Gentamicin

Gentamicin is a parenterally administered, broad spectrum aminoglycoside antibiotic typically used for moderate to severe bacterial infections, primarily gram negative bacteria and some aerobic gram positive organisms. Like other aminoglycosides, gentamicin is thought to act by binding to bacterial ribosomes and inhibiting protein synthesis. Nevertheless, gentamicin is considered bacteriocidal as well as bacteriostatic. Gentamicin and other aminoglycosides are typically used in combination with a penicillin or cephalosporin for treatment of severe infections with E. coli, Staphylococcus aureus, Enterobacter, Klebsiella, Serratia, Pseudomonas aeruginosa, and other gram negative bacteria resistant to less toxic antibiotics. Gentamicin is most commonly used for septicemia, bacterial endocarditis, peritonitis, meningitis, pelvic inflammatory disease and pneumonia. Gentamicin was first approved for use in the United States in 1970 and remains in wide use. Gentamicin is available in multiple generic parenteral formulations and the typical adult dose is 3 to 5 mg/kg per day intramuscularly (into a muscle) (IM) or intravenously (into a vein) (IV), usually in three divided doses and often after a loading dose. When gentamicin is injected intravenously, it is usually infused (injected slowly) over a period of 30 minutes to 2 hours once every 6 or 8 hours. Doses must be modified based upon renal function and monitoring of drug levels is advisable. The length of your treatment depends on the type of infection you have. Topical formulations are also available for local wound, tissue and ophthalmologic anti-bacterial therapy.

You may receive gentamicin injection in a hospital or you may administer the medication at home. If you will be receiving gentamicin 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 gentamicin injection. If your symptoms do not improve or get worse, call your doctor.

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

Gentamicin common side effects of gentamicin include dizziness, headache, confusion, nausea and skin rash. Important, dose related adverse effects include ototoxicity and nephrotoxicity, which are shared by all aminoglycosides.

Gentamicin drops

• Gentamicin ophthalmic preparations are used to treat infections of the eye.
• Gentamicin otic preparations are used to treat infections of the ear canal.

Gentamicin is available only with your doctor’s prescription.

Gentamicin otic preparations

To use:

1. Lie down or tilt the head so that the infected ear faces up. Gently pull the earlobe up and back for adults (down and back for children) to straighten the ear canal. Drop the medicine into the ear canal. Keep the ear facing up for about 1 or 2 minutes to allow the medicine to come into contact with the infection. A sterile cotton plug may be gently inserted into the ear opening to prevent the medicine from leaking out.
2. To keep the medicine as germ-free as possible, do not touch the applicator tip to any surface (including the ear). Also, keep the container tightly closed.

To help clear up your infection completely, keep using this medicine for the full time of treatment, even if your symptoms have disappeared. Do not miss any doses.

Gentamicin ophthalmic preparations

For patients using the eye drop form of this medicine:

The bottle is only partially full to provide proper drop control.

To instill the eye drops, follow these steps:

1. Wash your hands thoroughly with soap and water.
2. Check the dropper tip to make sure that it is not chipped or cracked.
3. Avoid touching the dropper tip against your eye or anything else; eye drops and droppers must be kept clean.
4. While tilting your head back, pull down the lower lid of your eye with your index finger to form a pocket.
5. Hold the dropper (tip down) with the other hand, as close to the eye as possible without touching it.
6. Brace the remaining fingers of that hand against your face.
7. While looking up, gently squeeze the dropper so that a single drop falls into the pocket made by the lower eyelid. Remove your index finger from the lower eyelid.
8. Close your eye for 2 to 3 minutes and tip your head down as though looking at the floor. Try not to blink or squeeze your eyelids.
9. Place a finger on the tear duct and apply gentle pressure.
10. Wipe any excess liquid from your face with a tissue.
11. If you are to use more than one drop in the same eye, wait at least 5 minutes before instilling the next drop.
12. Replace and tighten the cap on the dropper bottle. Do not wipe or rinse the dropper tip.
13. Wash your hands to remove any medication.

For patients using the eye ointment form of this medicine:

To apply the eye ointment, follow these steps:

1. Wash your hands thoroughly with soap and water.
2. Use a mirror or have someone else apply the ointment.
3. Avoid touching the tip of the tube against your eye or anything else. The ointment must be kept clean.
4. Tilt your head forward slightly.
5. Holding the tube between your thumb and index finger, place the tube as near as possible to your eyelid without touching it.
6. Brace the remaining fingers of that hand against your cheek or nose.
7. With the index finger of your other hand, pull the lower lid of your eye down to form a pocket.
8. Place a small amount of ointment into the pocket made by the lower lid and the eye. A 1/2-inch (1.25-centimeter) strip of ointment usually is enough unless otherwise directed by your doctor.
9. Gently close your eyes and keep them closed for 1 to 2 minutes to allow the medication to be absorbed.
10. Replace and tighten the cap right away.
11. Wipe off any excess ointment from your eyelids and lashes with a clean tissue. Wash your hands again.

To help clear up your infection completely, keep using this medicine for the full time of treatment, even if your symptoms have disappeared. Do not miss any doses.

Gentamicin mechanism of action

Gentamicin has bactericidal activity in which it binds to the bacteria ribosomal 30S subunit ¹. Specifically, gentamicin is believed to bind to the A-site on the 16S rRNA, a component of the ribosomal 30S subunit. Through this binding, the genetic code gets misread, and the translation is disrupted, leading to the bacteria being unable to carry out protein synthesis ².

Gentamicin contraindications

Gentamicin should be avoided in patients with myasthenia gravis because of the risk of prolonged neuromuscular blockade.

Gentamicin special precautions

Before using gentamicin injection:

• tell your doctor and pharmacist if you are allergic to gentamicin injection; other aminoglycoside antibiotics such as amikacin, kanamycin, neomycin, paromomycin, streptomycin, or tobramycin; sulfites; any other medications; or any of the ingredients in gentamicin 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; dimenhydrate (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 gentamicin, 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.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are using gentamicin 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.

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

Comments:

• Therapeutic blood levels in the mother do not equate with safety for the fetus.
• Some experts recommend: Aminoglycosides should be considered potentially ototoxic and nephrotoxic to the fetus.
• If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential harm to the fetus.

Breastfeeding

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

Comments:

• The American Academy of Pediatrics considers this drug compatible with breastfeeding.
• The WHO (World Health Organization) considers this drug compatible with breastfeeding; breastfed infants should be monitored for thrush and diarrhea.
• Breastfed infants should be monitored for candidiasis and gastrointestinal side effects (e.g., diarrhea, thrush, diaper rash, antibiotic-associated colitis).

Gentamicin 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 gentamicin, 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 gentamicin 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.

• Ataluren

Using gentamicin 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.

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

Using gentamicin 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.

• Indomethacin
• Methoxyflurane
• Polygeline

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 gentamicin. 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.
• Hypocalcemia (low calcium in the blood) or
• Hypokalemia (low potassium in the blood) or
• Hypomagnesemia (low magnesium in the blood)—Should be corrected before receiving this medicine. If these conditions are not corrected, this medicine may increase risk for more serious side effects.
• Kidney disease—Use with caution. The effects may be increased because of slower removal of this medicine from the body.
• Muscle problems or
• Myasthenia gravis (severe muscle weakness) or
• Nerve problems—Use with caution. May make these conditions worse.

Gentamicin uses

Gentamicin 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.

Gentamicin is also sometimes used to treat pelvic inflammatory disease, granuloma inguinale (donovanosis; a sexually transmitted disease), and other serious infections such as the plague and tularemia. Talk to your doctor about the risks of using this medication for your condition.

Antibiotics such as gentamicin 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.

Monitoring

Therapeutic drug monitoring is necessary with gentamicin to optimize patient outcome and limit toxicity. However, there is no universal agreement on the method of monitoring. Therapeutic drug monitoring has shown to reduce hospital stay duration and toxicities. Studies also suggest that therapeutic drug monitoring reduces mortality. It is important to note that monitoring clearance should be considered in critically ill, burn, and obese patients due to their abnormal distribution volume ³.

For toxicity purposes, renal function and cochlear function require monitoring. Serial audiometry may be considered to prevent irreversible hearing loss. Additionally, monitoring serum creatinine must be done to assess for nephrotoxicity in patients requiring gentamicin therapy ⁴.

Gentamicin dose

Gentamicin injection dose

A nurse or other trained health professional will give you the gentamicin injection. Gentamicin is given as a shot into a muscle or into a vein.

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

Your doctor will check your progress closely while you or your child are receiving gentamicin. This will allow your doctor to see if the gentamicin 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.

