at a site by opposing the local vasodilatory effects of lidocaine, therefore decreases the rate of absorption limiting systemic exposure and prolonging the duration of action.

Infusions of lidocaine (and procaine) have been used to supplement general anesthetic techniques, as they are capable of reducing the minimum alveolar concentration of volatile anesthetics by up to 40% as well as providing pain relief in the peri-operative phase ¹⁾. Given intravenously, lidocaine can be used during advanced airway management as an adjuvant to tracheal intubation, obtunding the hypertensive response to laryngoscopy and potentially reducing the incidence of myalgia and hyperkalemia when succinylcholine is given ²⁾. Lidocaine is a class Ib antiarrhythmic agent on the Vaughan-Williams classification, and its use is indicated in the management of acute ventricular tachydysrhythmias. It also has roles as an adjuvant analgesic in the management of chronic pain.

Lidocaine monitoring

Lidocaine local anesthetics are metabolized (N-dealkylation and hydroxylation) by microsomal P-450 enzymes in the liver ³⁾. Lidocaine has a narrow therapeutic index, and plasma level monitoring may be necessary for patients with hepatic impairment who are on prolonged infusions.

Lidocaine contraindications

Lidocaine is contraindicated in patients with a known severe adverse reaction. Anaphylactic reactions to lidocaine are possible but rare.

Methemoglobinemia can occur due to lidocaine metabolism to O-toluidine ⁴⁾. This metabolite is more likely when very high doses are given, but it may also occur with lower doses where the patient is taking other medications that can precipitate methemoglobinemia, or where the patient has a hemoglobinopathy or another cause of anemia.

Lidocaine should not be used as an antiarrhythmic if the dysrhythmia may be secondary to local anesthetic toxicity.

Lidocaine preparations containing epinephrine cause demonstrable cardiovascular effects even if only given in small amounts, and it is prudent for basic hemodynamic monitoring to be carried out before and during use solutions containing vasopressors, particularly if there is any specific concern over the patient’s cardiovascular status ⁵⁾.

How long does lidocaine last?

Lidocaine injection typically begins working within four minutes and lasts for half an hour and up to three hours.

Lidocaine mechanism of action

Lidocaine mechanism of anesthetic action is believed to be based upon inhibition of voltage-gated sodium ion channels on the internal surface of nerve cell membranes, which results in membrane stabilization and slowing of membrane depolarization and repolarization ⁶⁾. The uncharged form diffuses through neural sheaths into the axoplasm before it then ionizes by combining with hydrogen ions. The resulting cation binds reversibly to sodium channels from the inside, locking them in the open state and preventing nerve depolarization. As lidocaine is a weak base with a dissociation constant (pKa) of 7.7 ⁷⁾, approximately 25% of molecules will be un-ionized at a physiological pH of 7.4 and will be available to translocate inside the nerve cells, meaning that lidocaine has a more rapid onset of action than other local anesthetics with higher pKa values. Efficacy decreases in the presence of inflammation; this can be due to acidosis decreasing the proportion of un-ionized lidocaine molecules, a faster decrease in lidocaine concentration due to increased blood flow, and potentially also increased production of inflammatory mediators like peroxynitrite which act directly on sodium channels ⁸⁾.

In cardiac myocytes (heart muscle), lidocaine slows the rise of the cardiac action potential during phase 0, thereby increasing the effective threshold potential.

Lidocaine is 65% protein-bound to albumin and alpha1-acid glycoprotein in the plasma, giving it a medium duration of action compared to other local anesthetic agents. It is less lipid soluble than other agents, limiting its overall potency. Its volume of distribution is 0.7 to 1.5 L/kg and is hepatically metabolized.

Lidocaine special precautions

Before taking lidocaine:

You should not receive lidocaine if you are allergic to lidocaine injection or any other type of numbing medicine, or if you have:

• severe heart block;
• a heart rhythm disorder called Stokes-Adams syndrome (sudden slow heart beats that can cause you to faint); or
• a heart rhythm disorder called Wolff-Parkinson-White Syndrome (sudden fast heartbeats that can cause you to faint or become easily tired).

Tell your doctor if you have ever had:

• an allergy to corn products;
• liver disease;
• kidney disease;
• heart disease (unless you are being treated with lidocaine injection for a heart condition);
• coronary artery disease, circulation problems; or
• malignant hyperthermia.

Lidocaine may cause a rare, but serious blood problem called methemoglobinemia. The risk may be increased in children younger than 6 months of age, elderly patients, or patients with certain inborn defects. It is more likely to occur in patients receiving too much of the medicine, but can also occur with small amounts. Check with your doctor right away if you or your child has the following symptoms after receiving lidocaine: pale, gray, or blue-colored skin, lips, or nails, confusion, headache, lightheadedness, fast heartbeat, or unusual tiredness or weakness.

If you receive lidocaine into your lower back (epidural), you may experience temporary loss of sensation and movement, usually in the lower half of your body. Talk with your doctor if you have concerns.

It is not known whether lidocaine will harm an unborn baby. Tell your doctor if you are pregnant.

It may not be safe to breast-feed while using lidocaine. Ask your doctor about any risk.

Lidocaine may affect the results of certain medical tests.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

In deciding to use lidocaine, the risks of taking lidocaine must be weighed against the good it will do. This is a decision you and your doctor will make. For lidocaine, the following should be considered:

Lidocaine allergy

Tell your doctor if you have ever had any unusual or allergic reaction to lidocaine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Because of lidocaine’s toxicity, it should be used with extreme caution in children younger than 6 months of age. Recommended doses should not be exceeded, and the patient should be carefully monitored during treatment.

Geriatric

No information is available on the relationship of age to the effects of lidocaine injection in geriatric patients. However, because of lidocaine’s toxicity, it should be used with caution. Recommended doses should not be exceeded, and the patient should be carefully monitored during treatment.

Breastfeeding

Studies in women suggest that this medication poses minimal risk to the infant when used during breastfeeding.

Lidocaine Drug Interactions

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking lidocaine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using lidocaine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Dihydroergotamine
• Dronedarone
• Saquinavir
• Vernakalant

Using lidocaine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Amifampridine
• Amiodarone
• Amprenavir
• Arbutamine
• Atazanavir
• Bupivacaine Liposome
• Bupropion
• Cobicistat
• Dasabuvir
• Delavirdine
• Disopyramide
• Donepezil
• Encainide
• Etravirine
• Flecainide
• Fosamprenavir
• Fosphenytoin
• Fospropofol
• Hyaluronidase
• Lacosamide
• Lopinavir
• Metoprolol
• Mexiletine
• Moricizine
• Nadolol
• Ombitasvir
• Paritaprevir
• Phenytoin
• Procainamide
• Propafenone
• Propofol
• Propranolol
• Quinidine
• Sotalol
• St John’s Wort
• Succinylcholine
• Telaprevir
• Tocainide

Using lidocaine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Cimetidine
• Penbutolol

Other Interactions

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of lidocaine. Make sure you tell your doctor if you have any other medical problems, especially:

• Blood vessel disease or
• Heart disease or
• Hypertension (high blood pressure) or
• Liver disease—Use with caution. The chance of side effects may be increased.
• Brain or nerve disease or
• Heart block or
• Hypertension (high blood pressure), severe or
• Sepsis or
• Shock, severe or
• Spine problems—Use with caution.
• Glucose-6-phosphate dehydrogenase deficiency (G6PD) or
• Heart problems or
• Lung or breathing problems or
• Methemoglobinemia (blood disorder), hereditary or idiopathic (unknown cause)—Use with caution. May increase risk of having methemoglobinemia.

Lidocaine can impair the ability of iron in red blood cells to carry oxygen to the tissues. Methemoglobinemia is the condition of having blood that has this altered kind of iron. Methemoglobinemia can result even from normal use of lidocaine, especially in children. Because the blood is not able to carry enough oxygen to the tissues, people with methemoglobinemia appear very pale or even blue, feel very tired, and have shortness of breath. Methemoglobinemia can be life-threatening.

How is lidocaine injection given?

A nurse or other trained health professional will give you lidocaine in a medical facility. It is given through a needle placed into one of your veins, into your upper arm, into the head and neck area, or into the space around the spinal nerves in your lower back.

Lidocaine may cause significant pain on initial injection due to the agent stimulating nociceptors before it exerts its effects on sodium channels; this can be counteracted by buffering the lidocaine with small volumes of sodium bicarbonate shortly before use, making the solution less acidic ⁹⁾. Pain can also be reduced by warming the solution to body temperature, injecting more slowly, using narrow cannulas, and injecting at 90 degrees to the skin ¹⁰⁾.

When used to treat heart rhythm problems, lidocaine is given as an infusion into a vein.

When used as a local anesthetic, lidocaine is injected through the skin directly into the body area to be numbed.

Your breathing, blood pressure, oxygen levels, and other vital signs will be watched closely while you are receiving lidocaine injection in a hospital setting.

If you are being treated for irregular heart rhythm, your heart rate will be constantly monitored using an electrocardiograph or ECG (sometimes called an EKG). This will help your doctor determine how long to treat you with lidocaine injection.

Lidocaine side effects

Along with lidocaine’s needed effects, lidocaine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Lidocaine injection can cause side effects that may impair your thinking or reactions. Unless absolutely necessary, do not drive after receiving lidocaine injection.

Avoid eating or chewing within 1 hour after lidocaine injection is used to numb your mouth or throat. You may have trouble swallowing which could lead to choking. You may also accidentally bite the inside of your mouth if you are still numb an hour after treatment with lidocaine injection.

Most lidocaine side effects occur when lidocaine’s plasma concentrations rise to toxic levels. Lidocaine reaches the intravascular compartment most rapidly when it is administered into the intercostal space, followed by the caudal, epidural, brachial plexus, femoral and subcutaneous spaces. The maximum safe dose by body weight may be taken to be 3 mg/kg, or 7 mg/kg when using preparations with epinephrine, although the literature quotes various other doses ¹¹⁾. Smaller amounts than this can still result in side effects and toxicity if given intravascularly.

Lidocaine is thought to be more neurotoxic than other local anesthetics, especially when high concentrations applied directly to nervous tissue. Use of highly concentrated lidocaine (2.5 to 5%) for spinal anesthesia correlates with a greater incidence of transient radicular irritation syndrome, which is a self-limiting painful condition affecting the calves, thighs, and buttocks ¹²⁾.

Check with your doctor or nurse immediately if any of the following side effects occur:

Incidence not known:

• bluish-colored lips, fingernails, or palms blurred or double vision
• chest pain or discomfort
• cold, clammy, pale skin
• confusion
• continuing ringing or buzzing or other unexplained noise in the ears
• cough
• dark urine
• difficulty breathing
• difficulty swallowing
• dizziness or lightheadedness
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• drowsiness
• fast heartbeat
• fever
• headache
• hearing loss
• hives, itching, skin rash
• irregular heartbeat
• irregular, fast or slow, or shallow breathing
• loss of consciousness
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• rapid or slow heart rate
• seizures
• slow or irregular heartbeat
• sore throat
• sweating
• tightness in the chest
• tremor
• twitching
• unusual bleeding or bruising
• unusual tiredness or weakness

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Incidence not known

• cold or numb feeling
• false or unusual sense of well-being
• feeling of heat
• loss of bladder and bowel control
• loss of genital sensation and sexual function
• nervousness
• vomiting

Other lidocaine side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Lidocaine patch side effects

Lidocaine patches may cause side effects. If any of these symptoms occur, remove your patch and do not put it back on until the symptoms go away. Tell your doctor if any of these symptoms are severe or do not go away:

• burning or discomfort in the place you applied the patch
• redness or swelling of the skin under the patch

Some side effects can be serious. The following symptoms are uncommon, but if you experience any of them, call your doctor immediately:

• hives
• skin rash
• itching
• difficulty breathing or swallowing
• swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
• hoarseness
• cool, moist skin
• fast pulse or breathing
• unusual thirst
• nausea
• vomiting
• confusion
• weakness
• dizziness
• fainting

Lidocaine patches may cause other side effects. Call your doctor if you have any unusual problems while using lidocaine patches.

Lidocaine toxicity

Applied either by injection, inhalation, or as a topical agent to provide anesthesia, lidocaine has a good safety margin before reaching toxic blood levels.  Lidocaine toxicity not only is determined by the total dose (usually 4.5 mg/kg) but also by the rate of absorption, which is dependent on the blood flow of that tissue. To reduce blood flow to the injection site and therefore the rate of absorption, vasoconstrictors such as epinephrine 1:200,000 is frequently used and may increase the toxic dose to 7 mg/kg ¹³⁾. Patients who are likely to be more susceptible to local anesthetic toxicity are patients at the extremes of age and women who are pregnant. Rates of severe systemic toxicity (seizures with or without cardiac arrest) occur on the order of 1:10,000 for epidurals and up to 1:2000 for peripheral nerve blocks, depending on the type of block ¹⁴⁾.

Lidocaine toxicity to muscles and peripheral or neuraxial nerves can occur locally at the site of injection. Transient neurologic symptoms after high concentration lidocaine spinal anesthetics have been described multiple times and have led to either reducing the concentration of the dose or switching to a different agent.

In addition to direct nerve toxicity, systemic toxicity affecting the brain and/or cardiac muscle can lead to sudden and dramatic changes in the patient’s vital signs.

Finally, there are the side effects of a relative overdose at the site of injection, which can be quite dramatic. Examples include total spinal anesthesia or subdural injection of the drug that can cause severe hemodynamic compromise such as hypotension or bradycardia up to a cardiac and respiratory arrest.

Lidocaine toxicity to local nerves and muscles are thought to be a consequence of the prolonged application of high drug concentrations or the effect of preservatives in the local anesthetic solution or both ¹⁵⁾.

Systemic local anesthetic toxicity is due to high systemic plasma levels of lidocaine due to absorption of large doses of lidocaine, which depends mostly on the blood flow at the site of injection: tracheal > intercostal > caudal > paracervical > epidural > brachial plexus > subcutaneous.

Also, blind injection of large volumes into a large muscular area, such as for lumbar plexus block or sciatic nerve blocks, have all of the elements that could lead to systemic lidocaine toxicity.

Spinal anesthetics are very low in total dose and would not cause systemic lidocaine toxicity.

Inadvertent intra-arterial injections may cause local anesthetic toxicity in the tissue beds supplied by that artery even well under the systemic toxic concentration. This complication is seen mostly with injections into the neck, causing central nervous system (CNS) symptoms often during the injection or shortly after that without progressing to the feared cardiac toxicity.

Signs and symptoms of mild lidocaine toxicity become apparent at plasma levels greater than 5 mcg/mL, beginning with slurred speech, tinnitus, circumoral paresthesiae and feeling faint ¹⁶⁾. Above 10 mcg/mL, the patient may experience seizures or loss of consciousness. The myocardium and central nervous system are further depressed at 15 mcg/mL, progressing to cardiac arrhythmias, respiratory arrest and cardiac arrest above 20 mcg/mL ¹⁷⁾. Animal studies suggest that the dose of lidocaine required to result in cardiovascular collapse is 7.1 times higher than the dose needed to induce seizures ¹⁸⁾. This ratio is significantly higher than other local anesthetic agents, meaning that lidocaine may be less likely than other local anesthetics to progress rapidly through neurological signs and symptoms to full cardiovascular collapse in cases of toxic dosing.

Administration of the drug should immediately cease if toxicity is suspected. In the case of cardiorespiratory collapse, there should be airway support and breathing assistance to prevent the development of respiratory acidosis, which may exacerbate toxicity and potentiate lidocaine’s negative chronotropic and inotropic effects ¹⁹⁾. Vital function support including oxygen, IV fluids, and inotropes should be instituted if required. Intravenous lipid emulsion is indicated as a rescue therapy, especially in cases of refractory cardiovascular collapse ²⁰⁾.

Lidocaine toxicity treatment

Treatment of lidocaine toxicity is symptomatic by raising the seizure threshold through pharmacologic interventions such as administering benzodiazepines and/or barbiturates or propofol. Hyperventilation with high doses of oxygen reduces cerebral blood flow and also has been used to raise the seizure threshold ²¹⁾.

The other mainstay of treatment is to reduce the free available lidocaine concentration in the plasma by administration of lipid emulsions. Due to the high lipid solubility, infusion of lipid emulsions will bind free circulating lidocaine and lower the plasma levels. The following is the treatment algorithm suggested by the American Society of Regional Anesthesia and Pain Medicine:

“Call for Help”

• Even premonitory CNS (central nervous system) systems may progress to severe cardio-respiratory compromise, and many tasks may need to be done simultaneously such as getting code carts and fetching the lipid emulsion.

Initial Focus

• Airway management: ventilate with 100% oxygen
• Seizure suppression: benzodiazepines are preferred; AVOID propofol in patients having signs of cardiovascular instability

Alert the Nearest Facility Having Cardiopulmonary Bypass Capability

Management of Cardiac Arrhythmias

• Basic and Advanced Cardiac Life Support (ACLS) will require adjustment of medications and perhaps prolonged effort
• AVOID vasopressin, calcium channel blockers, beta-blockers, or local anesthetic
• REDUCE individual epinephrine doses to <1 mcg/kg

Lipid Emulsion (20%) Therapy (values in parenthesis are for 70kg patient)

• Bolus 1.5 mL/kg (lean body mass) intravenously over 1 minute (~100mL)
• Continuous infusion 0.25 mL/kg/min (~18 mL/min; adjust by roller clamp)
• Repeat bolus once or twice for persistent cardiovascular collapse
• Double the infusion rate to 0.5 mL/kg/min if blood pressure remains low
• Continue infusion for at least 10 minutes after attaining circulatory stability
• Recommended upper limit: Approximately ten mL/kg lipid emulsion over the first 30 minutes”

Resuscitation during lidocaine toxicity may need to include cardiopulmonary bypass, as successful outcomes have been reported even after prolonged resuscitation, which may, in part, be explained by suggestions in animal models that bupivacaine, when added to cardioplegia solution, actually improves function and reduces the cellular damage of rat isolated hearts after prolonged, cold storage.

Lidocaine toxicity prognosis

The prognosis of lidocaine toxicity depends on the site of manifestation. CNS toxicity is either self-limited or quite amenable to treatment with benzodiazepines, has a good prognosis without complications and does not need further neurologic testing. Cardiac toxicity may require prolonged resuscitation, but the prognosis after return to spontaneous circulation is often very good ²²⁾.

Desipramine

Desipramine is an oral tricyclic antidepressant (TCA) that widely used to treat depression. Desipramine has been used off-label to treat bulimia nervosa, irritable bowel syndrome, neuropathic pain, overactive bladder, post-herpetic neuralgia, and ADHD ¹⁾. Desipramine hydrochloride is found in the medicine called Norpramin. Desipramine works by increasing the amounts of certain natural substances in the brain that are needed for mental balance. Desipramine acts by inhibition of serotonin and norepinephrine reuptake within synaptic clefts in the central nervous system, thus increasing brain levels of these neurotransmitters. Desipramine was approved therapy of depression in the United States in 1964. Desipramine is available only with your doctor’s prescription.

Desipramine is available in generic forms and under the brand names of Norpramin in 10, 25, 50, 75, 100 and 150 mg tablets to be taken by mouth with or without food. The usual recommended dose for depression in adults is 100 to 200 mg daily in one or two divided doses. Desipramine can also be given as a single nighttime dose. Your doctor may start you on a low dose of desipramine and gradually increase your dose. Take desipramine at around the same time(s) every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take desipramine exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

It may take 2 to 3 weeks for you to feel the full benefit of desipramine. Continue to take desipramine even if you feel well. Do not stop taking desipramine without talking to your doctor. If you suddenly stop taking desipramine, you may experience withdrawal symptoms such as nausea, headache, and weakness. Your doctor will probably want to decrease your dose gradually.

Desipramine common side effects include dizziness, headache, insomnia, somnolence, restlessness, confusion, gastrointestinal upset, increased appetite, weight gain, blurred vision, dry mouth and urinary retention.

Desipramine mechanism of action

Currently, the most widely accepted theory of desipramine’s mechanism of action is that it blocks the reuptake of norepinephrine and serotonin in the presynaptic neuronal membrane. Secondary amine tricycle antidepressants such as desipramine have been proposed to have greater norepinephrine blockade compared to that of tertiary amine tricyclic antidepressants, which have greater blockade at serotonin receptors. Reuptake blockade increases the available amount of neurotransmitter in the synapse. Antinociceptive effects of desipramine are believed to be achieved via manipulation of norepinephrine. In addition to these mechanisms, desipramine appears to downregulate beta-adrenergic receptors and serotonin receptors. It also proposed to have alpha-1 blocking, antihistamine, and anticholinergic effects as well ²⁾.

What is desipramine used for?

Desipramine is U.S. Food and Drug Administration (FDA) approved for the treatment of depression. Desipramine is not considered the first line for depression due to the several adverse effects of this drug. Desipramine has been used off-label to treat bulimia nervosa, irritable bowel syndrome, neuropathic pain, overactive bladder, post-herpetic neuralgia, and ADHD ³⁾. Efficacy of desipramine can be established within the first 2 weeks of treatment of bulimia nervosa patients. This was established by a study of 77 patients plotted on a receiver operating character curve examining the relationship between time and symptom reduction. Alleviation of symptoms in irritable bowel syndrome and neuropathic pain is accomplished by the antinociceptive properties of Desipramine. Desipramine has been shown to have therapeutic antinociceptive benefits most likely via its influence of norepinephrine. In addition to patients with simple overactive bladder, desipramine was found useful in patients with complex overactive bladder caused by pelvic radiation and overactive bladder with pain. Desipramine has been established as one of the first-line drugs in treating postherpetic neuralgia, however, due to its toxic profile physicians are often inclined to use second-line medications such as gabapentin. Desipramine has shown mild effectiveness in the treatment of ADHD ⁴⁾.

Desipramine monitoring

The optimal range has not been established for desipramine, but some studies site the range is between 50ng/ml -300ng/ml. 115ng/ml was shown to be an important median in another research study showing efficacy in elderly melancholic patients. Patients below 115ng/ml tended to not respond to treatment. A similar conclusion was reached in younger patient populations with the same median. Treatment with this drug requires a minimum of 2-3 weeks to see the full effect. Desipramine is metabolized in the liver and should be monitored for possible under-metabolism or over-metabolism with other drugs that metabolize in the liver such as cimetidine. Another important point is to watch for worsening of depression or the emergence of suicidal ideas during the initial period of taking this medication in patients under 24. It is generally believed that antidepressants will precipitate a manic or mixed episode in a bipolar patient. Extreme precautions should be taken in a patient with cardiovascular disease due to conduction defects, tachycardia, stroke, and acute myocardial infarction. Patient with a family history of sudden death, cardiac dysrhythmia, or cardiac conduction distances should be intensely monitored. Widening of QRS complex greater than 100 msec is a common indicator of toxicity. Renal function should be assessed because Desipramine is primarily exerted in the urine. Although bone marrow suppression and acute hepatitis are adverse side effects of this drug, there is no need to monitor these situations in the absence of history or symptoms. Antidepressant discontinuation syndrome may occur if you abruptly discontinue desipramine. This syndrome consists of mild flu-like symptoms that can last up to 2 weeks. Additional symptoms include insomnia, nausea, dizziness, gastrointestinal complaints, imbalance, sensory disturbances, and hyperarousal. These symptoms can emerge hours to days after discontinuing this drug and are immediately relieved by the reestablishment of antidepressant therapy. Suspicion of this syndrome should lead to questioning of patients medication regime or of any scheduling where they skip days of treatment. To avoid antidepressant discontinuation syndrome, Desipramine should be slowly tapered over a period of weeks to months.

Desipramine Toxicity

Desipramine has resulted in a higher death rate compared to other tricyclic antidepressants. An overdose of desipramine results in cardiac dysrhythmia, critical hypotension, convulsions, becoming comatose, convulsions, hyperactive reflexes, stupid, drowsiness, hypothermia, and confusion. Serotonin syndrome is acquired to due excessive serotonin often causes but a mixture of antidepressant and monoamine oxidase inhibitors (MAOIs). Signs and symptoms of serotonin syndrome include hyperthermia, agitation, dilated pupils, dilated pupils, tremor, akathisia, muscle rigidity, increased bowel sounds, flushed skin, and diaphoresis. First line treatment for acute toxicity is supportive care, serum alkalization, ECG, and gastric decontamination. Observation must be for at least 6 hours for unexplained syncope shortness of breath palpitations and chest pain. Gastrointestinal decontamination should be initiated via activated charcoal as soon as possible. Emesis is contraindicated with the toxicity of desipramine. In patients with serotonin syndrome, management consists of supportive care and serotonin antagonists.

Desipramine contraindications

Desipramine is contraindicated in patients that have used monoamine oxidase inhibitors within the last 14 days to avoid serotonin syndrome. Such contraindicated drugs include tranylcypromine, phenelzine, isocarboxazid, selegiline, intravenous methylene blue, and linezolid. Desipramine is contraindicated in the acute recovery period following myocardial infarction. This drug should not be used in those who have had prior hypersensitivity to the drug. Having cross-sensitivity between this drug and other dibenzazepine drugs is possible.

Desipramine special precautions

Before taking desipramine:

• tell your doctor and pharmacist if you are allergic to desipramine, clomipramine (Anafranil), imipramine (Tofranil), trimipramine (Surmontil), any other medications, or any of the ingredients in desipramine tablets. Ask your doctor or pharmacist for a list of the ingredients.
• tell your doctor if you are taking a monoamine oxidase (MAO) inhibitor such as isocarboxazid (Marplan), linezolid (Zyvox), methylene blue, phenelzine (Nardil), selegiline (Eldepryl, Emsam, Zelapar), and tranylcypromine (Parnate), or if you have stopped taking an MAO inhibitor within the past 14 days. Your doctor will probably tell you not to take desipramine. If you stop taking desipramine, you should wait at least 14 days before you start to take an MAO inhibitor.
• tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, herbal products and nutritional supplements you are taking or plan to take. Be sure to mention any of the following: anticoagulants (blood thinners) such as warfarin (Coumadin); antihistamines; cimetidine (Tagamet); estrogens; flecainide (Tambocor); fluoxetine (Prozac); guanethidine (Ismelin); levodopa (Sinemet, Larodopa); lithium (Eskalith, Lithobid); medication for high blood pressure, seizures, Parkinson’s disease, diabetes, mental illness, nausea, asthma, colds, or allergies; methylphenidate (Ritalin); muscle relaxants; oral contraceptives; phenobarbital; propafenone (Rythmol); quinidine; sedatives; selective serotonin reuptake inhibitors (SSRIs) such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem), fluvoxamine (Luvox), paroxetine (Paxil), and sertraline (Zoloft); sleeping pills; thyroid medications; and tranquilizers. Your doctor may need to change the doses of your medications or monitor you carefully for side effects. Your doctor may tell you not to take desipramine if you have stopped taking fluoxetine during the past 5 weeks.
• tell your doctor if you have recently had a heart attack. Your doctor may tell you that you should not take desipramine.
• tell your doctor if anyone in your family has or has ever had an irregular heartbeat or has died suddenly. Also tell your doctor if you have or have ever had heart or blood vessel disease such as high blood pressure, atherosclerosis (hardening of the arteries), angina (chest pain), irregular heartbeat, or a heart attack; an enlarged prostate (a male reproductive gland) difficulty urinating; diabetes; seizures; an overactive thyroid gland; schizophrenia (a mental illness that causes disturbed or unusual thinking, loss of interest in life, and strong or inappropriate emotions); or liver or kidney disease.
• tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. If you become pregnant while taking desipramine, call your doctor.
• talk to your doctor about the risks and benefits of taking desipramine if you are 65 years of age or older. Older adults should not usually take desipramine because it is not as safe or effective as other medications that can be used to treat the same condition.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking desipramine.
  you should know that this medication may make you drowsy. Do not drive a car or operate machinery until you know how this medication affects you.
• ask your doctor about the safe use of alcohol while you are taking this medication.
• tell your doctor if you use tobacco products. Cigarette smoking may decrease the effectiveness of this medication.
• you should know that desipramine may cause angle-closure glaucoma (a condition where the fluid is suddenly blocked and unable to flow out of the eye causing a quick, severe increase in eye pressure which may lead to a loss of vision). Talk to your doctor about having an eye examination before you start taking this medication. If you have nausea, eye pain, changes in vision, such as seeing colored rings around lights, and swelling or redness in or around the eye, call your doctor or get emergency medical treatment right away.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of desipramine in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of desipramine in the elderly. However, elderly patients are more likely to have confusion, falling episodes, and age-related kidney problems, which may require an adjustment in the dose for patients receiving desipramine.

Breastfeeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Desipramine drug interactions

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking desipramine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using desipramine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Bepridil
• Bromopride
• Cisapride
• Dronedarone
• Furazolidone
• Grepafloxacin
• Iproniazid
• Isocarboxazid
• Levomethadyl
• Linezolid
• Mesoridazine
• Methylene Blue
• Metoclopramide
• Moclobemide
• Pargyline
• Phenelzine
• Pimozide
• Piperaquine
• Procarbazine
• Ranolazine
• Rasagiline
• Safinamide
• Selegiline
• Sparfloxacin
• Terfenadine
• Thioridazine
• Tranylcypromine
• Ziprasidone

Using desipramine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acecainide
• Aceclofenac
• Acemetacin
• Albuterol
• Alfentanil
• Alfuzosin
• Almotriptan
• Amiodarone
• Amisulpride
• Amitriptyline
• Amoxapine
• Amphetamine
• Amtolmetin Guacil
• Anagrelide
• Apomorphine
• Aprindine
• Aripiprazole
• Aripiprazole Lauroxil
• Arsenic Trioxide
• Asenapine
• Aspirin
• Astemizole
• Azimilide
• Azithromycin
• Benzhydrocodone
• Benzphetamine
• Bretylium
• Bromfenac
• Bufexamac
• Buprenorphine
• Bupropion
• Buserelin
• Butorphanol
• Celecoxib
• Ceritinib
• Chloral Hydrate
• Chloroquine
• Chlorpromazine
• Choline Salicylate
• Ciprofloxacin
• Clarithromycin
• Clofazimine
• Clomipramine
• Clonidine
• Clonixin
• Clozapine
• Codeine
• Crizotinib
• Cyclobenzaprine
• Dabrafenib
• Darifenacin
• Darunavir
• Dasatinib
• Degarelix
• Delamanid
• Deslorelin
• Desmopressin
• Desvenlafaxine
• Deutetrabenazine
• Dexibuprofen
• Dexketoprofen
• Dextroamphetamine
• Dextromethorphan
• Diclofenac
• Diflunisal
• Dihydrocodeine
• Dipyrone
• Disopyramide
• Dofetilide
• Dolasetron
• Domperidone
• Donepezil
• Doxorubicin
• Doxorubicin Hydrochloride Liposome
• Droperidol
• Droxicam
• Efavirenz
• Encorafenib
• Enflurane
• Entacapone
• Epinephrine
• Erythromycin
• Escitalopram
• Etodolac
• Etofenamate
• Etoricoxib
• Felbinac
• Fenoprofen
• Fentanyl
• Fepradinol
• Feprazone
• Fingolimod
• Flecainide
• Floctafenine
• Fluconazole
• Flufenamic Acid
• Fluoxetine
• Flurbiprofen
• Foscarnet
• Frovatriptan
• Gatifloxacin
• Gemifloxacin
• Glasdegib
• Glycopyrrolate
• Glycopyrronium Tosylate
• Gonadorelin
• Goserelin
• Granisetron
• Halofantrine
• Haloperidol
• Halothane
• Histrelin
• Hydrocodone
• Hydromorphone
• Hydroxychloroquine
• Hydroxytryptophan
• Hydroxyzine
• Ibuprofen
• Ibutilide
• Iloperidone
• Imipramine
• Indomethacin
• Inotuzumab Ozogamicin
• Iobenguane I 123
• Iobenguane I 131
• Isoflurane
• Isoproterenol
• Isradipine
• Ivabradine
• Ivosidenib
• Ketoconazole
• Ketoprofen
• Ketorolac
• Lapatinib
• Leuprolide
• Levalbuterol
• Levofloxacin
• Levomilnacipran
• Levorphanol
• Lidoflazine
• Lisdexamfetamine
• Lithium
• Lofexidine
• Lopinavir
• Lorcainide
• Lorcaserin
• Lornoxicam
• Loxapine
• Loxoprofen
• Lumefantrine
• Lumiracoxib
• Macimorelin
• Meclofenamate
• Mefenamic Acid
• Mefloquine
• Meloxicam
• Meperidine
• Metaxalone
• Methadone
• Methamphetamine
• Metronidazole
• Mifepristone
• Mirtazapine
• Moricizine
• Morniflumate
• Morphine
• Morphine Sulfate Liposome
• Moxifloxacin
• Nabumetone
• Nafarelin
• Nalbuphine
• Naproxen
• Naratriptan
• Nefopam
• Nepafenac
• Niflumic Acid
• Nilotinib
• Nimesulide
• Nimesulide Beta Cyclodextrin
• Norepinephrine
• Norfloxacin
• Nortriptyline
• Octreotide
• Ofloxacin
• Ondansetron
• Osimertinib
• Oxaprozin
• Oxycodone
• Oxymetazoline
• Oxymorphone
• Oxyphenbutazone
• Paliperidone
• Palonosetron
• Panobinostat
• Parecoxib
• Paroxetine
• Pasireotide
• Pazopanib
• Peginterferon Alfa-2b
• Pentamidine
• Pentazocine
• Phenylbutazone
• Phenylephrine
• Piketoprofen
• Pimavanserin
• Piroxicam
• Pitolisant
• Posaconazole
• Pranoprofen
• Procainamide
• Prochlorperazine
• Proglumetacin
• Promethazine
• Propafenone
• Propyphenazone
• Proquazone
• Protriptyline
• Quetiapine
• Quinidine
• Quinine
• Remifentanil
• Revefenacin
• Ribociclib
• Risperidone
• Rofecoxib
• Salicylic Acid
• Salsalate
• Scopolamine
• Secretin Human
• Sematilide
• Sertindole
• Sertraline
• Sevoflurane
• Siponimod
• Sodium Phosphate
• Sodium Phosphate, Dibasic
• Sodium Phosphate, Monobasic
• Sodium Salicylate
• Solifenacin
• Sorafenib
• Sotalol
• Spiramycin
• Sufentanil
• Sulfamethoxazole
• Sulindac
• Sulpiride
• Sultopride
• Sumatriptan
• Sunitinib
• Tacrolimus
• Tapentadol
• Tedisamil
• Tegafur
• Telavancin
• Telithromycin
• Tenoxicam
• Tetrabenazine
• Tiaprofenic Acid
• Tiotropium
• Tolfenamic Acid
• Tolmetin
• Toremifene
• Tramadol
• Trazodone
• Triclabendazole
• Trifluoperazine
• Trimethoprim
• Trimipramine
• Triptorelin
• Valdecoxib
• Vandetanib
• Vardenafil
• Vasopressin
• Vemurafenib
• Venlafaxine
• Vilanterol
• Vilazodone
• Vinflunine
• Voriconazole
• Vortioxetine
• Zolmitriptan
• Zotepine
• Zuclopenthixol

Using desipramine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acenocoumarol
• Alprazolam
• Arbutamine
• Atomoxetine
• Bethanidine
• Cannabis
• Carbamazepine
• Cimetidine
• Cinacalcet
• Citalopram
• Clonazepam
• Dicumarol
• Mibefradil
• Mirabegron
• Phenprocoumon
• Ritonavir
• S-Adenosylmethionine
• Zolpidem

Other Interactions

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Other Medical Problems

The presence of other medical problems may affect the use of desipramine. Make sure you tell your doctor if you have any other medical problems, especially:

• Behavior and mood changes or
• Diabetes or
• Glaucoma, angle-closure or history of or
• Heart rhythm problems (eg, arrhythmia) or
• Schizophrenia (mental illness) or
• Seizures, history of or
• Urinary retention (trouble urinating), history of—Use with caution. May make these conditions worse.
• Bipolar disorder (mood disorder with mania and depression), or risk of or
• Heart attack, recent—Should not be used in patients with these conditions.
• Heart or blood vessel disease or
• Thyroid disease—Use with caution. May cause side effects to become worse.
• Kidney disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

Desipramine dosage

Desipramine is administered orally and comes in tablets of 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, and 150 mg. For depression, the initial dosage should be started at 25 mg to 50 mg daily and increased to 100 mg to 200 mg. The maximum dose is 300 mg a day, usually in an inpatient or hospital setting to monitor for possible adverse effects.

The dose of desipramine will be different for different patients. Follow your doctor’s orders or the directions on the label. The following information includes only the average doses of desipramine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of desipramine that you take depends on the strength of the desipramine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take desipramine depend on the medical problem for which you are using desipramine.

For oral dosage form (tablets):

For depression:

• Adults—100 to 200 milligrams (mg) once a day or in divided doses during the day. Your doctor may adjust your dose if needed. However, the dose is usually not more than 300 mg per day.
• Older adults and teenagers—25 to 100 mg once a day or in divided doses during the day. Your doctor may adjust your dose if needed. However, the dose is usually not more than 150 mg per day.
• Children—Use and dose must be determined by your doctor.

What should I do if I forget a dose?

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Desipramine side effects

Desipramine has a wide toxic profile including an increased risk for suicide, orthostatic hypotension, cardiac abnormalities, seizures, ocular crisis, and fractures. A short-term study showed a significantly increased risk of suicide in children, adolescents and young adults ages 24 and younger. This is one of the most important adverse effects to consider when prescribing desipramine. Orthostatic hypotension, likely due to blockade of alpha one receptors, is a common reason for discontinuation of this drug. Cardiovascular side effects such as heart block, arrhythmias, and sudden death have been reported with this drug. Screening for conduction disease with special attention to QT interval and the history of cardiac disease within the family is highly recommended before the prescription ⁵⁾.

Anticholinergic properties lead to side effects such as blurred visions, constipation tachycardia, confusions, dry mouth, urinary retention, delirium, and the ocular crisis in patients with narrow-angle glaucoma. A recent study shows an increased risk for dementia due to the anticholinergic properties of this drug and that this risk is additive with other drugs that have anticholinergic properties. There is an increased risk of osteoporotic fracture with desipramine and all other antidepressants. Osteoblasts, osteocytes, and osteoclasts all have serotonin receptors, indicating a relationship between the neuroendocrine system and bone. Seizure threshold seems to decrease.

Other side effects include acute hepatitis, bone marrow toxicity, sexual dysfunction, seizures, sedation, tremors, and diaphoresis. Diaphoresis has been proposed to be caused by noradrenergic receptor manipulation. With sexual dysfunction, there have been reports of impaired arousal and orgasms likely due to serotonergic effects. Although less sedating compared to other tricyclics, desipramine’s antihistaminic properties lead to sedation. Relative to the drug class of tricyclic antidepressants, desipramine is the least likely to cause the side effects listed.

Desipramine may cause side effects. Call your doctor if any of these symptoms become severe or do not go away:

• nausea
• drowsiness
• weakness or tiredness
• nightmares
• dry mouth
• skin more sensitive to sunlight than usual
• changes in appetite or weight
• constipation
• difficulty urinating
• frequent urination
• changes in sex drive or ability
• excessive sweating

Some side effects can be serious. If you experience any of the following symptoms, or those listed in the IMPORTANT WARNING or SPECIAL PRECAUTIONS section, call your doctor immediately or get emergency medical treatment:

• jaw, neck, and back muscle spasms
• slow or difficult speech
• shuffling walk
• uncontrollable shaking or movement of a part of the body
• fever
• difficulty breathing or swallowing
• severe rash
• yellowing of the skin or eyes
• irregular heartbeat
• seizures
• sore throat, fever, and other signs of infection

Desipramine hydrochloride overdose

Your local poison control center can be reached directly by calling the national toll-free Poison Help hotline (1-800-222-1222) from anywhere in the United States. This national hotline will let you talk to experts in poisoning. They will give you further instructions.

This is a free and confidential service. All local poison control centers in the United States use this national number. You should call if you have any questions about poisoning or poison prevention. It does NOT need to be an emergency. You can call for any reason, 24 hours a day, 7 days a week.

Symptoms of desipramine overdose may include the following:

• irregular heartbeat
• seizures
• coma (loss of consciousness for a period of time)
• confusion
• hallucination (seeing things that do not exist)
• widened pupils (dark circles in the middle of the eyes)
• drowsiness
• agitation
• fever
• low body temperature
• stiff muscles
• vomiting

Below are symptoms of a desipramine hydrochloride overdose in different parts of the body.

AIRWAYS AND LUNGS

Breathing slowed and labored

BLADDER AND KIDNEYS

• Urine does not flow easily
• Cannot urinate

EYES, EARS, NOSE, MOUTH, AND THROAT

• Blurred vision
• Dilated (wide) pupils
• Dry mouth

STOMACH AND INTESTINES

• Vomiting

HEART AND BLOOD

• Irregular heartbeat
• Low blood pressure
• Rapid heartbeat
• Shock

NERVOUS SYSTEM

• Agitation, restlessness, confusion, hallucinations
• Seizures
• Drowsiness
• Stupor (lack of alertness), coma
• Uncoordinated movement

Desipramine hydrochloride overdose management

Take the container to the hospital with you, if possible.

Your health care provider will measure and monitor the patient’s vital signs, including temperature, pulse, breathing rate, and blood pressure.

Tests that may be done include:

• Chest x-ray
• ECG (electrocardiogram, or heart tracing)

Treatment may include:

• Fluids through a vein (by IV)
• Medicine called an antidote to reverse the effects of the poison and treat symptoms
• Laxative
• Activated charcoal
• Breathing support, including a tube through the mouth and breathing machine (ventilator)

Desipramine hydrochloride overdose prognosis

How well a person does depends on how quickly they receive treatment. The sooner the treatment, the greater the chance of recovery.

An overdose of desipramine hydrochloride can be very serious. Complications such as pneumonia, muscle damage from lying on a hard surface for a long period of time, or brain damage from lack of oxygen may result in permanent disability. Death can occur.

What is Tambocor

Tambocor is a brand name of an oral antiarrhythmic agent (Class 1C antiarrhythmic) called flecainide, that is used in certain situations to prevent or treat certain types of life-threatening irregular heartbeats (arrhythmias). Tambocor (flecainide) works by slowing electrical signals in the heart to stabilize the heart rhythm. Flecainide was approved for use in the United States in 1985. Tambocor (flecainide) current indications include prevention and suppression of life threatening ventricular arrhythmias and conversion of supraventricular tachyarrhythmias (SVTs) and subsequent maintenance of normal sinus rhythm in patients without structural heart disease, in whom other agents were unsuccessful.

Tambocor (flecainide) is available only with your doctor’s prescription.

Tambocor (flecainide) is a benzamide derivative analogue of the local anesthetic procaine and has electrophysiological effects that resemble quinidine. Tambocor (flecainide) appears to act by blocking open sodium channels and outward potassium channels ¹⁾. As a consequence, it decreases cardiac automaticity, increases refractory periods and slows conduction.

Flecainide is available in tablets of 50, 100 and 150 mg generically to be taken by mouth and under the brand name Tambocor. The usual maintenance dose in adults is 50 to 200 mg twice daily (once every 12 hours). Some people may take Tambocor (flecainide) once every 8 hours if they experience side effects or if their condition cannot be controlled by taking Tambocor (flecainide) every 12 hours. Take Tambocor (flecainide) at around the same times every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take Tambocor (flecainide) exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

You may be hospitalized when you begin your treatment with Tambocor (flecainide). Your doctor will monitor you carefully during this time and for as long as you continue to take Tambocor (flecainide). Your doctor will probably start you on a low dose of Tambocor (flecainide) and gradually increase your dose, not more than once every 4 days. Your doctor may also decrease your dose once your condition is controlled.

Tambocor (flecainide) may control your condition, but will not cure it. Continue to take Tambocor (flecainide) even if you feel well. Do not stop taking Tambocor (flecainide) without talking to your doctor. If you suddenly stop taking Tambocor (flecainide), your condition may become worse.

Tambocor (flecainide) most common side effects include dizziness, visual blurring, headache, fatigue, anxiety, gastrointestinal upset and nausea.

How long does it take for Tambocor to work?

Time to Peak

• Serum: ~3 hours (range: 1 to 6 hours)

Half-Life Elimination

• Newborns: Up to ≤29 hours; 3 months: 11 to 12 hours; 12 months: 6 hours
• Children: ~8 hours
• Adolescents 12 to 15 years: ~11 to 12 hours
• Adults: ~20 hours (range: 12 to 27 hours); increased in patients with heart failure (NYHA Class III) or renal dysfunction

After administration of one XL capsule, plasma Tambocor (flecainide) concentrations gradually increase after a lag time of 2 to 3 hours to reach a peak between the 21st and 25th hour and remain at plateau levels until after the 30th hour. After reaching the steady state concentration (3-5days), it exerts maximum action.

Tambocor contraindications

Hypersensitivity to Tambocor (flecainide) or any component of the formulation; pre-existing second- or third-degree AV block or with right bundle branch block when associated with a left hemiblock (bifascicular block) (except in patients with a functioning artificial pacemaker); cardiogenic shock; concurrent use of ritonavir

According to the American College of Cardiology/American Heart Association/European Society of Cardiology, the use of Tambocor (flecainide) is considered contraindicated in patients with structural heart disease.

Tambocor special precautions

Before taking Tambocor (flecainide):

• tell your doctor and pharmacist if you are allergic to Tambocor (flecainide) or any other medications.
• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: acetazolamide (Diamox); amiodarone (Cordarone, Pacerone); ammonium chloride; antacids; beta blockers such as atenolol (Tenormin), labetalol (Trandate), metoprolol (Lopressor, Toprol XL), nadolol (Corgard), and propranolol (Inderal); carbamazepine (Carbatrol, Tegretol); cimetidine (Tagamet); clozapine (Clozaril); dichlorphenamide; digoxin (Lanoxin); diltiazem (Cardizem, Tiazac); disopyramide (Norpace); methazolamide; nifedipine (Adalat, Procardia); phenytoin (Dilantin); phenobarbital; quinidine; sodium bicarbonate (baking soda, Citrocarbonate, Soda Mint); and verapamil (Calan, Verelan). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor if you have heart block (condition in which electrical signals are not passed normally from the upper chambers of the heart to the lower chambers). Your doctor may tell you not to take Tambocor (flecainide).
• tell your doctor if you have a pacemaker (device that is surgically placed under the skin to control irregular heartbeats) and if you have or have ever had a heart attack, heart failure, or any type of heart disease; low or high levels of potassium in the blood; or liver or kidney disease. Also tell your doctor if you follow a strict vegetarian diet.
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking Tambocor (flecainide), call your doctor.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking Tambocor (flecainide).
• if you are giving this medication to an infant, be sure to talk to the doctor if there will be any major changes in the amount of milk the infant drinks. Milk can affect how the medication is absorbed in the body.

It is important that your doctor check your progress at regular visits to make sure the medicine is working properly. This will allow for changes to be made in the amount of medicine you are taking, if necessary.

Check with your doctor right away if you develop any of the following:

• chest pain;
• shortness of breath;
• swelling of your hands, ankles, or feet; or weight gain.

These may be symptoms of heart failure.

This medicine can cause changes in your heart rhythm, such as conditions called PR, QRS, or QT prolongation. It may cause fainting or serious side effects in some patients. Contact your doctor right away if your symptoms do not improve or if they become worse.

Your doctor may want you to carry a medical identification card or bracelet stating that you are using Tambocor (flecainide).

Before having any kind of surgery (including dental surgery) or emergency treatment, tell the medical doctor or dentist in charge that you are taking Tambocor (flecainide).

Tambocor (flecainide) may cause some people to become dizzy, lightheaded, or less alert than they are normally. Make sure you know how you react to Tambocor (flecainide) before you drive, use machines, or do anything else that could be dangerous if you are dizzy or are not alert.

If you have been using Tambocor (flecainide) regularly for several weeks, do not suddenly stop using it. Check with your doctor for the best way to gradually reduce the amount you are taking before stopping completely.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Pregnancy

Pregnancy Category C: Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

Breastfeeding

Studies in women suggest that this medication poses minimal risk to the infant when used during breastfeeding.

Tambocor interactions

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking Tambocor (flecainide), it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using Tambocor (flecainide) with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Amisulpride
• Bepridil
• Cisapride
• Dronedarone
• Levomethadyl
• Mesoridazine
• Pimozide
• Piperaquine
• Ritonavir
• Saquinavir
• Sparfloxacin
• Terfenadine
• Thioridazine
• Tipranavir
• Vernakalant
• Ziprasidone

Using Tambocor (flecainide) with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acecainide
• Ajmaline
• Alfuzosin
• Amiodarone
• Amitriptyline
• Amoxapine
• Anagrelide
• Apomorphine
• Aprindine
• Arbutamine
• Aripiprazole
• Aripiprazole Lauroxil
• Arsenic Trioxide
• Artemether
• Asenapine
• Astemizole
• Azimilide
• Azithromycin
• Bedaquiline
• Bendroflumethiazide
• Boceprevir
• Bretylium
• Buprenorphine
• Bupropion
• Buserelin
• Ceritinib
• Chloral Hydrate
• Chloroquine
• Chlorothiazide
• Chlorpromazine
• Chlorthalidone
• Ciprofloxacin
• Citalopram
• Clarithromycin
• Clofazimine
• Clomipramine
• Clozapine
• Cobicistat
• Crizotinib
• Cyclobenzaprine
• Dabrafenib
• Darifenacin
• Dasabuvir
• Dasatinib
• Degarelix
• Delamanid
• Delavirdine
• Desipramine
• Deslorelin
• Deutetrabenazine
• Dibenzepin
• Disopyramide
• Dofetilide
• Dolasetron
• Domperidone
• Donepezil
• Droperidol
• Duloxetine
• Efavirenz
• Encorafenib
• Enflurane
• Erythromycin
• Escitalopram
• Etravirine
• Fingolimod
• Fluconazole
• Fluoxetine
• Foscarnet
• Gatifloxacin
• Gemifloxacin
• Glasdegib
• Gonadorelin
• Goserelin
• Granisetron
• Halofantrine
• Haloperidol
• Halothane
• Histrelin
• Hydrochlorothiazide
• Hydroflumethiazide
• Hydroquinidine
• Hydroxychloroquine
• Hydroxyzine
• Ibutilide
• Iloperidone
• Imipramine
• Inotuzumab Ozogamicin
• Isoflurane
• Isradipine
• Ivabradine
• Ivosidenib
• Ketoconazole
• Lacosamide
• Lapatinib
• Leuprolide
• Levofloxacin
• Lidocaine
• Lidoflazine
• Lofexidine
• Lorcainide
• Lumefantrine
• Macimorelin
• Mefloquine
• Methadone
• Metolazone
• Metronidazole
• Mifepristone
• Moxifloxacin
• Nafarelin
• Nilotinib
• Norfloxacin
• Nortriptyline
• Octreotide
• Ofloxacin
• Ombitasvir
• Ondansetron
• Osimertinib
• Paliperidone
• Panobinostat
• Paritaprevir
• Pasireotide
• Pazopanib
• Peginterferon Alfa-2b
• Pentamidine
• Pimavanserin
• Pirmenol
• Pitolisant
• Polythiazide
• Posaconazole
• Prajmaline
• Prilocaine
• Probucol
• Procainamide
• Prochlorperazine
• Promethazine
• Propafenone
• Protriptyline
• Quetiapine
• Quinidine
• Ranolazine
• Ribociclib
• Risperidone
• Salmeterol
• Sematilide
• Sertindole
• Sertraline
• Sevoflurane
• Simeprevir
• Siponimod
• Sodium Phosphate
• Sodium Phosphate, Dibasic
• Sodium Phosphate, Monobasic
• Solifenacin
• Sorafenib
• Sotalol
• Spiramycin
• Sulfamethoxazole
• Sulpiride
• Sultopride
• Sunitinib
• Tacrolimus
• Tedisamil
• Telaprevir
• Telavancin
• Telithromycin
• Tetrabenazine
• Tizanidine
• Toremifene
• Trazodone
• Trichlormethiazide
• Triclabendazole
• Trifluoperazine
• Trimethoprim
• Trimipramine
• Triptorelin
• Vandetanib
• Vardenafil
• Vasopressin
• Vemurafenib
• Vinflunine
• Voriconazole
• Zolmitriptan
• Zotepine
• Zuclopenthixol

Using Tambocor (flecainide) with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Cimetidine
• Digoxin
• Paroxetine
• Propranolol
• Verapamil

Other Interactions

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using Tambocor (flecainide) with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use Tambocor (flecainide), or give you special instructions about the use of food, alcohol, or tobacco.

• Milk

Using Tambocor (flecainide) with any of the following may cause an increased risk of certain side effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use Tambocor (flecainide), or give you special instructions about the use of food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of Tambocor (flecainide). Make sure you tell your doctor if you have any other medical problems, especially:

• AV block (type of abnormal heart rhythm), with no pacemaker or
• Bundle branch block (heart rhythm problem), with no pacemaker or
• Cardiogenic shock (shock caused by heart attack) or
• Chronic atrial fibrillation or
• Heart attack, recent—Should not be used in patients with these conditions.
• Congestive heart failure (severe) or
• Heart disease (e.g., cardiomyopathy) or
• Sick sinus syndrome (type of abnormal heart rhythm)—Use with caution. May make these conditions worse.
• Electrolyte imbalance (e.g., high or low potassium in the blood)—Should be corrected first before using Tambocor (flecainide).
• Kidney disease or
• Liver disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.
• If you have a permanent pacemaker—Use with caution. Tambocor (flecainide) may interfere with the pacemaker and require more careful follow-up by the doctor.

What is Tambocor used for?

Tambocor (flecainide) is used to prevent or treat certain types of life-threatening irregular heartbeats (arrhythmias) such as paroxysmal supraventricular tachycardia (PSVT) and paroxysmal atrial fibrillation/flutter (PAF). Tambocor (flecainide) is also used to prevent life-threatening sustained ventricular tachycardia (sustained VT). Tambocor (flecainide) is in a class of medications called antiarrhythmics. It works by slowing electrical signals in the heart to stabilize the heart rhythm.

There is a chance that Tambocor (flecainide) may cause new or make worse existing heart rhythm problems when it is used. Since it has been shown to cause severe problems in some patients, it is only used to treat serious heart rhythm problems. Discuss this possible effect with your doctor.

Tambocor dosage

The dose of Tambocor (flecainide) will be different for different patients. Follow your doctor’s orders or the directions on the label. The following information includes only the average doses of Tambocor (flecainide). If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

For oral dosage form (tablets):

• For paroxysmal supraventricular tachycardia (PSVT) and paroxysmal atrial fibrillation/atrial flutter:
  • Adults—At first, 50 milligrams (mg) every 12 hours. Your doctor may increase your dose as needed.
  • Children—Use and dose must be determined by your doctor. Dose is based on body size and must be determined by your child’s doctor. The starting dose is 100 milligrams (mg) per square meter (m²) per day for infants 6 months and older and 50 mg/m² per day in infants younger than 6 months. Doses are divided into two or three equal doses per day.
• For sustained ventricular tachycardia (sustained VT):
  • Adults—At first, 100 milligrams (mg) every 12 hours. Your doctor may increase your dose as needed. However, the dose is usually not more than 400 mg per day.
  • Children—Use and dose must be determined by your doctor. Dose is based on body size and must be determined by your child’s doctor. The starting dose is 100 milligrams (mg) per square meter (m²) per day for infants 6 months and older and 50 mg/m² per day in infants younger than 6 months. Doses are divided into two or three equal doses per day.

Adult dose for Ventricular Tachycardia

• Initial dose: 100 mg orally every 12 hours.
• Maintenance dose: May be increased in increments of 50 mg bid every 4 days until efficacy is achieved. Most patients with SUSTAINED VT do not require more than 150 mg every 12 hours (300 mg/day), and the maximum dose recommended is 400 mg/day.

Adult dose for Atrial Fibrillation

• Initial dose: 50 mg orally every 12 hours.
• Maintenance dose: May be increased in increments of 50 mg bid every 4 days until efficacy is achieved.

Adult dose for Atrial Flutter

• Initial dose: 50 mg orally every 12 hours.
• Maintenance dose: May be increased in increments of 50 mg bid every 4 days until efficacy is achieved.

Adult dose for Wolff-Parkinson-White Syndrome

• Initial dose: 50 mg orally every 12 hours.
• Maintenance dose: May be increased in increments of 50 mg bid every 4 days until efficacy is achieved.

Adult dose for Paroxysmal Supraventricular Tachycardia

• Initial dose: 50 mg orally every 12 hours.
• Maintenance dose: May be increased in increments of 50 mg bid every 4 days until efficacy is achieved.

Pediatric dose for Supraventricular Tachycardia

Less than 1 month:

• Supraventricular tachycardia: Limited data available: Initial: 2 mg/kg/day orally divided every 12 hours; titrate to clinical response, monitor serum concentration; mean dose required to suppress SVT: 3.35 ± 1.35 mg/kg/day in 17 neonates (n=20 treated neonates; mean PNA: 11.5 days; mean GA: 36.8 weeks; mean birthweight: 2.8 kg); study did not report resultant serum concentrations.

1 month or older:

• Initial: 1 to 3 mg/kg/day orally or 50 to 100 mg/m²/day orally in 3 divided doses; usual: 3 to 6 mg/kg/day or 100 to 150 mg/m²/day in 3 divided doses; up to 8 mg/kg/day or 200 mg/m²/day for uncontrolled patients with subtherapeutic levels; higher doses have been reported, however they may be associated with an increased risk of proarrhythmias; a review of world literature reports the average effective dose to be 4 mg/kg/day or 140 mg/m²/day.

Renal Dose Adjustments

• CrCl=35 mL/min or less: Initial dose: 100 mg orally once a day or 50 mg twice a day. It may take longer than 4 days before a new steady-state plasma level is reached following a dosage change.
• In patients with less severe renal dysfunction: Initial dose: 100 mg every 12 hours.

Liver Dose Adjustments

Tambocor (flecainide) should not be used in patients with significant liver dysfunction unless the potential benefits clearly outweigh the risks, as elimination from plasma can be markedly slower in patients with significant hepatic impairment. If it is deemed necessary, frequent and early plasma level monitoring is required to guide dosage and dosage increases should be made very cautiously when plasma levels have plateaued (after more than four days).

What should I do if I forget a dose?

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Tambocor side effects

Tambocor (flecainide) may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• dizziness
• changes in vision
• headache
• weakness
• uncontrollable shaking of a part of your body
• constipation
• stomach pain

Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately:

• fast, pounding, or irregular heartbeat
• chest pain
• shortness of breath
• extreme tiredness
• nausea
• loss of appetite
• persistent cough with blood-tinged mucus
• swelling of the hands, feet, ankles, or lower legs
• confusion
• unusual bleeding or bruising
• pain in the upper right part of the stomach
• yellowing of the skin or eyes
• flu-like symptoms

More common

• difficult or labored breathing
• dizziness, fainting, or lightheadedness
• fast, irregular, pounding, or racing heartbeat or pulse
• shortness of breath
• tightness in the chest
• wheezing

Less common

• burning, crawling, itching, numbness, prickling, “pins and needles”, or tingling feelings
• chest pain
• fainting
• feeling of warmth
• fever
• increased sweating
• partial or slight paralysis
• redness of the face, neck, arms, and occasionally, upper chest
• shakiness and unsteady walk
• shakiness in the legs, arms, hands, or feet
• swelling of the feet or lower legs
• trembling or shaking of the hands or feet
• unsteadiness, trembling, or other problems with muscle control or coordination

Rare

• arm, back, or jaw pain
• black, tarry stools
• bleeding gums
• blood in the urine or stools
• blurred vision
• chest discomfort
• chest tightness or heaviness
• chills
• confusion
• convulsions
• cough
• decrease in the frequency of urination
• decrease in urine volume
• difficulty in passing urine (dribbling)
• difficulty with breathing
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• frequent urination
• general feeling of discomfort or illness
• headache
• increased volume of pale, dilute urine
• nausea
• nervousness
• noisy breathing
• painful or difficult urination
• pinpoint red spots on the skin
• pounding in the ears
• sensation of pins and needles
• slow or fast heartbeat
• sore throat
• sores, ulcers, or white spots on the lips or in the mouth
• stabbing pain
• sweating
• swollen glands
• thickening of bronchial secretions
• troubled breathing
• unusual bleeding or bruising
• unusual tiredness or weakness
• yellow eyes or skin

Tambocor (flecainide) may cause other side effects. Call your doctor if you have any unusual problems while taking Tambocor (flecainide).

Tambocor toxicity

Broadly speaking, Tambocor (flecainide) like other sodium channel blockers cause metabolic, cardiac, and neurologic symptoms. This leads to hemodynamic compromise and metabolic acidosis, potentiating the effects of the medications and causing further sodium blockade ²⁾. Patients with potential Tambocor (flecainide) toxicity require an immediate electrocardiogram (ECG). Tambocor (flecainide) toxicity leads to a widening of the QRS complex, lengthening of the QT interval, a new right axis deviation, bradydysrhythmias, ventricular tachycardia, ventricular fibrillation or torsades des pointes ³⁾. Brugada phenocopy, a sodium channelopathy disorder, can also be seen during acute toxicity ⁴⁾.

Symptoms of Tambocor toxicity may include:

• nausea
• vomiting
• seizures
• slow, fast, or irregular heartbeat
• loss of consciousness
• sudden death

Sodium channel blockers cross the blood-brain barrier and act through multiple mechanisms. They inhibit the gamma-aminobutyric acid (GABA) system (primarily lidocaine), activate the sodium ouabain-sensitive current, stimulate 5-TH2C receptors, antagonize H1 receptors and block all noradrenaline activating effect. It is through these actions that adrenergic stimulation occurs. These medications in large doses are also pro-convulsant through the above mechanisms ⁵⁾.

Co-ingestion of other drugs can alter the elimination kinetics. A recent case report describes how propafenone delayed the metabolism of metoprolol by inhibition of CYP2D. This interaction of the two medications led to a more profound toxicity, and in this case cardiovascular collapse ⁶⁾.

It is vital to consider and evaluate for any other co-ingestion.

Obtain electrolyte, renal and hepatic profiles, acetaminophen level, salicylate level, arterial or venous blood gas, drug screen, and a complete blood count. Evaluate for an anion gap, and osmolal gap as this could indicate coingestants not detectable on standard testing.

Tambocor toxicity management

Immediate initial management must begin with an assessment of airway, breathing, and circulation. Many patients present with hypotension, bradycardia or tachycardia and altered mental status. An endotracheal tube or other advanced airways should be placed in patients who are unable to protect their airway.

The cornerstone of treatment is the administration of sodium bicarbonate. It is indicated for patients with an ECG demonstrating a QRS duration >100 ms or any suspicious QT prolongation or dysrhythmia ⁷⁾. Sodium bicarbonate is beneficial in raising the serum pH and increasing the extracellular sodium. Alkalinization leads to an increase of the electrochemical gradient across cell membranes which helps to offload sodium channels. It might also increase the protein binding of the offending agent. Patients should be given 1-2mEq/kg as a bolus dose ⁸⁾. Bolus doses can be administered until the QRS duration is less than 100 ms. This can be followed with a continuous infusion of sodium bicarbonate of 2-3 50mEq ampules in one liter of D5W (5% dextrose in water) ⁹⁾. Hypertonic saline has been used but is not routinely recommended; it remains an option in dire circumstances as reported in a case of Tambocor (flecainide) overdose ¹⁰⁾.

Management of hypotension requires a combination of volume resuscitation and vasopressor and inotropic support. Use of inotropic agents such as dobutamine helps increase cardiac output while the effects of the toxicity dissipate. Addition of vasopressors such as norepinephrine, vasopressin, or epinephrine might be considered for hemodynamic support. These agents lead to vasoconstriction and an increase in the systemic vascular resistance, resulting in increased systemic blood pressure.

Patients with sodium channel blocker toxicity from lidocaine have benefitted from the administration of 20% lipid emulsion if they are hemodynamically unstable ¹¹⁾. The mechanism of action of lipid emulsion is unclear; however, it is hypothesized that it acts as a lipid sink, with an electrochemical gradient drawing the lidocaine into the lipid. Patients should be given a 1.5mL/kg bolus followed by a 0.25mL/kg infusion ¹²⁾. Few studies exist on lipid emulsion for other sodium channel toxicities.

Extracorporeal membrane oxygenation (ECMO) has been used in a refractory case with reported survival ¹³⁾. In general, the drugs which cause sodium channel blockade toxicity are highly lipophilic, have a wide volume of distribution, and are not dialyzable.

Seizure management is accomplished with benzodiazepine medications, such as lorazepam and midazolam. For refractory seizures, loading of antiepileptic medications such as levetiracetam is recommended. Phenytoin and its derivatives should be avoided in this situation as phenytoin is itself a sodium channel blocker and will likely lead to clinical deterioration. Intubation and sedation with propofol should be considered for seizures refractory to other management.

Tambocor toxicity prognosis

Complications of sodium channel blocker toxicity include cardiogenic shock, hypotension, bradycardia or tachycardia, cardiovascular collapse, respiratory depression, encephalopathy, status epilepticus, and death.

Class I antiarrhythmic toxicity is associated with a significantly higher mortality rate (22.5%) compared with other drugs (1%) ¹⁴⁾. Prompt recognition and treatment are vital to minimize morbidity and mortality.

What is Vancomycin

Vancomycin is a broad spectrum tricyclic glycopeptide antibiotic that has activity against methicillin-resistant Staphylococcus aureus (MRSA) and is generally reserved for serious drug resistant gram-positive bacteria infections. Vancomycin antibiotic is originally derived from the organism Streptococcus orientalis with primary activity against gram positive bacteria ¹⁾. Vancomycin is also utilized for streptococci, enterococci, and methicillin-susceptible Staphylococcus aureus (MSSA) infections. Vancomycin has numerous FDA-approved and off-label clinical uses ²⁾. Vancomycin was first approved for use in the United States in 1958 and it continues to be widely used, particularly with the recent rise in incidence of serious methicillin-resistant Staphylococcus aureus (MRSA) infections.

Vancomycin has a large, complex and unusual structure and is believed to act by inhibition of bacterial cell wall synthesis via binding to the cell wall precursor molecules. Vancomycin is active against, and its major use is in therapy of, infections due to methicillin-resistant Staphylococcus aureus (MRSA), including antibiotic-induced pseudomembranous colitis, staphylococcal enterocolitis, bacterial endocarditis, and sepsis. For systemic infections, vancomycin is given intravenously. For localized or nonsystemic infections, other routes of administration are used, including oral, rectal, topical, inhalational, intrathecal, intraperitoneal, and intraventricular.

The recommended vancomycin parenteral dosage in adults is 500 mg iv every 6 hours or 1000 mg every 12 hours, with modification to achieve a therapeutic range as needed. The recommended oral dosage in the treatment of antibiotic induced pseudomembranous enterocolitis is 125 to 500 mg every 6 hours for 7 to 10 days. Vancomycin is available generically and under several commercial names including Vancoled, Vancor, Lyphocin, and Vancocin in 125 and 250 mg pulvules and as power for injection or oral administration.

Vancomycin is largely well tolerated; common side effects include diarrhea, nausea, nephrotoxicity and neutropenia.

Vancomycin mechanism of action

Vancomycin is a glycopeptide antibiotic that exerts its bactericidal effect by inhibiting the polymerization of peptidoglycans in the bacterial cell wall. The bacterial cell wall contains a rigid peptidoglycan layer that has a highly cross-linked structure composed of long polymers of N-acetylmuramic acid (NAM) and N-acetylglucosamine (NAG). Vancomycin binds to D-alanyl D-alanine which inhibits glucosyltransferase (peptidylglycan synthase) and the P-phospholipid carrier, thereby preventing the synthesis and polymerization of N-acetylmuramic acid and N-acetylglucosamine within in the peptidoglycan layer. This inhibition weakens bacterial cell walls and ultimately causes leakage of intracellular components, resulting in bacterial cell death. Vancomycin is only active against gram-positive bacteria ³⁾.

What is vancomycin used for?

Vancomycin injection is used alone or in combination with other medications to treat certain serious infections such as endocarditis (infection of the heart lining and valves), peritonitis (inflammation of the lining of the abdomen), and infections of the lungs, skin, blood, and bones. Vancomycin injection is in a class of medications called glycopeptide antibiotics. It works by killing bacteria that cause infections.

Antibiotics such as vancomycin injection will not work for colds, flu, or other viral infections. Taking or using antibiotics when they are not needed increases your risk of getting an infection later that resists antibiotic treatment.

FDA-approved clinical uses of Vancomycin ⁴⁾:

• Clostridium difficile-associated diarrhea (oral administration)
• Staphylococcus enterocolitis
• Pseudomembranous colitis
• Endocarditis: Diphtheroid, Enterococcal, Staphylococcal, and Streptococcal species.
• Staphylococcal infections: septicemia, skin and soft tissue infections, bone infections, lower respiratory tract infections, etc.

Off-Label clinical uses of Vancomycin include ⁵⁾:

• Catheter-related infections
• Community-acquired bacterial pneumonia
• Clostridium difficile infection
• Neonatal prophylaxis for Group B streptococcus
• Intra-abdominal infections due to MRSA or ampicillin-resistant enterococci
• Bacterial meningitis
• Bacterial endophthalmitis (systemic or intravitreal administration)
• Native vertebral osteomyelitis
• Peritonitis
• Prosthetic joint infection
• Necrotizing skin and soft tissue infections
• Surgical prophylaxis
• Surgical-site infections

Vancomycin contraindications

Vancomycin is contraindicated in patients with a known hypersensitivity reaction to the drug or any component within the formulation ⁶⁾.

Although vancomycin does not have many contraindications, there are some important clinical considerations to keep in mind during patient care.

Vancomycin special precautions

Before using vancomycin injection:

• tell your doctor and pharmacist if you are allergic to vancomycin, any other medications, or any of the ingredients in vancomycin injection. Ask your pharmacist for a list of the ingredients.
• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: amikacin, amphotericin (Abelcet, Ambisome, Amphotec), bacitracin (Baciim); cisplatin, colistin, kanamycin, neomycin (Neo-Fradin), paromomycin, polymyxin B, streptomycin, and tobramycin. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor if you have or have ever had hearing problems or kidney disease.
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while using vancomycin injection, call your doctor.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are receiving vancomycin injection.

Vancomycin may cause a rare but serious type of an allergic reaction called an infusion reaction. This can be life-threatening and require immediate medical attention. Tell your doctor right away if you or your child starts to have cough, difficulty with swallowing, dizziness, fast heartbeat, trouble with breathing, chest tightness, swelling in your face or hands, fever, chills, itching or hives, or lightheadedness or faintness while you are receiving vancomycin.

Tell your doctor right away if you or your child have confusion, dizziness, headache, decrease in how much or how often you urinate, rapid weight gain, swelling of your hands, ankles, or feet after receiving vancomycin. This may be symptom of a serious kidney problem.

Hearing loss may occur while you are receiving vancomycin. Tell your doctor if you or your child have ringing or buzzing in the ears, dizziness, feeling of fullness in the ears, or loss of balance after receiving vancomycin.

Vancomycin may cause diarrhea, and in some cases it can be severe. It may occur 2 months or more after you stop using vancomycin. Do not take any medicine to treat diarrhea without first checking with your doctor. If you have any questions or if mild diarrhea continues or gets worse, check with your doctor.

Vancomycin can temporarily lower the number of white blood cells in your blood, increasing the chance of getting an infection. If you can, avoid people with infections. Check with your doctor immediately if you think you are getting an infection or if you get a fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination.

Vancomycin may cause severe tenderness and pain at the injection site. Contact your doctor right away if you notice any of these side effects at the injection site: bleeding, blistering, burning, coldness, discoloration of the skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Geriatric

Elderly patients are more prone to vancomycin toxicity with IV administration due to age-related changes in renal function, the volume of distribution, and accumulation. These patients need to be carefully monitored and may require a more conservative dosage regimen.

Vancomycin in Pregnancy

Oral vancomycin capsules are currently listed as a category B drug for use in pregnancy whereas the intravenous vancomycin injection is listed as category C. Vancomycin should not be used during pregnancy unless the benefits outweigh the risks of the medication. If treatment with vancomycin is necessary, close monitoring of maternal blood is recommended to reduce the risk of ototoxicity and nephrotoxicity in the fetus. Animal studies have not yet determined any evidence of fetal harm from maternal vancomycin use. However, vancomycin crosses the placenta and has been detected in fetal serum, amniotic fluid, and cord blood. Patients who become pregnant while taking vancomycin should contact their healthcare provider immediately. Moreover, it is important to note that pregnant patients may require higher doses of vancomycin to achieve therapeutic concentrations due to alterations in pharmacokinetics, such as an increased volume of distribution and total plasma clearance.

Vancomycin in Breastfeeding

Vancomycin is excreted in breast milk following intravenous administration. In comparison, oral vancomycin has minimal systemic absorption, and therefore, limited excretion through breast milk. Breastfeeding mothers who receive intravenous vancomycin should be advised to consult with their provider before continuing as it may affect the health of their baby. Nevertheless, vancomycin is recommended for the treatment of Clostridium difficile infections in breastfeeding women. Careful assessment regarding the discontinuation of breastfeeding is recommended before initiating vancomycin therapy in nursing mothers.

Renal Impairment

The reduced renal function can cause vancomycin to accumulate in the body, thereby increasing the risk of adverse effects. Dosing adjustments are necessary for renal impairment. Close monitoring of vancomycin trough concentrations is necessary for all patients with renal impairment. Patients should be advised to contact their provider if they experience symptoms of reduced kidney function, such as decreased urine output, swelling, and abdominal pain as vancomycin may exacerbate renal impairment.

Bacterial Resistance

Similar to other antimicrobials, prolonged or inappropriate treatment with vancomycin can lead to bacterial resistance such as Vancomycin-resistant enterococci (VRE). Providers need to be aware of increased antimicrobial resistance patterns and practice appropriate antimicrobial stewardship. Moreover, patients should be counseled on the importance of medication adherence to prevent the development of multidrug-resistant infections.

Vancomycin Drug Interactions

Co-administration of other medications along with vancomycin may increase the risk of adverse effects and toxicity. Therefore dosing adjustments, additional monitoring, and consideration of alternative treatment should be considered when combining vancomycin with certain medications. Caution is advised when administering vancomycin with other nephrotoxic agents such as aminoglycosides, amphotericin products, and IV contrast.

Using vancomycin with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Amikacin
• Cholera Vaccine, Live
• Gentamicin
• Piperacillin
• Tobramycin

Using vancomycin with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Succinylcholine
• Warfarin

Other Interactions

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of vancomycin. Make sure you tell your doctor if you have any other medical problems, especially:

Allergy to corn or corn products—Should not be used in patients with this condition.

• Congestive heart failure or
• Hearing loss or
• Kidney disease—Use with caution. May cause side effects to become worse.

Vancomycin administration

Vancomycin is FDA-approved for administration by either intravenous injection or oral route. Rectal administration is an off-label use of vancomycin that can be used to treat Clostridium difficile infection. Administration is dependent on the type and location of the infection. Vancomycin has poor oral bioavailability; therefore, it must be administered intravenously in order to treat most infections ⁷⁾.

Intravenous vancomycin injection can be used to treat MRSA infections as well as other susceptible gram-positive organisms. The dose of vancomycin required is dependent on the type and severity of infection, the patient’s overall clinical presentation, renal function, and body weight. The desired intravenous dose should be administered slowly over at least 60 minutes. The frequency of administration ranges from every 8 to 24 hours and should be adjusted based on renal function, age, and serum trough concentrations. Serum trough concentrations should be closely monitored in all patients.

Oral vancomycin has low systemic absorption and is only effective for treating intestinal infections. Therefore, it is only indicated for treatment of Clostridium difficile-associated diarrhea, pseudomembranous colitis, and Staphylococcal enterocolitis. Oral vancomycin is not an appropriate treatment option for systemic infections affecting other organs or parts of the body. Oral vancomycin is currently available as capsules and an oral solution. It is typically administered four times a day for a period of 7 to 10 days. However, the exact dose and length of therapy are determined by multiple factors, including indication, assessment of the patient’s clinical presentation, and the severity of an infection. Oral vancomycin does not require dosage adjustment for renal impairment due to its low systemic absorption. Moreover, routine serum trough monitoring is not recommended for patients who are only receiving oral vancomycin ⁸⁾.

Pharmacodynamics/Kinetics:

• Route of administration: Intravenous, oral, rectal administration (off-label)
• Inhibition of bacterial growth: Slowly bactericidal
• PK/PD parameter: AUC:MIC
• Absorption: Oral vancomycin has a bioavailability of less than 10%.
• Onset of action: Vancomycin has a rapid onset of action with a serum peak concentration immediately following the completion of the intravenous infusion. The onset of action of oral vancomycin is currently unknown.
• Distribution: Large volume of distribution (0.4 L/kg to 1.0 L/kg) in body tissues and fluids, excluding cerebrospinal fluid (CSF) with non-inflammed meninges
• Protein Binding: approximately 55%
• Metabolism: No evident metabolism (excreted unchanged)
• Clearance: 0.71 mL/minute/kg to 1.31 mL/minute/kg in adults with normal renal function
• Half-life: Vancomycin has a bi-phasic elimination half-life with its initial half-life being relatively quick and terminal half-life of 4 to 6 hours in healthy adults with normal renal function. The elimination half-life is significantly prolonged in patients with renal dysfunction. Close monitoring is required in these patients.
• Excretion: Intravenous vancomycin injection is primarily eliminated by glomerular filtration in the kidney (75% via urine). Oral vancomycin is predominantly excreted in feces.
• Therapeutic drug monitoring/range: 10 to 20 mcg/mL (trough)
• AAP Recommendations:
  • Invasive MRSA infections: At least a 400 mghr/L 24-hour AUC to MIC ratio is recommended.
  • Neonates with a MIC 1 mg/L: 10 to 12 mg/L (trough)

Vancomycin dose

Vancomycin oral dose

The dose of vancomycin will be different for different patients. Follow your doctor’s orders or the directions on the label. The following information includes only the average doses of vancomycin. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

For oral dosage forms (capsules or oral liquid):

For treatment of C. difficile-associated diarrhea:

• Adults—125 milligrams (mg) 4 times a day for 10 days.
• Children—Dose is based on body weight and must be determined by the doctor. The usual dose is 40 milligrams per kilogram (mg/kg) of body weight, divided into 3 or 4 doses, and taken for 7 to 10 days. However, the total daily dose is usually not more than 2000 mg per day.

For treatment of Staphylococcal enterocolitis:

• Adults—500 to 2000 milligrams (mg) divided into 3 or 4 doses for 7 to 10 days.
• Children—Dose is based on body weight and must be determined by the doctor. The usual dose is 40 milligrams per kilogram (mg/kg) of body weight, divided into 3 or 4 doses, and taken for 7 to 10 days. However, the total daily dose is usually not more than 2000 mg per day.

What should I do if I forget a dose?

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Vancomycin IV dose

A nurse or other trained health professional will give you vancomycin IV in a hospital. Vancomycin is given through a needle placed in one of your veins.

Adult dose for Bacterial Infection

• 500 mg IV every 6 hours OR 1 g IV every 12 hours

Use: Empirical treatment of serious/severe staphylococcal infections caused by susceptible strains of methicillin-resistant staphylococci in patients who are allergic to penicillin, failed to respond/cannot receive other drugs (e.g., penicillins, cephalosporins), and/or to treat organisms that are resistant to other drugs

Comments:

• Vancomycin should be administered at a rate up to 10 mg/min or over 1 hour, whichever is longer.
• Doses should be determined by patient-specific factors (e.g., obesity, age).

Infectious Diseases Society of America (IDSA) Recommendations:

• 15 mg/kg IV every 12 hours

Uses:

• Preferred treatment for IV catheter-related bloodstream infections caused by methicillin-resistant Staphylococcus aureus (MRSA)/coagulase-negative staphylococci, ampicillin-resistant, vancomycin-sensitive E faecalis/E faecium, Corynebacterium jeikeium (Group JK)
• Alternative treatment for IV catheter-related bloodstream infections caused by methicillin-susceptible Staphylococcus aureus (MSSA)/coagulase-negative staphylococci, ampicillin-susceptible E faecalis/E faecium

Comments:

• Treatment plus an aminoglycoside should be used for ampicillin-resistant, vancomycin-sensitive Enterococcus faecalis/Enterococcus faecium.

Adult dose for Endocarditis

• 500 mg IV every 6 hours OR 1 g IV every 12 hours

Uses:

• Empirical treatment of staphylococcal endocarditis caused by susceptible strains of methicillin-resistant staphylococci in patients who are allergic to penicillin, failed to respond/cannot receive other drugs (e.g., penicillins, cephalosporins), and/or to treat organisms that are resistant to other drugs
• Empirical treatment (with an aminoglycoside) of endocarditis caused by enterococci, Streptococcus bovis, or Streptococcus viridans
• Empirical treatment (with an aminoglycoside and/or rifampin) of early-onset prosthetic valve endocarditis caused by Staphylococcus epidermidis or diphtheroids

Comments:

• Vancomycin should be administered at a rate up to 10 mg/min or over 1 hour, whichever is longer.
• Doses should be determined by patient-specific factors (e.g., obesity, age).
• Successful treatment of diphtheroid endocarditis has been reported.

American Heart Association (AHA) and IDSA Recommendations:

• 15 to 20 mg/kg per day IV every 8 to 12 hours
• Maximum dose: 2 g/dose

Duration of treatment:

• Native Valve Endocarditis: At least 4 weeks
• Prosthetic Valve Endocarditis: At least 6 weeks

Uses:

• Treatment of endocarditis caused by highly penicillin-susceptible and relatively resistant to penicillin viridians group streptococci (VGS) and Streptococcus gallolyticus (bovis) in patients who cannot tolerate penicillin or ceftriaxone
• Treatment of endocarditis involving a prosthetic value/other prosthetic material caused by VGS and S gallolyticus (bovis)
• Alternative treatment of endocarditis caused by oxacillin-resistant staphylococci in patients with immediate-type hypersensitivity to beta-lactam antibiotics
• Treatment of penicillin-resistant endocarditis caused by enterococci in patients unable to tolerate beta-lactam antibiotics

Comments:

• Patients may not require the addition of gentamicin or rifampin.
• Patients with native valve endocarditis caused by oxacillin-resistant staphylococci may require at least 6 weeks of treatment.

Adult dose for Pneumonia

• 500 mg IV every 6 hours OR 1 g IV every 12 hours

Use:

• Empirical treatment of lower respiratory tract infections caused by susceptible strains of methicillin-resistant staphylococci in patients who are allergic to penicillin, failed to respond/cannot receive other drugs (e.g., penicillins, cephalosporins), and/or to treat organisms that are resistant to other drugs

Comments:

• Vancomycin should be administered at a rate up to 10 mg/min or over 1 hour, whichever is longer.
• Doses should be determined by patient-specific factors (e.g., obesity, age).