Adult dose

• Systemic infections: 1 mg/kg IM or IV infusion (over 30 to 120 minutes) every 8 hours
• Duration of therapy: 7 to 10 days

Children dose

• Premature and full-term neonates 1 week of age or less: 2.5 mg/kg IM or IV every 12 hours
• Neonates and infants: 2.5 mg/kg IM or IV every 8 hours
• Children: 2 to 2.5 mg/kg IM or IV every 8 hours
• Duration of therapy: 7 to 10 days

American Academy of Pediatrics (AAP) Recommendations:

Severe Infections:

• 7 days or younger and 2 kg or less: 5 mg IM or IV every 48 hours
• 7 days or younger and greater than 2 kg: 4 mg IM or IV every 24 hours
• 8 to 28 days and 2 kg or less: 5 mg IM or IV every 24 hours
• 8 to 28 days and greater than 2 kg: 4 to 5 mg IM or IV every 24 hours
• Older than 28 days: 6 to 7.5 mg IM or IV in 2 to 3 doses OR 5 to 7.5 mg IM or IV once a day

Gentamicin ophthalmic dose

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

For gentamicin ophthalmic ointment dosage form:

• For eye infections: Adults and children—Use every eight to twelve hours.

For ophthalmic solution (eye drops) dosage form:

• For mild to moderate eye infections: Adults and children—One to two drops every four hours.
• For severe eye infections: Adults and children—One to two drops as often as once every hour as directed by your doctor.

Missed Dose

If you miss a dose of gentamicin, apply it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule.

Gentamicin otic dose

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

For gentamicin ear drops dosage form:

• For ear infections:
  • Adults and children 6 years of age and older—Place three or four drops in the infected ear three times a day.
  • Children younger than 6 years of age—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of gentamicin, apply it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule.

Gentamicin side effects

The main noted adverse effects of gentamicin are ototoxicity (toxic to the ear), nephrotoxicity (toxic to the kidneys) and neuromuscular blockade. Therefore, patients should be educated to look out for warning signs of these adverse effects before the initiation of gentamicin therapy ⁵.

Gentamicin-induced ototoxicity has been reported to occur in 2 to 45% of adults. The ototoxicity can be vestibular and/or cochlear and is typically dose-dependent. Gentamicin, streptomycin, and tobramycin more commonly cause vestibular damage while amikacin and kanamycin result in more cochlear damage ⁶. Studies have found that gentamicin seems to create reactive oxygen species within the inner ear; this, in turn, causes damage to the vestibular and cochlear sensory cells along with cochlear neurons. Often the vestibular loss is salvageable while hearing loss is irreversible ⁷.

Nephrotoxicity due to gentamicin may appear 10 to 25% of patients. In patients receiving gentamicin therapy, renal tubular toxicity decreased blood flow to the kidneys, and reduced GFR most commonly causes the nephrotoxicity seen. Renal effects with gentamicin generally are reversible. Furthermore, there are risk factors associated with the development of gentamicin-induced nephrotoxicity including dehydration, pregnancy, and hepatic dysfunction. Taking other medications concurrently with gentamicin that can cause nephrotoxicity, such as nonsteroidal anti-inflammatory drugs (NSAIDs), cyclosporine, and diuretics, also put a patient at risk for renal problems. It is important to monitor patient renal function when taking gentamicin ⁴.

Gentamicin have also demonstrated correlations with neuromuscular blockade. Although this is less common than ototoxicity and nephrotoxicity, patients with diseases affecting the neuromuscular junction and patients using medications prolonging neuromuscular blockade, most notably calcium channel blockers, should be cautious when using gentamicin ⁸.

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

• nausea
• vomiting
• diarrhea
• decreased appetite
• pain at the injection site
• headache
• fever
• joint pain
• unusual tiredness

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

Incidence not known

• abdominal or stomach cramps or pain
• agitation
• back pain
• black, tarry stools
• blood in the urine
• blurred or double vision
• burning, numbness, tingling, or painful sensations
• change in frequency of urination or amount of urine
• chest pain
• chills
• coma
• confusion
• continuing ringing or buzzing or other unexplained noise in the ears
• cough
• difficult or troubled breathing
• difficulty with swallowing
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• drowsiness
• dry mouth
• eye pain
• fast heartbeat
• fever with or without chills
• hallucinations
• headache
• hearing loss
• hives
• hoarseness
• increased thirst
• irregular heartbeats
• irregular, fast or slow, or shallow breathing
• irritability
• itching
• joint pain
• loss of appetite
• mood or mental changes
• muscle cramps in the hands, arms, feet, legs, or face
• muscle pain or weakness
• muscle spasms (tetany) or twitching
• nausea or vomiting
• nervousness
• numbness and tingling around the mouth, fingertips, or feet
• pale or blue lips, fingernails, or skin
• pale skin
• pinpoint red spots on the skin
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• right upper abdominal or stomach pain and fullness
• seizures
• sensation of spinning
• skin rash
• slow or fast heartbeat
• slow or irregular breathing
• sore throat
• sores, ulcers, or white spots on the lips or in the mouth
• stiff neck
• sweating
• swelling of the feet or lower legs
• swollen glands
• tightness in the chest
• trembling
• unusual bleeding or bruising
• unusual tiredness or weakness
• weight chest discomfort
• weight loss
• wheezing

Gentamicin may cause other side effects. Call your doctor if you have any unusual problems while using gentamicin.

Gentamicin toxicity

There is no antidote for toxicities of gentamicin. However, agents with protective effects on the ear and kidney may help prevent gentamicin-induced toxicity. In particular, N-acetylcysteine demonstrates promising protective effects on patients using gentamicin ⁹.

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Zovirax

Zovirax is a brand name of an antiviral drug called acyclovir. Zovirax (acyclovir) slows the growth and spread of the herpes and varicella-zoster virus in the body. Zovirax (acyclovir) will not cure herpes, but it can lessen the symptoms of the infection. Zovirax (acyclovir) is used to treat infections caused by herpes viruses, such as genital herpes, cold sores, shingles, and chicken pox.

Zovirax (acyclovir) is available only with your doctor’s prescription.

Zovirax (acyclovir) is indicated for therapy of localized as well as disseminated herpes simplex infections, both type 1 and 2 herpes simplex infections. Zovirax (acyclovir) is also used for varicella-zoster infections (chickenpox and shingles). Zovirax (acyclovir) was approved for use in herpes virus infections in the United States in 1982, and is still widely used in treatment and prophylaxis of genital and mucocutaneous herpes simplex infection with almost 5 million prescriptions filled yearly.

Zovirax (acyclovir) is an acyclic purine nucleoside analogue (acycloguanosine) which has antiviral activity against many herpes viruses, including herpes simplex 1 and 2, cytomegalovirus, Ebstein-Barr virus and varicella-zoster. Zovirax (acyclovir) is phosphorylated intracellularly by viral kinases, and the resultant triphosphate competes with guanosine for incorporation into viral DNA blocking viral DNA polymerase activity.

Acyclovir is available as capsules of 200 mg, tablets of 400 and 800 mg, oral suspensions, creams, ointments, and parenteral preparations in several generic forms, as well as under the brand name of Zovirax. The typical recommended oral dose in adults for genital or oral herpes simplex is 200 to 800 mg three to five times daily for 5 to 10 days; the usual prophylactic dose is 400 mg twice daily. The typical intravenous doses for severe infections is 5 to 10 mg/kg every 8 hours for 5 to 10 days.

Zovirax (acyclovir) side effects are uncommon with oral formulations, but can include myalgias, rash, temors, lethargy and confusion. Rare side effects include bone marrow toxicity and Stevens Johnson syndrome.

Zovirax uses

Zovirax (acyclovir) is used to decrease pain and speed the healing of sores or blisters in people who have varicella (chickenpox), herpes zoster (shingles; a rash that can occur in people who have had chickenpox in the past), and first-time or repeat outbreaks of genital herpes (a herpes virus infection that causes sores to form around the genitals and rectum from time to time). Zovirax (acyclovir) is also sometimes used to prevent outbreaks of genital herpes in people who are infected with the virus. Zovirax (acyclovir) works by stopping the spread of the herpes virus in the body.  Zovirax (acyclovir) will not cure genital herpes and may not stop the spread of genital herpes to other people.

Zovirax (acyclovir) is also sometimes used to treat eczema herpeticum (a skin infection caused by the herpes virus) to treat and prevent herpes infections of the skin, eyes, nose, and mouth in patients with human immunodeficiency virus (HIV), and to treat oral hairy leukoplakia (condition that causes hairy white or gray-colored patches on the tongue or inside of the cheek).

Zovirax topical uses

Zovirax (acyclovir) cream is used to treat cold sores (fever blisters; blisters that are caused by a virus called herpes simplex) on the face or lips. Zovirax (acyclovir) ointment is used to treat first outbreaks of genital herpes (a herpes virus infection that causes sores to form around the genitals and rectum from time to time) and to treat certain types of sores caused by the herpes simplex virus in people with weak immune systems. Zovirax (acyclovir) is in a class of antiviral medications called synthetic nucleoside analogues. It works by stopping the spread of the herpes virus in the body. Zovirax (acyclovir) does not cure cold sores or genital herpes, does not prevent outbreaks of these conditions, and does not stop the spread of these conditions to other people.

How should topical Zovirax be used?

Topical Zovirax (acyclovir) comes as a cream and an ointment to apply to the skin. Zovirax (acyclovir) cream is usually applied five times a day for 4 days. Zovirax (acyclovir) cream may be applied at any time during a cold sore outbreak, but it works best when it is applied at the very beginning of a cold sore outbreak, when there is tingling, redness, itching, or a bump but the cold sore has not yet formed. Zovirax (acyclovir) ointment is usually applied six times a day (usually 3 hours apart) for 7 days. It is best to begin using Zovirax (acyclovir) ointment as soon as possible after you experience the first symptoms of infection. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Use topical Zovirax (acyclovir) exactly as directed. Do not use more or less of it or use it more often than prescribed by your doctor.

Your symptoms should improve during your treatment with topical Zovirax (acyclovir). If your symptoms do not improve or if they get worse, call your doctor.

Zovirax (acyclovir) cream and ointment are for use only on the skin. Do not let Zovirax (acyclovir) cream or ointment get into your eyes, or inside your mouth or nose, and do not swallow the medication.

Zovirax (acyclovir) cream should only be applied to skin where a cold sore has formed or seems likely to form. Do not apply Zovirax (acyclovir) cream to any unaffected skin, or to genital herpes sores.

Do not apply other skin medications or other types of skin products such as cosmetics, sun screen, or lip balm to the cold sore area while using Zovirax (acyclovir) cream unless your doctor tells you that you should.

To use Zovirax (acyclovir) cream, follow these steps:

1. Wash your hands.
2. Clean and dry the area of skin where you will be applying the cream.
3. Apply a layer of cream to cover the skin where the cold sore has formed or seems likely to form.
4. Rub the cream into the skin until it disappears.
5. Leave the skin where you applied the medication uncovered. Do not apply a bandage or dressing unless your doctor tells you that you should.
6. Wash your hands with soap and water to remove any cream left on your hands.
7. Be careful not to wash the cream off of your skin. Do not bathe, shower, or swim right after applying Zovirax (acyclovir) cream.
8. Avoid irritation of the cold sore area while using Zovirax (acyclovir) cream.

To use Zovirax (acyclovir) ointment, follow these steps:

1. Put on a clean finger cot or rubber glove.
2. Apply enough ointment to cover all of your sores.
3. Take off the finger cot or rubber glove and dispose of it safely, so that it is out of reach of children.
4. Keep the affected area(s) clean and dry, and avoid wearing tight-fitting clothing over the affected area.

Ask your pharmacist or doctor for a copy of the manufacturer’s information for the patient. Read this information before you start using Zovirax (acyclovir) and each time you refill your prescription.

Zovirax special precautions

Before taking Zovirax (acyclovir):

• tell your doctor and pharmacist if you are allergic to acyclovir, valacyclovir (Valtrex), any other medications, or any of the ingredients in acyclovir. Ask your 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: amphotericin B (Fungizone); aminoglycoside antibiotics such as amikacin (Amikin), gentamicin (Garamycin), kanamycin (Kantrex), neomycin (Nes-RX, Neo-Fradin), paramomycin (Humatin), streptomycin, and tobramycin (Tobi, Nebcin); aspirin and other nonsteroidal anti-inflammatory drugs such as ibuprofen (Advil, Motrin), and naproxen (Aleve, Naprosyn); cyclosporine (Neoral, Sandimmune); medications to treat HIV or AIDS such as zidovudine (Retrovir, AZT); pentamidine (NebuPent); probenecid (Benemid); sulfonamides such as sulfamethoxazole and trimethoprim (Bactrim); tacrolimus (Prograf); and vancomycin. Many other medications may also interact with acyclovir, 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.
• tell your doctor if there is a possibility you may be dehydrated from a recent illness or activity, or if you have or have ever had problems with your immune system; human immunodeficiency virus infection (HIV); acquired immunodeficiency syndrome (AIDS); or kidney disease.
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking acyclovir, call your doctor.
• if you are taking acyclovir to treat genital herpes, you should know that genital herpes can be spread through sexual contact even if you don’t have blisters or other symptoms and possibly even if you are taking acyclovir. Talk to your doctor about ways to stop the spread of genital herpes and about whether your partner(s) should receive treatment.

Geriatric

Agitation, confusion, dizziness, and drowsiness may be especially likely to occur in elderly patients who are usually more sensitive than younger adults to the central nervous system effects of acyclovir.

Pregnancy

Pregnancy Category B: Animal studies have revealed no evidence of harm to the fetus, however, there are no adequate studies in pregnant women OR animal studies have shown an adverse effect, but adequate studies in pregnant women have failed to demonstrate a risk to the fetus.

Breastfeeding

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

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 Zovirax (acyclovir), 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 Zovirax (acyclovir) 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.

• Foscarnet
• Tolvaptan

Using Zovirax (acyclovir) 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.

• Fosphenytoin
• Phenytoin
• Valproic Acid

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 Zovirax (acyclovir). Make sure you tell your doctor if you have any other medical problems, especially:

• Dehydration or
• Kidney disease—Dehydration or kidney disease may increase blood levels of acyclovir, increasing the chance of side effects.
• Nervous system problems—Acyclovir may make these problems worse.

Zovirax dosage

Zovirax (acyclovir) is best used as soon as possible after the symptoms of herpes infection or shingles (for example, pain, burning, blisters) begin to appear.

If you are taking Zovirax (acyclovir) for the treatment of chickenpox, it is best to start taking Zovirax (acyclovir) as soon as possible after the first sign of the chickenpox rash, usually within one day.

Zovirax (acyclovir) capsules, tablets, and oral suspension may be taken with meals or on an empty stomach.

Zovirax (acyclovir) is best taken with a full glass (8 ounces) of water.

If you are using Zovirax (acyclovir) oral suspension, use a specially marked measuring spoon or other device to measure each dose accurately. The average household teaspoon may not hold the right amount of liquid.

To help clear up your herpes infection, chickenpox, or shingles, keep taking Zovirax (acyclovir) for the full time of treatment, even if your symptoms begin to clear up after a few days. Do not miss any doses. However, do not use this medicine more often or for a longer time than your doctor ordered.

If you are taking Zovirax (acyclovir) capsules, tablets, or oral suspension, you should drink plenty of water to avoid becoming dehydrated.

Acute treatment of Herpes Zoster

• 800 mg every 4 hours orally, 5 times daily for 7 to 10 days.

Genital Herpes

• Treatment of Initial Genital Herpes: 200 mg every 4 hours, 5 times daily for 10 days.
• Chronic Suppressive Therapy for Recurrent Disease: 400 mg 2 times daily for up to 12 months, followed by re-evaluation. Alternative regimens have included doses ranging from 200 mg 3 times daily to 200 mg 5 times daily.
• Intermittent Therapy: 200 mg every 4 hours, 5 times daily for 5 days. Therapy should be initiated at the earliest sign or symptom (prodrome) of recurrence.

The frequency and severity of episodes of untreated genital herpes may change over time. After 1 year of therapy, the frequency and severity of the patient’s genital herpes infection should be re-evaluated to assess the need for continuation of therapy with Zovirax.

Treatment of Chickenpox

• Children (2 years of age and older): 20 mg/kg per dose orally 4 times daily (80 mg/kg/day) for 5 days. Children over 40 kg should receive the adult dose for chickenpox.
• Adults and Children over 40 kg: 800 mg 4 times daily for 5 days.

Intravenous Zovirax is indicated for the treatment of varicella-zoster infections in immunocompromised patients.

When therapy is indicated, it should be initiated at the earliest sign or symptom of chickenpox. There is no information about the efficacy of therapy initiated more than 24 hours after onset of signs and symptoms.

Patients with acute or chronic renal impairment

In patients with renal impairment, the dose of Zovirax Capsules, Tablets, or Suspension should be modified as shown in Table 1.

Table 1. Zovirax dosage modification for renal impairment

Hemodialysis

For patients who require hemodialysis, the mean plasma half-life of acyclovir during hemodialysis is approximately 5 hours. This results in a 60% decrease in plasma concentrations following a 6-hour dialysis period. Therefore, the patient’s dosing schedule should be adjusted so that an additional dose is administered after each dialysis.

Peritoneal Dialysis

No supplemental dose appears to be necessary after adjustment of the dosing interval.

What should I do if I forget a dose?

Take the missed dose as soon as you remember it and take any remaining doses for that day at evenly spaced intervals. 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.