IDSA Recommendations:

• 15 mg/kg IV every 8 to 12 hours
• Some experts recommend a loading dose of 25 to 30 mg/kg IV ONCE (severe illness)

Uses:

• Empiric treatment of clinically suspected ventilator-associated pneumonia where MRSA coverage is appropriate
• Add-on empiric treatment of hospital-acquired pneumonia in patients not at high risk of mortality but with MRSA risk factors
• Add-on empiric treatment of hospital-acquired pneumonia in patients at high risk of mortality or with receipt of IV antibiotics within the previous 90 days

Adult dose for Nosocomial Pneumonia

• 500 mg IV every 6 hours OR 1 g IV every 12 hours

Use:

• Empirical treatment of lower respiratory tract infections caused by susceptible strains of methicillin-resistant staphylococci in patients who are allergic to penicillin, failed to respond/cannot receive other drugs (e.g., penicillins, cephalosporins), and/or to treat organisms that are resistant to other drugs

Comments:

• Vancomycin should be administered at a rate up to 10 mg/min or over 1 hour, whichever is longer.
• Doses should be determined by patient-specific factors (e.g., obesity, age).

IDSA Recommendations:

• 15 mg/kg IV every 8 to 12 hours
• Some experts recommend a loading dose of 25 to 30 mg/kg IV ONCE (severe illness)

Uses:

• Empiric treatment of clinically suspected ventilator-associated pneumonia where MRSA coverage is appropriate
• Add-on empiric treatment of hospital-acquired pneumonia in patients not at high risk of mortality but with MRSA risk factors
• Add-on empiric treatment of hospital-acquired pneumonia in patients at high risk of mortality or with receipt of IV antibiotics within the previous 90 days

Adult dose for Osteomyelitis

• 500 mg IV every 6 hours OR 1 g IV every 12 hours

Use:

• Empirical treatment of bone infections caused by susceptible strains of methicillin-resistant staphylococci in patients who are allergic to penicillin, failed to respond/cannot receive other drugs (e.g., penicillins, cephalosporins), and/or to treat organisms that are resistant to other drugs

Comments:

• Vancomycin  should be administered at a rate up to 10 mg/min or over 1 hour, whichever is longer.
• Doses should be determined by patient-specific factors (e.g., obesity, age).

IDSA Recommendations:

• 15 to 20 mg/kg IV every 12 hours
• Duration of therapy: 4 to 6 weeks

Uses:

• First choice treatment for native vertebral osteomyelitis caused by oxacillin-resistant staphylococci, penicillin-resistant Enterococcus species
• Alternative treatment for native vertebral osteomyelitis caused by oxacillin-susceptible staphylococci
• Alternative treatment for native vertebral osteomyelitis caused by penicillin-susceptible Enterococcus species, Enterobacteriaceae, beta-hemolytic streptococci, or Propionibacterium acnes in patients allergic to penicillin

Adult dose for Sepsis

• 500 mg IV every 6 hours OR 1 g IV every 12 hours

Use:

• Empirical treatment of septicemia caused by susceptible strains of methicillin-resistant staphylococci in patients who are allergic to penicillin, failed to respond/cannot receive other drugs (e.g., penicillins, cephalosporins), and/or to treat organisms that are resistant to other drugs

Comments:

• Vancomycin should be administered at a rate up to 10 mg/min or over 1 hour, whichever is longer.
• Doses should be determined by patient-specific factors (e.g., obesity, age).

Adult dose for Skin or Soft Tissue Infection

• 500 mg IV every 6 hours OR 1 g IV every 12 hours

Use:

• Empirical treatment of skin and skin structure infections caused by susceptible strains of methicillin-resistant staphylococci in patients who are allergic to penicillin, failed to respond/cannot receive other drugs (e.g., penicillins, cephalosporins), and/or to treat organisms that are resistant to other drugs

Comments:

• Vancomycin should be administered at a rate up to 10 mg/min or over 1 hour, whichever is longer.
• Doses should be determined by patient-specific factors (e.g., obesity, age).

IDSA Recommendations:

• 15 mg/kg IV every 6 to 12 hours

Comment: Multidrug resistant organisms may require daily doses up to 60 mg/kg.

Uses:

• First-line treatment of treatment of skin and soft tissue infections (SSTIs) caused by MRSA in patients who require parenteral treatment
• Alternative treatment of SSTIs in patients with penicillin allergies
• Treatment of incisional surgical site infections of the lower trunk or extremity away from the axilla/perineum
• First-line treatment of necrotizing infections of the skin, fascia, and muscle caused by mixed infections

Adult dose for Bacteremia

IDSA Recommendations:

• 15 to 20 mg/kg IV every 8 to 12 hours
• Duration of treatment: Up to 6 weeks, depending on the severity of infection

Use: Treatment of bacteremia

Adult dose for Meningitis

IDSA, American Academy of Neurology (AAN), American Association of Neurological Surgeons (AANS), and Neurocritical Care Society (NCS) Recommendations:

• 30 to 60 mg/kg IV per day, given in divided doses every 8 to 12 hours
• Some experts recommend: 15 mg/kg IV once, followed by 60 mg/kg per day continuous infusion
• Maximum dose: 2 g/dose
• Duration of treatment: At least 2 weeks

Comment: Surgical evaluation is recommended for patients with septic thromboses, empyema, and/or abscesses.

Uses:

• Treatment of patients with healthcare-associated ventriculitis and meningitis caused by methicillin-resistant staphylococci
• In combination with a third-generation cephalosporin, treatment of patients with healthcare-associated ventriculitis and meningitis caused by Streptococcus pneumoniae
• Alternative treatment of patients with healthcare-associated ventriculitis and meningitis caused by methicillin-sensitive staphylococci or P acnes
• Treatment of patients with brain abscess, subdural empyema, and/or spinal epidural abscess
• Treatment of patients with septic thrombosis of cavernous/dural venous sinus

Adult dose for CNS Infection

IDSA, American Academy of Neurology (AAN), American Association of Neurological Surgeons (AANS), and Neurocritical Care Society (NCS) Recommendations:

• 30 to 60 mg/kg IV per day, given in divided doses every 8 to 12 hours
• Some experts recommend: 15 mg/kg IV once, followed by 60 mg/kg per day continuous infusion
• Maximum dose: 2 g/dose
• Duration of treatment: At least 2 weeks

Comment: Surgical evaluation is recommended for patients with septic thromboses, empyema, and/or abscesses.

Uses:

• Treatment of patients with healthcare-associated ventriculitis and meningitis caused by methicillin-resistant staphylococci
• In combination with a third-generation cephalosporin, treatment of patients with healthcare-associated ventriculitis and meningitis caused by Streptococcus pneumoniae
• Alternative treatment of patients with healthcare-associated ventriculitis and meningitis caused by methicillin-sensitive staphylococci or P acnes
• Treatment of patients with brain abscess, subdural empyema, and/or spinal epidural abscess
• Treatment of patients with septic thrombosis of cavernous/dural venous sinus

Adult dose for Febrile Neutropenia

National Comprehensive Cancer Network (NCCN) Recommendations:

• 15 mg/kg IV every 12 hours

Use:

• Empiric prophylaxis in patients at high-risk for febrile neutropenia caused by serious gram-positive infections

Comments:

• Vancomycin should not be used as routine therapy for febrile neutropenia.
• Empiric therapy should be reassessed within 2 to 3 days of initiation. If gram-positive organisms are not found, discontinuation of treatment should be considered.
• Patients with resolved fever and neutrophil counts of at least 500 cells/mcL may discontinue therapy.

Adult dose for Intraabdominal Infection

Surgical Infection Society (SIS) and IDSA Recommendations:

• 15 to 20 mg/kg IV every 8 to 12 hours

Uses:

• Empiric treatment of complicated intra-abdominal infections
• Treatment of peritonitis caused by enterococci species or MRSA

Comment: Initial doses should be determined by total body weight.

International Society for Peritoneal Dialysis (ISPD) Recommendations:

• Intermittent: 15 to 30 mg/kg intraperitoneally every 5 to 7 days

Duration of therapy:

• Enterococcal peritonitis: 3 weeks
• Culture-negative peritonitis: 2 weeks

Use: Treatment of bacterial peritonitis

Adult dose for Peritonitis

Surgical Infection Society (SIS) and IDSA Recommendations:

• 15 to 20 mg/kg IV every 8 to 12 hours

Comment: Initial doses should be determined by total body weight.

Uses:

• Empiric treatment of complicated intra-abdominal infections
• Treatment of peritonitis caused by enterococci species or MRSA

International Society for Peritoneal Dialysis (ISPD) Recommendations:

• Intermittent: 15 to 30 mg/kg intraperitoneally every 5 to 7 days

Duration of therapy:

• Enterococcal peritonitis: 3 weeks
• Culture-negative peritonitis: 2 weeks

Use: Treatment of bacterial peritonitis

Adult dose for Prevention of Perinatal Group B Streptococcal Disease

US Centers for Disease Control and Prevention (US CDC) Recommendations:

• 1 g IV every 12 hours until delivery

Use:

• Prevention of early-onset Group B streptococcal disease in patients with penicillin hypersensitivity and susceptibility is unknown/not possible or the isolates are resistant to erythromycin or clindamycin

Adult dose for Shunt Infection

IDSA, AAN, AANS, and NCS Recommendations:

• Patients with slit ventricles: 5 mg via intraventricular route (plus gentamicin)
• Patients with normal-sized ventricles: 10 mg via intraventricular route (plus gentamicin)
• Patients with enlarged ventricles: 15 to 20 mg via intraventricular route (plus gentamicin)

Frequency of dosing:

• External drain output less than 50 mL/day: Every 3 days
• External drain output 50 to 100 mL/day: Every 2 days
• External drain output 100 to 150 mL/day: Once a day
• External drain output 150 to 200 mL/day: Increase the dose by 5 mg (plus gentamicin) and give once a day
• External drain output 200 to 250 mL/day: Increase the dose by 10 mg (plus gentamicin) and give once a day

Use: Treatment of healthcare-associated ventriculitis and meningitis in patients who respond poorly to systemic antibiotics

Adult dose for Surgical Prophylaxis

American Society of Health-System Pharmacists (ASHP), IDSA, SHEA, and SIS Recommendations:

• 15 mg/kg IV once, within 120 minutes before surgery

Uses:

Alternative agent for surgical prophylaxis in patients who have a beta-lactam allergy and are undergoing:

• Cardiac procedures (e.g., coronary artery bypass, cardiac device insertion, ventricular assist devices)
• Neurosurgery (e.g., elective craniotomy and cerebrospinal fluid-shunting procedures, implantation of intrathecal pumps)
• Thoracic procedures (e.g., lobectomy, pneumonectomy, lung resection, thoracotomy, or video-assisted thorascopic surgery)
• Some orthopedic procedures (e.g., spinal procedures without instrumentation, hip fracture repair)
• Some urologic procedures (e.g., clean surgery without entry into urinary tract)
• Heart, lung, and heart-lung transplantation procedures (e.g., heart transplantation, lung and heart-lung transplantation)
• Clean-contaminated or clean plastic surgery procedures with risk factors

Alternative agent (in combination with an aminoglycoside, aztreonam, or fluoroquinolone) for surgical prophylaxis in patients who have a beta-lactam allergy and are undergoing:

• Gastroduodenal procedures (e.g., procedures involving entry in to the lumen of the gastrointestinal tract or procedures not entering the GI tract in high-risk patients)
• Some urologic procedures (e.g., clean surgery involving implanted prosthesis)

Adult dose for Head Injury

Armed Forces Infectious Disease Society (AFIDS), SIS, and IDSA Recommendations:

• 1 g IV every 12 hours plus ciprofloxacin
• Duration of therapy: 5 days OR until cerebrospinal fluid leak is closed, whichever is longer

Use: Antimicrobial prophylaxis for patients with penicillin allergies who have a penetrating brain or spinal cord injury

Pediatric dose for Bacteremia

Neonates:

• Initial dose: 15 mg/kg IV ONCE
• Maintenance dose:
  • First week of life: 10 mg/kg IV every 12 hours
  • After first week of life: 10 mg/kg IV every 8 hours

Pediatric patients: 10 mg/kg IV every 6 hours

Comments:

• Vancomycin should be infused over 1 hour.
• Premature infants may require longer dosing intervals.
• Doses should be determined by patient-specific factors (e.g., obesity, age).

Uses:

• Empirical treatment of serious/severe staphylococcal infections caused by susceptible strains of methicillin-resistant staphylococci in patients who are allergic to penicillin, failed to respond/cannot receive other drugs (e.g., penicillins, cephalosporins), and/or to treat organisms that are resistant to other drugs
• Empirical treatment of septicemia caused by susceptible strains of methicillin-resistant staphylococci in patients who are allergic to penicillin, failed to respond/cannot receive other drugs (e.g., penicillins, cephalosporins), and/or to treat organisms that are resistant to other drugs
• Empirical treatment of bone infections caused by susceptible strains of methicillin-resistant staphylococci in patients who are allergic to penicillin, failed to respond/cannot receive other drugs (e.g., penicillins, cephalosporins), and/or to treat organisms that are resistant to other drugs

American Academy of Pediatrics (AAP) Recommendations:

• Empiric treatment:
  • Life-threatening infections: 15 mg/kg IV every 6 hours PLUS nafcillin OR oxacillin
  • Non-life-threatening infections without signs of sepsis: 15 mg/kg IV every 6 to 8 hours

Bacterial Infection:

• Neonates (Up to 28 postnatal days):
  • Loading dose: 20 mg/kg IV ONCE
• Gestational age 28 weeks or less:
  • Serum creatinine less than 0.5 mg/dL: 15 mg/kg IV every 12 hours
  • Serum creatinine 0.5 to 0.7 mg/dL: 20 mg/kg IV every 24 hours
  • Serum creatinine 0.8 to 1 mg/dL: 15 mg/kg IV every 24 hours
  • Serum creatinine 1.1 to 1.4 mg/dL: 10 mg/kg IV every 24 hours
  • Serum creatinine greater than 1.4 mg/dL: 15 mg/kg IV every 48 hours
• Gestational age greater than 28 weeks:
  • Serum creatinine less than 0.7 mg/dL: 15 mg/kg IV every 12 hours
  • Serum creatinine 0.7 to 0.9 mg/dL: 20 mg/kg IV every 24 hours
  • Serum creatinine 1 to 1.2 mg/dL: 15 mg/kg IV every 24 hours
  • Serum creatinine 1.3 to 1.6 mg/dL: 10 mg/kg IV every 24 hours
  • Serum creatinine greater than 1.6 mg/dL: 15 mg/kg IV every 48 hours

Pediatric patients greater than 28 days: 45 to 60 mg/kg IV per day, given in 3 to 4 divided doses

Nonmeningeal pneumococcal infections:

• Infants and Children: 40 to 45 mg/kg IV per day, given in divided doses every 6 to 8 hours

Comment: Serum concentrations should be used to guide ongoing treatment.

Uses:

• Drug of choice for the treatment of life-threatening infections (e.g., septicemia, central nervous system [CNS] infections)
• Drug of choice for the treatment of non-life-threatening infection without signs/symptoms of sepsis (e.g., skin infection, cellulitis, osteomyelitis, pyarthrosis) when rates of MRSA colonization and infection in the community are substantial.
• Alternative treatment of MSSA in patients with serious penicillin and cephalosporin allergy
• Drug of choice (with gentamicin) for the treatment of healthcare-associated, multi-drug resistant MRSA infections and oxacillin minimum inhibitory concentrations (MICs) of 4 mcg/mL or greater
• Drug of choice (with gentamicin) for the treatment of community-associated, not multi-drug resistant MRSA infections and oxacillin MICs of 4 mcg/mL or greater
• Alternative drug for the treatment of community-associated, not multi-drug resistant MRSA infections and oxacillin MICs of 4 mcg/mL or greater
• Alternative drug (with linezolid with/without gentamicin) for the treatment of vancomycin-intermediately susceptible Staphylococcus aureus (VISA) infections with MICs of 4 to 16 mcg/mL
• Alternative drug (with sulfamethoxazole-trimethoprim) for the treatment of VISA infections with MICs of 4 to 16 mcg/mL
• Treatment of invasive pneumococcal infections

IDSA Recommendations:

Bacteremia:

• 15 mg/kg IV every 6 hours
• Duration of therapy: 2 to 6 weeks, depending on the severity of infection

Bacterial Infection:

• 7 days or less and less than 1200 g: 15 mg/kg IV every 24 hours
• 7 days or less than 1200 to 2000 g: 10 to 15 mg/kg IV every 12 to 18 hours
• 7 days or less than greater than 2000 g: 10 to 15 mg/kg IV every 8 to 12 hours
• 8 to 30 days and less than 1200 g: 15 mg/kg IV every 24 hours
• 8 to 30 days and 1200 to 2000 g: 10 to 15 mg/kg IV every 8 to 12 hours
• 8 to 30 days and greater than 2000 g: 15 to 20 mg/kg IV every 8 hours
• 1 month to 18 years: 10 to 13.33 mg/kg IV every 6 to 8 hours

Maximum dose: 40 mg/kg/day

Uses:

• Preferred treatment for IV catheter-related bloodstream infections caused by MRSA/coagulase-negative staphylococci, ampicillin-resistant, vancomycin-sensitive E faecalis/E faecium, C jeikeium (Group JK)
• Alternative treatment for IV catheter-related bloodstream infections caused by MSSA/coagulase-negative staphylococci, ampicillin susceptible E faecalis/E faecium
• Treatment of bacteremia

Pediatric dose for Osteomyelitis

Neonates:

• Initial dose: 15 mg/kg IV ONCE
• Maintenance dose:
  • First week of life: 10 mg/kg IV every 12 hours
  • After first week of life: 10 mg/kg IV every 8 hours

Pediatric patients: 10 mg/kg IV every 6 hours

Comments:

• Vancomycin should be infused over 1 hour.
• Premature infants may require longer dosing intervals.
• Doses should be determined by patient-specific factors (e.g., obesity, age).

Uses:

• Empirical treatment of serious/severe staphylococcal infections caused by susceptible strains of methicillin-resistant staphylococci in patients who are allergic to penicillin, failed to respond/cannot receive other drugs (e.g., penicillins, cephalosporins), and/or to treat organisms that are resistant to other drugs
• Empirical treatment of septicemia caused by susceptible strains of methicillin-resistant staphylococci in patients who are allergic to penicillin, failed to respond/cannot receive other drugs (e.g., penicillins, cephalosporins), and/or to treat organisms that are resistant to other drugs
• Empirical treatment of bone infections caused by susceptible strains of methicillin-resistant staphylococci in patients who are allergic to penicillin, failed to respond/cannot receive other drugs (e.g., penicillins, cephalosporins), and/or to treat organisms that are resistant to other drugs

American Academy of Pediatrics (AAP) Recommendations:

Empiric treatment:

• Life-threatening infections: 15 mg/kg IV every 6 hours PLUS nafcillin OR oxacillin
• Non-life-threatening infections without signs of sepsis: 15 mg/kg IV every 6 to 8 hours

Bacterial Infection:

Neonates (Up to 28 postnatal days):

• Loading dose: 20 mg/kg IV ONCE

Gestational age 28 weeks or less:

• Serum creatinine less than 0.5 mg/dL: 15 mg/kg IV every 12 hours
• Serum creatinine 0.5 to 0.7 mg/dL: 20 mg/kg IV every 24 hours
• Serum creatinine 0.8 to 1 mg/dL: 15 mg/kg IV every 24 hours
• Serum creatinine 1.1 to 1.4 mg/dL: 10 mg/kg IV every 24 hours
• Serum creatinine greater than 1.4 mg/dL: 15 mg/kg IV every 48 hours

Gestational age greater than 28 weeks:

• Serum creatinine less than 0.7 mg/dL: 15 mg/kg IV every 12 hours
• Serum creatinine 0.7 to 0.9 mg/dL: 20 mg/kg IV every 24 hours
• Serum creatinine 1 to 1.2 mg/dL: 15 mg/kg IV every 24 hours
• Serum creatinine 1.3 to 1.6 mg/dL: 10 mg/kg IV every 24 hours
• Serum creatinine greater than 1.6 mg/dL: 15 mg/kg IV every 48 hours

Pediatric patients greater than 28 days: 45 to 60 mg/kg IV per day, given in 3 to 4 divided doses

Nonmeningeal pneumococcal infections:

• Infants and Children: 40 to 45 mg/kg IV per day, given in divided doses every 6 to 8 hours

Comment: Serum concentrations should be used to guide ongoing treatment.

Uses:

• Drug of choice for the treatment of life-threatening infections (e.g., septicemia, central nervous system [CNS] infections)
• Drug of choice for the treatment of non-life-threatening infection without signs/symptoms of sepsis (e.g., skin infection, cellulitis, osteomyelitis, pyarthrosis) when rates of MRSA colonization and infection in the community are substantial.
• Alternative treatment of MSSA in patients with serious penicillin and cephalosporin allergy
• Drug of choice (with gentamicin) for the treatment of healthcare-associated, multi-drug resistant MRSA infections and oxacillin minimum inhibitory concentrations (MICs) of 4 mcg/mL or greater
• Drug of choice (with gentamicin) for the treatment of community-associated, not multi-drug resistant MRSA infections and oxacillin MICs of 4 mcg/mL or greater
• Alternative drug for the treatment of community-associated, not multi-drug resistant MRSA infections and oxacillin MICs of 4 mcg/mL or greater
• Alternative drug (with linezolid with/without gentamicin) for the treatment of vancomycin-intermediately susceptible Staphylococcus aureus (VISA) infections with MICs of 4 to 16 mcg/mL
• Alternative drug (with sulfamethoxazole-trimethoprim) for the treatment of VISA infections with MICs of 4 to 16 mcg/mL
• Treatment of invasive pneumococcal infections

IDSA Recommendations:

Bacteremia:

• 15 mg/kg IV every 6 hours
• Duration of therapy: 2 to 6 weeks, depending on the severity of infection

Bacterial Infection:

• 7 days or less and less than 1200 g: 15 mg/kg IV every 24 hours
• 7 days or less than 1200 to 2000 g: 10 to 15 mg/kg IV every 12 to 18 hours
• 7 days or less than greater than 2000 g: 10 to 15 mg/kg IV every 8 to 12 hours
• 8 to 30 days and less than 1200 g: 15 mg/kg IV every 24 hours
• 8 to 30 days and 1200 to 2000 g: 10 to 15 mg/kg IV every 8 to 12 hours
• 8 to 30 days and greater than 2000 g: 15 to 20 mg/kg IV every 8 hours
• 1 month to 18 years: 10 to 13.33 mg/kg IV every 6 to 8 hours

Maximum dose: 40 mg/kg/day

Uses:

• Preferred treatment for IV catheter-related bloodstream infections caused by MRSA/coagulase-negative staphylococci, ampicillin-resistant, vancomycin-sensitive E faecalis/E faecium, C jeikeium (Group JK)
• Alternative treatment for IV catheter-related bloodstream infections caused by MSSA/coagulase-negative staphylococci, ampicillin susceptible E faecalis/E faecium
• Treatment of bacteremia

Pediatric dose for Bacterial Infection

Neonates:

• Initial dose: 15 mg/kg IV ONCE
• Maintenance dose:
  • First week of life: 10 mg/kg IV every 12 hours
  • After first week of life: 10 mg/kg IV every 8 hours

Pediatric patients: 10 mg/kg IV every 6 hours

Comments:

• This drug should be infused over 1 hour.
• Premature infants may require longer dosing intervals.
• Doses should be determined by patient-specific factors (e.g., obesity, age).

Uses:

• Empirical treatment of serious/severe staphylococcal infections caused by susceptible strains of methicillin-resistant staphylococci in patients who are allergic to penicillin, failed to respond/cannot receive other drugs (e.g., penicillins, cephalosporins), and/or to treat organisms that are resistant to other drugs
• Empirical treatment of septicemia caused by susceptible strains of methicillin-resistant staphylococci in patients who are allergic to penicillin, failed to respond/cannot receive other drugs (e.g., penicillins, cephalosporins), and/or to treat organisms that are resistant to other drugs
• Empirical treatment of bone infections caused by susceptible strains of methicillin-resistant staphylococci in patients who are allergic to penicillin, failed to respond/cannot receive other drugs (e.g., penicillins, cephalosporins), and/or to treat organisms that are resistant to other drugs

American Academy of Pediatrics (AAP) Recommendations:

Empiric treatment:

• Life-threatening infections: 15 mg/kg IV every 6 hours PLUS nafcillin OR oxacillin
• Non-life-threatening infections without signs of sepsis: 15 mg/kg IV every 6 to 8 hours

Bacterial Infection:

Neonates (Up to 28 postnatal days):

• Loading dose: 20 mg/kg IV ONCE

Gestational age 28 weeks or less:

• Serum creatinine less than 0.5 mg/dL: 15 mg/kg IV every 12 hours
• Serum creatinine 0.5 to 0.7 mg/dL: 20 mg/kg IV every 24 hours
• Serum creatinine 0.8 to 1 mg/dL: 15 mg/kg IV every 24 hours
• Serum creatinine 1.1 to 1.4 mg/dL: 10 mg/kg IV every 24 hours
• Serum creatinine greater than 1.4 mg/dL: 15 mg/kg IV every 48 hours

Gestational age greater than 28 weeks:

• Serum creatinine less than 0.7 mg/dL: 15 mg/kg IV every 12 hours
• Serum creatinine 0.7 to 0.9 mg/dL: 20 mg/kg IV every 24 hours
• Serum creatinine 1 to 1.2 mg/dL: 15 mg/kg IV every 24 hours
• Serum creatinine 1.3 to 1.6 mg/dL: 10 mg/kg IV every 24 hours
• Serum creatinine greater than 1.6 mg/dL: 15 mg/kg IV every 48 hours

Pediatric patients greater than 28 days: 45 to 60 mg/kg IV per day, given in 3 to 4 divided doses

Nonmeningeal pneumococcal infections:

• Infants and Children: 40 to 45 mg/kg IV per day, given in divided doses every 6 to 8 hours

Comment: Serum concentrations should be used to guide ongoing treatment.

Uses:

• Drug of choice for the treatment of life-threatening infections (e.g., septicemia, central nervous system [CNS] infections)
• Drug of choice for the treatment of non-life-threatening infection without signs/symptoms of sepsis (e.g., skin infection, cellulitis, osteomyelitis, pyarthrosis) when rates of MRSA colonization and infection in the community are substantial.
• Alternative treatment of MSSA in patients with serious penicillin and cephalosporin allergy
• Drug of choice (with gentamicin) for the treatment of healthcare-associated, multi-drug resistant MRSA infections and oxacillin minimum inhibitory concentrations (MICs) of 4 mcg/mL or greater
• Drug of choice (with gentamicin) for the treatment of community-associated, not multi-drug resistant MRSA infections and oxacillin MICs of 4 mcg/mL or greater
• Alternative drug for the treatment of community-associated, not multi-drug resistant MRSA infections and oxacillin MICs of 4 mcg/mL or greater
• Alternative drug (with linezolid with/without gentamicin) for the treatment of vancomycin-intermediately susceptible Staphylococcus aureus (VISA) infections with MICs of 4 to 16 mcg/mL
• Alternative drug (with sulfamethoxazole-trimethoprim) for the treatment of VISA infections with MICs of 4 to 16 mcg/mL
• Treatment of invasive pneumococcal infections

IDSA Recommendations:

Bacteremia:

• 15 mg/kg IV every 6 hours
• Duration of therapy: 2 to 6 weeks, depending on the severity of infection

Bacterial Infection:

• 7 days or less and less than 1200 g: 15 mg/kg IV every 24 hours
• 7 days or less than 1200 to 2000 g: 10 to 15 mg/kg IV every 12 to 18 hours
• 7 days or less than greater than 2000 g: 10 to 15 mg/kg IV every 8 to 12 hours
• 8 to 30 days and less than 1200 g: 15 mg/kg IV every 24 hours
• 8 to 30 days and 1200 to 2000 g: 10 to 15 mg/kg IV every 8 to 12 hours
• 8 to 30 days and greater than 2000 g: 15 to 20 mg/kg IV every 8 hours
• 1 month to 18 years: 10 to 13.33 mg/kg IV every 6 to 8 hours

Maximum dose: 40 mg/kg/day

Uses:

• Preferred treatment for IV catheter-related bloodstream infections caused by MRSA/coagulase-negative staphylococci, ampicillin-resistant, vancomycin-sensitive E faecalis/E faecium, C jeikeium (Group JK)
• Alternative treatment for IV catheter-related bloodstream infections caused by MSSA/coagulase-negative staphylococci, ampicillin susceptible E faecalis/E faecium
• Treatment of bacteremia

Pediatric dose for Sepsis

Neonates:

• Initial dose: 15 mg/kg IV ONCE
• Maintenance dose:
  • First week of life: 10 mg/kg IV every 12 hours
  • After first week of life: 10 mg/kg IV every 8 hours

Pediatric patients: 10 mg/kg IV every 6 hours

Comments:

• This drug should be infused over 1 hour.
• Premature infants may require longer dosing intervals.
• Doses should be determined by patient-specific factors (e.g., obesity, age).

Uses:

• Empirical treatment of serious/severe staphylococcal infections caused by susceptible strains of methicillin-resistant staphylococci in patients who are allergic to penicillin, failed to respond/cannot receive other drugs (e.g., penicillins, cephalosporins), and/or to treat organisms that are resistant to other drugs
• Empirical treatment of septicemia caused by susceptible strains of methicillin-resistant staphylococci in patients who are allergic to penicillin, failed to respond/cannot receive other drugs (e.g., penicillins, cephalosporins), and/or to treat organisms that are resistant to other drugs
• Empirical treatment of bone infections caused by susceptible strains of methicillin-resistant staphylococci in patients who are allergic to penicillin, failed to respond/cannot receive other drugs (e.g., penicillins, cephalosporins), and/or to treat organisms that are resistant to other drugs

American Academy of Pediatrics (AAP) Recommendations:

Empiric treatment:

• Life-threatening infections: 15 mg/kg IV every 6 hours PLUS nafcillin OR oxacillin
• Non-life-threatening infections without signs of sepsis: 15 mg/kg IV every 6 to 8 hours

Bacterial Infection:

Neonates (Up to 28 postnatal days):

• Loading dose: 20 mg/kg IV ONCE

Gestational age 28 weeks or less:

• Serum creatinine less than 0.5 mg/dL: 15 mg/kg IV every 12 hours
• Serum creatinine 0.5 to 0.7 mg/dL: 20 mg/kg IV every 24 hours
• Serum creatinine 0.8 to 1 mg/dL: 15 mg/kg IV every 24 hours
• Serum creatinine 1.1 to 1.4 mg/dL: 10 mg/kg IV every 24 hours
• Serum creatinine greater than 1.4 mg/dL: 15 mg/kg IV every 48 hours

Gestational age greater than 28 weeks:

• Serum creatinine less than 0.7 mg/dL: 15 mg/kg IV every 12 hours
• Serum creatinine 0.7 to 0.9 mg/dL: 20 mg/kg IV every 24 hours
• Serum creatinine 1 to 1.2 mg/dL: 15 mg/kg IV every 24 hours
• Serum creatinine 1.3 to 1.6 mg/dL: 10 mg/kg IV every 24 hours
• Serum creatinine greater than 1.6 mg/dL: 15 mg/kg IV every 48 hours

Pediatric patients greater than 28 days: 45 to 60 mg/kg IV per day, given in 3 to 4 divided doses

Nonmeningeal pneumococcal infections:

• Infants and Children: 40 to 45 mg/kg IV per day, given in divided doses every 6 to 8 hours

Comment: Serum concentrations should be used to guide ongoing treatment.

Uses:

• Drug of choice for the treatment of life-threatening infections (e.g., septicemia, central nervous system [CNS] infections)
• Drug of choice for the treatment of non-life-threatening infection without signs/symptoms of sepsis (e.g., skin infection, cellulitis, osteomyelitis, pyarthrosis) when rates of MRSA colonization and infection in the community are substantial.
  -Alternative treatment of MSSA in patients with serious penicillin and cephalosporin allergy
• Drug of choice (with gentamicin) for the treatment of healthcare-associated, multi-drug resistant MRSA infections and oxacillin minimum inhibitory concentrations (MICs) of 4 mcg/mL or greater
• Drug of choice (with gentamicin) for the treatment of community-associated, not multi-drug resistant MRSA infections and oxacillin MICs of 4 mcg/mL or greater
• Alternative drug for the treatment of community-associated, not multi-drug resistant MRSA infections and oxacillin MICs of 4 mcg/mL or greater
• Alternative drug (with linezolid with/without gentamicin) for the treatment of vancomycin-intermediately susceptible Staphylococcus aureus (VISA) infections with MICs of 4 to 16 mcg/mL
• Alternative drug (with sulfamethoxazole-trimethoprim) for the treatment of VISA infections with MICs of 4 to 16 mcg/mL
• Treatment of invasive pneumococcal infections

IDSA Recommendations:

Bacteremia:

• 15 mg/kg IV every 6 hours
• Duration of therapy: 2 to 6 weeks, depending on the severity of infection

Bacterial Infection:

• 7 days or less and less than 1200 g: 15 mg/kg IV every 24 hours
• 7 days or less than 1200 to 2000 g: 10 to 15 mg/kg IV every 12 to 18 hours
• 7 days or less than greater than 2000 g: 10 to 15 mg/kg IV every 8 to 12 hours
• 8 to 30 days and less than 1200 g: 15 mg/kg IV every 24 hours
• 8 to 30 days and 1200 to 2000 g: 10 to 15 mg/kg IV every 8 to 12 hours
• 8 to 30 days and greater than 2000 g: 15 to 20 mg/kg IV every 8 hours
• 1 month to 18 years: 10 to 13.33 mg/kg IV every 6 to 8 hours

Maximum dose: 40 mg/kg/day

Uses:

• Preferred treatment for IV catheter-related bloodstream infections caused by MRSA/coagulase-negative staphylococci, ampicillin-resistant, vancomycin-sensitive E faecalis/E faecium, C jeikeium (Group JK)
• Alternative treatment for IV catheter-related bloodstream infections caused by MSSA/coagulase-negative staphylococci, ampicillin susceptible E faecalis/E faecium
• Treatment of bacteremia

Pediatric dose for Endocarditis

Neonates:

• Initial dose: 15 mg/kg IV ONCE
• Maintenance dose:
  • First week of life: 10 mg/kg IV every 12 hours
  • After first week of life: 10 mg/kg IV every 8 hours

Pediatric patients: 10 mg/kg IV every 6 hours

Comments:

• This drug should be infused over 1 hour.
• Premature infants may require longer dosing intervals.
• Doses should be determined by patient-specific factors (e.g., obesity, age).
• Successful treatment of diphtheroid endocarditis has been reported.

Use:

• Empirical treatment of staphylococcal endocarditis caused by susceptible strains of methicillin-resistant staphylococci in patients who are allergic to penicillin, failed to respond/cannot receive other drugs (e.g., penicillins, cephalosporins), and/or to treat organisms that are resistant to other drugs
• Empirical treatment (with an aminoglycoside) of endocarditis caused by enterococci, S bovis, or S viridans
• Empirical treatment (with an aminoglycoside and/or rifampin) of early-onset prosthetic valve endocarditis caused by S epidermidis or diphtheroids

AAP Recommendations:

Empiric treatment:

• Life-threatening infections: 15 mg/kg IV every 6 hours PLUS nafcillin OR oxacillin
• Non-life-threatening infections without signs of sepsis: 15 mg/kg IV every 6 to 8 hours

Uses:

• Drug of choice for the treatment of life-threatening infections (e.g., endocarditis)
• Drug of choice for the treatment of non-life-threatening infection without signs/symptoms of sepsis when rates of MRSA colonization and infection in the community are substantial.
• Alternative treatment of MSSA in patients with serious penicillin and cephalosporin allergy
• Drug of choice (with gentamicin) for the treatment of healthcare-associated, multi-drug resistant MRSA infections and oxacillin MICs of 4 mcg/mL or greater
• Drug of choice (with gentamicin) for the treatment of community-associated, not multi-drug resistant MRSA infections and oxacillin MICs of 4 mcg/mL or greater
• Alternative drug for the treatment of community-associated, not multi-drug resistant MRSA infections and oxacillin MICs of 4 mcg/mL or greater
• Alternative drug (with linezolid with/without gentamicin) for the treatment of VISA infections with MICs of 4 to 16 mcg/mL
• Alternative drug (with sulfamethoxazole-trimethoprim) for the treatment of VISA infections with MICs of 4 to 16 mcg/mL

AHA Recommendations:

• 40 to 60 mg/kg IV per day, given in divided doses every 6 to 12 hours
• Maximum dose: 2 g/day

Duration of therapy:

• Empirical treatment: 4 to 6 weeks
• Staphylococci infection: 6 weeks

Comment: Gentamycin should be added to patients with enterococci infections.

Uses:

• Treatment of native valve and prosthetic valve infective endocarditis
• Empirical alternative treatment (with gentamicin) of community-acquired native valve or late prosthetic valve (over 1 year after surgery) endocarditis
• Empirical treatment of nosocomial endocarditis associated with vascular cannulae or early prosthetic valve endocarditis (1 year or less after surgery)
• Alternative treatment for streptococcal infections highly susceptible to penicillin G (e.g., Groups A, B, C, G nonenterococcal, Group D streptococci) and streptococci relatively resistant to penicillin (e.g., enterococci, less-susceptible S viridians)
• Alternative treatment for endocarditis caused by S aureus or coagulase-negative staphylococci susceptible or resistant to penicillin G and/or oxacillin in patients highly allergic to beta-lactam antibiotics

Pediatric dose for Skin or Soft Tissue Infection

Neonates:

• Initial dose: 15 mg/kg IV ONCE
• Maintenance dose:
  • First week of life: 10 mg/kg IV every 12 hours
  • After first week of life: 10 mg/kg IV every 8 hours

Pediatric patients: 10 mg/kg IV every 6 hours

Comments:

• This drug should be infused over 1 hour.
• Premature infants may require longer dosing intervals.
• Doses should be determined by patient-specific factors (e.g., obesity, age).

Use:

• Empirical treatment of skin and skin structure infections caused by susceptible strains of methicillin-resistant staphylococci in patients who are allergic to penicillin, failed to respond/cannot receive other drugs (e.g., penicillins, cephalosporins), and/or to treat organisms that are resistant to other drugs

AAP Recommendations:

Empiric treatment:

• Life-threatening infections: 15 mg/kg IM or IV every 6 hours PLUS nafcillin OR oxacillin
• Non-life-threatening infections without signs of sepsis: 15 mg/kg IM or IV every 6 to 8 hours

Uses:

• Drug of choice for the treatment of life-threatening infections (e.g., septicemia)
• Drug of choice for the treatment of non-life-threatening infection without signs/symptoms of sepsis (e.g., skin infection, cellulitis) when rates of MRSA colonization and infection in the community are substantial.
• Alternative treatment of MSSA in patients with serious penicillin and cephalosporin allergy
• Drug of choice (with gentamicin) for the treatment of healthcare-associated, multi-drug resistant MRSA infections and oxacillin MICs of 4 mcg/mL or greater
• Drug of choice (with gentamicin) for the treatment of community-associated, not multi-drug resistant MRSA infections and oxacillin MICs of 4 mcg/mL or greater
• Alternative drug for the treatment of community-associated, not multi-drug resistant MRSA infections and oxacillin MICs of 4 mcg/mL or greater
• Alternative drug (with linezolid with/without gentamicin) for the treatment of VISA infections with MICs of 4 to 16 mcg/mL
• Alternative drug (with sulfamethoxazole-trimethoprim) for the treatment of VISA infections with MICs of 4 to 16 mcg/mL

IDSA Recommendations:

• 10 to 15 mg/kg IV 3 to 4 times a day

Comments:

• Patients with necrotizing infections may require up to a 13 mg/kg dose given IV every 8 hours plus piperacillin.
• Patients with necrotizing infections caused by resistant S aureus may require 15 mg/kg given IV every 6 hours.

Use:

• First-line treatment of treatment of SSTIs caused by MRSA in patients who require parenteral treatment
• Alternative treatment of SSTIs in patients with penicillin allergies
• First-line treatment of necrotizing infections of the skin, fascia, and muscle caused by mixed infections

Pediatric dose for Pneumonia

Neonates:

• Initial dose: 15 mg/kg IV ONCE
• Maintenance dose:
  • First week of life: 10 mg/kg IV every 12 hours
  • After first week of life: 10 mg/kg IV every 8 hours

Pediatric patients: 10 mg/kg IV every 6 hours

Comments:

• This drug should be infused over 1 hour.
• Premature infants may require longer dosing intervals.
• Doses should be determined by patient-specific factors (e.g., obesity, age).

Use: Empirical treatment of lower respiratory tract infections caused by susceptible strains of methicillin-resistant staphylococci in patients who are allergic to penicillin, failed to respond/cannot receive other drugs (e.g., penicillins, cephalosporins), and/or to treat organisms that are resistant to other drugs

Pediatric Infectious Diseases Society (PIDS) and IDSA Recommendations:

• 10 to 20 mg/kg every 6 to 8 hours

Uses:

• Alternative treatment of community acquired pneumonia caused by S pneumoniae with penicillin MICs of less than or equal to 2 mcg/mL, S pneumoniae resistant to penicillin (MICs at least 4 mcg/mL), Group A Streptococcus, or MSSA
• Preferred treatment of community acquired pneumonia caused by MRSA (with/without susceptibility to clindamycin)

Pediatric dose for Intraabdominal Infection

AAP Recommendations:

Empiric treatment:

• Life-threatening infections: 15 mg/kg IM or IV every 6 hours PLUS nafcillin OR oxacillin
• Non-life-threatening infections without signs of sepsis: 15 mg/kg IM or IV every 6 to 8 hours

Uses:

• Drug of choice for the treatment of life-threatening infections (e.g., septicemia)
• Drug of choice for the treatment of non-life-threatening infection without signs/symptoms of sepsis (e.g., skin infection, cellulitis) when rates of MRSA colonization and infection in the community are substantial.
• Alternative treatment of MSSA in patients with serious penicillin and cephalosporin allergy
• Drug of choice (with gentamicin) for the treatment of healthcare-associated, multi-drug resistant MRSA infections and oxacillin MICs of 4 mcg/mL or greater
• Drug of choice (with gentamicin) for the treatment of community-associated, not multi-drug resistant MRSA infections and oxacillin MICs of 4 mcg/mL or greater
• Alternative drug for the treatment of community-associated, not multi-drug resistant MRSA infections and oxacillin MICs of 4 mcg/mL or greater
• Alternative drug (with linezolid with/without gentamicin) for the treatment of VISA infections with MICs of 4 to 16 mcg/mL
• Alternative drug (with sulfamethoxazole-trimethoprim) for the treatment of VISA infections with MICs of 4 to 16 mcg/mL

SIS and IDSA Recommendations:

• 40 mg/kg IV per day, divided and given every 6 to 8 hours

Comment: This drug should be given as a 1-hour infusion.

Uses:

• Treatment of complicated intra-abdominal infections
• Treatment of peritonitis caused by Enterococci species or MRSA

ISPD Recommendations:

Prophylaxis: 25 mg/L intraperitoneally once

Treatment: 30 mg/kg intraperitoneally once, then 15 mg/kg intraperitoneally every 3 to 5 days

Uses:

• Prophylaxis against peritonitis in patients with known MRSA colonization at risk of touch contamination during instillation of peritoneal dialysis fluid after system disconnection OR disconnection during peritoneal dialysis
• Treatment of bacterial peritonitis

Pediatric dose for Peritonitis

AAP Recommendations:

Empiric treatment:

• Life-threatening infections: 15 mg/kg IM or IV every 6 hours PLUS nafcillin OR oxacillin
• Non-life-threatening infections without signs of sepsis: 15 mg/kg IM or IV every 6 to 8 hours

Uses:

• Drug of choice for the treatment of life-threatening infections (e.g., septicemia)
• Drug of choice for the treatment of non-life-threatening infection without signs/symptoms of sepsis (e.g., skin infection, cellulitis) when rates of MRSA colonization and infection in the community are substantial.
• Alternative treatment of MSSA in patients with serious penicillin and cephalosporin allergy
• Drug of choice (with gentamicin) for the treatment of healthcare-associated, multi-drug resistant MRSA infections and oxacillin MICs of 4 mcg/mL or greater
• Drug of choice (with gentamicin) for the treatment of community-associated, not multi-drug resistant MRSA infections and oxacillin MICs of 4 mcg/mL or greater
• Alternative drug for the treatment of community-associated, not multi-drug resistant MRSA infections and oxacillin MICs of 4 mcg/mL or greater
• Alternative drug (with linezolid with/without gentamicin) for the treatment of VISA infections with MICs of 4 to 16 mcg/mL
• Alternative drug (with sulfamethoxazole-trimethoprim) for the treatment of VISA infections with MICs of 4 to 16 mcg/mL

SIS and IDSA Recommendations:

• 40 mg/kg IV per day, divided and given every 6 to 8 hours

Comment: This drug should be given as a 1-hour infusion.

Uses:

• Treatment of complicated intra-abdominal infections
• Treatment of peritonitis caused by Enterococci species or MRSA

ISPD Recommendations:

Prophylaxis: 25 mg/L intraperitoneally once

Treatment: 30 mg/kg intraperitoneally once, then 15 mg/kg intraperitoneally every 3 to 5 days

Uses:

• Prophylaxis against peritonitis in patients with known MRSA colonization at risk of touch contamination during instillation of peritoneal dialysis fluid after system disconnection OR disconnection during peritoneal dialysis
• Treatment of bacterial peritonitis

Pediatric dose for Surgical Prophylaxis

AAP Recommendations:

Neonates (72 hours) or older: 15 mg/kg IV ONCE

Uses:

Alternative agent for surgical prophylaxis in patients undergoing:

• Cardiac surgical procedures (e.g., prosthetic valve/pacemaker, ventricular assist devices) where Staphylococcus epidermidis (including methicillin-resistant Staphylococcus epidermidis [MRSE]), Staphylococcus aureus (including MRSA), Corynebacterium species, and/or enteric gram-negative bacilli are likely
• Neurosurgery (e.g., craniotomy, intrathecal baclofen shunt/ventricular shunt placement) where S epidermidis (including MRSE) or S aureus (including MRSA) are likely
• Orthopedic (e.g., internal fixation of fractures, implantation of materials including prosthetic joint and spinal procedures with/without instrumentation) where S epidermidis (including MRSE) or S aureus (including MRSA) are likely
• Thoracic (noncardiac) where S epidermidis S aureus (including MRSA), streptococci, or gram-negative enteric bacilli are likely

ASHP, IDSA, SHEA, and SIS Recommendations:

• 15 mg/kg IV once, within 120 minutes before surgery

Uses:

Alternative agent for surgical prophylaxis in patients who have a beta-lactam allergy and are undergoing:

• Cardiac procedures (e.g., coronary artery bypass, cardiac device insertion, ventricular assist devices)
• Neurosurgery (e.g., elective craniotomy and cerebrospinal fluid-shunting procedures, implantation of intrathecal pumps)
• Thoracic procedures (e.g., lobectomy, pneumonectomy, lung resection, thoracotomy, or video-assisted thorascopic surgery)
• Some orthopedic procedures (e.g., spinal procedures without instrumentation, hip fracture repair)
• Some urologic procedures (e.g., clean surgery without entry into urinary tract)
• Heart, lung, and heart-lung transplantation procedures (e.g., heart transplantation, lung and heart-lung transplantation)
• Clean-contaminated or clean plastic surgery procedures with risk factors

Alternative agent (in combination with an aminoglycoside, aztreonam, or fluoroquinolone) for surgical prophylaxis in patients who have a beta-lactam allergy and are undergoing:

• Gastroduodenal procedures (e.g., procedures involving entry in to the lumen of the gastrointestinal tract or procedures not entering the GI tract in high-risk patients)
• Some urologic procedures (e.g., clean surgery involving implanted prosthesis)

Pediatric dose for Meningitis

AAP Recommendations:

Empiric treatment:

• Life-threatening infections: 15 mg/kg IV every 6 hours PLUS nafcillin OR oxacillin
• Non-life-threatening infections without signs of sepsis: 15 mg/kg IV every 6 to 8 hours

Infants and Children:

• Meningitis: 60 mg/kg IV per day, given in divided doses every 6 hours

Uses:

• Drug of choice for the treatment of life-threatening infections (e.g., septicemia, CNS infections)
• Drug of choice for the treatment of non-life-threatening infection without signs/symptoms of sepsis when rates of MRSA colonization and infection in the community are substantial.
• Alternative treatment of MSSA in patients with serious penicillin and cephalosporin allergy
• Drug of choice (with gentamicin) for the treatment of healthcare-associated, multi-drug resistant MRSA infections and oxacillin MICs of 4 mcg/mL or greater
• Drug of choice (with gentamicin) for the treatment of community-associated, not multi-drug resistant MRSA infections and oxacillin MICs of 4 mcg/mL or greater
• Alternative drug for the treatment of community-associated, not multi-drug resistant MRSA infections and oxacillin MICs of 4 mcg/mL or greater
• Alternative drug (with linezolid with/without gentamicin) for the treatment of VISA infections with MICs of 4 to 16 mcg/mL
• Alternative drug (with sulfamethoxazole-trimethoprim) for the treatment of VISA infections with MICs of 4 to 16 mcg/mL
• Treatment of invasive pneumococcal meningitis

IDSA, AAN, AANS, and NCS Recommendations:

• 60 mg/kg IV per day, given in divided doses every 6 hours
• Duration of therapy: 2 weeks

Use: Treatment of patients with healthcare-associated ventriculitis and meningitis

Pediatric dose for CNS Infection

AAP Recommendations:

Empiric treatment:

• Life-threatening infections: 15 mg/kg IV every 6 hours PLUS nafcillin OR oxacillin
• Non-life-threatening infections without signs of sepsis: 15 mg/kg IV every 6 to 8 hours

Infants and Children:

• Meningitis: 60 mg/kg IV per day, given in divided doses every 6 hours

Uses:

• Drug of choice for the treatment of life-threatening infections (e.g., septicemia, CNS infections)
• Drug of choice for the treatment of non-life-threatening infection without signs/symptoms of sepsis when rates of MRSA colonization and infection in the community are substantial.
• Alternative treatment of MSSA in patients with serious penicillin and cephalosporin allergy
• Drug of choice (with gentamicin) for the treatment of healthcare-associated, multi-drug resistant MRSA infections and oxacillin MICs of 4 mcg/mL or greater
• Drug of choice (with gentamicin) for the treatment of community-associated, not multi-drug resistant MRSA infections and oxacillin MICs of 4 mcg/mL or greater
• Alternative drug for the treatment of community-associated, not multi-drug resistant MRSA infections and oxacillin MICs of 4 mcg/mL or greater
• Alternative drug (with linezolid with/without gentamicin) for the treatment of VISA infections with MICs of 4 to 16 mcg/mL
• Alternative drug (with sulfamethoxazole-trimethoprim) for the treatment of VISA infections with MICs of 4 to 16 mcg/mL
• Treatment of invasive pneumococcal meningitis

IDSA, AAN, AANS, and NCS Recommendations:

• 60 mg/kg IV per day, given in divided doses every 6 hours
• Duration of therapy: 2 weeks

Use: Treatment of patients with healthcare-associated ventriculitis and meningitis

Pediatric dose for Shunt Infection

IDSA, AAN, AANS, and NCS Recommendations:

• Patients with slit ventricles: 5 mg via intraventricular route (plus gentamicin)
• Patients with normal-sized ventricles: 10 mg via intraventricular route (plus gentamicin)
• Patients with enlarged ventricles: 15 to 20 mg via intraventricular route (plus gentamicin)

Frequency of dosing:

• External drain output less than 50 mL/day: Every 3 days
• External drain output 50 to 100 mL/day: Every 2 days
• External drain output 100 to 150 mL/day: Once a day
• External drain output 150 to 200 mL/day: Increase the dose by 5 mg (plus gentamicin) and give once a day
• External drain output 200 to 250 mL/day: Increase the dose by 10 mg (plus gentamicin) and give once a day

Comment: Some experts recommend decreasing the dose by 60% when treating infants to account for lower cerebrospinal fluid volume (compared to adults).

Use: Treatment of healthcare-associated ventriculitis and meningitis in patients who respond poorly to systemic antibiotics

Pediatric dose for Head Injury

AFIDS, SIS, and IDSA Recommendations:

• 60 mg/kg, divided and given every 6 to 8 hours
• Duration of therapy: 5 days OR until cerebrospinal fluid leak is closed, whichever is longer

Use: Antimicrobial prophylaxis for patients with penicillin allergies who have a penetrating brain or spinal cord injury

Renal dose Adjustments

Mild to moderate renal dysfunction:

• Initial dose: 15 mg/kg IV ONCE
• Maintenance dose: The manufacturer product information should be consulted regarding dose adjustments in patients with this level of renal dysfunction.

Severe renal dysfunction and functionally anephric patients:

• Initial dose: 15 mg/kg IV ONCE
• Maintenance dose: 1.9 mg/kg IV every 24 hours OR 250 to 1000 mg IV once every several days

Patients with anuria:

• Initial dose: 15 mg/kg IV ONCE
• Maintenance dose: 1000 mg IV once every 7 to 10 days

Liver Dose Adjustments

• Data not available

What should I do if I forget a dose?

Infuse the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not infuse a double dose to make up for a missed one.

Vancomycin side effects

Vancomycin adverse effects – Intravenous Vancomycin Injection

Common adverse effects of intravenous vancomycin injection include nephrotoxicity, hypotension, and hypersensitivity reactions. Anaphylaxis is a type of hypersensitivity reaction that can be seen with vancomycin ⁹⁾.

Red man syndrome is an infusion-related reaction associated with rapid intravenous infusion of vancomycin. Symptoms include flushing, pruritus, and an erythematous rash on the face, neck, and upper torso. Signs of red man syndrome often appear 4 to 10 minutes after starting or shortly after the completion of an infusion. The incidence of red man syndrome varies between 3.7% and 47% in patients. However, there is a direct correlation between the increased incidence of red man syndrome with faster rates of vancomycin administration. Rapid infusion of vancomycin can lead to angioedema and hypotension, which accompany red man syndrome. Reports show the most severe forms of this reaction frequently occur in children and patients younger than the age of 40. Prolonging the infusion time is the primary management strategy used to mitigate red man syndrome. Nevertheless, premedication with antihistamines, such as diphenhydramine or hydroxyzine, can be used to prevent the occurrence of red man syndrome.

Less common adverse effects include local phlebitis, chills, drug fever, skin rash, eosinophilia, and reversible neutropenia.

In rare situations, patients have reported DRESS syndrome (drug rash with eosinophilia and systemic symptoms), ototoxicity, thrombocytopenia, vasculitis, and Stevens-Johnson syndrome.

Vancomycin injection may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• pain, redness, or swelling at the injection site
• fever
• nausea
• chills

Some side effects can be serious. If you experience any of these symptoms or those listed in the HOW section, call your doctor immediately or get emergency medical treatment:

• severe diarrhea with watery or bloody stools (up to 2 months after your treatment)
• stomach pain or cramps
• rash
• peeling or blistering of the skin
• swelling of the eyes, face, throat, tongue, or lips
• difficulty breathing or swallowing
• hoarseness
• hearing loss, roaring or ringing in the ears, or dizziness

Vancomycin injection may cause other side effects. Call your doctor if you have any unusual problems while receiving vancomycin injection.

Vancomycin adverse effects – Oral Vancomycin

Gastrointestinal adverse effects, such as abdominal pain and nausea, are commonly seen with oral vancomycin. Dysgeusia or distorted sense of taste is a common adverse effect unique to vancomycin oral solution. Patients should be told to seek medical attention if these adverse effects are severe and bothersome. Note that many of these adverse effects are temporary.

Less common adverse effects of oral vancomycin include peripheral edema, fatigue, headache, diarrhea, flatulence, vomiting, back pain, urinary tract infection, and fever.

Rare cases of increased serum creatinine, red man syndrome, interstitial nephritis, nephrotoxicity, ototoxicity, thrombocytopenia, and vasculitis have also been reported with the use of oral vancomycin.

Vancomycin oral may cause side effects. Tell your doctor if this symptom is severe or does not go away:

• upset stomach

Some side effects can be serious. The following symptoms are uncommon, but if you experience any of them, call your doctor immediately:

• sore throat, fever, chills, and other signs of infection
• hives
• skin rash
• itching
• difficulty breathing or swallowing
• redness of the skin above the waist
• pain and muscle tightness of the chest and back
• unusual bleeding or bruising
• fainting
• dizziness
• blurred vision
• ringing in the ears

Vancomycin toxicity

Nephrotoxicity and ototoxicity have been associated with the use of vancomycin ¹⁰⁾. Although there are numerous case reports of acute renal failure attributed to vancomycin use, there is currently limited data suggesting a direct causal relationship. The proposed mechanism of nephrotoxicity is renal tubular ischemia due to the oxidative effect of vancomycin on cells of the proximal renal tubule. Common risk factors for nephrotoxicity include preexisting renal impairment, concurrent use of nephrotoxic medications, advanced age, and dehydration. Although vancomycin-induced nephrotoxicity is commonly reversible, it can be challenging to differentiate it from acute interstitial nephritis and worsening renal function due to an uncontrolled infection. Vancomycin-induced nephrotoxicity can be identified by increases in serum creatinine in the absence of a causative explanation. Dosing vancomycin based on estimated creatinine clearance is a commonly used technique to prevent nephrotoxicity. Patients who experience signs of acute renal failure precipitated by vancomycin use should promptly discontinue their therapy. It is also important to note that cases of nephrotoxicity have been reported with both oral and intravenous vancomycin use. Cases of nephrotoxicity associated with oral vancomycin have typically been reported in patients over 65 years of age.

Ototoxicity is a rare complication associated with vancomycin monotherapy. It is commonly reported in patients receiving excessive vancomycin doses, concurrent ototoxic medications (e.g., aminoglycosides, loop diuretics, antineoplastic agents), and those with underlying hearing loss conditions. Treatment should be discontinued if patients experience signs of ototoxicity such as tinnitus, loss of hearing, and unbalanced movements. It should be noted that vancomycin-induced ototoxicity may be irreversible in some cases. Auditory function testing may be beneficial to identify early symptoms.

Procainamide

Procainamide is an oral antiarrhythmic agent (antiarrhythmic Class 1A) that has been in wide use for more than 60 years ¹⁾, ²⁾. Procainamide is used to treat abnormal heart rhythms such as ventricular arrhythmias, supraventricular arrhythmias, atrial flutter, atrial fibrillation, and Wolf-Parkinson-White syndrome. Procainamide works by making your heart more resistant to abnormal activity by blocking open sodium channels and outward potassium channels. As a consequence, it decreases cardiac automaticity, increases refractory periods and slows conduction. Procainamide was approved for use in the United States in 1950, and current indications include suppression of symptomatic premature ventricular contractions and life threatening ventricular tachycardia, as well as maintenance of normal sinus rhythm after conversion of atrial fibrillation or flutter. Because of its safety profile, procainamide is now rarely used. Procainamide is available only with your doctor’s prescription.

The oral dosage forms of procainamide are no longer available in the United States but is available in Canada. Procainamide is available in capsules and tablets of 250, 375 and 500 mg generically as well as under the brand name Pronestyl; it is also available as extended release forms of 250, 500, 750 and 1,000 mg under the brand name Procanbid. Immediate-acting procainamide usually is taken every 3 or 4 hours. The long-acting product is usually taken every 6 or 12 hours. Do not cut, crush, or chew extended-release (long-acting) tablets; swallow them whole. You may see a waxy core in your stool if you are taking the extended-release product; this is normal. Procainamide is currently available in the United States as a solution for intravenous infusion. The usual maintenance dose in adults is 500 to 1000 mg every 4 to 6 hours.

Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take procainamide exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Procainamide helps control your condition but will not cure it. Continue to take procainamide even if you feel well. Do not stop taking procainamide without talking to your doctor.

Procainamide is broken down by your liver via acetylation to form N-acetyl procainamide (NAPA) via a substrate of CYP2D6. This compound is then excreted as N-acetyl procainamide (NAPA). The half-life of procainamide is 2.5 to 5 hours, and the maximum dose in current recommendations is 17 mg/kg. As such, clinicians may consider decreasing the dosing or frequency of procainamide in cases of hepatic impairment ³⁾.

Procainamide most common side effects include headache, nervousness, anxiety, nausea, decreased appetite, palpitations and disturbed sleep. Rare but potentially severe adverse effects include cardiac toxicity, bradycardia, hypotension, aplastic anemia, agranulocytosis, drug hypersensitivity reactions, induction of autoantibodies including antinuclear antibody and drug-induced lupus erythematosus-like syndrome ⁴⁾. QRS, QTc, and PR prolongation are the most potentially harmful cardiac side effects of procainamide and may become worse when levels of procainamide rise. Serial electrocardiograms are useful for monitoring these toxic effects during treatment with procainamide. Procainamide infusion may also increase the number of premature ventricular contractions in patients.

Another side effect of procainamide is hypotension, more commonly seen at doses of 20 mg/min. Drug-induced lupus erythematosus-like syndrome is rare and occurs due to the creation of positive ANA titers when taking the medication chronically. The symptoms of chronic use may include arthritis, arthralgias, and pleuritis and commonly resolve when usage stops.

Lastly, procainamide is known to cause certain blood dyscrasias. Procainamide has been known to cause bone marrow toxicity, leading to pancytopenia or agranulocytosis; this is usually due to hypersensitivity or varied immunologic mechanisms ⁵⁾, ⁶⁾.

Procainamide mechanism of action

Procainamide is an analogue of the local anesthetic procaine and has electrophysiological effects that resemble quinidine. Procainamide is a class 1A anti-arrhythmic that appears to act by blocking fast sodium channels and outward potassium channels inhibiting recovery after repolarization. Procainamide also prolongs the action potential and reduces the speed of impulse conduction. This action results in decreased myocardial excitability, slowed conduction velocity, and reduced myocardial contractility. It is possible that it acts as a negative inotrope and may cause peripheral vasodilation and hypotension, which may require cardioversion.

Procainamide special precautions

Before taking procainamide:

• tell your doctor and pharmacist if you are allergic to procainamide, anesthetics, aspirin, or any other drugs.
• tell your doctor and pharmacist what prescription and nonprescription medications you are taking, especially digoxin (Lanoxin) or drugs for high blood pressure, and vitamins.
• in addition to the condition listed in the IMPORTANT WARNING section, tell your doctor if you have or have ever had lupus, heart disease, high blood pressure, kidney or liver disease, or myasthenia gravis.
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking procainamide, call your doctor.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking procainamide.
• you should know that this drug may make you dizzy. Do not drive a car or operate machinery until you know how this drug affects you.
• remember that alcohol can add to the dizziness caused by this drug.
• talk to your doctor about the use of cigarettes and caffeine-containing beverages. These products may increase the irritability of your heart and interfere with the action of procainamide.

It is important that your doctor check your progress carefully while you are receiving procainamide to make sure it is working properly. This will allow necessary changes in the amount of medicine you receive and may also help reduce side effects.

Dizziness or lightheadedness may occur with procainamide, especially in elderly patients and when large doses are used. Patients should use extra care to avoid falling. Make sure you know how you react to procainamide before you drive, use machines, or do anything else that could be dangerous if you are dizzy or not alert.

Procainamide in Pregnancy

Pregnancy Category C: Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

Procainamide in Breastfeeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Procainamide Drug Interactions

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking procainamide, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using procainamide with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Amisulpride
• Bepridil
• Cisapride
• Dronedarone
• Fingolimod
• Grepafloxacin
• Levomethadyl
• Mesoridazine
• Pimozide
• Piperaquine
• Saquinavir
• Sparfloxacin
• Terfenadine
• Thioridazine
• Vernakalant
• Ziprasidone

Using procainamide with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acecainide
• Ajmaline
• Alcuronium
• Alfuzosin
• Amiodarone
• Amitriptyline
• Amoxapine
• Anagrelide
• Apomorphine
• Aprindine
• Aripiprazole
• Aripiprazole Lauroxil
• Arsenic Trioxide
• Artemether
• Asenapine
• Astemizole
• Atracurium
• Azithromycin
• Buprenorphine
• Bupropion
• Buserelin
• Ceritinib
• Chloral Hydrate
• Chloroquine
• Chlorpromazine
• Ciprofloxacin
• Cisatracurium
• Citalopram
• Clarithromycin
• Clofazimine
• Clomipramine
• Clozapine
• Crizotinib
• Dabrafenib
• Dasatinib
• Degarelix
• Delamanid
• Desipramine
• Deslorelin
• Deutetrabenazine
• Disopyramide
• Dofetilide
• Dolasetron
• Domperidone
• Donepezil
• Doxacurium
• Doxepin
• Droperidol
• Efavirenz
• Eliglustat
• Encorafenib
• Enflurane
• Erythromycin
• Escitalopram
• Flecainide
• Fluconazole
• Fluoxetine
• Foscarnet
• Gallamine
• Gatifloxacin
• Gemifloxacin
• Glasdegib
• Gonadorelin
• Goserelin
• Granisetron
• Halofantrine
• Haloperidol
• Halothane
• Hexafluorenium
• Histrelin
• Hydroquinidine
• Hydroxychloroquine
• Hydroxyzine
• Ibutilide
• Iloperidone
• Imipramine
• Inotuzumab Ozogamicin
• Isoflurane
• Isradipine
• Ivabradine
• Ivosidenib
• Ketoconazole
• Lacosamide
• Lapatinib
• Leuprolide
• Levofloxacin
• Lidocaine
• Lidoflazine
• Lofexidine
• Lopinavir
• Lorcainide
• Lumefantrine
• Macimorelin
• Mefloquine
• Methadone
• Metocurine
• Metronidazole
• Mifepristone
• Mivacurium
• Moricizine
• Moxifloxacin
• Nafarelin
• Nalidixic Acid
• Nilotinib
• Norfloxacin
• Nortriptyline
• Octreotide
• Ofloxacin
• Ondansetron
• Osimertinib
• Paliperidone
• Pancuronium
• Pasireotide
• Pazopanib
• Pentamidine
• Pimavanserin
• Pipecuronium
• Pirmenol
• Pitolisant
• Posaconazole
• Prilocaine
• Probucol
• Promethazine
• Propafenone
• Protriptyline
• Quetiapine
• Quinidine
• Quinine
• Ribociclib
• Risperidone
• Rocuronium
• Salmeterol
• Sertindole
• Sertraline
• Sevoflurane
• Siponimod
• Sodium Phosphate
• Sodium Phosphate, Dibasic
• Sodium Phosphate, Monobasic
• Solifenacin
• Sorafenib
• Sotalol
• Spiramycin
• Succinylcholine
• Sulfamethoxazole
• Sulpiride
• Sultopride
• Sunitinib
• Tacrolimus
• Telavancin
• Telithromycin
• Tetrabenazine
• Tizanidine
• Toremifene
• Trazodone
• Triclabendazole
• Trifluoperazine
• Trimethoprim
• Trimipramine
• Triptorelin
• Tubocurarine
• Vandetanib
• Vardenafil
• Vasopressin
• Vecuronium
• Vemurafenib
• Vinflunine
• Voriconazole
• Zolmitriptan
• Zotepine
• Zuclopenthixol

Using procainamide with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Cimetidine

Other Interactions

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of procainamide. Make sure you tell your doctor if you have any other medical problems, especially:

• Heart block or
• Heart rhythm problem (e.g., QT prolongation) or
• Lupus erythematosus, history of—Should not use in patients with these conditions.
• Heart failure, congestive or
• Myasthenia gravis—May make these conditions worse.
• Kidney disease or
• Liver disease—Use with caution. The effects may be increased because of slower removal from the body.

Procainamide contraindications

Hypersensitivity to procainamide, procaine, other ester-type local anesthetics, or any component of the formulation; complete heart block; second-degree AV block or various types of hemiblock (without a functional artificial pacemaker); systemic lupus erythematosus (SLE); Torsade de Pointes.

Use with caution in patients with heart failure, electrolyte imbalances (particularly hypokalemia and hypomagnesemia), myasthenia gravis patients, and in hepatic or renal impairment. Procainamide also crosses the placenta and may be present in the milk of breastfeeding mothers, and as such, chronic use requires caution in this population ⁷⁾.

Canadian labeling: Additional contraindications (not in US labeling):

• Myasthenia gravis;
• Severe heart failure (IV);
• Renal failure (IV);
• Shock (IV).

Procainamide uses

Procainamide is used to treat abnormal heart rhythms. It works by making your heart more resistant to abnormal activity.

Ventricular arrhythmias: Intravenous: Treatment of life-threatening ventricular arrhythmias

Supraventricular arrhythmias: Oral [Canadian product]: Treatment of supraventricular arrhythmias.

Note: In the treatment of atrial fibrillation (AF), use only when preferred treatment is ineffective or cannot be used. Use in paroxysmal atrial tachycardia when reflex stimulation or other measures are ineffective.

Procainamide is indicated in patients with Wolf-Parkinson-White syndrome as it is important for acute termination of antidromic AV re-entrant tachycardia in stable patients ⁸⁾. In particular, because the use of an AV nodal blocking agent in this patient population may enhance conduction down the accessory pathway and therefore induce ventricular tachycardia or ventricular fibrillation ⁹⁾.

Procainamide has also historically been used in diagnostic testing for Brugada syndrome; this was known as the “procainamide challenge,” which produces the standard Brugada-like pattern on ECG, which may have been otherwise unnoticed and thus identifying patients at risk for sudden cardiac death ¹⁰⁾. However, this usage has fallen out of favor, as it has low sensitivity for detecting Brugada-like patterns and may also put the patient at risk of going into ventricular arrhythmia ¹¹⁾.

Procainamide has been used for chemical cardioversion in atrial flutter and atrial fibrillation. These are common arrhythmias seen in emergency department patients, but there is no consensus for optimal management. Stiell et al. looked at the usage of IV procainamide in 341 patients over five years. Adverse events were infrequent and included hypotension, bradycardia, atrioventricular block, and ventricular tachycardia. There were no cases of torsades de pointes, cerebrovascular accidents, or death. Most patients (94.4%) received a discharge to home. IV procainamide had a 52% conversion rate of atrial fibrillation to normal sinus and a 28% conversion rate from atrial flutter to normal sinus ¹²⁾.

Researchers have also studied the utility of procainamide compared to lidocaine in terminating sustained ventricular tachycardia in patients with structural heart defects. In this retrospective study from Circulation Journal, procainamide was found to be more effective than lidocaine in the termination of the arrhythmia ¹³⁾.

One recent major study looked at the difference between amiodarone and procainamide in stable ventricular tachycardia. The PROCAMIO study ¹⁴⁾ has concluded that in patients with stable ventricular tachycardia, procainamide should be considered over the traditionally used amiodarone due to faster resolution of the arrhythmia, fewer major cardiac events, and is more efficacious in a subgroup of patients with structural heart disease.

Off Label Uses

Atrial fibrillation (preexcited)

Based on the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science and the 2014 American Heart Association/American College of Cardiology/Heart Rhythm Society Guideline (AHA/ACC/HRS) for the Management of Patients With Atrial Fibrillation (AF), procainamide may be considered for the treatment of hemodynamically stable preexcited AF with rapid ventricular response in adults with preserved left ventricular function.

Junctional tachycardia

Based on the American Heart Association, American College of Clinical Cardiology and Heart Rhythm Society Guideline for the Management of Patients with Supraventricular Tachycardia, procainamide may be considered for the treatment of hemodynamically, acute junctional tachycardia when beta-blocker therapy is ineffective. Dosing not specified.

Stable monomorphic ventricular tachycardia

Based on the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science, procainamide is an effective and recommended treatment alternative for hemodynamically stable monomorphic ventricular tachycardia in adults with preserved left ventricular function. Use should be avoided in those with a prolonged QT interval.

Procainamide dose

Procainamide is given IV or Oral with the onset of action in 10 to 30 minutes ¹⁵⁾. The loading dose of IV procainamide is 10 to 17 mg/kg and administered at a rate of 20 to 50 mg/min ¹⁶⁾. Alternatively, IV procainamide may be dosed at 100 mg every 5 minutes in adult patients. The administration of this maintenance dose is from 1 to 4 mg/minute; however, the manufacturer labeling recommends 2 to 6 mg/minute.

Administration of oral procainamide dosing for supraventricular arrhythmia is at 50 mg/kg/24 hours divided into doses every 6 hours.

In children, IV procainamide dosing divides into those less than 12 months in which a bolus dose of 7 to 10 mg/kg given over 15 to 30 minutes and those older than 12 months in which a bolus dose of 10 to 15 mg/kg is the regimen. An infusion rate of 20 to 50 mcg/kg/min follows the initial bolus ¹⁷⁾.

Adult dose for Arrhythmias

IV:

• Loading dose: 15 to 18 mg/kg administered as slow infusion over 25 to 30 minutes or 100 mg/dose at a rate not to exceed 50 mg/minute repeated every 5 minutes as needed to a total dose of 1 gram.
• Maintenance dose: 1 to 4 mg/minute by continuous infusion. Maintenance infusions should be reduced by one-third in patients with moderate renal or cardiac impairment and by two-thirds in patients with severe renal or cardiac impairment.

ACLS guidelines: Loading dose: Infuse 20 mg/minute (up to 50 mg/minute for more urgent situations) until arrhythmia is controlled, hypotension occurs, QRS complex widens by 50% of its original width, or total of 17 mg/kg is given. Note: Not recommended for use in ongoing ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT) due to prolonged administration time and uncertain efficacy. Follow with maintenance dose as continuous infusion.

IM:

• 50 mg/kg divided into fractional amounts of 1/8 to 1/4 and injected every 3 to 6 hours or 0.5 to 1 gram every 4 to 8 hours.

Oral: ORAL procainamide is not available in the US but is available in Canada.

40 to 50 kg:

• Immediate-release: 250 mg orally every 3 hours.
• Sustained-release: 500 mg every 6 hours.
• Twice daily formulation: 1000 mg every 12 hours.

60 to 70 kg:

• Immediate-release: 375 mg every 3 hours.
• Sustained-release: 750 mg every 6 hours.
• Twice daily formulation: 1500 mg every 12 hours.

80 to 90 kg:

• Immediate-release: 500 mg every 3 hours.
• Sustained-release: 1000 mg every 6 hours.
• Twice daily formulation: 2000 mg every 12 hours.

100 kg or more

• Immediate-release: 625 mg every 3 hours.
• Sustained-release: 1250 mg every 6 hours.
• Twice daily formulation: 2500 mg every 12 hours.

Pediatric dose for Arrhythmias

Less than 1 month:

• Loading dose: 7 to 10 mg/kg IV infused over 60 minutes followed by a continuous IV infusion of 20 to 80 mcg/kg/minute; a retrospective study of 20 neonates (GA: 25 weeks or older) reported a mean loading dose of 9.6 ± 1.5 mg/kg and a mean continuous infusion rate of 37.56 ± 13.52 mcg/kg/minute.
• Note: Procainamide serum concentrations were supratherapeutic in five neonates studied; four of the five were less than 36 weeks GA and all five had Clcr less than 30 mL/minute/1.73 m2; these results indicate that doses may need to be decreased in preterm neonates and in those with renal impairment.

1 year or older:

• Oral: (ORAL procainamide is not available in the US but is available in Canada.)
• 15 to 50 mg/kg/day divided every 3 to 6 hours. Maximum 4 g/day.

IV:

• Loading dose: 3 to 6 mg/kg over 5 minutes (not to exceed 100 mg per dose), may repeat every 5 to 10 minutes to maximum total loading dose of 15 mg/kg; do not exceed 500 mg in 30 minutes.
• Maintenance dose: continuous IV infusion: 20 to 80 mcg/kg/minute; maximum dose: 2 g/day.

IM:

• 20 to 30 mg/kg/day divided every 4 to 6 hours. Maximum 4 g/day.

Stable wide complex tachycardia of unknown origin (atrial or ventricular) or SVT (PALS, 2010): Note: Avoid or use extreme caution when administering procainamide with other drugs that prolong QT interval (e.g., amiodarone); consider consulting with expert.

Loading dose: 15 mg/kg infused intravenously over 30 to 60 minutes; monitor ECG and blood pressure; stop the infusion if hypotension occurs or QRS complex widens by more than 50% of baseline

Renal Dose Adjustments

Oral:

• CrCl less than 10 mL/min: A dosing interval of every 8 to 24 hours is recommended.
• CrCl 10 to 50 mL/min: A dosing interval of every 6 to 12 hours is recommended.

IV:

• Reduce loading dose to 12 mg/kg in severe renal impairment.
• Maintenance infusions should be reduced by one-third in patients with moderate renal impairment and by two-thirds in patients with severe renal impairment.

Liver Dose Adjustments

A 50% reduction in the dose is recommended.

What should I do if I forget a dose?

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Procainamide side effects

Procainamide may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• dizziness or lightheadedness
• loss of appetite
• upset stomach
• vomiting
• bitter taste

If you experience the following symptom or any of those listed in the IMPORTANT WARNING section, call your doctor immediately:

• irregular heartbeat

Less common

• fever and chills
• joint pain or swelling
• pains with breathing
• skin rash or itching

Rare

• Bleeding, blistering, burning, coldness, discoloration of skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, or warmth at the injection site
• Confusion
• Fever or sore mouth, gums, or throat
• Hallucinations (seeing, hearing, or feeling things that are not there)
• Mental depression
• Unusual bleeding or bruising
• Unusual tiredness or weakness

Get emergency help immediately if any of the following symptoms of overdose occur:

Symptoms of procainamide overdose

• decrease in urination
• dizziness (severe) or fainting
• drowsiness
• fast or irregular heartbeat
• nausea and vomiting

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• diarrhea
• hardening or thickening of the skin where the needle is placed
• loss of appetite

Less common

• dizziness or lightheadedness

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Procainamide injection side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Tell your caregivers at once if you have a serious side effect such as:

• a new or a worsening irregular heartbeat pattern;
• chest pain, wheezing, trouble breathing;
• feeling like you might pass out;
• signs of infection such as fever, chills, sore throat, flu symptoms, pale skin, easy bruising or bleeding (nosebleeds, bleeding gums), loss of appetite, nausea and vomiting, sores in your mouth and throat, unusual weakness;
• depressed mood, hallucinations, severe dizziness;
• upper stomach pain, itching, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes); or
• joint pain or swelling with fever, swollen glands, muscle pain or weakness, unusual thoughts or behavior, patchy skin color, red spots.

Less serious side effects may include:

• mild dizziness or tired feeling;
• flushing (warmth, redness, or tingly feeling); or
• mild itching or rash.

Flecainide

Flecainide is an oral antiarrhythmic agent (antiarrhythmic Class 1C) that is used in certain situations to prevent or treat certain types of life-threatening irregular heartbeats (arrhythmias) that include paroxysmal supraventricular tachycardias (PSVTs), atrioventricular nodal re-entrant tachycardia (AVNRT), AV re-entrant tachycardia (AVRT), and paroxysmal atrial fibrillation or atrial flutter in patients who do not have structural heart disease and arrhythmic long QT syndromes (LQTS), as well as the Ca²⁺-mediated, catecholaminergic polymorphic ventricular tachycardia (CPVT) ¹⁾, ²⁾. However, flecainide can also exert pro‐arrhythmic effects most notably following myocardial infarction and when used to diagnose Brugada syndrome ³⁾. Flecainide works by slowing electrical signals in the heart to stabilize the heart rhythm. Flecainide appears to act by blocking open sodium channels and outward potassium channels ⁴⁾, ⁵⁾, ⁶⁾, ⁷⁾, ⁸⁾. As a consequence, it decreases cardiac automaticity, increases refractory periods and slows conduction. Flecainide was approved for use in the United States in 1985. Flecainide current indications include prevention and treating life-threatening ventricular arrhythmias and conversion of paroxysmal supraventricular tachycardia (PSVTs), Wolf-Parkinson-White syndrome, atrioventricular nodal re-entrant tachycardia (AVNRT), AV re-entrant tachycardia (AVRT), and atrial fibrillation/atrial flutter in patients who do not have structural heart disease, in whom other agents were unsuccessful.

Flecainide is available only with your doctor’s prescription.

Flecainide is a benzamide derivative analogue of the local anesthetic procaine and has electrophysiological effects that resemble quinidine. Flecainide appears to act by blocking open sodium channels and outward potassium channels ⁹⁾. As a consequence, it decreases cardiac automaticity, increases refractory periods and slows conduction.

Oral bioavailability of Flecainide is nearly 100% but decreases when administered with milk ¹⁰⁾. Flecainide is 40% protein-bound, and half-life elimination varies across age groups. In newborns: less than 28 hours, 3 months: 11 to 12 hours, 12 months: 6 hours. In children: 8 hours, adolescents 12 to 15 years: approximately 11 hours, adults: 12 to 24 hours. It takes 1 to 6 hours to peak in serum after administration. Flecainide is metabolized by your liver via the CYP450 system; specifically, it is a CYP2D6 substrate. Flecainide is excreted in the urine (30%) and, to a lesser extent, the feces (5%) ¹¹⁾, ¹²⁾, ¹³⁾. Its half-life is approximately 20 hours ¹⁴⁾.

Flecainide is available in tablets of 50, 100 and 150 mg generically to be taken by mouth and under the brand name Tambocor. The usual maintenance dose in adults is 50 to 200 mg twice daily (once every 12 hours). Some people may take flecainide once every 8 hours if they experience side effects or if their condition cannot be controlled by taking flecainide every 12 hours. Take flecainide at around the same times every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take flecainide exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

You may be hospitalized when you begin your treatment with flecainide. Your doctor will monitor you carefully during this time and for as long as you continue to take flecainide. Your doctor will probably start you on a low dose of flecainide and gradually increase your dose, not more than once every 4 days. Your doctor may also decrease your dose once your condition is controlled.

Flecainide may control your condition, but will not cure it. Continue to take flecainide even if you feel well. Do not stop taking flecainide without talking to your doctor. If you suddenly stop taking flecainide, your condition may become worse.

Flecainide most common side effects include dizziness, visual blurring, headache, fatigue, anxiety, gastrointestinal upset and nausea.

How long does it take for flecainide to work?

Time to Peak

• Serum: ~3 hours (range: 1 to 6 hours)

Half-Life Elimination

• Newborns: Up to ≤29 hours; 3 months: 11 to 12 hours; 12 months: 6 hours
• Children: ~8 hours
• Adolescents 12 to 15 years: ~11 to 12 hours
• Adults: ~20 hours (range: 12 to 27 hours); increased in patients with heart failure (NYHA Class III) or renal dysfunction

After administration of one XL capsule, plasma flecainide concentrations gradually increase after a lag time of 2 to 3 hours to reach a peak between the 21st and 25th hour and remain at plateau levels until after the 30th hour. After reaching the steady state concentration (3-5days), it exerts maximum action.