Zovirax side effects

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

• upset stomach
• vomiting
• diarrhea
• dizziness
• tiredness
• agitation
• pain, especially in the joints
• hair loss
• changes in vision

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

• hives
• rash or blisters
• itching
• difficulty breathing or swallowing
• swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
• hoarseness
• fast heartbeat
• weakness
• pale skin
• difficulty sleeping
• fever, sore throat, chills, cough, and other signs of infection
• unusual bruising or bleeding
• blood in the urine
• stomach pain or cramps
• bloody diarrhea
• decreased urination
• headache
• hallucinations (seeing things or hearing voices that do not exist)
• confusion
• aggressive behavior
• difficulty speaking
• numbness, burning, or tingling in the arms or legs
• temporary inability to move parts of your body
• shaking of a part of your body that you cannot control
• seizures
• loss of consciousness

Zovirax (acyclovir) may cause other side effects. Call your doctor if you have any unusual problems while you are taking Zovirax (acyclovir).

Symptoms of Zovirax (acyclovir) overdose may include:

• agitation
• seizures
• extreme tiredness
• loss of consciousness
• swelling of the hands, feet, ankles, or lower legs
• decreased urination

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

• dry or cracked lips
• flaky, peeling, or dry skin
• burning or stinging skin
• redness, swelling, or irritation in the place where you applied the medication

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

• hives
• rash
• itching
• difficulty breathing or swallowing
• swelling of the face, throat, lips, eyes, hands, feet, ankles, or lower legs
• hoarseness

Topical Zovirax (acyclovir) may cause other side effects. Call your doctor if you have any unusual problems while using topical Zovirax (acyclovir).

Zolmitriptan

Zolmitriptan is used to treat the symptoms of migraine headaches (severe throbbing headaches that sometimes are accompanied by nausea and sensitivity to sound and light). Zolmitriptan is in a class of medications called selective serotonin receptor agonists. It works by narrowing blood vessels around the brain, stopping pain signals from being sent to the brain, and blocking the release of certain natural substances that cause pain, nausea, and other symptoms of migraine. Zolmitriptan does not prevent migraine attacks or reduce the number of headaches you have and is not used for cluster headaches.

Many people find that their headaches go away completely after they take zolmitriptan. Other people find that their headaches are much less painful, and that they are able to go back to their normal activities even though their headaches are not completely gone. Zolmitriptan often relieves symptoms that occur together with a migraine headache, such as nausea, vomiting, sensitivity to light, and sensitivity to sound.

Zolmitriptan is not an ordinary pain reliever. It should not be used to relieve any kind of pain other than migraine headaches. This medicine is usually used for people whose headaches are not relieved by acetaminophen, aspirin, or other pain relievers. Zolmitriptan is available only with your doctor’s prescription.

Zolmitriptan comes as a tablet and an orally disintegrating tablet (tablet that dissolves quickly in the mouth) to take by mouth. It is usually taken at the first sign of a migraine headache. If your symptoms improve after you take zolmitriptan but return after 2 hours or longer, you may take a second tablet. However, if your symptoms do not improve after you take zolmitriptan, do not take a second tablet without calling your doctor. Your doctor will tell you the maximum number of tablets or orally disintegrating tablets you may take in a 24-hour period. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take zolmitriptan exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

You may take your first dose of zolmitriptan in a doctor’s office or other medical facility where you can be monitored for serious reactions.

If your doctor has prescribed a dose lower than 2.5 mg, you may use your fingers to break the 2.5-mg tablet on the line that divides it in half. However, you should not break or split the orally disintegrating tablet.

To take the orally disintegrating tablet, use dry hands to peel back the foil packaging. Immediately take out the tablet and place it on your tongue. The tablet will quickly dissolve and can be swallowed with saliva. No water is needed to swallow disintegrating tablets. Do not open the foil packaging or remove the orally disintegrating tablet until just before you are ready to take it.

Call your doctor if your headaches do not get better or occur more frequently after taking zolmitriptan.

If you take zolmitriptan more often or for longer than the recommended period of time, your headaches may get worse or may occur more frequently. You should not take zolmitriptan or any other headache medication for more than 10 days per month. Call your doctor if you need to take zolmitriptan to treat more than three headaches in a 1-month period.

Zolmitriptan has caused serious side effects in some people, especially people who have heart or blood vessel disease. Be sure that you discuss with your doctor the risks of using this medicine as well as the benefits that it can do.

What is zolmitriptan used for?

Zolmitriptan is used to treat acute migraine headaches in adults. Zolmitriptan is not used to prevent migraine headaches and is not used for cluster headaches. Zolmitriptan works in the brain to relieve the pain from migraine headaches. Zolmitriptan belongs to the group of medicines called triptans.

Many people find that their headaches go away completely after they take zolmitriptan. Other people find that their headaches are much less painful, and that they are able to go back to their normal activities even though their headaches are not completely gone. Zolmitriptan often relieves symptoms that occur together with a migraine headache, such as nausea, vomiting, sensitivity to light, and sensitivity to sound.

Zolmitriptan is not an ordinary pain reliever. It should not be used to relieve any kind of pain other than migraine headaches. This medicine is usually used for people whose headaches are not relieved by acetaminophen, aspirin, or other pain relievers.

The triptans are synthetic serotonin receptor agonists that are used in the therapy of migraine and vascular headache. Serotonin (5-hydroxytryptamine or 5-HT) is a monoamine that has multiple actions, acting as a neurotransmitter and bioactive amine. The diversity of actions of serotonin is partially due to the multitude of different serotonin receptors and their tissue location. There are at least 15 classes of serotonin receptors which have overlapping actions, but variable distribution and intracellular pathways of response to stimulation and inhibition. The triptans are serotonin agonists with high affinity for the 5-HT1B and 5-HT1D receptors which are found on smooth-muscle cells of blood vessels. Simulation of the 5-HT1D receptor results in constriction of intracranial blood vessels. The triptans may also block the release of vasoactive peptides from perivascular trigeminal neurons through their action at presynaptic 5-HT1D receptors on nerve terminals. Regardless, the triptans have been found to be effective in preventing or aborting migraine headaches with shortening of the period of pain and symptoms. The triptans are considered “first line” agents for patients whose vascular headaches do not reliably respond to conventional analgesics. They generally have a more rapid onset of action and fewer side effects than the ergot alkaloids. Seven triptans are approved for use in the United States including almotriptan, eletriptan, forvatriptan, naratriptan, rizatriptan, sumatriptan and zolmitriptan. Generic formulations are available for most agents. The short acting triptans include sumatriptan, almotriptan, eletriptan, rizatriptan and rolmitriptan and generally provide relief within 30 to 60 minutes. The longer activing oral triptans include naratriptan and frovatriptan which have a slower onset of action but may be better tolerated. Intranasal formulations may have a more rapid onset of action as do subcutaneous administered forms.

Zolmitriptan special precautions

Before taking zolmitriptan:

• tell your doctor and pharmacist if you are allergic to zolmitriptan, any other medications, or any of the ingredients in zolmitriptan tablets or orally disintegrating tablets. Ask your pharmacist for a list of the ingredients.
• do not take zolmitriptan if you have taken any of the following medications in the past 24 hours: other selective serotonin receptor agonists such as almotriptan (Axert), eletriptan (Relpax), frovatriptan (Frova), naratriptan (Amerge), rizatriptan (Maxalt), or sumatriptan (Imitrex, in Treximet); or ergot-type medications such as bromocriptine (Parlodel), cabergoline , dihydroergotamine (D.H.E. 45, Migranal), ergoloid mesylates (Hydergine), ergonovine (Ergotrate), ergotamine (Cafergot, Ergomar, Wigraine), methylergonovine (Methergine), methysergide (Sansert), and pergolide (Permax).
• do not take zolmitriptan if you are taking a monoamine oxidase A (MAO-A) inhibitor such as isocarboxazid (Marplan), phenelzine (Parnate), or tranylcypromine (Nardil) or if you have taken one of these medications in the past 2 weeks.
• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, or herbal products you are taking or plan to take. Be sure to mention any of the following: acetaminophen (Tylenol); antidepressants such as amitriptyline (Elavil), amoxapine (Asendin), clomipramine (Anafranil), desipramine (Norpramin), doxepin (Adapin, Sinequan), imipramine (Tofranil), nortriptyline (Aventyl, Pamelor), protriptyline (Vivactil), and trimipramine (Surmontil); aspirin and other nonsteroidal anti-inflammatory medications (NSAIDs) such as ibuprofen (Advil, Motrin) and naproxen (Aleve, Naprosyn); cimetidine (Tagamet); oral contraceptives (‘birth control pills’); propranolol (Inderal); selective serotonin reuptake inhibitors (SSRIs) such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem, in Symbyax), fluvoxamine (Luvox), paroxetine (Paxil), and sertraline (Zoloft); and selective serotonin/norepinephrine reuptake inhibitors (SNRIs) such as desvenlafaxine (Pristiq), duloxetine (Cymbalta), sibutramine (Meridia), and venlafaxine (Effexor). 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 heart disease; a heart attack; angina (chest pain); irregular heartbeats; stroke or ‘mini-stroke’; or circulation problems such as varicose veins, blood clots in the legs, Raynaud’s disease (problems with blood flow to the fingers, toes, ears, and nose), or ischemic bowel disease (bloody diarrhea and stomach pain caused by decreased blood flow to the intestines). Your doctor may tell you not to take zolmitriptan.
• tell your doctor if you smoke or are overweight; if you have or have ever had high blood pressure, high cholesterol, diabetes, or liver or kidney disease; if you have gone through menopause (change of life); or if any family members have or have ever had heart disease or stroke.
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you plan to be sexually active while you are taking this medication, talk to your doctor about effective methods of birth control. If you become pregnant while taking zolmitriptan, call your doctor.
• you should know that this medication may make you drowsy or dizzy. Do not drive a car or operate machinery until you know how zolmitriptan affects you.
• talk to your doctor about your headache symptoms to make sure they are caused by migraine. Zolmitriptan should not be used to treat certain types of migraine headaches (hemiplegic or basilar) or other types of headaches (such as cluster headaches).
• if you have phenylketonuria (PKU, an inherited condition in which a special diet must be followed to prevent mental retardation), you should know that the orally disintegrating tablets contain aspartame that forms phenylalanine.