Flecainide mechanism of action

Flecainide acts on the fast-inward sodium (Na⁺) ion channel and has a high affinity to activated or open sodium (Na⁺) channels ¹⁵⁾. Flecainide prolongs depolarization and increases refractoriness due to slow release from its binding site. Flecainide potently acts on the His-Purkinje system. It also works by inhibiting rapid delayed rectifier (IKr) channels, delaying potassium rectifier current resulting in prolongation of action potential duration in both ventricular and atrial muscle fibers ¹⁶⁾. Flecainide is shown to block ryanodine receptor opening, which reduces calcium release from sarcoplasmic reticulum resulting after depolarization and triggered activity ¹⁷⁾. Hence, indications for flecainide include catecholaminergic polymorphic ventricular tachycardia (CPVT).

Flecainide contraindications

According to the American College of Cardiology/American Heart Association/European Society of Cardiology, the use of flecainide is considered contraindicated in patients with structural heart disease. Other contraindications include hypersensitivity, documented second or third-degree AV block, sick sinus syndrome, bundle branch block, cardiogenic shock, and acquired/congenital QT prolongation with a history of Torsades de Pointes.

Caution is also advised in myocardial dysfunction, congestive heart failure, QT prolongation, electrolyte abnormalities, and pacemaker use ¹⁸⁾.

Significant drug interactions include ritonovir, cisapride, despiramine, dronedarone, quinidine, saquinavir, and tipranavir. Concurrent use with these agents is contraindicated. It interacts with many other drugs where therapy modification may be necessary, so thorough medication reconciliation is necessary with flecainide, as with all drugs.

Flecainide special precautions

Before taking flecainide:

• tell your doctor and pharmacist if you are allergic to flecainide or any other medications.
• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: acetazolamide (Diamox); amiodarone (Cordarone, Pacerone); ammonium chloride; antacids; beta blockers such as atenolol (Tenormin), labetalol (Trandate), metoprolol (Lopressor, Toprol XL), nadolol (Corgard), and propranolol (Inderal); carbamazepine (Carbatrol, Tegretol); cimetidine (Tagamet); clozapine (Clozaril); dichlorphenamide; digoxin (Lanoxin); diltiazem (Cardizem, Tiazac); disopyramide (Norpace); methazolamide; nifedipine (Adalat, Procardia); phenytoin (Dilantin); phenobarbital; quinidine; sodium bicarbonate (baking soda, Citrocarbonate, Soda Mint); and verapamil (Calan, Verelan). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor if you have heart block (condition in which electrical signals are not passed normally from the upper chambers of the heart to the lower chambers). Your doctor may tell you not to take flecainide.
• tell your doctor if you have a pacemaker (device that is surgically placed under the skin to control irregular heartbeats) and if you have or have ever had a heart attack, heart failure, or any type of heart disease; low or high levels of potassium in the blood; or liver or kidney disease. Also tell your doctor if you follow a strict vegetarian diet.
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking flecainide, call your doctor.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking flecainide.
• if you are giving this medication to an infant, be sure to talk to the doctor if there will be any major changes in the amount of milk the infant drinks. Milk can affect how the medication is absorbed in the body.

It is important that your doctor check your progress at regular visits to make sure the medicine is working properly. This will allow for changes to be made in the amount of medicine you are taking, if necessary.

Check with your doctor right away if you develop any of the following:

• chest pain;
• shortness of breath;
• swelling of your hands, ankles, or feet; or weight gain.

These may be symptoms of heart failure.

This medicine can cause changes in your heart rhythm, such as conditions called PR, QRS, or QT prolongation. It may cause fainting or serious side effects in some patients. Contact your doctor right away if your symptoms do not improve or if they become worse.

Your doctor may want you to carry a medical identification card or bracelet stating that you are using flecainide.

Before having any kind of surgery (including dental surgery) or emergency treatment, tell the medical doctor or dentist in charge that you are taking flecainide.

Flecainide may cause some people to become dizzy, lightheaded, or less alert than they are normally. Make sure you know how you react to flecainide before you drive, use machines, or do anything else that could be dangerous if you are dizzy or are not alert.

If you have been using flecainide regularly for several weeks, do not suddenly stop using it. Check with your doctor for the best way to gradually reduce the amount you are taking before stopping completely.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Pregnancy

Pregnancy Category C: Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

Using flecainide during pregnancy may pose some risk to the fetus, so clinicians must perform a risk/benefit analysis. Fetal risks include fetal heart rate variability, acceleration impairment, and QT interval abnormalities ¹⁹⁾. Fetuses may also experience neonatal hyperbilirubinemia, although this data is unclear.

Breastfeeding

Flecainide is present in breast milk; the relative infant dose is 8% when the maternal dosing is 200mg/day. The relative infant dosing is calculated using the highest average breast milk concentration compared to the maternal dosage. Breastfeeding is acceptable as long as relative infant dosing is under 10% ²⁰⁾.

Flecainide interactions

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking flecainide, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using flecainide with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Amisulpride
• Bepridil
• Cisapride
• Dronedarone
• Levomethadyl
• Mesoridazine
• Pimozide
• Piperaquine
• Ritonavir
• Saquinavir
• Sparfloxacin
• Terfenadine
• Thioridazine
• Tipranavir
• Vernakalant
• Ziprasidone

Using flecainide with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acecainide
• Ajmaline
• Alfuzosin
• Amiodarone
• Amitriptyline
• Amoxapine
• Anagrelide
• Apomorphine
• Aprindine
• Arbutamine
• Aripiprazole
• Aripiprazole Lauroxil
• Arsenic Trioxide
• Artemether
• Asenapine
• Astemizole
• Azimilide
• Azithromycin
• Bedaquiline
• Bendroflumethiazide
• Boceprevir
• Bretylium
• Buprenorphine
• Bupropion
• Buserelin
• Ceritinib
• Chloral Hydrate
• Chloroquine
• Chlorothiazide
• Chlorpromazine
• Chlorthalidone
• Ciprofloxacin
• Citalopram
• Clarithromycin
• Clofazimine
• Clomipramine
• Clozapine
• Cobicistat
• Crizotinib
• Cyclobenzaprine
• Dabrafenib
• Darifenacin
• Dasabuvir
• Dasatinib
• Degarelix
• Delamanid
• Delavirdine
• Desipramine
• Deslorelin
• Deutetrabenazine
• Dibenzepin
• Disopyramide
• Dofetilide
• Dolasetron
• Domperidone
• Donepezil
• Droperidol
• Duloxetine
• Efavirenz
• Encorafenib
• Enflurane
• Erythromycin
• Escitalopram
• Etravirine
• Fingolimod
• Fluconazole
• Fluoxetine
• Foscarnet
• Gatifloxacin
• Gemifloxacin
• Glasdegib
• Gonadorelin
• Goserelin
• Granisetron
• Halofantrine
• Haloperidol
• Halothane
• Histrelin
• Hydrochlorothiazide
• Hydroflumethiazide
• Hydroquinidine
• Hydroxychloroquine
• Hydroxyzine
• Ibutilide
• Iloperidone
• Imipramine
• Inotuzumab Ozogamicin
• Isoflurane
• Isradipine
• Ivabradine
• Ivosidenib
• Ketoconazole
• Lacosamide
• Lapatinib
• Leuprolide
• Levofloxacin
• Lidocaine
• Lidoflazine
• Lofexidine
• Lorcainide
• Lumefantrine
• Macimorelin
• Mefloquine
• Methadone
• Metolazone
• Metronidazole
• Mifepristone
• Moxifloxacin
• Nafarelin
• Nilotinib
• Norfloxacin
• Nortriptyline
• Octreotide
• Ofloxacin
• Ombitasvir
• Ondansetron
• Osimertinib
• Paliperidone
• Panobinostat
• Paritaprevir
• Pasireotide
• Pazopanib
• Peginterferon Alfa-2b
• Pentamidine
• Pimavanserin
• Pirmenol
• Pitolisant
• Polythiazide
• Posaconazole
• Prajmaline
• Prilocaine
• Probucol
• Procainamide
• Prochlorperazine
• Promethazine
• Propafenone
• Protriptyline
• Quetiapine
• Quinidine
• Ranolazine
• Ribociclib
• Risperidone
• Salmeterol
• Sematilide
• Sertindole
• Sertraline
• Sevoflurane
• Simeprevir
• Siponimod
• Sodium Phosphate
• Sodium Phosphate, Dibasic
• Sodium Phosphate, Monobasic
• Solifenacin
• Sorafenib
• Sotalol
• Spiramycin
• Sulfamethoxazole
• Sulpiride
• Sultopride
• Sunitinib
• Tacrolimus
• Tedisamil
• Telaprevir
• Telavancin
• Telithromycin
• Tetrabenazine
• Tizanidine
• Toremifene
• Trazodone
• Trichlormethiazide
• Triclabendazole
• Trifluoperazine
• Trimethoprim
• Trimipramine
• Triptorelin
• Vandetanib
• Vardenafil
• Vasopressin
• Vemurafenib
• Vinflunine
• Voriconazole
• Zolmitriptan
• Zotepine
• Zuclopenthixol

Using flecainide with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Cimetidine
• Digoxin
• Paroxetine
• Propranolol
• Verapamil

Other Interactions

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using flecainide with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use flecainide, or give you special instructions about the use of food, alcohol, or tobacco.

• Milk

Using flecainide with any of the following may cause an increased risk of certain side effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use flecainide, or give you special instructions about the use of food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of flecainide. Make sure you tell your doctor if you have any other medical problems, especially:

• AV block (type of abnormal heart rhythm), with no pacemaker or
• Bundle branch block (heart rhythm problem), with no pacemaker or
• Cardiogenic shock (shock caused by heart attack) or
• Chronic atrial fibrillation or
• Heart attack, recent—Should not be used in patients with these conditions.
• Congestive heart failure (severe) or
• Heart disease (e.g., cardiomyopathy) or
• Sick sinus syndrome (type of abnormal heart rhythm)—Use with caution. May make these conditions worse.
• Electrolyte imbalance (e.g., high or low potassium in the blood)—Should be corrected first before using flecainide.
• Kidney disease or
• Liver disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.
• If you have a permanent pacemaker—Use with caution. Flecainide may interfere with the pacemaker and require more careful follow-up by the doctor.

What is flecainide used for?

Flecainide is used to prevent  or treat certain types of life-threatening irregular heartbeats (arrhythmias) such as paroxysmal supraventricular tachycardia (PSVT) and paroxysmal atrial fibrillation/flutter (PAF). Flecainide is also used to prevent life-threatening sustained ventricular tachycardia (sustained VT). Flecainide is in a class of medications called antiarrhythmics. It works by slowing electrical signals in the heart to stabilize the heart rhythm.

There is a chance that flecainide may cause new or make worse existing heart rhythm problems when it is used. Since it has been shown to cause severe problems in some patients, it is only used to treat serious heart rhythm problems. Discuss this possible effect with your doctor.

Flecainide dose

The dose of flecainide will be different for different patients. Follow your doctor’s orders or the directions on the label. The following information includes only the average doses of flecainide. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

For oral dosage form (tablets) per American College of Cardiology, American Heart Association and Heart Rhythm Society guidelines:

• For paroxysmal supraventricular tachycardia (PSVT) and paroxysmal atrial fibrillation/atrial flutter:
  • Adults: 50 to 300 milligrams (mg) daily by mouth divided into 8 to 12-hour intervals. Start with 50 mg orally every 12 hours, then increase 100 mg per day every four days. The maximum dose is 300 mg daily. Dose adjustment is made based on serum levels. Your doctor may increase your dose as needed.
  • Children: Use and dose must be determined by your doctor. Dose is based on body size and must be determined by your child’s doctor. The starting dose is 100 milligrams (mg) per square meter (m²) per day for infants 6 months and older and 50 mg/m² per day in infants younger than 6 months. Doses are divided into two or three equal doses per day.
• For sustained ventricular tachycardia (sustained VT) prophylaxis:
  • Adults: 100 to 400 milligrams (mg) daily by mouth, divided into 8 or 12-hour intervals. Start 100 mg daily every 12 hours, and increase dosing by 100 mg per day every four days. The maximum dose is 400 mg daily. Dose adjustment is made based on serum levels. Your doctor may increase your dose as needed. However, the dose is usually not more than 400 mg per day.
  • Children: Use and dose must be determined by your doctor. Dose is based on body size and must be determined by your child’s doctor. The starting dose is 100 milligrams (mg) per square meter (m²) per day for infants 6 months and older and 50 mg/m² per day in infants younger than 6 months. Doses are divided into two or three equal doses per day.

No dosage changes are necessary for liver disease, as per the manufacturer. With kidney disease and CrCl less than 35ml/min/1.73m², caution is necessary when increasing the dose at 4-day intervals.

There are an increased response and a steep relationship between dose and concentration. Plasma levels require monitoring in patients with severe kidney failure or hepatic disease. Drug overdose could be fatal with flecainide. The prescriber should adjust dosing based on clinical response ²¹⁾.

In patients with renal failure or hepatic impairment, it is prudent to monitor EKG and blood pressure and to obtain periodic serum trough concentration. Therapeutic trough concentration is between 0.2 to 1 mcg/ml. Lower trough concentration is sufficient in pediatric patients.

Consult facility guidelines or manufacturer prescribing data for pediatric dose regimens.

Adult dose for Ventricular Tachycardia

• Initial dose: 100 mg orally every 12 hours.
• Maintenance dose: May be increased in increments of 50 mg bid every 4 days until efficacy is achieved. Most patients with SUSTAINED VT do not require more than 150 mg every 12 hours (300 mg/day), and the maximum dose recommended is 400 mg/day.

Adult dose for Atrial Fibrillation

• Initial dose: 50 mg orally every 12 hours.
• Maintenance dose: May be increased in increments of 50 mg bid every 4 days until efficacy is achieved.

Adult dose for Atrial Flutter

• Initial dose: 50 mg orally every 12 hours.
• Maintenance dose: May be increased in increments of 50 mg bid every 4 days until efficacy is achieved.

Adult dose for Wolff-Parkinson-White Syndrome

• Initial dose: 50 mg orally every 12 hours.
• Maintenance dose: May be increased in increments of 50 mg bid every 4 days until efficacy is achieved.

Adult dose for Paroxysmal Supraventricular Tachycardia

• Initial dose: 50 mg orally every 12 hours.
• Maintenance dose: May be increased in increments of 50 mg bid every 4 days until efficacy is achieved.

Pediatric dose for Supraventricular Tachycardia

Less than 1 month:

• Supraventricular tachycardia: Limited data available: Initial: 2 mg/kg/day orally divided every 12 hours; titrate to clinical response, monitor serum concentration; mean dose required to suppress SVT: 3.35 ± 1.35 mg/kg/day in 17 neonates (n=20 treated neonates; mean PNA: 11.5 days; mean GA: 36.8 weeks; mean birthweight: 2.8 kg); study did not report resultant serum concentrations.

1 month or older:

• Initial: 1 to 3 mg/kg/day orally or 50 to 100 mg/m²/day orally in 3 divided doses; usual: 3 to 6 mg/kg/day or 100 to 150 mg/m²/day in 3 divided doses; up to 8 mg/kg/day or 200 mg/m²/day for uncontrolled patients with subtherapeutic levels; higher doses have been reported, however they may be associated with an increased risk of proarrhythmias; a review of world literature reports the average effective dose to be 4 mg/kg/day or 140 mg/m²/day.

Renal Dose Adjustments

• CrCl=35 mL/min or less: Initial dose: 100 mg orally once a day or 50 mg twice a day. It may take longer than 4 days before a new steady-state plasma level is reached following a dosage change.
• In patients with less severe renal dysfunction: Initial dose: 100 mg every 12 hours.

Liver Dose Adjustments

Flecainide should not be used in patients with significant liver dysfunction unless the potential benefits clearly outweigh the risks, as elimination from plasma can be markedly slower in patients with significant hepatic impairment. If it is deemed necessary, frequent and early plasma level monitoring is required to guide dosage and dosage increases should be made very cautiously when plasma levels have plateaued (after more than four days).

What should I do if I forget a dose?

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Flecainide side effects

Flecainide may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• dizziness
• changes in vision
• headache
• weakness
• uncontrollable shaking of a part of your body
• constipation
• stomach pain

Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately:

• fast, pounding, or irregular heartbeat
• chest pain
• shortness of breath
• extreme tiredness
• nausea
• loss of appetite
• persistent cough with blood-tinged mucus
• swelling of the hands, feet, ankles, or lower legs
• confusion
• unusual bleeding or bruising
• pain in the upper right part of the stomach
• yellowing of the skin or eyes
• flu-like symptoms

More common

• difficult or labored breathing
• dizziness, fainting, or lightheadedness
• fast, irregular, pounding, or racing heartbeat or pulse
• shortness of breath
• tightness in the chest
• wheezing

Less common

• burning, crawling, itching, numbness, prickling, “pins and needles”, or tingling feelings
• chest pain
• fainting
• feeling of warmth
• fever
• increased sweating
• partial or slight paralysis
• redness of the face, neck, arms, and occasionally, upper chest
• shakiness and unsteady walk
• shakiness in the legs, arms, hands, or feet
• swelling of the feet or lower legs
• trembling or shaking of the hands or feet
• unsteadiness, trembling, or other problems with muscle control or coordination

Rare

• arm, back, or jaw pain
• black, tarry stools
• bleeding gums
• blood in the urine or stools
• blurred vision
• chest discomfort
• chest tightness or heaviness
• chills
• confusion
• convulsions
• cough
• decrease in the frequency of urination
• decrease in urine volume
• difficulty in passing urine (dribbling)
• difficulty with breathing
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• frequent urination
• general feeling of discomfort or illness
• headache
• increased volume of pale, dilute urine
• nausea
• nervousness
• noisy breathing
• painful or difficult urination
• pinpoint red spots on the skin
• pounding in the ears
• sensation of pins and needles
• slow or fast heartbeat
• sore throat
• sores, ulcers, or white spots on the lips or in the mouth
• stabbing pain
• sweating
• swollen glands
• thickening of bronchial secretions
• troubled breathing
• unusual bleeding or bruising
• unusual tiredness or weakness
• yellow eyes or skin

Flecainide may cause other side effects. Call your doctor if you have any unusual problems while taking flecainide.

Flecainide toxicity

Broadly speaking, flecainide like other sodium channel blockers cause metabolic, cardiac, and neurologic symptoms. This leads to hemodynamic compromise and metabolic acidosis, potentiating the effects of the medications and causing further sodium blockade ²²⁾. Patients with potential flecainide toxicity require an immediate electrocardiogram (ECG). Flecainide toxicity leads to a widening of the QRS complex, lengthening of the QT interval, a new right axis deviation, bradydysrhythmias, ventricular tachycardia, ventricular fibrillation or torsades des pointes ²³⁾. Brugada phenocopy, a sodium channelopathy disorder, can also be seen during acute toxicity ²⁴⁾.

Symptoms of flecainide toxicity may include:

• nausea
• vomiting
• seizures
• slow, fast, or irregular heartbeat
• loss of consciousness
• sudden death

Sodium channel blockers cross the blood-brain barrier and act through multiple mechanisms. They inhibit the gamma-aminobutyric acid (GABA) system (primarily lidocaine), activate the sodium ouabain-sensitive current, stimulate 5-TH2C receptors, antagonize H1 receptors and block all noradrenaline activating effect. It is through these actions that adrenergic stimulation occurs. These medications in large doses are also pro-convulsant through the above mechanisms ²⁵⁾.

Co-ingestion of other drugs can alter the elimination kinetics. A recent case report describes how propafenone delayed the metabolism of metoprolol by inhibition of CYP2D. This interaction of the two medications led to a more profound toxicity, and in this case cardiovascular collapse ²⁶⁾.

It is vital to consider and evaluate for any other co-ingestion.

Obtain electrolyte, renal and hepatic profiles, acetaminophen level, salicylate level, arterial or venous blood gas, drug screen, and a complete blood count. Evaluate for an anion gap, and osmolal gap as this could indicate coingestants not detectable on standard testing.

Flecainide toxicity management

Immediate initial management must begin with an assessment of airway, breathing, and circulation. Many patients present with hypotension, bradycardia or tachycardia and altered mental status. An endotracheal tube or other advanced airways should be placed in patients who are unable to protect their airway.

The cornerstone of treatment is the administration of sodium bicarbonate. It is indicated for patients with an ECG demonstrating a QRS duration >100 ms or any suspicious QT prolongation or dysrhythmia ²⁷⁾. Sodium bicarbonate is beneficial in raising the serum pH and increasing the extracellular sodium. Alkalinization leads to an increase of the electrochemical gradient across cell membranes which helps to offload sodium channels. It might also increase the protein binding of the offending agent. Patients should be given 1-2mEq/kg as a bolus dose ²⁸⁾. Bolus doses can be administered until the QRS duration is less than 100 ms. This can be followed with a continuous infusion of sodium bicarbonate of 2-3 50mEq ampules in one liter of D5W (5% dextrose in water) ²⁹⁾. Hypertonic saline has been used but is not routinely recommended; it remains an option in dire circumstances as reported in a case of flecainide overdose ³⁰⁾.

Management of hypotension requires a combination of volume resuscitation and vasopressor and inotropic support. Use of inotropic agents such as dobutamine helps increase cardiac output while the effects of the toxicity dissipate. Addition of vasopressors such as norepinephrine, vasopressin, or epinephrine might be considered for hemodynamic support. These agents lead to vasoconstriction and an increase in the systemic vascular resistance, resulting in increased systemic blood pressure.

Patients with sodium channel blocker toxicity from lidocaine have benefitted from the administration of 20% lipid emulsion if they are hemodynamically unstable ³¹⁾. The mechanism of action of lipid emulsion is unclear; however, it is hypothesized that it acts as a lipid sink, with an electrochemical gradient drawing the lidocaine into the lipid. Patients should be given a 1.5mL/kg bolus followed by a 0.25mL/kg infusion ³²⁾. Few studies exist on lipid emulsion for other sodium channel toxicities.

Extracorporeal membrane oxygenation (ECMO) has been used in a refractory case with reported survival ³³⁾. In general, the drugs which cause sodium channel blockade toxicity are highly lipophilic, have a wide volume of distribution, and are not dialyzable.

Seizure management is accomplished with benzodiazepine medications, such as lorazepam and midazolam. For refractory seizures, loading of antiepileptic medications such as levetiracetam is recommended. Phenytoin and its derivatives should be avoided in this situation as phenytoin is itself a sodium channel blocker and will likely lead to clinical deterioration. Intubation and sedation with propofol should be considered for seizures refractory to other management.

Flecainide toxicity prognosis

Complications of sodium channel blocker toxicity include cardiogenic shock, hypotension, bradycardia or tachycardia, cardiovascular collapse, respiratory depression, encephalopathy, status epilepticus, and death.

Class I antiarrhythmic toxicity is associated with a significantly higher mortality rate (22.5%) compared with other drugs (1%) ³⁴⁾. Prompt recognition and treatment are vital to minimize morbidity and mortality.

Amikacin

Amikacin is a broad spectrum semisynthetic aminoglycoside antibiotic that kills bacteria. Amikacin is used to treat severe or serious gram negative infections including those resistant to gentamicin or tobramycin. Amikacin injection is used to treat certain serious infections that are caused by bacteria such as meningitis (infection of the membranes that surround the brain and spinal cord) and infections of the blood, abdomen (stomach area), lungs, skin, bones, joints, and urinary tract. Amikacin is also sometimes used with other medications to treat tuberculosis (TB; a serious infection that affects the lungs and sometimes other parts of the body). Amikacin injection is for short-term use only (7 to 10 days). Talk to your doctor about the risks of using amikacin for your condition.

Like other aminoglycosides, amikacin is thought to act by binding to bacterial ribosomes and inhibiting protein synthesis. Nevertheless, amikacin is considered bacteriocidal as well as bacteriostatic. Amikacin and other aminoglycosides are typically used in combination with a penicillin or cephalosporin for treatment of severe infections with Pseudomonas aeruginosa, Enterobacter, Klebsiella, Serratia and other gram-negative bacteria resistant to less toxic antibiotics. Amikacin is most commonly used for septicemia, bacterial endocarditis, peritonitis, meningitis, pelvic inflammatory disease and pneumonia. Amikacin is also used in therapy of tuberculosis in combination with other antitubercular drugs.

Amikacin was approved for use in the United States in 1981 and is available in several generic parenteral formulations. The typical adult dose is 15 mg/kg per day im or iv, usually in two or three divided doses over 5 to 10 days. The dose of amikacin must be modified based upon renal function and monitoring of drug levels is advisable. Amikacin common side effects include dizziness, headache, confusion, nausea and skin rash. Importantly, dose related adverse effects of amikacin include oto- and nephrotoxicity, which are shared by all aminoglycosides.

Antibiotics such as amikacin injection will not work for colds, flu or other viral infections. Taking antibiotics when they are not needed increases your risk of getting an infection later that resists antibiotic treatment.

Amikacin injection comes as a liquid to be injected intravenously (into a vein) or intramuscularly (into a muscle) every 8 or 12 hours (two or three times a day). When amikacin is injected intravenously, it is usually infused (injected slowly) over a period of 30 to 60 minutes. The length of your treatment depends on the type of infection you have.

You may receive amikacin injection in a hospital or you may administer the medication at home. If you will be receiving amikacin injection at home, your healthcare provider will show you how to use the medication. Be sure that you understand these directions, and ask your healthcare provider if you have any questions.

You should begin to feel better during the first few days of treatment with amikacin injection. If your symptoms do not improve or get worse, call your doctor.

Use amikacin injection until you finish the prescription, even if you feel better. If you stop using amikacin injection too soon or skip doses, your infection may not be completely treated and the bacteria may become resistant to antibiotics.

Amikacin mechanism of action

Amikacin binds irreversibly to the 30S bacterial ribosome subunit, resulting in interference with a reading of the genetic code and inhibition of protein synthesis. Amikacin, as well as the rest of the aminoglycosides, are generally bacteriocidal and probably have an additional mechanism of action which is yet to be determined.

Amikacin indications

Amikacin is rarely used alone and often combined with other antibiotics.

Amikacin indications include

• Hospital-Acquired/Ventilator-Associated/Healthcare-Associated Pneumonia
• Endophthalmitis, bacterial (intravitreal injection, OFF LABEL)
• Meningitis (IV) or (Intrathecal/Intraventricular, OFF LABEL)
• Wound infections caused by susceptible organisms
• Urinary tract infections (Generally only if caused by resistant organisms, OFF LABEL)
• Gram-negative Bacteremia/Sepsis (OFF LABEL)

Amikacin injection

Amikacin and other aminoglycosides are typically used in combination with a penicillin or cephalosporin for treatment of severe infections with Pseudomonas aeruginosa, Enterobacter, Klebsiella, Serratia and other gram-negative bacteria resistant to less toxic antibiotics. Amikacin is most commonly used for septicemia, bacterial endocarditis, peritonitis, meningitis, pelvic inflammatory disease and pneumonia. Amikacin is also used in therapy of tuberculosis in combination with other antitubercular drugs.

Amikacin injection is usually used for serious bacterial infections for which other medicines may not work. However, it may also cause some serious side effects, including damage to your hearing, sense of balance, and kidneys. These side effects may be more likely to occur in elderly patients and newborn infants. You and your doctor should talk about the benefits of this medicine as well as the risks.

Amikacin injection to be administered only by or under the immediate supervision of your doctor.

Amikacin inhalation

Amikacin inhalation (amikacin liposome) is used to treat adults with refractory (difficult to treat) Mycobacterium avium complex (MAC) lung disease as part of a combination antibacterial drug treatment plan (regimen). Amikacin inhalation (amikacin liposome) is available only with your doctor’s prescription.

Amikacin special precautions

Before receiving amikacin injection:

• tell your doctor and pharmacist if you are allergic to amikacin injection; other aminoglycoside antibiotics such as gentamicin, kanamycin, neomycin, streptomycin, or tobramycin; sulfites; any other medications; or any of the ingredients in amikacin injection. Ask your pharmacist for a list of the ingredients.
• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, and nutritional supplements, you are taking or plan to take. Be sure to mention the medications listed in the IMPORTANT WARNING section and any of the following: other antibiotics such as amoxicillin (Amoxil, Larotid, Moxatag, in Augmentin, in Prevpac), ampicillin, or penicillin; dimenhydrinate (Dramamine); meclizine (Bonine); or nonsteroidal anti-inflammatory drugs such as indomethacin (Indocin, Tivorbex). Your doctor may need to change the doses of your medications or monitor you carefully for side effects. Many other medications may also interact with amikacin, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list.
• tell your doctor if you are or have or have ever had cystic fibrosis (an inherited condition that affects the lungs and digestive system), problems with your muscles such as myasthenia gravis or Parkinson’s disease.
• Tell your doctor if you are pregnant or plan to become pregnant or breastfeed. If you become pregnant while using amikacin injection, call your doctor immediately. Amikacin may harm the fetus.

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of amikacin injection in children. However, this medicine should be used with caution in premature and newborn infants.

Geriatric

No information is available on the relationship of age to the effects of amikacin injection in geriatric patients. However, elderly patients are more likely to have kidney problems, which may require caution and an adjustment in the dose for patients receiving amikacin injection.

Pregnancy

Pregnancy Category D: Studies in pregnant women have demonstrated a risk to the fetus. However, the benefits of therapy in a life threatening situation or a serious disease, may outweigh the potential risk.

Breastfeeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Amikacin injection drug interactions

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are receiving amikacin, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using amikacin with any of the following medicines is not recommended. Your doctor may decide not to treat you with amikacin or change some of the other medicines you take.

• Ataluren

Using amikacin with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Alcuronium
• Atracurium
• Cholera Vaccine, Live
• Cidofovir
• Cisatracurium
• Colistimethate Sodium
• Decamethonium
• Doxacurium
• Ethacrynic Acid
• Fazadinium
• Foscarnet
• Furosemide
• Gallamine
• Hexafluorenium
• Lysine
• Mannitol
• Metocurine
• Mivacurium
• Pancuronium
• Pipecuronium
• Rapacuronium
• Rocuronium
• Succinylcholine
• Tubocurarine
• Urea
• Vancomycin
• Vecuronium

Using amikacin with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Ibuprofen

Other Interactions

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Asthma or
• Sulfite allergy, history of—This medicine contains sodium metabisulfite which may cause an allergic reaction in patients with these conditions.
• Kidney disease, severe or
• Muscle problems or
• Myasthenia gravis (severe muscle weakness) or
• Nerve problems or
• Parkinson’s disease—Use with caution. May make these condition worse.
• Kidney disease—Use with caution. The effects may be increased because of slower removal of this medicine from the body.

Amikacin inhalation drug interactions

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Ethacrynic Acid
• Furosemide
• Mannitol
• Urea

Other Interactions

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Asthma or
• Bronchospasm or
• Chronic obstructive pulmonary disease (COPD) or
• Hyperreactive airway disease—Must be treated first before using this medicine.
• Ear or hearing problems or
• Lung or breathing problems or
• Nerve or muscle problems (eg, myasthenia gravis)—Use with caution. May make these conditions worse.

Amikacin administration

Amikacin can be administered parenterally or via nebulization. There is no oral formula of the drug available because the drug is not absorbed from the gastrointestinal tract. A nurse or other trained health professional will give you amikacin injection. Amikacin can be administered as a shot into a muscle (intramuscularly or IM) when intravenous (IV) access is not available. In some patients with meningitis, amikacin can be administered intrathecally and reaches high levels in the cerebrospinal fluid immediately ¹⁾.

To help clear up your infection completely, keep using amikacin injection for the full time of treatment, even if you begin to feel better after a few days. Also, amikacin injection works best when there is a constant amount in the blood. To help keep the amount constant, you must receive amikacin injection on a regular schedule.

To keep your kidneys working well and help prevent kidney problems, drink extra fluids so you will pass more urine while you or your child are receiving amikacin injection.

Your doctor will check your progress closely while you or your child are receiving amikacin. This will allow your doctor to see if amikacin is working properly and to decide if you or your child should continue to receive it. Blood, urine, hearing, and nerve tests may be needed to check for unwanted effects.

If your or your child’s symptoms do not improve within a few days, or if they become worse, check with your doctor.

Using amikacin while you are pregnant can harm your unborn baby. Use an effective form of birth control to keep from getting pregnant. If you think you have become pregnant while using amikacin, tell your doctor right away.

This medicine may cause serious allergic reactions, including anaphylaxis, which can be life-threatening and require immediate medical attention. Call your doctor right away if you or your child have itching; hives; hoarseness; shortness of breath; trouble breathing; trouble swallowing; or any swelling of your hands, face, or mouth after you receive amikacin.

Stop using amikacin and check with your doctor right away if you or your child have sudden decrease in hearing or loss of hearing, which may be accompanied by dizziness and ringing in the ears. Tell your doctor if you or your child have dizziness or lightheadedness; feeling of constant movement of self or surroundings; or sensation of spinning. These may be symptoms of a damage to your hearing or sense of balance.

Tell your doctor right away if you have trouble using your muscles or trouble breathing while receiving amikacin.

Check with your doctor right away if you or your child have blood in the urine, change in frequency of urination or amount of urine, difficulty with breathing, drowsiness, increased thirst, loss of appetite, nausea or vomiting, swelling of feet or lower legs, or weakness. These may be symptoms of a serious kidney problem.

This medicine may cause nerve problems. Check with your doctor right away if you or your child have numbness, skin tingling, muscle twitching, or seizures.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Amikacin dose adjustments

Therapeutic drug monitoring/range:

• Peak: Less than 35 mcg/mL
• Trough: Less than 10 mcg/mL
• Peak and trough levels should be measured intermittently throughout treatment.

Lack of clinical response within 3 to 5 days:

• Stop treatment and recheck antibiotic susceptibility of the organism.

Signs/symptoms of ototoxicity (e.g., dizziness, hearing loss, raring in the ears, tinnitus, vertigo): Discontinue the drug OR adjust the dose.

Amikacin inhalation

Amikacin inhalation is given through the Lamira™ Nebulizer System. Follow the instructions carefully on how to use it. Do not use the nebulizer system with any other medicine.

If you are using a bronchodilator (reliever) medicine for your lung or breathing problem, you should take it first before using amikacin inhalation.

Keep using amikacin inhalation for the full treatment time even if you feel better after the first few doses. Your infection may not clear up if you stop using the medicine too soon.

Amikacin dose

Amikacin dosing is based on your body weight (Kg) ²⁾:

• Underweight or Nonobese: dose on ACTUAL body weight
• Obese (ACTUAL body weight/Ideal Body Weight > or = to 1.25): dose on DOSING body weight (DOSING body weight = Ideal Body Weight + 0.4(Actual body weight – Ideal Body Weight)

Adult Dosing:

• Conventional Dosing: 5mg/kg IV every 8 hours, Elderly often require only each 12 hr interval
• Adjustment for renal impairment (assuming every 8-hr dosing)
  • > 50 mL/min
  • (creatinine clearance [not GFR])
  • : no adjustment
  • 30-50 mL/min: every 12 to 18 hrs
  • 10-29 mL/min: every 18 to 24 hr
  • < 10 mL/min: dose based on levels or consult a pharmacist.

Once Daily Dosing:

• Not to be used in patients with ascites, > 20% Body Surface Area (BSA) burns, pregnant patients, or patients on dialysis. (Use conventional dosing or consult pharmacist.)
• 15 mg/kg per dose once daily

Adjustment for renal impairment:

• 60 mL/min (creatinine clearance [not GFR]) and above: every 24 hours
• 40-59 mL/min: every 36 hours
• 30-39 mL/min: every 48 hours
• < 30mL/min: Use conventional dosing method

Intravitreal:

• 0.4 mg/0.1 mL of Normal Saline (preservative free formulation, OFF LABEL)

Intrathecal/intraventricular:

• 5 to 50mg/day, usual dose is 30mg (preservative free formulation, OFF LABEL)

Amikacin inhalation

There is also liposomal amikacin undergoing clinical trials for the treatment of respiratory infections in patients with cystic fibrosis and bronchiectasis. In the trials, the liposomal formula is being used to treat nontuberculous bacteria and pseudomonas aeruginosa.

Adult Dose for Bacteremia

• 15 mg/kg IM or IV (over 30 to 60 minutes) per day, given in 2 to 3 equal doses at equally divided intervals
• Maximum dose: 15 mg/kg/day
• Duration of therapy: 7 to 10 days

Comments:

• Heavier patients should not exceed 1.5 grams/day.
• Some recommended dose regimens include 7.5 mg/kg IM every 12 hours or 5 mg/kg IM every 8 hours.
• Most infections typically respond in 24 to 48 hours; if clinical response does not occur within 3 to 5 days, treatment should be stopped and the susceptibility pattern of the organism should be rechecked.
• Drug serum levels, renal, auditory, and vestibular functions should be monitored in patients who require treatment beyond 10 days.

Uses:

• Short-term treatment of susceptible strains of Gram-negative bacteria, including Pseudomonas species, Escherichia coli, indole-positive/-negative species of Proteus, Providencia species, Klebsiella-Enterobacter-Serratia species, and Acinetobacter (Mima-Herellea) species causing the following infections:
• Bacterial septicemia
• Serious infections of the bones and joints, burns, intraabdominal infections, respiratory tract, skin and soft tissue
• Serious postoperative infections, including postvascular surgery
• Initial/empirical therapy in severe infection, with suspected gram-negative, staphylococcal, or mixed staphylococcal/gram-negative infections, or in patients allergic to other antibiotics

Surgical Infection Society (SIS) and Infectious Diseases Society of America (IDSA) Recommendations:

• 15 to 20 mg/kg IV every 24 hours

Comments:

• Initial doses should be based on body weight.
• Maintenance doses should be determined by concentration monitoring.

Uses:

• Empirical treatment of patients with healthcare-associated intra-abdominal infections
• Treatment of patients with severe reactions to beta-lactam antibiotics who have complicated intra-abdominal infections

American Thoracic Society (ATS) and IDSA Recommendations:

• 10 to 15 mg/kg IV once a day OR 25 mg/kg IV 3 times a week

Duration of therapy:

• Initial therapy: At least 2 weeks
• Serious skin and soft tissue infections: At least 4 months
• Bone infections: At least 6 months

Comments:

• Patients 50 years of age and older or those with prolonged treatment (greater than 3 weeks) should be given lower daily doses (10 mg/kg/day).
• This drug should be given with azithromycin, clarithromycin, high-dose cefoxitin, or imipenem.

Use: Treatment of serous skin, soft tissue, and bone infections caused by Mycoplasma abscessus

Adult Dose for Intraabdominal Infection

• 15 mg/kg IM or IV (over 30 to 60 minutes) per day, given in 2 to 3 equal doses at equally divided intervals
• Maximum dose: 15 mg/kg/day
• Duration of therapy: 7 to 10 days

Comments:

• Heavier patients should not exceed 1.5 grams/day.
• Some recommended dose regimens include 7.5 mg/kg IM every 12 hours or 5 mg/kg IM every 8 hours.
• Most infections typically respond in 24 to 48 hours; if clinical response does not occur within 3 to 5 days, treatment should be stopped and the susceptibility pattern of the organism should be rechecked.
• Drug serum levels, renal, auditory, and vestibular functions should be monitored in patients who require treatment beyond 10 days.

Uses:

• Short-term treatment of susceptible strains of Gram-negative bacteria, including Pseudomonas species, Escherichia coli, indole-positive/-negative species of Proteus, Providencia species, Klebsiella-Enterobacter-Serratia species, and Acinetobacter (Mima-Herellea) species causing the following infections:
• Bacterial septicemia
• Serious infections of the bones and joints, burns, intraabdominal infections, respiratory tract, skin and soft tissue
• Serious postoperative infections, including postvascular surgery
• Initial/empirical therapy in severe infection, with suspected gram-negative, staphylococcal, or mixed staphylococcal/gram-negative infections, or in patients allergic to other antibiotics

Surgical Infection Society (SIS) and Infectious Diseases Society of America (IDSA) Recommendations:

• 15 to 20 mg/kg IV every 24 hours

Comments:

• Initial doses should be based on body weight.
• Maintenance doses should be determined by concentration monitoring.

Uses:

• Empirical treatment of patients with healthcare-associated intra-abdominal infections
• Treatment of patients with severe reactions to beta-lactam antibiotics who have complicated intra-abdominal infections

American Thoracic Society (ATS) and IDSA Recommendations:

• 10 to 15 mg/kg IV once a day OR 25 mg/kg IV 3 times a week

Duration of therapy:

• Initial therapy: At least 2 weeks
• Serious skin and soft tissue infections: At least 4 months
• Bone infections: At least 6 months

Comments:

• Patients 50 years of age and older or those with prolonged treatment (greater than 3 weeks) should be given lower daily doses (10 mg/kg/day).
• This drug should be given with azithromycin, clarithromycin, high-dose cefoxitin, or imipenem.

Use: Treatment of serous skin, soft tissue, and bone infections caused by Mycoplasma abscessus

Adult Dose for Joint Infection

• 15 mg/kg IM or IV (over 30 to 60 minutes) per day, given in 2 to 3 equal doses at equally divided intervals
• Maximum dose: 15 mg/kg/day
• Duration of therapy: 7 to 10 days

Comments:

• Heavier patients should not exceed 1.5 grams/day.
• Some recommended dose regimens include 7.5 mg/kg IM every 12 hours or 5 mg/kg IM every 8 hours.
• Most infections typically respond in 24 to 48 hours; if clinical response does not occur within 3 to 5 days, treatment should be stopped and the susceptibility pattern of the organism should be rechecked.
• Drug serum levels, renal, auditory, and vestibular functions should be monitored in patients who require treatment beyond 10 days.