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.

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 zolmitriptan, 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 zolmitriptan 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.

• Almotriptan
• Bromocriptine
• Cisapride
• Dihydroergotamine
• Eletriptan
• Ergoloid Mesylates
• Ergonovine
• Ergotamine
• Frovatriptan
• Isocarboxazid
• Levomethadyl
• Linezolid
• Mesoridazine
• Methylene Blue
• Methylergonovine
• Methysergide
• Naratriptan
• Phenelzine
• Procarbazine
• Rizatriptan
• Sumatriptan
• Terfenadine
• Thioridazine
• Tranylcypromine

Using zolmitriptan 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
• Alfentanil
• Amiodarone
• Amitriptyline
• Amoxapine
• Amphetamine
• Aprindine
• Azimilide
• Benzhydrocodone
• Benzphetamine
• Bretylium
• Chloroquine
• Citalopram
• Codeine
• Desipramine
• Desvenlafaxine
• Dextroamphetamine
• Dibenzepin
• Dihydrocodeine
• Disopyramide
• Dofetilide
• Dolasetron
• Doxepin
• Droperidol
• Duloxetine
• Erythromycin
• Escitalopram
• Fentanyl
• Flecainide
• Fluconazole
• Fluoxetine
• Fluvoxamine
• Foscarnet
• Gemifloxacin
• Granisetron
• Halofantrine
• Hydrocodone
• Hydromorphone
• Hydroquinidine
• Ibutilide
• Imipramine
• Isradipine
• Levomilnacipran
• Levorphanol
• Lidoflazine
• Lisdexamfetamine
• Lithium
• Lorcainide
• Lorcaserin
• Mefloquine
• Meperidine
• Metaxalone
• Methadone
• Methamphetamine
• Milnacipran
• Mirtazapine
• Morphine
• Morphine Sulfate Liposome
• Nefazodone
• Nortriptyline
• Octreotide
• Oxycodone
• Oxymorphone
• Palonosetron
• Paroxetine
• Pentamidine
• Pirmenol
• Pixantrone
• Prajmaline
• Probucol
• Procainamide
• Prochlorperazine
• Propafenone
• Protriptyline
• Quinidine
• Reboxetine
• Remifentanil
• Sematilide
• Sertraline
• Sibutramine
• Sotalol
• Spiramycin
• St John’s Wort
• Sufentanil
• Tapentadol
• Tedisamil
• Tramadol
• Trazodone
• Trifluoperazine
• Trimipramine
• Vasopressin
• Venlafaxine
• Vilazodone
• Vortioxetine
• Ziprasidone

Using zolmitriptan 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. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using zolmitriptan 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 zolmitriptan, or give you special instructions about the use of food, alcohol, or tobacco.

• Tobacco

Other Medical Problems

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

• Angina (chest pain) or
• Arrhythmia (heart rhythm problem) or
• Basilar migraine (migraine with vision and hearing problems), history of or
• Heart attack, history of or
• Heart or blood vessel disease or
• Hemiplegic migraine (migraine with some paralysis), history of or
• Hypertension (high blood pressure), uncontrolled or
• Ischemic bowel disease (bowels have low blood supply) or
• Peripheral vascular disease (clogged arteries) or
• Stroke, history of or
• Transient ischemic attack (TIA), history of or
• Wolff-Parkinson-White Syndrome (heart rhythm problem)—Should not be used in patients with these conditions.
• Coronary artery disease, family history of or
• Diabetes or
• Hypertension (high blood pressure) or
• Obesity or
• Raynaud’s syndrome—Use with caution. May be at increased risk for certain side effects.
• Heart rhythm problems (e.g., ventricular fibrillation, ventricular tachycardia)—Use with caution. May make these conditions worse.
• Liver disease, moderate to severe—Use of oral disintegrating tablet is not recommended in patients with this condition because these tablets should not be broken in half.
• Phenylketonuria (PKU)—The oral disintegrating tablets contains phenylalanine, which can make your condition worse.

Zolmitriptan dosage

The dose of zolmitriptan 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 zolmitriptan. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of zolmitriptan that you take depends on the strength of the zolmitriptan. 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 zolmitriptan.

For oral dosage forms (oral tablets):

• For migraine headaches:
  • Adults—At first, 1.25 or 2.5 milligrams (mg) (tablet may be broken in half) as a single dose. If the migraine comes back after being relieved, another dose may be taken if at least 2 hours have passed since the first dose. Do not take more than 5 mg in a single dose, or 10 mg in any 24-hour period.
  • Children—Use is not recommended.

For oral dosage form (oral disintegrating tablets):

• For migraine headaches:
  • Adults—2.5 mg placed on top of your tongue. If the migraine comes back after being relieved, another dose may be taken if at least 2 have passed since the first dose. Do not take more than 5 mg in a single dose or 10 mg in any 24-hour period.
  • Children—Use is not recommended.

Zolmitriptan side effects

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

• feeling warm or cold
• drowsiness
• dry mouth
• nausea
• heartburn
• sweating
• dizziness or faintness

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

• pain, tightness, pressure, or heaviness in the chest, throat, neck, or jaw
• slow or difficult speech
• weakness or numbness of an arm or leg
• fast, pounding, or irregular heartbeat
• bloody diarrhea
• sudden or severe stomach pain
• paleness or blue color of the fingers and toes
• shortness of breath
• swelling of the eyes, face, lips, tongue, or throat
• difficulty breathing or swallowing
• hoarseness
• rash
• hives
• pain, burning, or tingling in the hands or feet

Symptoms of zolmitriptan overdose may include:

• extreme drowsiness

Zidovudine

Zidovudine is a synthetic analogue of thymidine (3’-azido-3’- deoxythymidine) also called AZT and nucleoside reverse transcriptase inhibitor (NRTI) used in combination with other agents in the therapy and prophylaxis of the human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome (AIDS). Zidovudine is given to HIV-positive pregnant women to reduce the chance of passing the infection to the baby. Zidovudine works by decreasing the amount of HIV in the blood. Although zidovudine does not cure HIV, it may decrease your chance of developing acquired immunodeficiency syndrome (AIDS) and HIV-related illnesses such as serious infections or cancer. Taking these medications along with practicing safer sex and making other life-style changes may decrease the risk of transmitting (spreading) the HIV virus to other people.

Zidovudine is also used along with other medications in certain situations to treat healthcare workers and other individuals exposed to HIV infection after accidental contact with HIV-contaminated blood, tissues, or other body fluids. Talk to your doctor about the possible risks of using Zidovudine for your condition.

Zidovudine may also be used off-label to treat some conditions associated with human herpesvirus-8 (HHV-8) infection in people with HIV.

Zidovudine was the first antiretroviral agent that was approved for use in treating HIV infection in the United States [1987] ¹ and was subsequently frequently used in antiretroviral regimens for many years. Recently, zidovudine has been replaced by better tolerated nucleoside analogues and it is no longer commonly used in developed countries. Zidovudine is currently indicated for the treatment of HIV infection in combination with other HIV medications such as lamivudine and abacavir.

Zidovudine is available as a single agent in multiple generic forms and under the trade name Retrovir in 100 mg capsules, 300 mg tablets, and as an oral syrup; in combination with lamivudine as Combivir; and in combination with abacavir and lamivudine as Trizivir. The recommended dose of zidovudine in adults is 600 mg orally, daily or 1 mg/kg every 4 hours. Zidovudine is usually taken twice a day by adults and two to three times a day by infants and children. Infants 6 weeks of age and younger may take zidovudine every 6 hours. When zidovudine is taken by pregnant women, it may be taken 5 times a day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take zidovudine exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Your doctor may temporarily stop your treatment if you experience serious side effects.

Zidovudine controls HIV infection but does not cure it. Continue to take zidovudine even if you feel well. Do not stop taking zidovudine without talking to your doctor. When your supply of zidovudine starts to run low, get more from your doctor or pharmacist. If you miss doses or stop taking zidovudine, your condition may become more difficult to treat.

Zidovudine common side effects include asthenia, constipation, headache, insomnia, loss of appetite, malaise, nausea, and vomiting.

Some side effects of zidovudine can be serious. Serious side effects of zidovudine include lactic acidosis, liver problems, myopathy, and blood disorders such as severe anemia or neutropenia.

Other possible side effects of zidovudine include:

• Changes in your immune system (called immune reconstitution inflammatory syndrome or IRIS). IRIS is a condition that sometimes occurs when the immune system begins to recover after treatment with an HIV medicine. As the immune system gets stronger, it may have an increased response to a previously hidden infection.
• Loss of body fat (lipoatrophy).

Tell your health care provider if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of zidovudine. To learn more about possible side effects of zidovudine, read the drug label or package insert or talk to your health care provider or pharmacist.

Zidovudine toxicity

Zidovudine can cause serious, life-threatening side effects. These include hypersensitivity reaction or rash, a buildup of lactic acid in the blood (lactic acidosis), liver problems, muscle weakness (myopathy), and blood disorders, such as extremely reduced numbers of red blood cells (severe anemia) or reduced numbers of white blood cells (neutropenia).

Contact your health care provider right away if you have any of the following symptoms that could be signs of a hypersensitivity reaction:

• Rash
• Blistering or peeling of the skin
• Hives
• Itching
• Difficulty breathing or swallowing
• Swelling of the eyes, face, tongue, lips, or throat

Contact your health care provider immediately or get emergency medical treatment right away if you have any of the following symptoms that could be signs of liver problems or lactic acidosis:

• Nausea or vomiting
• Pain in the upper right part of your stomach
• Loss of appetite
• Extreme tiredness
• Weakness
• Dizziness or lightheadedness
• Fast or irregular heartbeat
• Trouble breathing
• Dark-colored urine
• Light-colored bowel movements
• Yellowing of your skin or the whites of your eyes (jaundice)
• Feeling cold, especially in your arms or legs
• Unusual muscle pain

Contact your health care provider if you have any of the following symptoms of myopathy:

• Tiredness
• Muscle pain
• Weakness

Contact your health care provider right away if you have any of the following symptoms of severe anemia or neutropenia:

• Unusual bleeding or bruising
• Fever, chills, or other symptoms of infection
• Unusual tiredness or weakness
• Pale skin

Worsening of liver disease (sometimes resulting in death) has occurred in people with both HIV and hepatitis C virus infection (HCV) who were taking HIV medicines and also being treated for hepatitis C virus infection (HCV) with interferon with or without ribavirin. If you are taking zidovudine as well as interferon with or without ribavirin and you experience side effects, tell your health care provider.

While taking zidovudine, it is important to keep all of your appointments with your health care provider.

Zidovudine mechanism of action

Zidovudine belongs to a group of HIV drugs called nucleoside reverse transcriptase inhibitors (NRTIs). Nucleoside reverse transcriptase inhibitors (NRTIs) block an HIV enzyme called reverse transcriptase. By blocking reverse transcriptase, NRTIs prevent HIV from multiplying and can reduce the amount of HIV in the body.

Zidovudine uses

Zidovudine is a prescription medicine approved by the U.S. Food and Drug Administration (FDA) for the following uses:

• To treat HIV infection in adults and children 4 weeks of age and older. When zidovudine is used to treat HIV infection, the medicine is always used in combination with other HIV medicines.
• To prevent mother-to-child transmission of HIV. When used to prevent mother-to-child transmission, zidovudine is given to women with HIV during pregnancy and childbirth and to their infants for 6 weeks after birth.

Zidovudine is also used along with other medications in certain situations to treat healthcare workers and other individuals exposed to HIV infection after accidental contact with HIV-contaminated blood, tissues, or other body fluids. Talk to your doctor about the possible risks of using Zidovudine for your condition.

Zidovudine may also be used off-label to treat some conditions associated with human herpesvirus-8 (HHV-8) infection in people with HIV.

Zidovudine special precautions

Before taking zidovudine:

• tell your doctor and pharmacist if you are allergic to zidovudine, any other medications, or any of the other ingredients in zidovudine products. Ask your pharmacist for a list of the ingredients.
• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, you are taking or plan to take. Be sure to mention any of the following: chemotherapy medications for cancer, doxorubicin (Doxil), ganciclovir (Cytovene, Valcyte), interferon alfa, ribavirin (Copegus, Rebetol, Ribasphere), and stavudine (Zerit). 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 kidney disease.
• tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. If you become pregnant while taking zidovudine, call your doctor. You should not breastfeed if you are infected with HIV or if you are taking zidovudine.
• you should know that you may have a loss of body fat from your face, legs, and arms. Talk to your doctor if you notice this change.
• you should know that while you are taking medications to treat HIV infection, your immune system may get stronger and begin to fight other infections that were already in your body. This may cause you to develop symptoms of those infections. If you have new or worsening symptoms after starting treatment with zidovudine, be sure to tell your doctor.

It is very important that your doctor check your or your child’s progress at regular visits to make sure that this medicine is working properly. Blood tests may be needed to check for unwanted effects.

Zidovudine may cause blood problems. These problems may result in a greater chance of certain infections and slow healing. Therefore, you should be careful when using regular toothbrushes, dental floss, and toothpicks not to damage your or your child’s gums. Check with your or your child’s medical doctor or dentist if you have any questions about proper oral hygiene (mouth care) during treatment with this medicine.

Check with your doctor if you or your child has muscle pain, tenderness, wasting, or unusual tiredness or weakness while you are using this medicine.

Zidovudine may cause blood and bone marrow problems. Symptoms of bone marrow problems include fever, chills, sore throat pale skin, or unusual tiredness or weakness. These problems may require blood transfusions or temporarily stopping treatment with zidovudine. Check with your or your child’s doctor if any new health problems or symptoms occur while you or your child are taking zidovudine.

Two rare but serious reactions to this medicine are lactic acidosis (too much acid in the blood) and liver toxicity, which includes an enlarged liver. These are more common if you are female, very overweight (obese), or have been taking anti-HIV medicines for a long time. Call your doctor right away if you or your child have more than one of these symptoms: abdominal discomfort or cramping, dark urine, decreased appetite, diarrhea, general feeling of discomfort, light-colored stools, muscle cramping or pain, nausea, unusual tiredness or weakness, trouble breathing, vomiting, or yellow eyes or skin.

Your immune system may get stronger when you start taking HIV medicines. Tell your doctor right away if you or your child notices any changes in your health. Sometimes the immune system will start to fight infections that were hidden in your body, such as pneumonia or tuberculosis. Autoimmune disorders (eg, Graves’ disease, polymyositis, or Guillain-Barré syndrome) may also occur.

This medicine may decrease or lose body fat, especially in your face, arms, legs, or buttocks, when this medicine is used for a long time. Talk to your doctor if you have concerns.

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.

Zidovudine dose

The dose of Zidovudine 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 Zidovudine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of Zidovudine that you take depends on the strength of the Zidovudine. 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 HIV infection:

• For oral dosage forms (capsules, solution, syrup, and tablets):
  • Adults—300 milligrams (mg) 2 times a day in combination with other anti-HIV medicines.
  • Children and infants 4 weeks of age and older—Dose is based on body weight or body size and must be determined by your child’s doctor.
    • Weighs 30 kilograms (kg) or more—600 milligrams (mg) per day or 480 milligrams per square meter of body surface area (mg/m²) a day in divided doses.
    • Weighs 9 kg to less than 30 kg—18 mg per kg per day in divided doses.
    • Weighs 4 kg to less than 9 kg—24 mg per kg per day in divided doses.

To help prevent pregnant women from passing HIV to their babies during pregnancy and at birth:

• For oral dosage form (capsules, syrup):
  • Pregnant women (after 14 weeks of pregnancy, up to the start of labor)—100 milligrams (mg) 5 times a day until the start of labor.
  • Newborn infants—Dose is based on body weight and must be determined by your doctor. The usual dose is 2 milligrams (mg) per kilogram (kg) of body weight every 6 hours starting 12 hours after birth and continuing through 6 weeks of age.
• For oral dosage form (solution):
  • Pregnant women (after 14 weeks of pregnancy, up to the start of labor)—100 milligrams (mg) 5 times a day, 200 mg every 8 hours, or 300 mg every 12 hours until the start of labor.
  • Newborn infants—Dose is based on body weight and must be determined by your doctor. The usual dose is 2 milligrams (mg) per kilogram (kg) (0.9 mg per pound) of body weight every 6 hours starting within 8 to 12 hours of birth and continuing through 6 weeks of age.