Uses:

• Short-term treatment of susceptible strains of Gram-negative bacteria, including Pseudomonas species, Escherichia coli, indole-positive/-negative species of Proteus, Providencia species, Klebsiella-Enterobacter-Serratia species, and Acinetobacter (Mima-Herellea) species causing the following infections:
• Bacterial septicemia
• Serious infections of the bones and joints, burns, intraabdominal infections, respiratory tract, skin and soft tissue
• Serious postoperative infections, including postvascular surgery
• Initial/empirical therapy in severe infection, with suspected gram-negative, staphylococcal, or mixed staphylococcal/gram-negative infections, or in patients allergic to other antibiotics

Surgical Infection Society (SIS) and Infectious Diseases Society of America (IDSA) Recommendations:

• 15 to 20 mg/kg IV every 24 hours

Comments:

• Initial doses should be based on body weight.
• Maintenance doses should be determined by concentration monitoring.

Uses:

• Empirical treatment of patients with healthcare-associated intra-abdominal infections
• Treatment of patients with severe reactions to beta-lactam antibiotics who have complicated intra-abdominal infections

American Thoracic Society (ATS) and IDSA Recommendations:

• 10 to 15 mg/kg IV once a day OR 25 mg/kg IV 3 times a week

Duration of therapy:

• Initial therapy: At least 2 weeks
• Serious skin and soft tissue infections: At least 4 months
• Bone infections: At least 6 months

Comments:

• Patients 50 years of age and older or those with prolonged treatment (greater than 3 weeks) should be given lower daily doses (10 mg/kg/day).
• This drug should be given with azithromycin, clarithromycin, high-dose cefoxitin, or imipenem.

Use: Treatment of serous skin, soft tissue, and bone infections caused by Mycoplasma abscessus

Adult Dose for Osteomyelitis

• 15 mg/kg IM or IV (over 30 to 60 minutes) per day, given in 2 to 3 equal doses at equally divided intervals
• Maximum dose: 15 mg/kg/day
• Duration of therapy: 7 to 10 days

Comments:

• Heavier patients should not exceed 1.5 grams/day.
• Some recommended dose regimens include 7.5 mg/kg IM every 12 hours or 5 mg/kg IM every 8 hours.
• Most infections typically respond in 24 to 48 hours; if clinical response does not occur within 3 to 5 days, treatment should be stopped and the susceptibility pattern of the organism should be rechecked.
• Drug serum levels, renal, auditory, and vestibular functions should be monitored in patients who require treatment beyond 10 days.

Uses:

• Short-term treatment of susceptible strains of Gram-negative bacteria, including Pseudomonas species, Escherichia coli, indole-positive/-negative species of Proteus, Providencia species, Klebsiella-Enterobacter-Serratia species, and Acinetobacter (Mima-Herellea) species causing the following infections:
• Bacterial septicemia
• Serious infections of the bones and joints, burns, intraabdominal infections, respiratory tract, skin and soft tissue
• Serious postoperative infections, including postvascular surgery
• Initial/empirical therapy in severe infection, with suspected gram-negative, staphylococcal, or mixed staphylococcal/gram-negative infections, or in patients allergic to other antibiotics

Surgical Infection Society (SIS) and Infectious Diseases Society of America (IDSA) Recommendations:

• 15 to 20 mg/kg IV every 24 hours

Comments:

• Initial doses should be based on body weight.
• Maintenance doses should be determined by concentration monitoring.

Uses:

• Empirical treatment of patients with healthcare-associated intra-abdominal infections
• Treatment of patients with severe reactions to beta-lactam antibiotics who have complicated intra-abdominal infections

American Thoracic Society (ATS) and IDSA Recommendations:

• 10 to 15 mg/kg IV once a day OR 25 mg/kg IV 3 times a week

Duration of therapy:

• Initial therapy: At least 2 weeks
• Serious skin and soft tissue infections: At least 4 months
• Bone infections: At least 6 months

Comments:

• Patients 50 years of age and older or those with prolonged treatment (greater than 3 weeks) should be given lower daily doses (10 mg/kg/day).
• This drug should be given with azithromycin, clarithromycin, high-dose cefoxitin, or imipenem.

Use: Treatment of serous skin, soft tissue, and bone infections caused by Mycoplasma abscessus

Adult Dose for Pneumonia

• 15 mg/kg IM or IV (over 30 to 60 minutes) per day, given in 2 to 3 equal doses at equally divided intervals
• Maximum dose: 15 mg/kg/day
• Duration of therapy: 7 to 10 days

Comments:

• Heavier patients should not exceed 1.5 grams/day.
• Some recommended dose regimens include 7.5 mg/kg IM every 12 hours or 5 mg/kg IM every 8 hours.
• Most infections typically respond in 24 to 48 hours; if clinical response does not occur within 3 to 5 days, treatment should be stopped and the susceptibility pattern of the organism should be rechecked.
• Drug serum levels, renal, auditory, and vestibular functions should be monitored in patients who require treatment beyond 10 days.

Uses:

• Short-term treatment of susceptible strains of Gram-negative bacteria, including Pseudomonas species, Escherichia coli, indole-positive/-negative species of Proteus, Providencia species, Klebsiella-Enterobacter-Serratia species, and Acinetobacter (Mima-Herellea) species causing the following infections:
• Bacterial septicemia
• Serious infections of the bones and joints, burns, intraabdominal infections, respiratory tract, skin and soft tissue
• Serious postoperative infections, including postvascular surgery
• Initial/empirical therapy in severe infection, with suspected gram-negative, staphylococcal, or mixed staphylococcal/gram-negative infections, or in patients allergic to other antibiotics

Surgical Infection Society (SIS) and Infectious Diseases Society of America (IDSA) Recommendations:

• 15 to 20 mg/kg IV every 24 hours

Comments:

• Initial doses should be based on body weight.
• Maintenance doses should be determined by concentration monitoring.

Uses:

• Empirical treatment of patients with healthcare-associated intra-abdominal infections
• Treatment of patients with severe reactions to beta-lactam antibiotics who have complicated intra-abdominal infections

American Thoracic Society (ATS) and IDSA Recommendations:

• 10 to 15 mg/kg IV once a day OR 25 mg/kg IV 3 times a week

Duration of therapy:

• Initial therapy: At least 2 weeks
• Serious skin and soft tissue infections: At least 4 months
• Bone infections: At least 6 months

Comments:

• Patients 50 years of age and older or those with prolonged treatment (greater than 3 weeks) should be given lower daily doses (10 mg/kg/day).
• This drug should be given with azithromycin, clarithromycin, high-dose cefoxitin, or imipenem.

Use: Treatment of serous skin, soft tissue, and bone infections caused by Mycoplasma abscessus

Adult Dose for Skin or Soft Tissue Infection

• 15 mg/kg IM or IV (over 30 to 60 minutes) per day, given in 2 to 3 equal doses at equally divided intervals
• Maximum dose: 15 mg/kg/day
• Duration of therapy: 7 to 10 days

Comments:

• Heavier patients should not exceed 1.5 grams/day.
• Some recommended dose regimens include 7.5 mg/kg IM every 12 hours or 5 mg/kg IM every 8 hours.
• Most infections typically respond in 24 to 48 hours; if clinical response does not occur within 3 to 5 days, treatment should be stopped and the susceptibility pattern of the organism should be rechecked.
• Drug serum levels, renal, auditory, and vestibular functions should be monitored in patients who require treatment beyond 10 days.

Uses:

• Short-term treatment of susceptible strains of Gram-negative bacteria, including Pseudomonas species, Escherichia coli, indole-positive/-negative species of Proteus, Providencia species, Klebsiella-Enterobacter-Serratia species, and Acinetobacter (Mima-Herellea) species causing the following infections:
• Bacterial septicemia
• Serious infections of the bones and joints, burns, intraabdominal infections, respiratory tract, skin and soft tissue
• Serious postoperative infections, including postvascular surgery
• Initial/empirical therapy in severe infection, with suspected gram-negative, staphylococcal, or mixed staphylococcal/gram-negative infections, or in patients allergic to other antibiotics

Surgical Infection Society (SIS) and Infectious Diseases Society of America (IDSA) Recommendations:

• 15 to 20 mg/kg IV every 24 hours

Comments:

• Initial doses should be based on body weight.
• Maintenance doses should be determined by concentration monitoring.

Uses:

• Empirical treatment of patients with healthcare-associated intra-abdominal infections
• Treatment of patients with severe reactions to beta-lactam antibiotics who have complicated intra-abdominal infections

American Thoracic Society (ATS) and IDSA Recommendations:

• 10 to 15 mg/kg IV once a day OR 25 mg/kg IV 3 times a week

Duration of therapy:

• Initial therapy: At least 2 weeks
• Serious skin and soft tissue infections: At least 4 months
• Bone infections: At least 6 months

Comments:

• Patients 50 years of age and older or those with prolonged treatment (greater than 3 weeks) should be given lower daily doses (10 mg/kg/day).
• This drug should be given with azithromycin, clarithromycin, high-dose cefoxitin, or imipenem.

Use: Treatment of serous skin, soft tissue, and bone infections caused by Mycoplasma abscessus

Adult Dose for Urinary Tract Infection

• Serious complicated/recurrent urinary tract infections: 15 mg/kg IM or IV (over 30 to 60 minutes) per day, given in 2 to 3 equal doses at equally divided intervals
• Uncomplicated urinary tract infections: 250 mg IM or IV (over 30 to 60 minutes) 2 times a day
• Maximum dose: 15 mg/kg/day
• Duration of therapy: 7 to 10 days

Comments:

• Heavier patients should not exceed 1.5 grams/day.
• Some recommended dose regimens include 7.5 mg/kg IM every 12 hours or 5 mg/kg IM every 8 hours.
• Most infections typically respond in 24 to 48 hours; if clinical response does not occur within 3 to 5 days, treatment should be stopped and the susceptibility pattern of the organism should be rechecked.
• Drug serum levels, renal, auditory, and vestibular functions should be monitored in patients who require treatment beyond 10 days.
• This drug should not be used to treat initial uncomplicated urinary tract infections unless the causative organisms are not susceptible to less potent antibiotics.

Uses:

• Short-term treatment of serious complicated and recurrent urinary tract infections caused by susceptible strains of Gram-negative bacteria, including Pseudomonas species, E coli, indole-positive/-negative species of Proteus, Providencia species, Klebsiella-Enterobacter-Serratia species, and Acinetobacter (Mima-Herellea) species
• Uncomplicated initial episodes of urinary tract infections caused by organisms not susceptible to antibiotics having less potential toxicity

Adult Dose for Meningitis

• 15 mg/kg IM or IV (over 30 to 60 minutes) per day, given in 2 to 3 equal doses at equally divided intervals
• Maximum dose: 15 mg/kg/day
• Duration of therapy: 7 to 10 days

Comments:

• Heavier patients should not exceed 1.5 grams/day.
• Some recommended dose regimens include 7.5 mg/kg IM every 12 hours or 5 mg/kg IM every 8 hours.
• Most infections typically respond in 24 to 48 hours; if clinical response does not occur within 3 to 5 days, treatment should be stopped and the susceptibility pattern of the organism should be rechecked.
• Drug serum levels, renal, auditory, and vestibular functions should be monitored in patients who require treatment beyond 10 days.

Use: Treatment of meningitis and serious infections of the central nervous system caused by susceptible strains of Gram-negative bacteria, including Pseudomonas species, E coli, indole-positive/-negative species of Proteus, Providencia species, Klebsiella-Enterobacter-Serratia species, and Acinetobacter (Mima-Herellea) species

IDSA, American Academy of Neurology (AAN), American Association of Neurological Surgeons (AANS), and Neurocritical Care Society (NCS) Recommendations:

• Healthcare-Associated Ventriculitis and Meningitis:
  • IV: 15 mg/kg IV per day, given in divided doses every 8 hours
  • Intraventricular: 5 to 50 mg via intraventricular route once a day

Duration of therapy:

• Neisseria meningitis or Haemophilus influenzae: 7 days
• Coagulase-negative staphylococcus or Propionibacterium acnes with no/minimal cerebrospinal fluid pleocytosis, normal CSF glucose, few symptoms/systemic features: 10 days
• Coagulase-negative staphylococcus or P acnes with significant CSF pleocytosis, Staphylococcus aureus or gram-negative bacilli with/without significant CSF pleocytosis, CSF hypoglycorrhachia, or symptoms/systemic features: 10 to 14 days
• Streptococcus pneumoniae: 10 to 14 days
• Streptococcus agalactiae: 14 to 21 days
• Aerobic gram-negative bacilli: 21 days
• Listeria monocytogenes: At least 21 days
• Repeatedly positive CSF cultures on appropriate antimicrobial treatment: Continue treatment for 10 to 14 days after the last positive culture

Comments:

• The usual intraventricular dose was 30 mg/day.
• The intraventricular drain should be clamped for approximately 15 to 60 minutes to allow the drug to equilibrate.

Use: Treatment of healthcare-associated ventriculitis and meningitis

Adult Dose for Peritonitis

• 15 mg/kg IM or IV (over 30 to 60 minutes) per day, given in 2 to 3 equal doses at equally divided intervals
• Maximum dose: 15 mg/kg/day
• Duration of therapy: 7 to 10 days

Comments:

• Heavier patients should not exceed 1.5 grams/day.
• Some recommended dose regimens include 7.5 mg/kg IM every 12 hours or 5 mg/kg IM every 8 hours.
• Most infections typically respond in 24 to 48 hours; if clinical response does not occur within 3 to 5 days, treatment should be stopped and the susceptibility pattern of the organism should be rechecked.
• Drug serum levels, renal, auditory, and vestibular functions should be monitored in patients who require treatment beyond 10 days.

Use: Treatment of peritonitis caused by susceptible strains of Gram-negative bacteria, including Pseudomonas species, E coli, indole-positive/-negative species of Proteus, Providencia species, Klebsiella-Enterobacter-Serratia species, and Acinetobacter (Mima-Herellea) species

International Society for Peritoneal Dialysis (ISPD) Recommendations:

• Intermittent (1 exchange daily): 2 mg/kg intraperitoneally once a day
• Continuous (all exchanges):
  • Loading dose: 25 mg/L
  • Maintenance dose: 4 mg/L

Comments:

• Intermittent dosing is recommended, and should be allowed to dwell for at least 6 hours.
• Prolonged courses of treatment should be avoided.

Use: Treatment of peritonitis

Adult Dose for Bacterial Infection

US Department of Health and Human Services (US HHS), National Institutes of Health (NIH), Health Resources and Services Administration (HRSA), and US Centers for Disease Control and Prevention (US CDC) Recommendations:

• 10 to 15 mg/kg IV once OR 25 mg/kg IV 3 times a week

Use: Treatment of mycobacterial infections

Adult Dose for Tuberculosis – Active

ATS, US CDC, IDSA Recommendations:

• 15 mg/kg IM or IV once a day OR 25 mg IM or IV 3 times a week

Comment: Patients with renal dysfunction and/or those who are older may require 15 mg/kg given 3 times a week.

Use: Second-line treatment of drug-susceptible tuberculosis caused by susceptible organisms

Adult Dose for Mycobacterium avium-intracellulare

ATS and IDSA Recommendations:

• Severe, extensive (multilobar) fibro cavitary disease OR previously treated disease: 25 mg/kg IV 3 times a week
  • Duration of therapy: 2 to 3 months
• Nodular/bronchiectatic disease: 8 to 10 mg/kg IM or IV 2 to 3 times a week
  • Maximum dose: 500 mg/dose (patients older than 50 years)
  • Duration of therapy: At least 2 months (extensive disease)

Comment: A longer duration of therapy may be used in patients with very extensive disease and/or in those who cannot tolerate other agents.

US HHS, NIH, HRSA, and US CDC Recommendations:

• 10 to 15 mg/kg IV once a day

Comment: This drug may be considered as a third or fourth drug in patients with advanced immunosuppression (e.g., CD4 counts less than 50 cells/mcL), high mycobacterial loads (greater than 2 log CFU/mL), or in the absence of effective antiretroviral therapy.

Use: Third or fourth drug option as an alternative treatment in patients with disseminated Mycobacterium avium complex (MAC) disease

Geriatric Dose for Bacteremia

• 15 mg/kg IM or IV (over 30 to 60 minutes) per day, given in 2 to 3 equal doses at equally divided intervals
• Maximum dose: 15 mg/kg/day
• Duration of therapy: 7 to 10 days

Comments:

• Heavier patients should not exceed 1.5 grams/day.
• Some recommended dose regimens include 7.5 mg/kg IM every 12 hours or 5 mg/kg IM every 8 hours.
• Most infections typically respond in 24 to 48 hours; if clinical response does not occur within 3 to 5 days, treatment should be stopped and the susceptibility pattern of the organism should be rechecked.
• Drug serum levels, renal, auditory, and vestibular functions should be monitored in patients who require treatment beyond 10 days.

Use:

• Short-term treatment of susceptible strains of Gram-negative bacteria, including Pseudomonas species, E coli, indole-positive/-negative species of Proteus, Providencia species, Klebsiella-Enterobacter-Serratia species, and Acinetobacter (Mima-Herellea) species causing the following infections:
• Bacterial septicemia
• Serious infections of the bones and joints, burns, intraabdominal infections, respiratory tract, skin and soft tissue
• Serious postoperative infections, including postvascular surgery
• Initial/empirical therapy in severe infection, with suspected gram-negative, staphylococcal, or mixed staphylococcal/gram-negative infections, or in patients allergic to other antibiotics

ATS and IDSA Recommendations:

• 10 to 15 mg/kg IV once a day OR 25 mg/kg IV 3 times a week

Duration of therapy:

• Initial therapy: At least 2 weeks
• Serious skin and soft tissue infections: At least 4 months
• Bone infections: At least 6 months

Comments:

• Patients 50 years of age and older or those with prolonged treatment (greater than 3 weeks) should be given lower daily doses (10 mg/kg/day).
• This drug should be given with azithromycin, clarithromycin, high-dose cefoxitin, or imipenem.

Use: Treatment of serous skin, soft tissue, and bone infections caused by M abscessus

Geriatric Dose for Intraabdominal Infection

• 15 mg/kg IM or IV (over 30 to 60 minutes) per day, given in 2 to 3 equal doses at equally divided intervals
• Maximum dose: 15 mg/kg/day
• Duration of therapy: 7 to 10 days

Comments:

• Heavier patients should not exceed 1.5 grams/day.
• Some recommended dose regimens include 7.5 mg/kg IM every 12 hours or 5 mg/kg IM every 8 hours.
• Most infections typically respond in 24 to 48 hours; if clinical response does not occur within 3 to 5 days, treatment should be stopped and the susceptibility pattern of the organism should be rechecked.
• Drug serum levels, renal, auditory, and vestibular functions should be monitored in patients who require treatment beyond 10 days.

Use:

Short-term treatment of susceptible strains of Gram-negative bacteria, including Pseudomonas species, E coli, indole-positive/-negative species of Proteus, Providencia species, Klebsiella-Enterobacter-Serratia species, and Acinetobacter (Mima-Herellea) species causing the following infections:

• Bacterial septicemia
• Serious infections of the bones and joints, burns, intraabdominal infections, respiratory tract, skin and soft tissue
• Serious postoperative infections, including postvascular surgery
• Initial/empirical therapy in severe infection, with suspected gram-negative, staphylococcal, or mixed staphylococcal/gram-negative infections, or in patients allergic to other antibiotics

ATS and IDSA Recommendations:

• 10 to 15 mg/kg IV once a day OR 25 mg/kg IV 3 times a week

Duration of therapy:

• Initial therapy: At least 2 weeks
• Serious skin and soft tissue infections: At least 4 months
• Bone infections: At least 6 months

Comments:

• Patients 50 years of age and older or those with prolonged treatment (greater than 3 weeks) should be given lower daily doses (10 mg/kg/day).
• This drug should be given with azithromycin, clarithromycin, high-dose cefoxitin, or imipenem.

Use: Treatment of serous skin, soft tissue, and bone infections caused by M abscessus

Geriatric Dose for Joint Infection

• 15 mg/kg IM or IV (over 30 to 60 minutes) per day, given in 2 to 3 equal doses at equally divided intervals
• Maximum dose: 15 mg/kg/day
• Duration of therapy: 7 to 10 days

Comments:

• Heavier patients should not exceed 1.5 grams/day.
• Some recommended dose regimens include 7.5 mg/kg IM every 12 hours or 5 mg/kg IM every 8 hours.
• Most infections typically respond in 24 to 48 hours; if clinical response does not occur within 3 to 5 days, treatment should be stopped and the susceptibility pattern of the organism should be rechecked.
• Drug serum levels, renal, auditory, and vestibular functions should be monitored in patients who require treatment beyond 10 days.

Use:

Short-term treatment of susceptible strains of Gram-negative bacteria, including Pseudomonas species, E coli, indole-positive/-negative species of Proteus, Providencia species, Klebsiella-Enterobacter-Serratia species, and Acinetobacter (Mima-Herellea) species causing the following infections:

• Bacterial septicemia
• Serious infections of the bones and joints, burns, intraabdominal infections, respiratory tract, skin and soft tissue
• Serious postoperative infections, including postvascular surgery
• Initial/empirical therapy in severe infection, with suspected gram-negative, staphylococcal, or mixed staphylococcal/gram-negative infections, or in patients allergic to other antibiotics

ATS and IDSA Recommendations:

• 10 to 15 mg/kg IV once a day OR 25 mg/kg IV 3 times a week

Duration of therapy:

• Initial therapy: At least 2 weeks
• Serious skin and soft tissue infections: At least 4 months
• Bone infections: At least 6 months

Comments:

• Patients 50 years of age and older or those with prolonged treatment (greater than 3 weeks) should be given lower daily doses (10 mg/kg/day).
• This drug should be given with azithromycin, clarithromycin, high-dose cefoxitin, or imipenem.

Use: Treatment of serous skin, soft tissue, and bone infections caused by M abscessus

Geriatric Dose for Osteomyelitis

• 15 mg/kg IM or IV (over 30 to 60 minutes) per day, given in 2 to 3 equal doses at equally divided intervals
• Maximum dose: 15 mg/kg/day
• Duration of therapy: 7 to 10 days

Comments:

• Heavier patients should not exceed 1.5 grams/day.
• Some recommended dose regimens include 7.5 mg/kg IM every 12 hours or 5 mg/kg IM every 8 hours.
• Most infections typically respond in 24 to 48 hours; if clinical response does not occur within 3 to 5 days, treatment should be stopped and the susceptibility pattern of the organism should be rechecked.
• Drug serum levels, renal, auditory, and vestibular functions should be monitored in patients who require treatment beyond 10 days.

Use:

Short-term treatment of susceptible strains of Gram-negative bacteria, including Pseudomonas species, E coli, indole-positive/-negative species of Proteus, Providencia species, Klebsiella-Enterobacter-Serratia species, and Acinetobacter (Mima-Herellea) species causing the following infections:

• Bacterial septicemia
• Serious infections of the bones and joints, burns, intraabdominal infections, respiratory tract, skin and soft tissue
• Serious postoperative infections, including postvascular surgery
• Initial/empirical therapy in severe infection, with suspected gram-negative, staphylococcal, or mixed staphylococcal/gram-negative infections, or in patients allergic to other antibiotics

ATS and IDSA Recommendations:

• 10 to 15 mg/kg IV once a day OR 25 mg/kg IV 3 times a week

Duration of therapy:

• Initial therapy: At least 2 weeks
• Serious skin and soft tissue infections: At least 4 months
• Bone infections: At least 6 months

Comments:

• Patients 50 years of age and older or those with prolonged treatment (greater than 3 weeks) should be given lower daily doses (10 mg/kg/day).
• This drug should be given with azithromycin, clarithromycin, high-dose cefoxitin, or imipenem.

Use: Treatment of serous skin, soft tissue, and bone infections caused by M abscessus

Geriatric Dose for Pneumonia

• 15 mg/kg IM or IV (over 30 to 60 minutes) per day, given in 2 to 3 equal doses at equally divided intervals
• Maximum dose: 15 mg/kg/day
• Duration of therapy: 7 to 10 days

Comments:

• Heavier patients should not exceed 1.5 grams/day.
• Some recommended dose regimens include 7.5 mg/kg IM every 12 hours or 5 mg/kg IM every 8 hours.
• Most infections typically respond in 24 to 48 hours; if clinical response does not occur within 3 to 5 days, treatment should be stopped and the susceptibility pattern of the organism should be rechecked.
• Drug serum levels, renal, auditory, and vestibular functions should be monitored in patients who require treatment beyond 10 days.

Use:

Short-term treatment of susceptible strains of Gram-negative bacteria, including Pseudomonas species, E coli, indole-positive/-negative species of Proteus, Providencia species, Klebsiella-Enterobacter-Serratia species, and Acinetobacter (Mima-Herellea) species causing the following infections:

• Bacterial septicemia
• Serious infections of the bones and joints, burns, intraabdominal infections, respiratory tract, skin and soft tissue
• Serious postoperative infections, including postvascular surgery
• Initial/empirical therapy in severe infection, with suspected gram-negative, staphylococcal, or mixed staphylococcal/gram-negative infections, or in patients allergic to other antibiotics

ATS and IDSA Recommendations:

• 10 to 15 mg/kg IV once a day OR 25 mg/kg IV 3 times a week

Duration of therapy:

• Initial therapy: At least 2 weeks
• Serious skin and soft tissue infections: At least 4 months
• Bone infections: At least 6 months

Comments:

• Patients 50 years of age and older or those with prolonged treatment (greater than 3 weeks) should be given lower daily doses (10 mg/kg/day).
• This drug should be given with azithromycin, clarithromycin, high-dose cefoxitin, or imipenem.

Use: Treatment of serous skin, soft tissue, and bone infections caused by M abscessus

Geriatric Dose for Skin or Soft Tissue Infection

• 15 mg/kg IM or IV (over 30 to 60 minutes) per day, given in 2 to 3 equal doses at equally divided intervals
• Maximum dose: 15 mg/kg/day
• Duration of therapy: 7 to 10 days

Comments:

• Heavier patients should not exceed 1.5 grams/day.
• Some recommended dose regimens include 7.5 mg/kg IM every 12 hours or 5 mg/kg IM every 8 hours.
• Most infections typically respond in 24 to 48 hours; if clinical response does not occur within 3 to 5 days, treatment should be stopped and the susceptibility pattern of the organism should be rechecked.
• Drug serum levels, renal, auditory, and vestibular functions should be monitored in patients who require treatment beyond 10 days.

Use:

Short-term treatment of susceptible strains of Gram-negative bacteria, including Pseudomonas species, E coli, indole-positive/-negative species of Proteus, Providencia species, Klebsiella-Enterobacter-Serratia species, and Acinetobacter (Mima-Herellea) species causing the following infections:

• Bacterial septicemia
• Serious infections of the bones and joints, burns, intraabdominal infections, respiratory tract, skin and soft tissue
• Serious postoperative infections, including postvascular surgery
• Initial/empirical therapy in severe infection, with suspected gram-negative, staphylococcal, or mixed staphylococcal/gram-negative infections, or in patients allergic to other antibiotics

ATS and IDSA Recommendations:

• 10 to 15 mg/kg IV once a day OR 25 mg/kg IV 3 times a week

Duration of therapy:

• Initial therapy: At least 2 weeks
• Serious skin and soft tissue infections: At least 4 months
• Bone infections: At least 6 months

Comments:

• Patients 50 years of age and older or those with prolonged treatment (greater than 3 weeks) should be given lower daily doses (10 mg/kg/day).
• This drug should be given with azithromycin, clarithromycin, high-dose cefoxitin, or imipenem.

Use: Treatment of serous skin, soft tissue, and bone infections caused by M abscessus

Geriatric Dose for Tuberculosis – Active

ATS, US CDC, and IDSA Recommendations:

• 15 mg/kg IM or IV once a day OR 15 to 25 mg IM or IV 3 times a week

Comment: Patients with renal dysfunction and/or those who are older may require 15 mg/kg given 3 times a week.

Use: Second-line treatment of drug-susceptible tuberculosis caused by susceptible organisms

Pediatric Dose for Bacteremia

Newborns:

• Loading dose: 10 mg/kg IM once
• Maintenance dose: 7.5 mg/kg IM or via IV infusion (over 1 to 2 hours) every 12 hours
• Maximum dose: 15 mg/kg/day
• Duration of therapy: 7 to 10 days

Older infants and children:

• Serious complicated/recurrent urinary tract infections: 15 mg/kg IM or IV per day, given in 2 to 3 equal doses at equally divided intervals
• Uncomplicated urinary tract infections: 250 mg IM or IV 2 times a day
• Maximum dose: 15 mg/kg/day
• Duration of therapy: 7 to 10 days

Older infants and children: 15 mg/kg IM or IV (over 30 to 60 minutes) per day, given in 2 to 3 equal doses at equally divided intervals

• Maximum dose: 15 mg/kg/day
• Duration of therapy: 7 to 10 days

Comments:

• Infants should receive an IV infusion over 1 to 2 hours; children should be administered IV formulations over 30 to 60 minutes.
• Heavier patients should not exceed 1.5 grams/day.
• Some recommended dose regimens include 7.5 mg/kg IM every 12 hours or 5 mg/kg IM every 8 hours.
• Most infections typically respond in 24 to 48 hours; if clinical response does not occur within 3 to 5 days, treatment should be stopped and the susceptibility pattern of the organism should be rechecked.
• Drug serum levels, renal, auditory, and vestibular functions should be monitored in patients who require treatment beyond 10 days.
• Concomitant therapy with a penicillin-type agent may be needed in the treatment of neonatal sepsis.

Uses:

Short-term treatment of susceptible strains of Gram-negative bacteria, including Pseudomonas species, E coli, indole-positive/-negative species of Proteus, Providencia species, Klebsiella-Enterobacter-Serratia species, and Acinetobacter (Mima-Herellea) species causing the following infections:

• Bacterial septicemia
• Neonatal sepsis
• Serious infections of the bones and joints, burns, intraabdominal infections, respiratory tract, skin and soft tissue
• Serious postoperative infections, including postvascular surgery
• Initial/empirical therapy in severe infection, with suspected gram-negative, staphylococcal, or mixed staphylococcal/gram-negative infections, or in patients allergic to other antibiotics

SIS and IDSA Recommendations:

• 15 to 22.5 mg/kg IV per day, given in divided doses every 8 to 24 hours

Comments:

• Initial doses should be based on body weight.
• Maintenance doses should be determined by concentration monitoring.

Uses:

• Treatment of patients with complicated intra-abdominal infections
• Treatment of patients with severe reactions to beta-lactam antibiotics who have complicated intra-abdominal infections
  Pediatric Dose for Intraabdominal Infection

Newborns:

• Loading dose: 10 mg/kg IM once
• Maintenance dose: 7.5 mg/kg IM or via IV infusion (over 1 to 2 hours) every 12 hours
• Maximum dose: 15 mg/kg/day
• Duration of therapy: 7 to 10 days

Older infants and children:

• Serious complicated/recurrent urinary tract infections: 15 mg/kg IM or IV per day, given in 2 to 3 equal doses at equally divided intervals
• Uncomplicated urinary tract infections: 250 mg IM or IV 2 times a day
• Maximum dose: 15 mg/kg/day
• Duration of therapy: 7 to 10 days

Older infants and children: 15 mg/kg IM or IV (over 30 to 60 minutes) per day, given in 2 to 3 equal doses at equally divided intervals

• Maximum dose: 15 mg/kg/day
• Duration of therapy: 7 to 10 days

Comments:

• Infants should receive an IV infusion over 1 to 2 hours; children should be administered IV formulations over 30 to 60 minutes.
• Heavier patients should not exceed 1.5 grams/day.
• Some recommended dose regimens include 7.5 mg/kg IM every 12 hours or 5 mg/kg IM every 8 hours.
• Most infections typically respond in 24 to 48 hours; if clinical response does not occur within 3 to 5 days, treatment should be stopped and the susceptibility pattern of the organism should be rechecked.
• Drug serum levels, renal, auditory, and vestibular functions should be monitored in patients who require treatment beyond 10 days.
• Concomitant therapy with a penicillin-type agent may be needed in the treatment of neonatal sepsis.

Uses:

Short-term treatment of susceptible strains of Gram-negative bacteria, including Pseudomonas species, E coli, indole-positive/-negative species of Proteus, Providencia species, Klebsiella-Enterobacter-Serratia species, and Acinetobacter (Mima-Herellea) species causing the following infections:

• Bacterial septicemia
• Neonatal sepsis
• Serious infections of the bones and joints, burns, intraabdominal infections, respiratory tract, skin and soft tissue
• Serious postoperative infections, including postvascular surgery
• Initial/empirical therapy in severe infection, with suspected gram-negative, staphylococcal, or mixed staphylococcal/gram-negative infections, or in patients allergic to other antibiotics

SIS and IDSA Recommendations:

• 15 to 22.5 mg/kg IV per day, given in divided doses every 8 to 24 hours

Comments:

• Initial doses should be based on body weight.
• Maintenance doses should be determined by concentration monitoring.

Uses:

• Treatment of patients with complicated intra-abdominal infections
• Treatment of patients with severe reactions to beta-lactam antibiotics who have complicated intra-abdominal infections

Pediatric Dose for Joint Infection

Newborns:

• Loading dose: 10 mg/kg IM once
• Maintenance dose: 7.5 mg/kg IM or via IV infusion (over 1 to 2 hours) every 12 hours
• Maximum dose: 15 mg/kg/day
• Duration of therapy: 7 to 10 days

Older infants and children:

• Serious complicated/recurrent urinary tract infections: 15 mg/kg IM or IV per day, given in 2 to 3 equal doses at equally divided intervals
• Uncomplicated urinary tract infections: 250 mg IM or IV 2 times a day
• Maximum dose: 15 mg/kg/day
• Duration of therapy: 7 to 10 days

Older infants and children: 15 mg/kg IM or IV (over 30 to 60 minutes) per day, given in 2 to 3 equal doses at equally divided intervals

• Maximum dose: 15 mg/kg/day
• Duration of therapy: 7 to 10 days

Comments:

• Infants should receive an IV infusion over 1 to 2 hours; children should be administered IV formulations over 30 to 60 minutes.
• Heavier patients should not exceed 1.5 grams/day.
• Some recommended dose regimens include 7.5 mg/kg IM every 12 hours or 5 mg/kg IM every 8 hours.
• Most infections typically respond in 24 to 48 hours; if clinical response does not occur within 3 to 5 days, treatment should be stopped and the susceptibility pattern of the organism should be rechecked.
• Drug serum levels, renal, auditory, and vestibular functions should be monitored in patients who require treatment beyond 10 days.
• Concomitant therapy with a penicillin-type agent may be needed in the treatment of neonatal sepsis.

Uses:

Short-term treatment of susceptible strains of Gram-negative bacteria, including Pseudomonas species, E coli, indole-positive/-negative species of Proteus, Providencia species, Klebsiella-Enterobacter-Serratia species, and Acinetobacter (Mima-Herellea) species causing the following infections:

• Bacterial septicemia
• Neonatal sepsis
• Serious infections of the bones and joints, burns, intraabdominal infections, respiratory tract, skin and soft tissue
• Serious postoperative infections, including postvascular surgery
• Initial/empirical therapy in severe infection, with suspected gram-negative, staphylococcal, or mixed staphylococcal/gram-negative infections, or in patients allergic to other antibiotics

SIS and IDSA Recommendations:

• 15 to 22.5 mg/kg IV per day, given in divided doses every 8 to 24 hours

Comments:

• Initial doses should be based on body weight.
• Maintenance doses should be determined by concentration monitoring.

Uses:

• Treatment of patients with complicated intra-abdominal infections
• Treatment of patients with severe reactions to beta-lactam antibiotics who have complicated intra-abdominal infections

Pediatric Dose for Osteomyelitis

Newborns:

• Loading dose: 10 mg/kg IM once
• Maintenance dose: 7.5 mg/kg IM or via IV infusion (over 1 to 2 hours) every 12 hours
• Maximum dose: 15 mg/kg/day
• Duration of therapy: 7 to 10 days

Older infants and children:

• Serious complicated/recurrent urinary tract infections: 15 mg/kg IM or IV per day, given in 2 to 3 equal doses at equally divided intervals
• Uncomplicated urinary tract infections: 250 mg IM or IV 2 times a day
• Maximum dose: 15 mg/kg/day
• Duration of therapy: 7 to 10 days

Older infants and children: 15 mg/kg IM or IV (over 30 to 60 minutes) per day, given in 2 to 3 equal doses at equally divided intervals

• Maximum dose: 15 mg/kg/day
• Duration of therapy: 7 to 10 days

Comments:

• Infants should receive an IV infusion over 1 to 2 hours; children should be administered IV formulations over 30 to 60 minutes.
• Heavier patients should not exceed 1.5 grams/day.
• Some recommended dose regimens include 7.5 mg/kg IM every 12 hours or 5 mg/kg IM every 8 hours.
• Most infections typically respond in 24 to 48 hours; if clinical response does not occur within 3 to 5 days, treatment should be stopped and the susceptibility pattern of the organism should be rechecked.
• Drug serum levels, renal, auditory, and vestibular functions should be monitored in patients who require treatment beyond 10 days.
• Concomitant therapy with a penicillin-type agent may be needed in the treatment of neonatal sepsis.

Uses:

Short-term treatment of susceptible strains of Gram-negative bacteria, including Pseudomonas species, E coli, indole-positive/-negative species of Proteus, Providencia species, Klebsiella-Enterobacter-Serratia species, and Acinetobacter (Mima-Herellea) species causing the following infections:

• Bacterial septicemia
• Neonatal sepsis
• Serious infections of the bones and joints, burns, intraabdominal infections, respiratory tract, skin and soft tissue
• Serious postoperative infections, including postvascular surgery
• Initial/empirical therapy in severe infection, with suspected gram-negative, staphylococcal, or mixed staphylococcal/gram-negative infections, or in patients allergic to other antibiotics

SIS and IDSA Recommendations:

• 15 to 22.5 mg/kg IV per day, given in divided doses every 8 to 24 hours

Comments:

• Initial doses should be based on body weight.
• Maintenance doses should be determined by concentration monitoring.

Uses:

• Treatment of patients with complicated intra-abdominal infections
• Treatment of patients with severe reactions to beta-lactam antibiotics who have complicated intra-abdominal infections

Pediatric Dose for Pneumonia

Newborns:

• Loading dose: 10 mg/kg IM once
• Maintenance dose: 7.5 mg/kg IM or via IV infusion (over 1 to 2 hours) every 12 hours
• Maximum dose: 15 mg/kg/day
• Duration of therapy: 7 to 10 days

Older infants and children:

• Serious complicated/recurrent urinary tract infections: 15 mg/kg IM or IV per day, given in 2 to 3 equal doses at equally divided intervals
• Uncomplicated urinary tract infections: 250 mg IM or IV 2 times a day
• Maximum dose: 15 mg/kg/day
• Duration of therapy: 7 to 10 days

Older infants and children: 15 mg/kg IM or IV (over 30 to 60 minutes) per day, given in 2 to 3 equal doses at equally divided intervals

• Maximum dose: 15 mg/kg/day
• Duration of therapy: 7 to 10 days

Comments:

• Infants should receive an IV infusion over 1 to 2 hours; children should be administered IV formulations over 30 to 60 minutes.
• Heavier patients should not exceed 1.5 grams/day.
• Some recommended dose regimens include 7.5 mg/kg IM every 12 hours or 5 mg/kg IM every 8 hours.
• Most infections typically respond in 24 to 48 hours; if clinical response does not occur within 3 to 5 days, treatment should be stopped and the susceptibility pattern of the organism should be rechecked.
• Drug serum levels, renal, auditory, and vestibular functions should be monitored in patients who require treatment beyond 10 days.
• Concomitant therapy with a penicillin-type agent may be needed in the treatment of neonatal sepsis.

Uses:

Short-term treatment of susceptible strains of Gram-negative bacteria, including Pseudomonas species, E coli, indole-positive/-negative species of Proteus, Providencia species, Klebsiella-Enterobacter-Serratia species, and Acinetobacter (Mima-Herellea) species causing the following infections:

• Bacterial septicemia
• Neonatal sepsis
• Serious infections of the bones and joints, burns, intraabdominal infections, respiratory tract, skin and soft tissue
• Serious postoperative infections, including postvascular surgery
• Initial/empirical therapy in severe infection, with suspected gram-negative, staphylococcal, or mixed staphylococcal/gram-negative infections, or in patients allergic to other antibiotics

SIS and IDSA Recommendations:

• 15 to 22.5 mg/kg IV per day, given in divided doses every 8 to 24 hours

Comments:

• Initial doses should be based on body weight.
• Maintenance doses should be determined by concentration monitoring.

Uses:

• Treatment of patients with complicated intra-abdominal infections
• Treatment of patients with severe reactions to beta-lactam antibiotics who have complicated intra-abdominal infections

Pediatric Dose for Skin or Soft Tissue Infection

Newborns:

• Loading dose: 10 mg/kg IM once
• Maintenance dose: 7.5 mg/kg IM or via IV infusion (over 1 to 2 hours) every 12 hours
• Maximum dose: 15 mg/kg/day
• Duration of therapy: 7 to 10 days

Older infants and children:

• Serious complicated/recurrent urinary tract infections: 15 mg/kg IM or IV per day, given in 2 to 3 equal doses at equally divided intervals
• Uncomplicated urinary tract infections: 250 mg IM or IV 2 times a day
• Maximum dose: 15 mg/kg/day
• Duration of therapy: 7 to 10 days

Older infants and children: 15 mg/kg IM or IV (over 30 to 60 minutes) per day, given in 2 to 3 equal doses at equally divided intervals

• Maximum dose: 15 mg/kg/day
• Duration of therapy: 7 to 10 days

Comments:

• Infants should receive an IV infusion over 1 to 2 hours; children should be administered IV formulations over 30 to 60 minutes.
• Heavier patients should not exceed 1.5 grams/day.
• Some recommended dose regimens include 7.5 mg/kg IM every 12 hours or 5 mg/kg IM every 8 hours.
• Most infections typically respond in 24 to 48 hours; if clinical response does not occur within 3 to 5 days, treatment should be stopped and the susceptibility pattern of the organism should be rechecked.
• Drug serum levels, renal, auditory, and vestibular functions should be monitored in patients who require treatment beyond 10 days.
• Concomitant therapy with a penicillin-type agent may be needed in the treatment of neonatal sepsis.

Uses:

Short-term treatment of susceptible strains of Gram-negative bacteria, including Pseudomonas species, E coli, indole-positive/-negative species of Proteus, Providencia species, Klebsiella-Enterobacter-Serratia species, and Acinetobacter (Mima-Herellea) species causing the following infections:

• Bacterial septicemia
• Neonatal sepsis
• Serious infections of the bones and joints, burns, intraabdominal infections, respiratory tract, skin and soft tissue
• Serious postoperative infections, including postvascular surgery
• Initial/empirical therapy in severe infection, with suspected gram-negative, staphylococcal, or mixed staphylococcal/gram-negative infections, or in patients allergic to other antibiotics

SIS and IDSA Recommendations:

• 15 to 22.5 mg/kg IV per day, given in divided doses every 8 to 24 hours

Comments:

• Initial doses should be based on body weight.
• Maintenance doses should be determined by concentration monitoring.

Uses:

• Treatment of patients with complicated intra-abdominal infections
• Treatment of patients with severe reactions to beta-lactam antibiotics who have complicated intra-abdominal infections

Pediatric Dose for Meningitis

Newborns:

• Loading dose: 10 mg/kg IM once
• Maintenance dose: 7.5 mg/kg IM or via IV infusion (over 1 to 2 hours) every 12 hours
• Maximum dose: 15 mg/kg/day
• Duration of therapy: 7 to 10 days

Older infants and children:

• Serious complicated/recurrent urinary tract infections: 15 mg/kg IM or IV per day, given in 2 to 3 equal doses at equally divided intervals
• Uncomplicated urinary tract infections: 250 mg IM or IV 2 times a day
• Maximum dose: 15 mg/kg/day
• Duration of therapy: 7 to 10 days

Older infants and children: 15 mg/kg IM or IV (over 30 to 60 minutes) per day, given in 2 to 3 equal doses at equally divided intervals

• Maximum dose: 15 mg/kg/day
• Duration of therapy: 7 to 10 days

Comments:

• Infants should receive an IV infusion over 1 to 2 hours; children should be administered IV formulations over 30 to 60 minutes.
• Heavier patients should not exceed 1.5 grams/day.
• Some recommended dose regimens include 7.5 mg/kg IM every 12 hours or 5 mg/kg IM every 8 hours.
• Most infections typically respond in 24 to 48 hours; if clinical response does not occur within 3 to 5 days, treatment should be stopped and the susceptibility pattern of the organism should be rechecked.
• Drug serum levels, renal, auditory, and vestibular functions should be monitored in patients who require treatment beyond 10 days.
• Concomitant therapy with a penicillin-type agent may be needed in the treatment of neonatal sepsis.

Use: Treatment of meningitis and serious infections of the central nervous system caused by susceptible strains of Gram-negative bacteria, including Pseudomonas species, E coli, indole-positive/-negative species of Proteus, Providencia species, Klebsiella-Enterobacter-Serratia species, and Acinetobacter (Mima-Herellea) species

IDSA Recommendations:

Bacterial Meningitis:

• 0 to 7 days: 15 to 20 mg/kg IV per day, given in divided doses every 12 hours
• 8 to 28 days: 30 mg/kg IV per day, given in divided doses every 8 hours
• Infants and children: 20 to 30 mg/kg IV per day, given in divided doses every 8 hours

Use: Adjunct empirical treatment of purulent meningitis caused by S agalactiae, E coli, L monocytogenes, Klebsiella species in patients younger than 1 month

IDSA, AAN, AANS, and NCS Recommendations:

Healthcare-associated Ventriculitis and Meningitis:

Infants and children:

• IV: 22.5 mg/kg IV per day, given in divided doses every 8 hours
• Intraventricular: 5 to 50 mg via intraventricular route once a day

Duration of therapy:

• Neisseria meningitis or Haemophilus influenzae: 7 days
• Coagulase-negative staphylococcus or P acnes with no/minimal cerebrospinal fluid pleocytosis, normal CSF glucose, few symptoms/systemic features: 10 days
• Coagulase-negative staphylococcus or P acnes with significant CSF pleocytosis, S aureus or gram-negative bacilli with/without significant CSF pleocytosis, CSF hypoglycorrhachia, or symptoms/systemic features: 10 to 14 days
• S pneumoniae: 10 to 14 days
• S agalactiae: 14 to 21 days
• Aerobic gram-negative bacilli: 21 days
• L monocytogenes: At least 21 days
• Repeatedly positive CSF cultures on appropriate antimicrobial treatment: Continue treatment for 10 to 14 days after the last positive culture

Comments:

• Neonate duration of therapy is 2 weeks beyond the first sterile CSF culture OR at least 3 weeks, whichever is longer.
• The usual intraventricular dose was 30 mg/day.
• The intraventricular drain should be clamped for approximately 15 to 60 minutes to allow the drug to equilibrate.

Use: Treatment of healthcare-associated ventriculitis and meningitis

Pediatric Dose for Peritonitis

Newborns:

• Loading dose: 10 mg/kg IM once
• Maintenance dose: 7.5 mg/kg IM or via IV infusion (over 1 to 2 hours) every 12 hours
• Maximum dose: 15 mg/kg/day
• Duration of therapy: 7 to 10 days

Older infants and children:

• Serious complicated/recurrent urinary tract infections: 15 mg/kg IM or IV per day, given in 2 to 3 equal doses at equally divided intervals
• Uncomplicated urinary tract infections: 250 mg IM or IV 2 times a day
• Maximum dose: 15 mg/kg/day
• Duration of therapy: 7 to 10 days

Older infants and children: 15 mg/kg IM or IV (over 30 to 60 minutes) per day, given in 2 to 3 equal doses at equally divided intervals

• Maximum dose: 15 mg/kg/day
• Duration of therapy: 7 to 10 days

Comments:

• Infants should receive an IV infusion over 1 to 2 hours; children should be administered IV formulations over 30 to 60 minutes.
• Heavier patients should not exceed 1.5 grams/day.
• Some recommended dose regimens include 7.5 mg/kg IM every 12 hours or 5 mg/kg IM every 8 hours.
• Most infections typically respond in 24 to 48 hours; if clinical response does not occur within 3 to 5 days, treatment should be stopped and the susceptibility pattern of the organism should be rechecked.
• Drug serum levels, renal, auditory, and vestibular functions should be monitored in patients who require treatment beyond 10 days.
• Concomitant therapy with a penicillin-type agent may be needed in the treatment of neonatal sepsis.

Use: Treatment of peritonitis caused by susceptible strains of Gram-negative bacteria, including Pseudomonas species, E coli, indole-positive/-negative species of Proteus, Providencia species, Klebsiella-Enterobacter-Serratia species, and Acinetobacter (Mima-Herellea) species

ISPD Recommendations:

Continuous peritoneal dialysis:

• Loading dose: 25 mg/L
• Maintenance dose: 12 mg/L

Intermittent peritoneal dialysis:

• Anuric patients: 0.6 mg/kg intraperitoneally once a day
• Non-anuric patients: 0.75 mg/kg intraperitoneally once a day

Comments:

• Continuous: Loading doses should be allowed to dwell for at least 3 to 6 hours.
• Intermittent: Doses should be administered via the long-dwell (unless otherwise specified) and be allowed to dwell for at least 6 hours.
• Prolonged courses of treatment should be avoided.

Use: Treatment of peritonitis

Pediatric Dose for Urinary Tract Infection

Newborns:

• Loading dose: 10 mg/kg IM once
• Maintenance dose: 7.5 mg/kg IM or via IV infusion (over 1 to 2 hours) every 12 hours
• Maximum dose: 15 mg/kg/day
• Duration of therapy: 7 to 10 days

Older infants and children:

• Serious complicated/recurrent urinary tract infections: 15 mg/kg IM or IV per day, given in 2 to 3 equal doses at equally divided intervals
• Uncomplicated urinary tract infections: 250 mg IM or IV 2 times a day
• Maximum dose: 15 mg/kg/day
• Duration of therapy: 7 to 10 days

Comments:

• Infants should receive an IV infusion over 1 to 2 hours; children should be administered IV formulations over 30 to 60 minutes.
• Heavier patients should not exceed 1.5 grams/day.
• Some recommended dose regimens include 7.5 mg/kg IM every 12 hours or 5 mg/kg IM every 8 hours.
• Most infections typically respond in 24 to 48 hours; if clinical response does not occur within 3 to 5 days, treatment should be stopped and the susceptibility pattern of the organism should be rechecked.
• Drug serum levels, renal, auditory, and vestibular functions should be monitored in patients who require treatment beyond 10 days.
• This drug should not be used to treat initial uncomplicated urinary tract infections unless the causative organisms are not susceptible to less potent antibiotics.

Uses:

• Short-term treatment of serious complicated and recurrent urinary tract infections caused by susceptible strains of Gram-negative bacteria, including Pseudomonas species, E coli, indole-positive/-negative species of Proteus, Providencia species, Klebsiella-Enterobacter-Serratia species, and Acinetobacter (Mima-Herellea) species
• Uncomplicated initial episodes of urinary tract infections caused by organisms not susceptible to antibiotics having less potential toxicity

Pediatric Dose for Bacterial Infection

American Academy of Pediatrics (AAP) Recommendations:

Severe Infections:

• 7 days or younger and 2 kg or less: 15 mg IV or IM every 48 hours
• 7 days or younger and greater than 2 kg: 15 mg IV or IM every 24 hours
• 8 to 28 days and 2 kg or less: 15 mg IV or IM every 24 hours
• 8 to 28 days and greater than 2 kg: 17.5 mg every 24 hours
• Older than 28 days: 15 to 22.5 mg IV or IM in 2 to 3 doses OR 15 to 20 mg IV or IM once a day

Comments:

• Serum concentrations should guide ongoing treatment.
• Patients with cystic fibrosis should receive higher doses.

Pediatric Dose for Mycobacterium avium-intracellulare

US HHS, NIH, HRSA, and US CDC Recommendations:

• 15 to 30 mg/kg IV in 1 to 2 divided doses per day
• Maximum dose: 1.5 grams/day
• Duration of therapy: At least 12 months

Comments:

• If rifabutin cannot be administered AND a third agent must be added to a macrolide and ethambutol, this drug may be used.
• This drug may be added in patients with more severe symptoms or disseminated disease requiring a fourth agent.

Use: Third or fourth drug option as an alternative treatment in patients with disseminated MAC disease

Pediatric Dose for Tuberculosis – Active

SIS and IDSA Recommendations:

• Children: 15 to 20 mg/kg IM or IV once a day OR 25 to 30 mg/kg IM or IV 2 times a week

Comment: Patients with renal dysfunction may require 15 mg/kg given 3 times a week.

Use: Second-line treatment of drug-susceptible tuberculosis caused by susceptible organisms

AAP, US HHS, NIH, HRSA, and US CDC Recommendations:

• Infants, Children, and Adolescents: 15 to 30 mg/kg IM or IV once a day
  • Maximum dose: 1 gram
  • Duration of therapy: 2 months (with isoniazid, rifampin, and pyrazinamide)

Comment: Some experts state that this regimen may be used as an adjunctive treatment/second-line for drug-susceptible tuberculosis in HIV-infected patients undergoing DOT.

Uses:

• Adjunctive treatment of drug-resistant tuberculosis
• Adjunctive treatment of drug-susceptible meningitis caused by M bovis in geographic areas where resistance to streptomycin is common

Renal Dose Adjustments

Known/suspected renal dysfunction: Frequent monitoring recommended.

IM Administration:

• Prolonged intervals (creatinine clearance unknown): Administer the recommended single dose (7.5 mg/kg IM) at the dosage interval determined by multiplying the serum creatinine by 9
• Reduced dose (serum assay concentrations unknown):
  • Loading dose: 7.5 mg/kg IM once
  • Maintenance dose given IM every 12 hours: (observed creatinine clearance divided by normal creatinine clearance) multiplied by the loading dose OR recommended dose divided by the steady state creatinine clearance

Signs/symptoms of renal irritation occurring during treatment (e.g., casts, white/red cells, albumin): Increase hydration.

Evidence of renal dysfunction occurring during treatment (e.g., decreased creatinine clearance, decreased urine specific gravity, increased blood urea nitrogen/creatinine, oliguria): Dose reductions should be considered; closely monitor renal and eighth nerve function.

Increased azotemia OR a progressive decrease in urinary output occurring during treatment: Stop treatment.

Evidence of nephrotoxicity: Discontinue the drug OR adjust the dose.

SIS and IDSA Recommendations:

• Renal dysfunction: Patients may require 15 mg/kg given 3 times a week

US HHS, NIH, HRSA, and US CDC Recommendations:

Renal dysfunction: Use with caution; dose adjustments should be determined by target peak and trough concentrations.

Liver Dose Adjustments

• Data not available

Amikacin inhalation dose

The dose of this medicine will be different for different patients. Follow your doctor’s orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

For inhalation dosage form (suspension):

• For Mycobacterium avium complex lung disease:
  • Adults—One inhalation once a day using the Lamira™ Nebulizer System. Each dose contains 590 milligrams (mg) per 8.4 milliliters (mL) of amikacin.
  • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of amikacin inhalation, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Amikacin side effects

Amikacin may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• nausea
• vomiting
• diarrhea
• headache
• fever

Some side effects can be serious. If you experience any of these symptoms or those listed in the IMPORTANT WARNING section, call your doctor immediately or get emergency medical treatment:

• rash
• peeling or blistering of the skin
• itching
• hives
• swelling of the eyes, face, throat, tongue, or lips
• difficulty breathing or swallowing
• hoarseness
• severe diarrhea (watery or bloody stools) that may occur with or without fever and stomach cramps (may occur up to 2 months or more after your treatment)

Incidence not known:

• agitation
• black, tarry stools
• bloody or cloudy urine
• bluish lips or skin
• blurred vision
• burning, crawling, itching, numbness, prickling, “pins and needles”, or tingling feelings
• chest pain
• chills
• coma
• confusion
• cough
• decrease in the amount of urine
• decreased urine output
• depression
• difficulty with breathing
• difficulty with moving
• dizziness
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• drowsiness
• dry mouth
• feeling of fullness in the ears
• fever
• headache
• hearing loss
• irritability
• lethargy
• loss of balance
• loss or change in hearing
• muscle pain or stiffness
• muscle twitching
• nausea
• not breathing
• pain in the joints
• pain in the lower back or side
• painful or difficult urination
• pale skin
• rapid weight gain
• ringing or buzzing in the ears
• seizures
• shakiness in the legs, arms, hands, or feet
• shortness of breath
• sore throat
• sores, ulcers, or white spots on the lips or in the mouth
• stupor
• sweating
• swelling of the face, ankles, or hands
• swollen glands
• thirst
• trembling or shaking of the hands or feet
• trouble with hearing
• troubled breathing with exertion
• unusual bleeding or bruising
• unusual tiredness or weakness

Amikacin may cause other side effects. Call your doctor if you have any unusual problems while taking amikacin.

Dexamethasone

Dexamethasone is a corticosteroid, is similar to a natural human adrenal hormone cortisol produced by your adrenal glands. Dexamethasone often is used to replace the adrenal hormone cortisol when your body does not make enough of it. Dexamethasone has potent antiinflammatory and immunosuppressive properties and are widely used in medicine. Dexamethasone relieves inflammation (swelling, heat, redness, and pain) and is used to treat certain forms of arthritis; skin, blood, kidney, eye, thyroid, and intestinal disorders (e.g., colitis); severe allergies; and asthma. Dexamethasone is also used to treat certain types of cancer.

Dexamethasone is used with other drugs to treat the following types of cancer:

• Leukemia.
• Lymphoma.
• Mycosis fungoides (a type of cutaneous T-cell lymphoma).

Dexamethasone is also used alone or with other drugs to prevent or treat the following conditions related to cancer:

• Anemia.
• Cerebral edema (fluid build-up in the brain) associated with brain tumors.
• Drug hypersensitivity (allergic reactions).
• Hypercalcemia (high blood levels of calcium).
• Thrombocytopenia (low platelet levels).

Dexamethasone is also used alone or with other drugs to treat many other diseases and conditions. Dexamethasone continues to be studied in the treatment of many types of cancer and other conditions.

Dexamethasone is available only with your doctor’s prescription.

Dexamethasone comes as a tablet and a solution to take by mouth. Your doctor will prescribe a dosing schedule that is best for you. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take dexamethasone exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Do not stop taking dexamethasone without talking to your doctor. Stopping the drug abruptly can cause loss of appetite, upset stomach, vomiting, drowsiness, confusion, headache, fever, joint and muscle pain, peeling skin, and weight loss. If you take large doses for a long time, your doctor probably will decrease your dose gradually to allow your body to adjust before stopping the drug completely. Watch for these side effects if you are gradually decreasing your dose and after you stop taking the tablets or oral liquid, even if you switch to an inhalation corticosteroid medication. If these problems occur, call your doctor immediately. You may need to increase your dose of tablets or liquid temporarily or start taking them again.

Dexamethasone mechanism of action

Dexamethasone is a potent glucocorticoid with very little, if any, mineralocorticoid activity ¹⁾. Dexamethasone’s effect on the body is seen in a variety of ways. It has been shown to work is by suppressing migration of neutrophils and decreasing lymphocyte colony proliferation. It has been shown that capillary membrane becomes less permeable as well. Lysosomal membranes have increased stability. There are higher concentrations of vitamin A compounds in the serum, and prostaglandin and some cytokines (interleukin-1, interleukin-12, interleukin-18, tumor necrosis factor, interferon gamma, and granulocyte-macrophage colony stimulating factor) are inhibited. Increased levels of surfactant and improved pulmonary circulation have also been shown with dexamethasone use. Dexamethasone is metabolized by the liver and excreted in the urine mainly. Dexamethasone has a half-life of approximately 3 hours.

Dexamethasone special precautions

Before taking dexamethasone:

• tell your doctor and pharmacist if you are allergic to dexamethasone, aspirin, tartrazine (a yellow dye in some processed foods and drugs), or any other drugs.
• tell your doctor and pharmacist what prescription and nonprescription medications you are taking especially anticoagulants (‘blood thinners’) such as warfarin (Coumadin), arthritis medications, aspirin, cyclosporine (Neoral, Sandimmune), digoxin (Lanoxin), diuretics (‘water pills’), ephedrine, estrogen (Premarin), ketoconazole (Nizoral), oral contraceptives, phenobarbital, phenytoin (Dilantin), rifampin (Rifadin), theophylline (Theo-Dur), and vitamins.
  if you have a fungal infection (other than on your skin), do not take dexamethasone without talking to your doctor.
  tell your doctor if you have or have ever had liver, kidney, intestinal, or heart disease; diabetes; an underactive thyroid gland; high blood pressure; mental illness; myasthenia gravis; osteoporosis; herpes eye infection; seizures; tuberculosis (TB); or ulcers.
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking dexamethasone, call your doctor.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking dexamethasone.
• if you have a history of ulcers or take large doses of aspirin or other arthritis medication, limit your consumption of alcoholic beverages while taking this drug. Dexamethasone makes your stomach and intestines more susceptible to the irritating effects of alcohol, aspirin, and certain arthritis medications: this effect increases your risk of ulcers.

Special dietary instructions

Your doctor may instruct you to follow a low-sodium, low-salt, potassium-rich, or high-protein diet. Follow these directions.

Dexamethasone may cause an upset stomach. Take dexamethasone with food or milk.

Pregnancy

Pregnancy Category C: Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

Breastfeeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Dexamethasone interactions

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking dexamethasone, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using dexamethasone with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Artemether
• Desmopressin
• Praziquantel
• Rilpivirine
• Rotavirus Vaccine, Live

Using dexamethasone with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Aceclofenac
• Acemetacin
• Aldesleukin
• Alfentanil
• Amtolmetin Guacil
• Balofloxacin
• Bemiparin
• Benzhydrocodone
• Besifloxacin
• Boceprevir
• Bromfenac
• Bufexamac
• Buprenorphine
• Bupropion
• Celecoxib
• Ceritinib
• Choline Salicylate
• Ciprofloxacin
• Clarithromycin
• Clonixin
• Cobicistat
• Codeine
• Conivaptan
• Daclatasvir
• Darunavir
• Desogestrel
• Dexibuprofen
• Dexketoprofen
• Diclofenac
• Dienogest
• Diflunisal
• Dihydrocodeine
• Dipyrone
• Doxorubicin
• Doxorubicin Hydrochloride Liposome
• Dronedarone
• Drospirenone
• Droxicam
• Efavirenz
• Elvitegravir
• Enoxacin
• Enzalutamide
• Estradiol
• Ethinyl Estradiol
• Ethynodiol
• Etodolac
• Etofenamate
• Etonogestrel
• Etoricoxib
• Etravirine
• Felbinac
• Fenoprofen
• Fentanyl
• Fepradinol
• Feprazone
• Fleroxacin
• Floctafenine
• Flufenamic Acid
• Flumequine
• Flurbiprofen
• Fosamprenavir
• Gatifloxacin
• Gemifloxacin
• Gestodene
• Hemin
• Hydrocodone
• Ibuprofen
• Indomethacin
• Ixabepilone
• Ketoprofen
• Ketorolac
• Lapatinib
• Levofloxacin
• Levonorgestrel
• Lomefloxacin
• Lornoxicam
• Loxoprofen
• Lumiracoxib
• Macimorelin
• Meclofenamate
• Mefenamic Acid
• Meloxicam
• Meperidine
• Mestranol
• Methadone
• Morniflumate
• Moxifloxacin
• Nabumetone
• Nadifloxacin
• Nadroparin
• Naproxen
• Nepafenac
• Nevirapine
• Nifedipine
• Niflumic Acid
• Nilotinib
• Nimesulide
• Nimesulide Beta Cyclodextrin
• Nimodipine
• Norethindrone
• Norfloxacin
• Norgestimate
• Norgestrel
• Ofloxacin
• Oxaprozin
• Oxycodone
• Oxyphenbutazone
• Parecoxib
• Pazufloxacin
• Pefloxacin
• Pentazocine
• Phenylbutazone
• Piketoprofen
• Piperaquine
• Piroxicam
• Pranoprofen
• Proglumetacin
• Propyphenazone
• Proquazone
• Prulifloxacin
• Ritonavir
• Rofecoxib
• Rufloxacin
• Salicylic Acid
• Salsalate
• Saquinavir
• Sargramostim
• Sodium Salicylate
• Sparfloxacin
• Sufentanil
• Sulindac
• Sunitinib
• Tacrolimus
• Telaprevir
• Tenoxicam
• Thalidomide
• Tiaprofenic Acid
• Ticagrelor
• Tolfenamic Acid
• Tolmetin
• Tosufloxacin
• Tramadol
• Ulipristal
• Valdecoxib
• Velpatasvir
• Vincristine Sulfate Liposome
• Vortioxetine
• Voxilaprevir

Using dexamethasone with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Alcuronium
• Aminoglutethimide
• Aprepitant
• Aspirin
• Atracurium
• Auranofin
• Caspofungin
• Fluindione
• Fosaprepitant
• Fosnetupitant
• Fosphenytoin
• Gallamine
• Hexafluorenium
• Licorice
• Metocurine
• Netupitant
• Ospemifene
• Pancuronium
• Phenobarbital
• Phenytoin
• Rifampin
• Rifapentine
• Saiboku-To
• Vecuronium
• Warfarin

Other Interactions

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of dexamethasone. Make sure you tell your doctor if you have any other medical problems, especially:

• Cataracts or
• Congestive heart failure or
• Cushing’s syndrome (adrenal gland problem) or
• Diabetes or
• Eye infection or
• Fluid retention or
• Glaucoma or
• Hyperglycemia (high blood sugar) or
• Hypertension (high blood pressure) or
• Infection (eg, bacterial, virus, fungus) or
• Mood changes, including depression or
• Myasthenia gravis (severe muscle weakness) or
• Osteoporosis (weak bones) or
• Peptic ulcer, active or history of or
• Personality changes or
• Stomach or intestinal problems (eg, diverticulitis, ulcerative colitis) or
• Tuberculosis, inactive—Use with caution. May make these conditions worse.
• Fungal infections or
• Herpes simplex eye infection—Should not be used in patients with these conditions.

Dexamethasone vs Prednisone

Prednisone and dexamethasone are both a synthetic, anti-inflammatory glucocorticoid that derives from cortisone. Like dexamethasone, prednisone reduces inflammation. Prednisone also damps down your immune system, which can help in autoimmune illnesses like rheumatoid arthritis, where your immune system mistakenly attacks its own tissues. Prednisone is biologically inert and converted to prednisolone in the liver ²⁾. Prednisone is an FDA-approved as an anti-inflammatory or immunosuppressive agent used to treat a wide range of health problems including immunosuppressive/endocrine, rheumatic, collagen, dermatologic, allergic states, ophthalmic, respiratory, blood disorders, skin diseases, infections, certain cancers, edematous, gastrointestinal (GI), acute exacerbations of multiple sclerosis, and as an anti-inflammatory and an antineoplastic agent and to prevent organ rejection after a transplant. Prednisone is a corticosteroid (cortisone-like medicine or steroid). Prednisone works on the immune system to help relieve swelling, redness, itching, and allergic reactions. Prednisone is available only with a doctor’s prescription ³⁾.

Prednisone is available only on prescription as tablets and as a liquid to drink. It can also be given by injection but this is usually only done in hospital.

What is dexamethasone used for?

Dexamethasone has a wide variety of uses in the medical field. Dexamethasone provides relief for inflamed areas of the body. It is used to treat a number of different conditions, such as inflammation (swelling), severe allergies, adrenal problems, arthritis, asthma, blood or bone marrow problems, kidney problems, skin conditions, and flare-ups of multiple sclerosis. Dexamethasone is a corticosteroid (cortisone-like medicine or steroid). It works on the immune system to help relieve swelling, redness, itching, and allergic reactions. As a treatment, dexamethasone has been useful in the treatment of acute exacerbations of multiple sclerosis, allergies, cerebral edema, inflammation, and shock ⁴⁾. Patients with conditions such as asthma, atopic and contact dermatitis, and drug hypersensitivity reactions have benefited from the use of dexamethasone ⁵⁾.

In endocrinology, dexamethasone has been found useful as a test for Cushing syndrome ⁶⁾. This test begins with a low dose test. There are 2 versions of this test: the standard two-day test and the overnight test. With the standard test, 0.5 mg oral dose of dexamethasone is given every 6 hours for 2 days. Six hours after the final dose is given serum cortisol levels are measured. The overnight test begins with a 1 mg oral dose of dexamethasone at 11:00 pm with a second 1 mg oral dose at midnight. The following morning, serum cortisol levels are tested between 8:00 am and 9:00 am. The test is read as a positive screening test for Cushing syndrome if the final cortisol reading is high, signaling that the more specific confirmative high dose dexamethasone suppression test should be ordered. The high dose dexamethasone suppression test has three forms: the standard 2-day test, the overnight test, and the intravenous (IV) test. With all 3 versions of the test, baseline serum cortisol levels need to be determined before commencing with the test. Baseline serum can be measured with a 24-hour urinary free cortisol test ⁷⁾. The standard 2-day test uses 2 mg of oral dexamethasone given every 6 hours for 2 days. During the 2-day exam, urine is collected and tested for free cortisol and 6 hours after the final dose of dexamethasone; blood is drawn to measure the serum cortisol level. The overnight test begins with an 8 mg oral dose of dexamethasone at 11:00 pm. The following morning between 8:00 am, and 9:00 am, serum cortisol is measured. The IV test is the shortest of the test. One milligram of dexamethasone is given via continuous intravenous infusion per hour for 7 hours. Serum cortisol is measured at the end of 7 hours.

Off-label indications are as follows. Dexamethasone is used in the treatment of chemotherapy-induced nausea and vomiting. It is used in the prevention and treatment of altitude sickness. It has also been used in the treatment of spinal cord compression due to metastases in oncological cases ⁸⁾.

Dexamethasone contraindications

Dexamethasone use is contraindicated if patients have systemic fungal infections, hypersensitivity to dexamethasone, or cerebral malaria. It is also contraindicated to administer live or live-attenuated vaccines during the use of dexamethasone as the immune system is being suppressed and will less like form a strong enough immune response placing the patient at risk. It is still okay to administer killed or inactivated vaccines although it should be noted that immune response may be attenuated and it is unpredictable if immunity with developing as a result ⁹⁾.

In patients with cirrhosis, diverticulitis, myasthenia gravis, renal insufficiency, or ulcerative diseases such as peptic ulcer disease or ulcerative colitis, it is important to use caution when prescribing dexamethasone. It is also recommended to use dexamethasone with caution during pregnancy as there is an increased risk of oral cleft formations. It has been shown that large doses can increase blood pressure. In patients with recent myocardial infarction, it is advised to proceed with caution as an increase in free wall rupture of the left ventricle has been reported with use of dexamethasone. Suppression of the hypothalamus pituitary adrenal axis (HPA axis) occurs with use, and therefore rapid withdrawal of dexamethasone is not recommended. It is important to gradually increase and/or decrease any corticosteroid due to its effect on the hypothalamus pituitary adrenal axis.

Latent diseases such as fungal (Candida, Cryptococcus, Pneumocystis), parasitic (Toxoplasmosis, Amebiasis, Strongyloides), and bacterial (Mycobacterium, Nocardia) infections may become active due to suppression of the immune system ¹⁰⁾.

Steroid use may inhibit bone formation and may lead to the formation of osteoporosis. Caution should be taken when prescribing dexamethasone to populations at higher risk for osteoporosis.

Dexamethasone dosage

Dexamethasone is available in various formulations. As a tablet, it is available in strengths ranging from 0.5 mg to 6 mg. Other forms of administration are as an injectable suspension or as an oral solution ¹¹⁾.

• In the treatment of inflammation, it is advised to begin with low doses of 0.75 mg/day, which may be titrated to 9 mg/day, with dosing divided into 2 to 4 doses throughout the day. This applies to intravenous, intramuscular, and oral administrations. Less may be used when directly administered to the lesion or tissue with dosing ranging from 0.2 to 6 mg per day ¹²⁾.
• For the treatment of acute multiple sclerosis exacerbations, 30 mg oral daily doses taken for seven days is recommended followed by 1 month of 4 to 12 mg oral daily doses.
• As cerebral edema may be a life-threatening condition, aggressive treatment is necessary. It is recommended that 10 mg of intravenous dexamethasone be administered followed by 4 mg of intramuscular administration given every 6 hours. In this instance, it is necessary to titrate down over 7 days to discontinue dexamethasone therapy ¹³⁾.
• In the treatment of circulatory shock, it is advised to administer 1 to 6 mg/kg of intravenous dexamethasone as a one-time bolus. This regiment may be substituted for 40 mg given intravenously every 2 to 6 hours as needed. Treatment with high dose dexamethasone is not recommended beyond 2 to 3 days.
• Allergic reactions have been shown to improve with a 6-day regiment beginning with 4 to 8 mg intramuscular injection on the first day. This is followed by oral doses on days 2 to 6 beginning with 1.5 mg every 12 hours for days 2 and 3, 0.75 mg every 12 hours for the third day, and finally 0.75 mg daily for days 5 and 6. The patient should appropriately be titrated down by day 7 with no dosing necessary on day 7.

Adult dose for Acute Mountain Sickness

Uses:

• For the prevention of Acute Mountain Sickness and High-Altitude Cerebral Edema (HACE).
• For the treatment of Acute Mountain Sickness and High-Altitude Cerebral Edema (HACE), and to treat concurrent High-Altitude Cerebral Edema (HACE) and High Altitude Pulmonary Edema (HAPE) when neurologic dysfunctions do not resolve rapidly with administration of supplemental oxygen.

Prevention of Acute Mountain Sickness and High-Altitude Cerebral Edema (HACE):

• Dose: 2 mg orally every 6 hours OR 4 mg orally every 12 hours
• Very High Risk Situations (e.g. military, search and rescue at altitudes greater than 3500 m): 4 mg orally every 6 hours
• Duration of Therapy: Should not exceed 10 days to prevent glucocorticoid toxicity or adrenal suppression

Treatment of Acute Mountain Sickness: 4 mg orally/IV/IM every 6 hours

Treatment of High-Altitude Cerebral Edema (HACE): 8 mg orally/IV/IM once; followed by 4 mg orally/IV/IM every 6 hours

Comments:

• Dosing based on Wilderness and Environmental Medicine guidance.
• This drug has shown benefit for the prevention of acute mountain sickness (AMS) and high altitude cerebral edema (HACE), however, the evidence for prevention of high altitude pulmonary edema (HAPE) is lacking; this drug should be used in conjunction with non-pharmacologic measures and only in situations when the risk profile is favorable.
• Treatment does not facilitate acclimation; further ascent should be delayed until the patient is asymptomatic while off the medication.

Adult dose for Cerebral Edema

Use: For the treatment of cerebral edema.

• Initial dose: 10 mg IV once, followed by 4 mg IM every 6 hours until maximal response is noted
• After 2 to 4 days, dose should be reduced and then gradually discontinued over a period of 5 to 7 days

Comments:

• After symptoms subside, may switch to oral therapy (1 to 3 mg orally 3 times a day) and then taper gradually over 5 to 7 days.
• In patients undergoing brain surgery, may continue treatment for several days postoperatively.
• In nonoperative cases, continuous therapy may be needed to remain symptom-free.

Adult dose for Testing for Cushing’s syndrome

Uses: Diagnostic testing for Cushing’s syndrome.

Dexamethasone Suppression Tests:

• Short suppression test: 1 mg orally at 11 PM; draw plasma cortisol at 8 AM the following morning
• Long suppression test: 0.5 mg orally every 6 hours for 48 hours; 24-hour urine collections are made before, during, and at the end of the test for determination of 17-hydroxycorticosteroids
• Test to distinguish Cushing’s syndrome: 2 mg orally every 6 hours for 48 hours; 24-hour urine collections are made before, during, and at the end of the test for determination of 17-hydroxycorticosteroids

Comment: The long suppression test provides greater accuracy in diagnosing Cushing’s syndrome.

Adult dose for Nausea/Vomiting – Chemotherapy Induced

Use: For prophylaxis and treatment of chemotherapy induced nausea and vomiting.

Highly emetogenic chemotherapy regimens:

• 12 to 20 mg oral/IV prior to chemotherapy followed by 8 mg oral/IV once or twice a day for 2 to 4 days

Moderately emetogenic chemotherapy regimens:

• 8 mg oral/IV prior to chemotherapy followed by 4 to 8 mg oral/IV on days 2 and 3

Low emetogenic chemotherapy regimens:

• 4 to 8 mg oral/IV prior to chemotherapy

Comments:

• This drug may be used alone but is most often used in combination with other agents, e.g. neurokinin 1 (NK1) antagonists and 5-hydroxytryptamine-3 (5-HT3) antagonists.
• When used in combination regimens, it is the combination of agents that defines the dose and duration of use for this drug; this is not a labeled indication.
• When receiving combination chemotherapy, the agent with the most emetic potential should determine the regimen of anti-emetic therapy that should be used.

Adult dose for Shock

Use: For the treatment of unresponsive shock.

Unresponsive shock:

• 1 to 6 mg/kg IV as a single dose or up to 40 mg initially followed by repeat IV doses every 2 to 6 hours while shock persists

Published protocols:

• 20 mg IV as a single dose followed by IV infusion of 3 mg/kg/24 hours
• 1 to 6 mg/kg IV as a single dose
• 40 mg IV as a single dose followed by repeat IV doses every 4 to 6 hours while shock persists

Comments:

• High-dose therapy should only be continued until patient’s condition has stabilized and usually no longer than 48 to 72 hours.

Adult dose for Multiple Myeloma

Use: For the treatment of multiple myeloma.

40 mg oral/IV on days 1, 8, 15, 22, and repeated every 4 weeks

Comments:

• This drug is a part of most major treatment regimens in multiple myeloma; treatment regimens should be consulted.
• In regimens containing bortezomib, the day 1 dexamethasone dose may be split to provide 20 mg on the day of and 20 mg on the day after bortezomib.
• Doses may need to be adjusted for performance status or other toxicities

Adult dose for Multiple Sclerosis

Use: For the treatment of acute exacerbations of multiple sclerosis.

Acute exacerbation: 30 mg orally once a day for 1 week followed by 4 to 8 mg orally every other day for 1 month

Comments:

• Short-term high-dose corticosteroids are an accepted standard of care for treating relapses of multiple sclerosis; chronic daily corticosteroids are not recommended.
• IV methylprednisolone, oral prednisone and prednisolone are the corticosteroids most studied and cited in clinical guidelines; while this drug has been used, efficacy studies and comparative data are lacking.

Adult dose for Anti-inflammatory

Uses: For use as a potent anti-inflammatory agent in managing disorders, diseases, and conditions affecting many organ systems including endocrine, dermatologic, ophthalmic, nervous. gastrointestinal, respiratory, musculoskeletal, and hematologic.

Dosing should be individualized on the basis of disease and patient response

Oral:

• Initial dose: 0.75 mg to 9 mg orally per day

Parenteral:

• Initial dose: 0.5 mg to 9 mg IV or IM per day in divided doses every 12 hours

Maintenance dose: After a favorable initial response, dose should be decreased in small amounts to the lowest dose that maintains an adequate clinical response; if a positive response is not achieved after a reasonable period of time, alternative therapy should be sought.

Comments:

• Lower doses, including doses lower than recommended doses, may suffice in less severe disease; doses in excess of recommended doses may be required in severe disease; in life-threatening situations, doses exceeding multiples of the oral dose may be justified.
• When oral therapy is not feasible IV or IM therapy in doses ranging from one-third to one-half the oral dose may be given every 12 hours.
• Patients should be closely monitored for signs requiring dose adjustments; if therapy is to be stopped after more than a few days, it should be gradually withdrawn.

Adult dose for Immunosuppression

Uses: For use as a potent anti-inflammatory agent in managing disorders, diseases, and conditions affecting many organ systems including endocrine, dermatologic, ophthalmic, nervous. gastrointestinal, respiratory, musculoskeletal, and hematologic.

Dosing should be individualized on the basis of disease and patient response

Oral:

• Initial dose: 0.75 mg to 9 mg orally per day

Parenteral:

• Initial dose: 0.5 mg to 9 mg IV or IM per day in divided doses every 12 hours

Maintenance dose: After a favorable initial response, dose should be decreased in small amounts to the lowest dose that maintains an adequate clinical response; if a positive response is not achieved after a reasonable period of time, alternative therapy should be sought.

Comments:

• Lower doses, including doses lower than recommended doses, may suffice in less severe disease; doses in excess of recommended doses may be required in severe disease; in life-threatening situations, doses exceeding multiples of the oral dose may be justified.
• When oral therapy is not feasible IV or IM therapy in doses ranging from one-third to one-half the oral dose may be given every 12 hours.
• Patients should be closely monitored for signs requiring dose adjustments; if therapy is to be stopped after more than a few days, it should be gradually withdrawn.

Adult dose for Brain/Intracranial Tumor

Use: For palliative management of recurrent or inoperable brain tumors.

• 2 mg oral/IV/IM 2 to 3 times a day

Adult dose for Allergic Reaction

Use: For the treatment of acute, self-limited allergic disorder or exacerbation of chronic allergic disorder.

• First day: 4 to 8 mg IM once
• Second and third day: 1.5 mg orally twice per day
• Fourth day: 0.75 mg orally twice per day
• Fifth and sixth day: 0.75 mg orally once a day
• Seventh day: No treatment
• Eighth day: Reassessment

Comments: This dosing schedule is designed to ensure adequate therapy during an acute episode while minimizing the risk of overdose in chronic cases.

Adult dose for Bursitis

Use: As adjunctive therapy for an acute episode or exacerbation of synovitis of osteoarthritis, rheumatoid arthritis, acute and subacute bursitis, acute gouty arthritis, epicondylitis, acute nonspecific tenosynovitis, and posttraumatic osteoarthritis.

Suggested doses:

• Large joints: 2 to 4 mg
• Small joints: 0.8 to 1 mg
• Bursae: 2 to 4 mg
• Tendon Sheaths: 0.4 to 1 mg

Injections may be repeated from once every 3 to 5 days to once every 2 to 3 weeks

Comments:

• Dose will vary according to the degree of inflammation and the size and location of the affected site.
• Intrasynovial and soft tissue injections should be limited to 1 or 2 sites; frequent intra-articular injections may cause damage to joint tissue.

Adult dose for Osteoarthritis

Use: As adjunctive therapy for an acute episode or exacerbation of synovitis of osteoarthritis, rheumatoid arthritis, acute and subacute bursitis, acute gouty arthritis, epicondylitis, acute nonspecific tenosynovitis, and posttraumatic osteoarthritis.