What should I do if I forget a dose?

Skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Zidovudine side effects

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

• stomach pain or cramps
• heartburn
• diarrhea (especially in children)
• constipation
• headache
• difficulty falling asleep or staying asleep

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

• rash
• blistering or peeling of the skin
• hives
• itching
• difficulty breathing or swallowing
• swelling of the eyes, face, tongue, lips, or throat

More common side effects:

• black, tarry stools
• chills
• cough
• feeling of fullness
• fever
• lower back or side pain
• painful or difficult urination
• pale skin
• right upper abdominal pain and fullness
• sore throat
• stomach pain
• swelling or inflammation of the mouth
• swollen lymph nodes
• ulcers, sores, or white spots in the mouth
• unusual bleeding or bruising
• unusual tiredness or weakness

Rare side effects:

• confusion
• diarrhea
• fast, shallow breathing
• general feeling of discomfort
• loss of appetite
• mood or mental changes
• muscle pain, tenderness, weakness, or cramping
• nausea
• seizures
• sleepiness
• stomach discomfort

Incidence not known:

• back or leg pain
• bleeding gums
• blistering, peeling, or loosening of the skin
• bloating
• blood in the urine
• blurred vision or other change in vision
• bone pain
• burning, crawling, itching, numbness, prickling, “pins and needles”, or tingling feelings
• clay-colored stools
• constipation
• dark urine
• decreased appetite
• decreased urine output
• difficult or labored breathing
• difficulty in moving
• difficulty in swallowing
• dilated neck veins
• dizziness
• extreme tiredness or weakness
• fainting
• fast, irregular, or pounding heartbeat
• general body swelling
• general tiredness and weakness
• headache
• high fever
• hives, skin rash
• hoarseness
• increased need to urinate
• indigestion
• irregular breathing
• irritation or soreness of the mouth
• joint or muscle pain
• lack of coordination
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or genitals
• light-colored stools
• muscle pain, cramp, spasm, or stiffness
• nosebleeds
• pains in the stomach, side, or abdomen, possibly radiating to the back
• passing urine more often
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• red skin lesions, often with a purple center
• red, irritated eyes
• redness, soreness, or itching skin
• runny nose
• shakiness in the legs, arms, hands, or feet
• shivering
• sores, welts, or blisters
• stabbing pain
• sweating
• swollen joints
• swollen or painful glands
• tightness in the chest
• trouble sleeping
• unexplained bleeding or bruising
• unpleasant breath odor
• vomiting
• vomiting of blood
• weight gain
• yellow eyes or skin

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

• difficulty having a bowel movement
• headache (severe)
• lack or loss of strength
• muscle soreness
• weight loss

Less common

• bluish-brown colored bands on nails
• changes in skin color

Incidence not known

• belching
• heartburn
• stomach cramps

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

1. Kemnic TR, Gulick PG. HIV Antiretroviral Therapy. [Updated 2019 Feb 15]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2019 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK513308[↩]

Vibramycin

Vibramycin is a brand name of an antibiotic called doxycycline, which is a semisynthetic tetracycline related bacteriostatic antibiotic. Vibramycin (doxycycline) works to treat infections by preventing the growth and spread of bacteria. Vibramycin (doxycycline) works to treat acne by killing the bacteria that infects pores and decreasing a certain natural oily substance that causes acne. Vibramycin (doxycycline) is used for mild-to-moderate infections due to susceptible organisms. Vibramycin (doxycycline), like other tetracyclines, is active against a wide spectrum of gram-positive and gram-negative bacteria as well as against several rickettsia, spirochetes, chlamydia and mycoplasma. Unlike tetracycline and oxytetracycline, Vibramycin (doxycycline) has excellent oral availability and wide tissue penetration. Vibramycin (doxycycline) indications include upper respiratory, skin, or soft tissue infections due to susceptible bacteria, gonorrhea and syphilis in penicillin-allergic patients, non-gonococcal urethritis, acute pelvic inflammatory disease, epididymitis, oorchitis, Lyme disease, and as prophylaxis against traveler’s diarrhea. Vibramycin (doxycycline) is also used chronically as treatment of acne. Vibramycin (doxycycline) works to treat rosacea by decreasing the inflammation that causes this condition.

Vibramycin (doxycycline) was approved for use in the United States in 1967 and is still widely used, with more than 11 million prescriptions filled yearly. Vibramycin (doxycycline) is available in multiple generic forms in capsules and tablets ranging from 20 to 100 mg, and as oral suspensions for pediatric use. Typical adult doses are 100 to 200 mg twice daily for 7 to 30 days. Parenteral forms for intravenous or intramuscular administration are also available.

Other trade names for doxycycline include Oracea, Adoxa, Monodox and Doxycin.

Vibramycin (doxycycline) common side effects include headache, dizziness, nausea, gastrointestinal upset, skin and tooth discoloration and rash.

Vibramycin uses

Vibramycin (doxycycline) is used to treat many different bacterial infections, such as acne, urinary tract infections, intestinal infections, eye infections, pneumonia and other respiratory tract infections, gonorrhea, chlamydia, periodontitis (gum disease), and infections of the lymphatic system; and certain other infections that are spread by ticks, lice, mites, infected animals, or contaminated food and water. Vibramycin may also be used to treat Lyme disease or to prevent Lyme disease in certain people who have been bitten by a tick.

Vibramycin (doxycycline) is also used to treat blemishes, bumps, and acne-like lesions caused by rosacea. Vibramycin (doxycycline) will not treat facial redness caused by rosacea.

Vibramycin (doxycycline) is also used to treat or prevent anthrax (a serious infection that may be spread on purpose as part of a bioterror attack), in people who may have been exposed to anthrax in the air, and to treat plague and tuleramia (serious infections that may be spread on purpose as part of a bioterror attack). Doxycycline delayed-release capsules, delayed-release tablets, and tablets is also used to prevent malaria and treat anthrax infection after possible exposure and other conditions as determined by your doctor.

Vibramycin (doxycycline) can also be used in people who cannot be treated with penicillin to treat certain types of food poisoning. Doxycycline (Oracea) is used only to treat pimples and bumps caused by rosacea (a skin disease that causes redness, flushing, and pimples on the face).

Vibramycin may also be used to prevent infection in people who were sexually attacked.

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

Vibramycin special precautions

Before taking Vibramycin (doxycycline):

• tell your doctor and pharmacist if you are allergic to Vibramycin (doxycycline), minocycline, tetracycline, demeclocycline, any other medications, sulfites, or any of the ingredients in Vibramycin (doxycycline) capsules, extended-release capsules, tablets, extended-release tablets, or suspension. Ask your pharmacist for a list of the ingredients.
• tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, and nutritional supplements you are taking or plan to take. Be sure to mention any of the following: acitretin (Soriatane); anticoagulants (‘blood thinners’) such as warfarin (Coumadin, Jantoven); barbiturates such as butabarbital (Butisol), phenobarbital, and secobarbital (Seconal); bismuth subsalicylate; carbamazepine (Epitol, Tegretol, others); isotretinoin (Absorica, Amnesteem, Clavaris, Myorisan, Zenatane); penicillin; phenytoin (Dilantin, Phenytek); and proton pump inhibitors such as dexlansoprazole (Dexilant), esomeprazole (Nexium, in Vimovo), lansoprazole (Prevacid, in Prevpac), omeprazole (Prilosec, in Yosprala, Zegerid), pantoprazole (Protonix), and rabeprazole (Aciphex). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• be aware that antacids containing magnesium, aluminum, or calcium, calcium supplements, iron products, and laxatives containing magnesium interfere with Vibramycin (doxycycline), making it less effective. Take Vibramycin (doxycycline) 2 hours before or 6 hours after taking antacids, calcium supplements, and laxatives containing magnesium. Take Vibramycin (doxycycline) 2 hours before or 4 hours after iron preparations and vitamin products that contain iron.
• tell your doctor if you have or have ever had lupus (condition in which the immune system attacks many tissues and organs including the skin, joints, blood, and kidneys), intracranial hypertension (pseudotumor cerebri; high pressure in the skull that may cause headaches, blurry or double vision, vision loss, and other symptoms), a yeast infection in your mouth or vagina, surgery on your stomach, asthma, or kidney or liver disease.
  you should know that Vibramycin (doxycycline) may decrease the effectiveness of hormonal contraceptives (birth control pills, patches, rings, or injections). Talk to your doctor about using another form of birth control.
• tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. If you become pregnant while taking Vibramycin (doxycycline), call your doctor immediately. Vibramycin (doxycycline) can harm the fetus.
• plan to avoid unnecessary or prolonged exposure to sunlight and to wear protective clothing, sunglasses, and sunscreen. Vibramycin (doxycycline) may make your skin sensitive to sunlight. Tell your doctor right away if you get a sunburn.
• you should know that when you are receiving Vibramycin (doxycycline) for prevention of malaria, you should also use protective measures such as effective insect repellent, mosquito nets, clothing covering the whole body, and staying in well-screened areas, especially from early nighttime until dawn. Taking Vibramycin (doxycycline) does not give you full protection against malaria.
• you should know that when Vibramycin (doxycycline) is used during pregnancy or in babies or children up to 8 years of age, it can cause the teeth to become permanently stained. Vibramycin (doxycycline) should not be used in children under 8 years of age except for inhalational anthrax, Rocky Mountain spotted fever, or if your doctor decides it is needed.