Suggested doses:

• Large joints: 2 to 4 mg
• Small joints: 0.8 to 1 mg
• Bursae: 2 to 4 mg
• Tendon Sheaths: 0.4 to 1 mg

Injections may be repeated from once every 3 to 5 days to once every 2 to 3 weeks

Comments:

• Dose will vary according to the degree of inflammation and the size and location of the affected site.
• Intrasynovial and soft tissue injections should be limited to 1 or 2 sites; frequent intra-articular injections may cause damage to joint tissue.

Adult dose for Rheumatoid Arthritis

Use: As adjunctive therapy for an acute episode or exacerbation of synovitis of osteoarthritis, rheumatoid arthritis, acute and subacute bursitis, acute gouty arthritis, epicondylitis, acute nonspecific tenosynovitis, and posttraumatic osteoarthritis.

Suggested doses:

• Large joints: 2 to 4 mg
• Small joints: 0.8 to 1 mg
• Bursae: 2 to 4 mg
• Tendon Sheaths: 0.4 to 1 mg

Injections may be repeated from once every 3 to 5 days to once every 2 to 3 weeks

Comments:

• Dose will vary according to the degree of inflammation and the size and location of the affected site.
• Intrasynovial and soft tissue injections should be limited to 1 or 2 sites; frequent intra-articular injections may cause damage to joint tissue.

Adult dose for Tendonitis

Use: As adjunctive therapy for an acute episode or exacerbation of synovitis of osteoarthritis, rheumatoid arthritis, acute and subacute bursitis, acute gouty arthritis, epicondylitis, acute nonspecific tenosynovitis, and posttraumatic osteoarthritis.

Suggested doses:

• Large joints: 2 to 4 mg
• Small joints: 0.8 to 1 mg
• Bursae: 2 to 4 mg
• Tendon Sheaths: 0.4 to 1 mg

Injections may be repeated from once every 3 to 5 days to once every 2 to 3 weeks

Comments:

• Dose will vary according to the degree of inflammation and the size and location of the affected site.
• Intrasynovial and soft tissue injections should be limited to 1 or 2 sites; frequent intra-articular injections may cause damage to joint tissue.

Adult dose for Gouty Arthritis

Use: As adjunctive therapy for an acute episode or exacerbation of synovitis of osteoarthritis, rheumatoid arthritis, acute and subacute bursitis, acute gouty arthritis, epicondylitis, acute nonspecific tenosynovitis, and posttraumatic osteoarthritis.

Suggested doses:

• Large joints: 2 to 4 mg
• Small joints: 0.8 to 1 mg
• Bursae: 2 to 4 mg
• Tendon Sheaths: 0.4 to 1 mg

Injections may be repeated from once every 3 to 5 days to once every 2 to 3 weeks

Comments:

• Dose will vary according to the degree of inflammation and the size and location of the affected site.
• Intrasynovial and soft tissue injections should be limited to 1 or 2 sites; frequent intra-articular injections may cause damage to joint tissue.

Adult dose for Epicondylitis

Use: As adjunctive therapy for an acute episode or exacerbation of synovitis of osteoarthritis, rheumatoid arthritis, acute and subacute bursitis, acute gouty arthritis, epicondylitis, acute nonspecific tenosynovitis, and posttraumatic osteoarthritis.

Suggested doses:

• Large joints: 2 to 4 mg
• Small joints: 0.8 to 1 mg
• Bursae: 2 to 4 mg
• Tendon Sheaths: 0.4 to 1 mg

Injections may be repeated from once every 3 to 5 days to once every 2 to 3 weeks

Comments:

• Dose will vary according to the degree of inflammation and the size and location of the affected site.
• Intrasynovial and soft tissue injections should be limited to 1 or 2 sites; frequent intra-articular injections may cause damage to joint tissue.

Adult dose for Alopecia

Uses: As adjunctive therapy for keloids; localized hypertrophic, infiltrated, inflammatory lesion of lichen planus, psoriatic plaques, granuloma annulare, and lichen simplex chronicus (neurodermatitis); discoid lupus erythematosus; necrobiosis lipoidica diabeticorum; alopecia areata. May be useful in cystic tumors of an aponeurosis tendon (ganglia).

Suggested doses:

• Soft tissue infiltration: 2 to 6 mg
• Ganglia: 1 to 2 mg

Comments:

• Dose will vary according to the degree of inflammation and the size and location of the affected site.
• Soft tissue and intralesional injections should be limited to 1 or 2 sites.

Adult dose for Lichen Simplex Chronicus

Uses: As adjunctive therapy for keloids; localized hypertrophic, infiltrated, inflammatory lesion of lichen planus, psoriatic plaques, granuloma annulare, and lichen simplex chronicus (neurodermatitis); discoid lupus erythematosus; necrobiosis lipoidica diabeticorum; alopecia areata. May be useful in cystic tumors of an aponeurosis tendon (ganglia).

Suggested doses:

• Soft tissue infiltration: 2 to 6 mg
• Ganglia: 1 to 2 mg

Comments:

• Dose will vary according to the degree of inflammation and the size and location of the affected site.
• Soft tissue and intralesional injections should be limited to 1 or 2 sites.

Adult dose for Psoriasis

Uses: As adjunctive therapy for keloids; localized hypertrophic, infiltrated, inflammatory lesion of lichen planus, psoriatic plaques, granuloma annulare, and lichen simplex chronicus (neurodermatitis); discoid lupus erythematosus; necrobiosis lipoidica diabeticorum; alopecia areata. May be useful in cystic tumors of an aponeurosis tendon (ganglia).

Suggested doses:

• Soft tissue infiltration: 2 to 6 mg
• Ganglia: 1 to 2 mg

Comments:

• Dose will vary according to the degree of inflammation and the size and location of the affected site.
• Soft tissue and intralesional injections should be limited to 1 or 2 sites.

Adult dose for Granuloma Annulare

Uses: As adjunctive therapy for keloids; localized hypertrophic, infiltrated, inflammatory lesion of lichen planus, psoriatic plaques, granuloma annulare, and lichen simplex chronicus (neurodermatitis); discoid lupus erythematosus; necrobiosis lipoidica diabeticorum; alopecia areata. May be useful in cystic tumors of an aponeurosis tendon (ganglia).

Suggested doses:

• Soft tissue infiltration: 2 to 6 mg
• Ganglia: 1 to 2 mg

Comments:

• Dose will vary according to the degree of inflammation and the size and location of the affected site.
• Soft tissue and intralesional injections should be limited to 1 or 2 sites.

Adult dose for Lichen Planus

Uses: As adjunctive therapy for keloids; localized hypertrophic, infiltrated, inflammatory lesion of lichen planus, psoriatic plaques, granuloma annulare, and lichen simplex chronicus (neurodermatitis); discoid lupus erythematosus; necrobiosis lipoidica diabeticorum; alopecia areata. May be useful in cystic tumors of an aponeurosis tendon (ganglia).

Suggested doses:

• Soft tissue infiltration: 2 to 6 mg
• Ganglia: 1 to 2 mg

Comments:

• Dose will vary according to the degree of inflammation and the size and location of the affected site.
• Soft tissue and intralesional injections should be limited to 1 or 2 sites.

Adult dose for Keloids

Uses: As adjunctive therapy for keloids; localized hypertrophic, infiltrated, inflammatory lesion of lichen planus, psoriatic plaques, granuloma annulare, and lichen simplex chronicus (neurodermatitis); discoid lupus erythematosus; necrobiosis lipoidica diabeticorum; alopecia areata. May be useful in cystic tumors of an aponeurosis tendon (ganglia).

Suggested doses:

• Soft tissue infiltration: 2 to 6 mg
• Ganglia: 1 to 2 mg

Comments:

• Dose will vary according to the degree of inflammation and the size and location of the affected site.
• Soft tissue and intralesional injections should be limited to 1 or 2 sites.

Adult dose for Idiopathic (Immune) Thrombocytopenic Purpura

Use: For the treatment of immune thrombocytopenia.

• 40 mg orally once a day for 4 days
• An additional 4-day course may be given if bleeding symptoms are present on day 7 or platelet count remains below 30 x10(9)/L

Comments:

• The American Society of Hematology (2011) has recommended a longer course of corticosteroids (e.g. prednisone for 21 days) over a shorter course (high-dose dexamethasone) due to longer time to loss of response, however, a recent prospective multicenter trial has shown 1 or 2 courses of high-dose dexamethasone are at least comparable to longer courses.

Pediatric dose for Cerebral Edema

Use: For the treatment of cerebral edema

• 0.2 mg/kg/24 hr oral/IV/IM in divided doses

Comments:

• The smallest effective dose should be used, preferably oral.

Pediatric dose for Meningitis

Use: To reduce hearing loss and neurological sequelae associated with meningitis.

Meningitis (H. influenzae type b):

• Infants and Children 6 weeks or older: 0.15 mg/kg/dose IV every 6 hours for the first 2 to 4 days of antibiotic treatment

Comments:

• Dexamethasone should be started 10 to 20 minutes before or with the first dose of antibiotic; if antibiotics have already been administered, dexamethasone use has not been shown to improve patient outcomes and is not recommended.
• This is not a labeled indication.
• This drug has not been shown to reduce overall mortality, but has been shown to reduce hearing loss and neurological sequelae.

Note: For pneumococcal meningitis, data has not shown clear benefit from dexamethasone administration; risk and benefits should be considered prior to use.

Pediatric dose for Anti-inflammatory

Uses: For use as a potent anti-inflammatory agent in managing disorders, diseases, and conditions affecting many organ systems including endocrine, dermatologic, ophthalmic, nervous. gastrointestinal, respiratory, musculoskeletal, and hematologic.

Dosing should be individualized on the basis of disease and patient response

Oral:

• Initial dose: 0.02 mg to 0.3 mg/kg/day OR 0.6 to 9 mg/m2/day orally in 3 or 4 divided doses
• Maintenance dose: After a favorable initial response, dose should be decreased in small amounts to the lowest dose that maintains an adequate clinical response; if a positive response is not achieved after a reasonable period of time, alternative therapy should be sought.

Comments:

• Lower doses, including doses lower than recommended doses may suffice in less severe disease, while doses in excess of recommended doses may be required in severe disease; in life-threatening situations, doses exceeding multiples of the oral dose may be justified.
• When oral therapy is not feasible IV or IM therapy in doses ranging from one-third to one-half the oral dose may be given every 12 hours.
• Patients should be observed closely for signs that require dose adjustments; if therapy is to be stopped after more than a few days, it should be gradually withdrawn.

Pediatric dose for Immunosuppression

Uses: For use as a potent anti-inflammatory agent in managing disorders, diseases, and conditions affecting many organ systems including endocrine, dermatologic, ophthalmic, nervous. gastrointestinal, respiratory, musculoskeletal, and hematologic.

Dosing should be individualized on the basis of disease and patient response

Oral:

• Initial dose: 0.02 mg to 0.3 mg/kg/day OR 0.6 to 9 mg/m2/day orally in 3 or 4 divided doses
• Maintenance dose: After a favorable initial response, dose should be decreased in small amounts to the lowest dose that maintains an adequate clinical response; if a positive response is not achieved after a reasonable period of time, alternative therapy should be sought.

Comments:

• Lower doses, including doses lower than recommended doses may suffice in less severe disease, while doses in excess of recommended doses may be required in severe disease; in life-threatening situations, doses exceeding multiples of the oral dose may be justified.
• When oral therapy is not feasible IV or IM therapy in doses ranging from one-third to one-half the oral dose may be given every 12 hours.
• Patients should be observed closely for signs that require dose adjustments; if therapy is to be stopped after more than a few days, it should be gradually withdrawn.

Pediatric dose for Nausea/Vomiting – Chemotherapy Induced

Use: For the prevention of nausea and vomiting associated with chemotherapy.

Highly Emetogenic Chemotherapy Regimens:

• 6 mg/m2 oral/IV every 6 hours

Moderately Emetogenic Chemotherapy Regimens:

• BSA 0.6 m² or less: 2 mg IV/oral every 12 hours
• BSA greater than 0.6 m²: 4 mg IV/oral every 12 hours

Comments:

• The addition of dexamethasone to anti-emetic regimens improves control of vomiting, although the risk-benefit remains uncertain.
• For regimens containing aprepitant, the dose of dexamethasone should be reduced by one-half.
• This is not a labeled indication, but recommended in many anti-emetic protocols.

Pediatric dose for Asthma – Acute

Use: For the treatment of acute asthma exacerbation.

• 0.6 mg/kg oral/IV/IM once

Comments:

• Studies have shown dexamethasone in single doses (0.3 mg/kg up to 1.7 mg/kg; maximum single dose 36 mg) or multiple doses (0.6 mg/kg once a day for 2 days) is comparable to a 5-day course of prednisone/prednisolone in the treatment of acute asthma exacerbations.

Pediatric dose for Croup

Use: For the treatment of childhood croup (laryngotracheobronchitis).

• 0.6 mg/kg oral/IM/ IV once
• Maximum dose: 16 mg

Comment: Further dosing and route of administration determined by clinical course

Pediatric dose for Acute Mountain Sickness

Use: For the treatment of acute mountain sickness.

• 0.15 mg/kg oral/IV/IM every 6 hours

Comments:

• Dosing based on Wilderness and Environmental Medicine guidance.
• Prophylactic use of this drug for acute mountain sickness (AMS) is not recommended in pediatric patients due to the potential for toxicity; safer alternatives such as graded ascent and acetazolamide should be considered.
• Treatment does not facilitate acclimation; further ascent should be delayed until the patient is asymptomatic while off the medication.

Pediatric dose for Idiopathic (Immune) Thrombocytopenic Purpura

Use: For the treatment of immune thrombocytopenia.

• 0.6 mg/kg/day oral/IV for 4 days every 4 weeks for 6 cycles

Comments:

• High-dose dexamethasone may be considered appropriate second-line treatment in those who have significant bleeding despite IVIg, anti-D, or a short course of corticosteroids.
• Additionally, it may be considered in patients with chronic immune thrombocytopenia as an alternative to splenectomy or in patients who do not response to splenectomy.
• There is limited data on use of this drug in the pediatric population; the above dose is from a study in a small number of patients.

Renal Dose Adjustments

• No dose adjustment recommended

Liver Dose Adjustments

• Use with caution

What should I do if I forget a dose?

When you start to take dexamethasone, ask your doctor what to do if you forget a dose. Write down these instructions so that you can refer to them later.

If you take dexamethasone once a day, take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Dexamethasone side effects

Most frequent dexamethasone side effect reported by patients is the presence of insomnia after use. Some other frequent adverse effects reported by patients include acne, indigestion, weight gain, increased appetite, anorexia, nausea, vomiting, acne, agitation, and depression. There have been reports of adrenal suppression, arrhythmias, spermatogenic changes, glaucoma, hypokalemia, pulmonary edema, pseudotumor cerebri, and increased intracranial pressure ¹⁴⁾.

Dexamethasone may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• upset stomach
• stomach irritation
• vomiting
• headache
• dizziness
• insomnia
• restlessness
• depression
• anxiety
• acne
• increased hair growth
• easy bruising
• irregular or absent menstrual periods

If you experience any of the following symptoms, call your doctor immediately:

• skin rash
• swollen face, lower legs, or ankles
• vision problems
• cold or infection that lasts a long time
• muscle weakness
• black or tarry stool

Carbamazepine

Carbamazepine is an aromatic anticonvulsant that is widely used in therapy for epilepsy, trigeminal neuralgia, and acute manic and mixed episodes in bipolar I disorder ¹⁾. Carbamazepine works by decreasing nerve impulses that cause seizures and nerve pain, such as tregimenal neuralgia and diabetic neuropathy. Carbamazepine indications for epilepsy are specifically for partial seizures with complex symptomatology (psychomotor, temporal lobe), generalized tonic seizures (grand mal), and mixed seizure patterns ²⁾. Carbamazepine is not indicted for absence seizures ³⁾. Carbamazepine is FDA indicated as first-line treatment trigeminal neuralgia or tic douloureux. Randomized control trials have shown that carbamazepine has similar efficacy to lithium in acute manic episodes.

Carbamazepine was approved for use in epilepsy in the United States in 1968 and it is still in common use with more than 2 million prescriptions being written yearly. Current indications include prevention and management of partial, complex, mixed and generalized seizures. It is used alone or in combination with other anticonvulsants. Carbamazepine is also effective in trigeminal neuralgia and peripheral neuropathies, but the mechanisms of its analgesic actions are not known. Carbamazepine is used off label for behavioral disorders and depression.

Carbamazepine is used off-label for refractory schizophrenia ⁴⁾. Simple well designed trials have shown efficacy in patients with schizophrenia with EEG abnormalities, schizophrenia with violent episodes, and schizoaffective disorder. Carbamazepine improves both positive and negative symptoms in schizophrenic patients ⁵⁾. Other off-label uses of this drug include treatment of restless leg syndrome and decreasing agitation and aggression in patients with dementia ⁶⁾. Another prominent off-label use of this drug is the treatment of neuropathic pain and fibromyalgia ⁷⁾. In patients with moderate to severe alcohol withdrawal syndrome, Carbamazepine has been shown to have clinical efficacy in treatment. However, this is not approved by the FDA, and it has not been shown to prevent alcohol withdrawal seizures as compared to benzodiazepines ⁸⁾.

Carbamazepine is available as conventional tablets, extended-release tablets (Tegretol XR), suspensions, and solutions. Tablets of 100 mg and 200 mg and extended release capsules of 100, 200 and 400 mg (Carbatrol, Equetro) are available, as are liquid formations and chewable forms for use in pediatrics. The liquid formation is absorbed faster than the other two modes of administration, and the extended-release tablet is absorbed slightly slower than conventional tablets. Carbamazepine is available in multiple generic forms and under the commercial names as Tegretol, Carbatrol, Equetro and Epitol. The recommended starting dose in adults for seizures is 200 mg twice daily in adults and 100 twice daily in children under 12 or 100 mg four times daily, with increase in dose by 100 to 200 mg at weekly intervals based upon clinical response, but generally not exceeding 1200 mg daily. Doses in children are based upon body weight. Minimum effectively levels in adults and children over 12 years is 800 mg to 1200mg daily for treatment of epilepsy. In children from six to 12 years, the effective level for treatment of epilepsy is 400 mg to 800 mg daily ⁹⁾. Typically, lower doses are used for trigeminal neuralgia and other less established indications (restless leg syndrome, bipolar disorders, chorea).

The extended-release tablet (Tegretol XR) is usually taken twice a day with meals. The extended-release capsule (Carbatrol, Equetro) is usually taken twice a day with or without meals. To help you remember to take carbamazepine, take it at around the same times every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take carbamazepine exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Swallow the extended-release tablets whole; do not split, chew, or crush them. The extended-release capsules may be opened and the beads inside sprinkled over food, such as a teaspoon of applesauce or similar food. Do not crush or chew the extended-release capsules or the beads inside them.

Shake the suspension well before each use to mix the medication evenly.

Carbamazepine may help control your condition but will not cure it. It usually takes a couple of weeks for carbamazepine to work. Continue to take carbamazepine even if you feel well. Do not stop taking carbamazepine without talking to your doctor, even if you experience side effects such as unusual changes in behavior or mood. If you have a seizure disorder and you suddenly stop taking carbamazepine, your seizures may become worse. Your doctor will probably decrease your dose gradually.

Common side effects of carbamazepine include feeling sleepy (drowsiness), sedation, dizziness, headaches, ataxia, blurred vision, nausea, vomiting, and skin rash. These are usually mild and go away by themselves.

Carbamazepine mechanism of action

Currently, the mechanism of action for carbamazepine in humans is still not understood completely by researchers. It has been proposed via animal research that this drug works by reducing polysynaptic responses and blocking the post-tetanic potentiation. Carbamazepine is an iminostilbene that is chemically related to tricyclic antidepressants and unrelated in structure to other anticonvulsants. Carbamazepine suppresses spread of seizure activity by reduction in the post-tetanic potentiation of synaptic transmission.

It was also shown to reduce pain that is caused by stimulation of an infraorbital nerve in cats and rats. Another group of findings was the reduction of the action potential in the nucleus ventralis of the thalamus and depression of the lingual mandibular reflex. This reduction of action potential occurs by carbamazepine binding to voltage-dependent sodium channels and inhibiting the generation of rapid action potentials. This effect increases with increased rates of neuronal firing ¹⁰⁾.

Carbamazepine special precautions

Before taking carbamazepine:

• tell your doctor and pharmacist if you are allergic (rash, wheezing, hives, difficulty swallowing or breathing, swelling of your face, eyes, eyelids, lips, or tongue) to carbamazepine, amitriptyline (Elavil), amoxapine, clomipramine (Anafranil), desipramine (Norpramin), doxepin (Silenor, Zonalon), imipramine (Tofranil), nortriptyline (Pamelor), oxcarbazepine (Trileptal), protriptyline (Vivactil), other medications for seizures such as phenobarbital, phenytoin (Dilantin, Phenytek), or primidone (Mysoline), any other medications, or any of the ingredients in carbamazepine preparations. Ask your pharmacist or check the Medication Guide for a list of the ingredients.
• tell your doctor if you are taking nefazadone or certain non-nucleoside reverse transcriptase inhibitors (NNRTIs) such as delavirdine (Rescriptor). Your doctor will probably tell you not take carbamazepine with these medications. Also, tell your doctor if you are taking a monoamine oxidase (MAO) inhibitor such as isocarboxazid (Marplan), linezolid (Zyvox), methylene blue, phenelzine (Nardil), selegiline (Eldepryl, Emsam, Zelapar), and tranylcypromine (Parnate), or if you have stopped taking an MAO inhibitor within the past 14 days. Your doctor will probably tell you not to take carbamazepine. If you stop taking carbamazepine, you should wait at least 14 days before you start to take an MAO inhibitor.
• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, and nutritional supplements you are taking or plan to take. Be sure to mention any of the following: acetaminophen (Tylenol); acetazolamide (Diamox); albendazole (Albenza); alprazolam (Panax); aminophylline; anticoagulants (‘blood thinners’) such as apixaban (Eliquis), dabigatran (Pradaxa), edoxaban (Savaysa), rivaroxaban (Xarelto), and warfarin (Coumadin, Jantoven); antidepressants such as amitriptyline (Elavil), bupropion (Wellbutrin, Zyban), buspirone (BuSpar), citalopram (Celexa), clomipramine (Anafranil), desipramine (Norpramin), fluoxetine (Prozac, Sarafem), fluvoxamine (Luvox), mirtazapine (Remeron), nortriptyline (Pamelor); antifungals such as fluconazole (Diflucan), itraconazole (Onmel, Sporanox), ketoconazole, and voriconazole (Vfend); aprepitant (Emend); aripiprazole (Abilify); buprenorphine (Butrans, Sublocade); bupropion (Aplenzin, Wellbutrin, Zyban); cimetidine (Tagamet); ciprofloxacin; cisplatin (Platinol); corticosteroids such as dexamethasone and prednisolone (Prelone); clarithromycin (Biaxin, in Prevpac); clonazepam (Klonopin); clozapine (Clozaril); cyclophosphamide; cyclosporine (Gengraf, Neoral, Sandimmune); dalfopristin and quinupristin (Synercid); danazol (Danocrine); dantrolene (Dantrium); diltiazem (Cardizem, Diltzac, Tiazac, others); diuretics (water pills); doxorubicin (Adriamycin, Rubex); doxycycline (Vibramycin); erythromycin (E.E.S., E-Mycin, Erythrocin); eslicarbazepine (Aptiom); everolimus (Afinitor, Zortress); felodipine (Plendil); haloperidol (Haldol); HIV protease inhibitors including atazanavir (Reyataz), indinavir (Crixivan), lopinavir (in Kaletra), nelfinavir (Viracept), ritonavir (Norvir, in Kaletra), and saquinavir (Fortovase, Invirase); ibuprofen (Advil); imatinib (Gleevec); isoniazid (INH, Laniazid, in Rifater); levothyroxine (Levoxyl, Synthroid); lithium (Lithobid); loratadine (Claritin); lorazepam (Ativan); loxapine (Adasuve); certain medications to treat malaria such as chloroquine (Aralen) and mefloquine ; medications for anxiety or mental illness; other medications for seizures such as ethosuximide (Zarontin), felbamate (Felbatol), fosphenytoin (Cerebyx); lamotrigine (Lamictal), methsuximide (Celontin), oxcarbazepine (Trileptal), phenobarbital, phensuximide (Milontin) (not available in the US), phenytoin (Dilantin, Phenytek), primidone (Mysoline), tiagabine (Gabitril), topiramate (Topamax), and valproic acid (Depakene, Depakote); lapatinib; methadone (Dolophine, Methadose); midazolam; niacinamide (nicotinamide, Vitamin B3); olanzapine; omeprazole; oxybutynin; propoxyphene (Darvon); praziquantel (Biltricide); quetiapine; quinine; rifampin (Rifadin, Rimactane); risperidone; sedatives; sertraline (Zoloft); sirolimus; sleeping pills; tacrolimus (Prograf); tadalafil (Adcirca, Cialis); temsirolimus (Torisel); terfenadine (Seldane) (not available in the US); theophylline (Theo-24, Theochron, others); ticlopidine; tramadol (Ultram); tranquilizers; trazodone; troleandomycin (TAO); verapamil (Calan, Verelan); zileuton (Zyflo); ziprasidone (Geodon), and zonisamide (Zonegran). Many other medications may also interact with carbamazepine, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• if you are taking any other liquid medications, do not take them at the same time as carbamazepine suspension.
• tell your doctor if you have or have ever had glaucoma (a condition in which increased pressure in the eye can lead to gradual loss of vision); or heart, kidney, thyroid, or liver disease.
• you should know that carbamazepine may decrease the effectiveness of hormonal contraceptives (birth control pills, patches, rings, injections, implants, or intrauterine devices). Use another form of birth control while taking carbamazepine. Tell your doctor if you have unexpected vaginal bleeding or think you may be pregnant while you are taking carbamazepine.
• tell your doctor if you are pregnant or plan to become pregnant. Carbamazepine may harm the fetus. If you become pregnant while taking carbamazepine, call your doctor immediately.
• do not breastfeed while you are taking carbamazepine.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking carbamazepine.
• you should know that carbamazepine may make you drowsy. Do not drive a car or operate machinery until you know how this medication affects you.
  remember that alcohol can add to the drowsiness caused by this medication.
  you should know that your mental health may change in unexpected ways and you may become suicidal (thinking about harming or killing yourself or planning or trying to do so) while you are taking carbamazepine for the treatment of epilepsy, mental illness, or other conditions. A small number of adults and children 5 years of age and older (about 1 in 500 people) who took anticonvulsants such as carbamazepine to treat various conditions during clinical studies became suicidal during their treatment. Some of these people developed suicidal thoughts and behavior as early as one week after they started taking the medication. There is a risk that you may experience changes in your mental health if you take an anticonvulsant medication such as carbamazepine, but there may also be a risk that you will experience changes in your mental health if your condition is not treated. You and your doctor will decide whether the risks of taking an anticonvulsant medication are greater than the risks of not taking the medication. You, your family, or your caregiver should call your doctor right away if you experience any of the following symptoms: panic attacks; agitation or restlessness; new or worsening irritability, anxiety, or depression; acting on dangerous impulses; difficulty falling or staying asleep; aggressive, angry, or violent behavior; mania (frenzied, abnormally excited mood); talking or thinking about wanting to hurt yourself or end your life; withdrawing from friends and family; preoccupation with death and dying; giving away prized possessions; or any other unusual changes in behavior or mood. Be sure that your family or caregiver knows which symptoms may be serious so they can call the doctor if you are unable to seek treatment on your own.
• if you have fructose intolerance (an inherited condition in which the body lacks the protein needed to break down fructose [a fruit sugar found in certain sweeteners such as sorbitol]), you should know that the oral suspension is sweetened with sorbitol. Tell your doctor if you have fructose intolerance.

Special dietary instructions

Talk to your doctor about eating grapefruit or drinking grapefruit juice while taking carbamazepine.

Carbamazepine in pregnancy

Studies looking at women who have taken carbamazepine during the first trimester of pregnancy have found a 1% chance (1/100 births) of neural tube defects (the spinal cord or skull do not form properly). The most common neural tube defect is spina bifida. Other studies have reported a 2 to 3 times greater chance for other major birth defects, such as heart defects or cleft lip.

Some studies have also suggested an increased chance for minor birth defects such as a small nose with a long space between the nose and upper lip, and small finger and toenails. Other studies have reported an increased chance of growth issues and small head size.

Folic acid has been found to reduce the chance for neural tube defects. Because women taking carbamazepine have a higher chance of having a baby with a neural tube defect, healthcare providers recommend that all women taking carbamazepine take extra folic acid before and during pregnancy. Speak with your healthcare provider to discuss how much folic acid you should take.

Can taking carbamazepine during pregnancy affect my baby’s development?

More studies are needed before we can be sure of the long-term effects of carbamazepine. Researchers are just beginning to look at the development of children who have been exposed to carbamazepine during pregnancy. Some studies have found a small increased chance for developmental delays. Other studies have found no differences in development or IQ.

Are there any other concerns with carbamazepine use during pregnancy?

Rarely, maternal use of carbamazepine during pregnancy has been associated with bleeding problems in the newborn due to low vitamin K levels. It has been recommended that women taking these medications receive vitamin K supplements near the end of their pregnancy and that their infants receive vitamin K supplement at birth. Women taking carbamazepine in pregnancy should discuss this with their healthcare provider and their child’s pediatrician before delivery.

Should I stop taking carbamazepine during my pregnancy?

You should contact your health care providers before becoming pregnant, or when you find out that you are pregnant, to discuss making any changes to your medication. The benefits of taking carbamazepine must be weighed against the possible risks to the developing baby.

I have been taking carbamazepine for the last few years and I just found out I am pregnant. What tests are available to see if my baby has spina bifida or other birth defects?

Screening tests are available for neural tube defects and other birth defects in your pregnancy. There are blood tests and ultrasounds. Discuss your screening options with your healthcare providers. There are no tests that can tell if there has been any effect on behavior or ability to learn.

I am taking carbamazepine, but I would like to stop taking it before becoming pregnant. How long does carbamazepine stay in your body?

Each person’s ability to break down the medication can be different. When you first start to take carbamazepine, your body breaks it down slowly. It can take 5-14 days to clear from your body. After long-term treatment, most of the carbamazepine should be gone from your body 3-5 days after the last dose.

Pregnant women should not change their medications during pregnancy without talking to a health care provider. Having a seizure while pregnant may be harmful to the baby. Women with bipolar disorder who stop taking medication during their pregnancy may be at an increased risk for episodes of depression or mania that could be harmful to both the mother and the baby.

If possible, women with seizure disorders or bipolar disorder who could become pregnant should discuss their options for treatment, including medications, with their health care provider before becoming pregnant.

I have been taking carbamazepine for many years. Can this affect my ability to get pregnant?

Studies have found that long-term use of seizure medications in women with seizure disorders is associated with menstrual irregularities and difficulty getting pregnant. Talk to your healthcare provider if you are experiencing difficulty in becoming pregnant.

What could happen to my baby if I stopped taking my carbamazepine and then had a seizure during my pregnancy?

About 1 in 3 women with epilepsy experiences an increase in frequency of seizures during pregnancy. Problems for the mother and fetus depend on how often she has a seizure and how long they last. Epileptic seizures and convulsions could cause a lack of oxygen in the blood. This could potentially lead to brain damage and developmental issues for the child, or could be life-threatening. In addition, a seizure could cause the mother to fall and physically injure herself.

Breastfeeding

Carbamazepine passes into breast milk. However, the amount of carbamazepine found in an infant’s blood is usually below a therapeutic level, meaning it would not be expected to affect the infant. There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Breastfeeding while taking carbamazepine monotherapy does not appear to affect infant growth or development. Some healthcare providers can measure levels of carbamazepine in the newborn if there is concern. Be sure to talk to your health care provider about all your breastfeeding questions.

What if the father takes carbamazepine?

One small animal study and a couple small human studies have suggested that carbamazepine might affect sperm development, but the studies did not look at whether or not this went on to cause problems getting a woman pregnant. More studies are needed to know if men who take carbamazepine have a harder time getting their partners pregnant. In general, exposures that fathers have are unlikely to increase risks to a pregnancy.

Carbamazepine Drug Interactions

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using carbamazepine with any of the following medicines is not recommended. Your doctor may decide not to treat you with carbamazepine or change some of the other medicines you take.

• Artemether
• Atazanavir
• Boceprevir
• Clorgyline
• Cobicistat
• Daclatasvir
• Darunavir
• Dasabuvir
• Delamanid
• Delavirdine
• Doravirine
• Efavirenz
• Elbasvir
• Elvitegravir
• Furazolidone
• Grazoprevir
• Iproniazid
• Isavuconazonium
• Isocarboxazid
• Linezolid
• Lorlatinib
• Lumefantrine
• Lurasidone
• Maraviroc
• Methylene Blue
• Moclobemide
• Nefazodone
• Nialamide
• Ombitasvir
• Pargyline
• Paritaprevir
• Phenelzine
• Praziquantel
• Procarbazine
• Ranolazine
• Rasagiline
• Rilpivirine
• Ritonavir
• Selegiline
• Telaprevir
• Tenofovir Alafenamide
• Toloxatone
• Tranylcypromine
• Voriconazole

Using carbamazepine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Abemaciclib
• Abiraterone Acetate
• Acalabrutinib
• Acetazolamide
• Adenosine
• Afatinib
• Alfentanil
• Almotriptan
• Alprazolam
• Amiodarone
• Amphetamine
• Amprenavir
• Apixaban
• Apremilast
• Aprepitant
• Aripiprazole
• Axitinib
• Bedaquiline
• Benzhydrocodone
• Benzphetamine
• Bictegravir
• Bosutinib
• Brexpiprazole
• Brigatinib
• Buprenorphine
• Bupropion
• Butorphanol
• Cabozantinib
• Calcifediol
• Cariprazine
• Ceritinib
• Chloroquine
• Chlorpromazine
• Cisatracurium
• Clarithromycin
• Clonazepam
• Clozapine
• Cobimetinib
• Codeine
• Conivaptan
• Copanlisib
• Crizotinib
• Cyclophosphamide
• Cyclosporine
• Dabigatran Etexilate
• Dasatinib
• Deflazacort
• Desmopressin
• Desogestrel
• Desvenlafaxine
• Dextroamphetamine
• Dienogest
• Dihydrocodeine
• Diltiazem
• Dolasetron
• Dolutegravir
• Doxorubicin
• Doxorubicin Hydrochloride Liposome
• Dronedarone
• Drospirenone
• Duvelisib
• Eliglustat
• Encorafenib
• Enzalutamide
• Eravacycline
• Erdafitinib
• Erlotinib
• Erythromycin
• Escitalopram
• Eslicarbazepine Acetate
• Estradiol
• Ethinyl Estradiol
• Ethynodiol
• Etonogestrel
• Etravirine
• Everolimus
• Exemestane
• Ezogabine
• Felodipine
• Fentanyl
• Fluconazole
• Fluoxetine
• Fosamprenavir
• Fosaprepitant
• Fosnetupitant
• Fosphenytoin
• Fostamatinib
• Gefitinib
• Gestodene
• Gilteritinib
• Glasdegib
• Glecaprevir
• Granisetron
• Hemin
• Hydrocodone
• Hydromorphone
• Hydroxytryptophan
• Ibrutinib
• Idelalisib
• Ifosfamide
• Imatinib
• Indinavir
• Irinotecan
• Irinotecan Liposome
• Isoniazid
• Itraconazole
• Ivabradine
• Ivacaftor
• Ivosidenib
• Ixabepilone
• Ixazomib
• Ketoconazole
• Lamotrigine
• Lapatinib
• Larotrectinib
• Ledipasvir
• Levomilnacipran
• Levonorgestrel
• Levorphanol
• Linagliptin
• Lisdexamfetamine
• Lomitapide
• Lopinavir
• Loratadine
• Lorcaserin
• Loxapine
• Macimorelin
• Macitentan
• Manidipine
• Medroxyprogesterone
• Mefloquine
• Meperidine
• Mestranol
• Metaxalone
• Methadone
• Methamphetamine
• Midostaurin
• Mifepristone
• Mirtazapine
• Morphine
• Morphine Sulfate Liposome
• Nalbuphine
• Naloxegol
• Nelfinavir
• Neratinib
• Netupitant
• Nifedipine
• Nilotinib
• Nimodipine
• Nintedanib
• Norethindrone
• Norgestimate
• Norgestrel
• Olanzapine
• Olaparib
• Orlistat
• Osimertinib
• Oxcarbazepine
• Oxycodone
• Oxymorphone
• Paclitaxel
• Palbociclib
• Paliperidone
• Palonosetron
• Panobinostat
• Pazopanib
• Pentazocine
• Perampanel
• Phenytoin
• Pibrentasvir
• Piperaquine
• Ponatinib
• Propoxyphene
• Quetiapine
• Quinine
• Regorafenib
• Remifentanil
• Ribociclib
• Rivaroxaban
• Rolapitant
• Romidepsin
• Saquinavir
• Sertraline
• Simvastatin
• Sofosbuvir
• Sonidegib
• Stiripentol
• Sufentanil
• Sunitinib
• Tacrolimus
• Tamoxifen
• Tapentadol
• Tasimelteon
• Telithromycin
• Temsirolimus
• Terfenadine
• Tezacaftor
• Thioridazine
• Thiotepa
• Ticagrelor
• Tipranavir
• Tofacitinib
• Tolvaptan
• Trabectedin
• Tramadol
• Trazodone
• Ulipristal
• Valbenazine
• Vandetanib
• Velpatasvir
• Vemurafenib
• Venetoclax
• Verapamil
• Vigabatrin
• Vilazodone
• Vincristine
• Vincristine Sulfate Liposome
• Vinflunine
• Vorapaxar
• Vortioxetine
• Voxilaprevir
• Zileuton
• Ziprasidone

Using carbamazepine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acetaminophen
• Acetylcysteine
• Aminophylline
• Amitriptyline
• Amoxapine
• Anisindione
• Aripiprazole Lauroxil
• Caspofungin
• Dalfopristin
• Danazol
• Desipramine
• Dicumarol
• Doxepin
• Etretinate
• Felbamate
• Flunarizine
• Furosemide
• Ginkgo
• Haloperidol
• Hydrochlorothiazide
• Imipramine
• Influenza Virus Vaccine
• Levetiracetam
• Lithium
• Methylphenidate
• Methylprednisolone
• Metronidazole
• Mianserin
• Midazolam
• Miokamycin
• Nafimidone
• Niacinamide
• Nortriptyline
• Omeprazole
• Ospemifene
• Phenobarbital
• Phenprocoumon
• Pipecuronium
• Primidone
• Protriptyline
• Psyllium
• Quinupristin
• Remacemide
• Rifampin
• Rifapentine
• Risperidone
• Rocuronium
• Rufinamide
• Sabeluzole
• Theophylline
• Tiagabine
• Ticlopidine
• Topiramate
• Troleandomycin
• Valnoctamide
• Valproic Acid
• Vecuronium
• Viloxazine
• Warfarin

Other Interactions

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using carbamazepine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Grapefruit Juice
• Black Tea

Other Medical Problems

The presence of other medical problems may affect the use of carbamazepine. Make sure you tell your doctor if you have any other medical problems, especially:

• Anemia or
• Behavior or mood problems or
• Blood vessel disease or
• Depression, history of or
• Diabetes or
• Glaucoma, or history of or
• Heart block or
• Heart disease or
• Heart rhythm problems, history of or
• Hyponatremia (low sodium in the blood) or
• Liver disease, history of or
• Porphyria (an inherited disease) or
• Problems with urination or
• Stevens-Johnson syndrome (severe skin disease) or
• Toxic epidermal necrolysis (severe skin disease)—Use with caution. May make these conditions worse.
• Asian ancestry (eg, Chinese, Filipino, Japanese, Korean, Taiwanese)—May increase the risk for serious skin reactions. Your doctor may order a special test before prescribing this medicine.
• Bone marrow depression, history of—Should not be used in patients with this condition.
• Fructose intolerance (rare inherited problem)—Tegretol® oral liquid contains sorbitol and should not be given to patients with this condition.

What is carbamazepine used for?

Carbamazepine is an anticonvulsant medication used to control seizures in the treatment of epilepsy specifically for partial seizures with complex symptomatology (psychomotor, temporal lobe), generalized tonic seizures (grand mal), and mixed seizure patterns ¹¹⁾. Carbamazepine is also used to treat bipolar affective disorder, schizophrenia, trigeminal neuralgia and other specific pain disorders. Carbamazepine is also sometimes used to treat mental illnesses, depression, posttraumatic stress disorder, drug and alcohol withdrawal, restless legs syndrome, diabetes insipidus, certain pain syndromes, and a disease in children called chorea.

Carbamazepine is used off-label for refractory schizophrenia ¹²⁾. Simple well designed trials have shown efficacy in patients with schizophrenia with EEG abnormalities, schizophrenia with violent episodes, and schizoaffective disorder. Carbamazepine improves both positive and negative symptoms in schizophrenic patients ¹³⁾. Other off-label uses of this drug include treatment of restless leg syndrome and decreasing agitation and aggression in patients with dementia ¹⁴⁾. Another prominent off-label use of this drug is the treatment of neuropathic pain and fibromyalgia ¹⁵⁾. In patients with moderate to severe alcohol withdrawal syndrome, Carbamazepine has been shown to have clinical efficacy in treatment. However, this is not approved by the FDA, and it has not been shown to prevent alcohol withdrawal seizures as compared to benzodiazepines ¹⁶⁾.

Carbamazepine administration

Take carbamazepine exactly as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. To do so may increase the chance of side effects

Carbamazepine should be taken with meals to lessen unwanted effects (eg, stomach upset, nausea, vomiting).