Pediatric

Doxycycline may cause permanent discoloration of the teeth and slow down the growth of bones. This medicine should not be given to children 8 years of age and younger (except for the treatment of exposure to inhalational anthrax or rickettsia infection), unless directed by the child’s doctor.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of doxycycline in the elderly. However, elderly patients are more likely to have kidney, liver, or heart problems which may require caution and an adjustment in the dose for patients receiving doxycycline.

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.

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 (Vibramycin (doxycycline) 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.

• Acitretin

Using (Vibramycin (doxycycline) 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.

• Amoxicillin
• Ampicillin
• Ascorbic Acid
• Bacampicillin
• Bexarotene
• Cholera Vaccine, Live
• Cloxacillin
• Dicloxacillin
• Etretinate
• Isotretinoin
• Methicillin
• Methotrexate
• Methoxyflurane
• Nafcillin
• Oxacillin
• Penicillin G
• Penicillin G Benzathine
• Penicillin G Procaine
• Penicillin V
• Piperacillin
• Pivampicillin
• Sultamicillin
• Temocillin
• Tretinoin

Using (Vibramycin (doxycycline) 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.

• Aluminum Carbonate, Basic
• Aluminum Hydroxide
• Aluminum Phosphate
• Aminolevulinic Acid
• Bismuth Subsalicylate
• Calcium
• Dihydroxyaluminum Aminoacetate
• Dihydroxyaluminum Sodium Carbonate
• Iron
• Magaldrate
• Magnesium Carbonate
• Magnesium Hydroxide
• Magnesium Oxide
• Magnesium Trisilicate
• Rifampin
• Rifapentine

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 (Vibramycin (doxycycline). Make sure you tell your doctor if you have any other medical problems, especially:

• Asthma—Vibramycin® syrup contains sodium metabisulfite, which can cause allergic and life-threatening reactions in patients with this condition.
• Diarrhea or
• Intracranial hypertension (pseudotumor cerebri), or history of or
• Vaginal candidiasis (yeast) infections—Use with caution. May make these conditions worse.
• Kidney problems—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

Vibramycin dosage

The usual dosage and frequency of administration of Vibramycin (doxycycline) differs from that of the other tetracyclines. Exceeding the recommended dosage may result in an increased incidence of side effects.

Adults

The usual dose of oral Vibramycin (doxycycline) is 200 mg on the first day of treatment (administered 100 mg every 12 hours) followed by a maintenance dose of 100 mg/day. In the management of more severe infections (particularly chronic infections of the urinary tract), 100 mg every 12 hours is recommended.

Pediatric patients

For all pediatric patients weighing less than 45 kg with severe or life-threatening infections (e.g., anthrax, Rocky Mountain spotted fever), the recommended dosage is 2.2 mg/kg of body weight administered every 12 hours. Children weighing 45 kg or more should receive the adult dose.

For pediatric patients with less severe disease (greater than 8 years of age and weighing less than 45 kg), the recommended dosage schedule is 4.4 mg/kg of body weight divided into two doses on the first day of treatment, followed by a maintenance dose of 2.2 mg/kg of body weight (given as a single daily dose or divided into twice daily doses). For pediatric patients weighing over 45 kg, the usual adult dose should be used.

The therapeutic antibacterial serum activity will usually persist for 24 hours following recommended dosage.

When used in streptococcal infections, therapy should be continued for 10 days.

Administration of adequate amounts of fluid along with capsule and tablet forms of drugs in the tetracycline class is recommended to wash down the drugs and reduce the risk of esophageal irritation and ulceration.

If gastric irritation occurs, it is recommended that Vibramycin (doxycycline) be given with food or milk. The absorption of Vibramycin (doxycycline) is not markedly influenced by simultaneous ingestion of food or milk.

Studies to date have indicated that administration of Vibramycin (doxycycline) at the usual recommended doses does not lead to excessive accumulation of Vibramycin (doxycycline) in patients with renal impairment.

Uncomplicated gonococcal infections in adults (except anorectal infections in men): 100 mg, by mouth, twice a day for 7 days. As an alternate single visit dose, administer 300 mg stat followed in one hour by a second 300 mg dose. The dose may be administered with food, including milk or carbonated beverage, as required.

Uncomplicated urethral, endocervical, or rectal infection in adults caused by Chlamydia trachomatis: 100 mg, by mouth twice a day for 7 days.

Nongonococcal urethritis (NGU) caused by Chlamydia trachomatis or Ureaplasma urealyticum: 100 mg by mouth, twice a day for 7 days.

Syphilis – early: Patients who are allergic to penicillin should be treated with Vibramycin (doxycycline) 100 mg, by mouth, twice a day for 2 weeks.

Syphilis of more than one year’s duration: Patients who are allergic to penicillin should be treated with Vibramycin (doxycycline) 100 mg, by mouth, twice a day for 4 weeks.

Acute epididymo-orchitis caused by Neisseria gonorrhoeae: 100 mg, by mouth, twice a day for at least 10 days.

Acute epididymo-orchitis caused by Chlamydia trachomatis: 100 mg, by mouth, twice a day for at least 10 days.

For prophylaxis of malaria: For adults, the recommended dose is 100 mg daily. For children over 8 years of age, the recommended dose is 2 mg/kg given once daily up to the adult dose. Prophylaxis should begin 1–2 days before travel to the malarious area. Prophylaxis should be continued daily during travel in the malarious area and for 4 weeks after the traveler leaves the malarious area.

Inhalational anthrax (post-exposure):

• Adults: 100 mg of Vibramycin (doxycycline), by mouth, twice a day for 60 days.
• Children: weighing less than 45 kg; 2.2 mg/kg of body weight by mouth, twice a day for 60 days. Children weighing 45 kg or more should receive the adult dose.

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.

Vibramycin side effects

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

• nausea
• vomiting
• diarrhea
• loss of appetite
• itching of the rectum or vagina
• sore or irritated throat
• swollen tongue
• dry mouth
• anxiety
• back pain
• changes in color of skin, scars, nails, eyes, or mouth

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

• headache
• blurred vision, seeing double, or loss of vision
• rash that may occur with fever or swollen glands
• hives
• skin redness, peeling or blistering
• difficulty breathing or swallowing
• swelling of the eyes, face, throat, tongue, or lips
• unusual bleeding or bruising
• watery or bloody stools, stomach cramps, or fever during treatment or for up to two or more months after stopping treatment
• a return of fever, sore throat, chills, or other signs of infection
• joint pain
• chest pain
• discoloration of permanent (adult) teeth

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

Triptan drugs

Triptans are a group of synthetic serotonin receptor agonists that are used in the therapy of migraine and vascular headaches. Serotonin (5-hydroxytryptamine or 5-HT) is a monoamine that has multiple actions, acting as a neurotransmitter and bioactive amine. The triptans are serotonin agonists with high affinity for the 5-HT_1B and 5-HT_1D receptors which are found on smooth-muscle cells of blood vessels. Simulation of the 5-HT_1D receptor results in constriction of intracranial blood vessels. The triptans may also block the release of vasoactive peptides from perivascular trigeminal neurons through their action at presynaptic 5-HT_1D receptors on nerve terminals. Regardless, the triptans have been found to be effective in preventing or aborting migraine headaches with shortening of the period of pain and symptoms. The triptans are considered “first line” agents for patients whose vascular headaches do not reliably respond to conventional analgesics. Triptans generally have a more rapid onset of action and fewer side effects than the ergot alkaloids. Triptans may be taken subcutaneously, orally as tablets, capsules, or quick-dissolving wafers, or intranasally as a spray.

Currently, seven triptans are approved for use in the United States including almotriptan, eletriptan, forvatriptan, naratriptan, rizatriptan, sumatriptan and zolmitriptan, as well as a fixed-dose combination product containing sumatriptan plus naproxen. Generic formulations are available for most agents. The short acting triptans include sumatriptan, almotriptan, eletriptan, rizatriptan and rolmitriptan and generally provide relief within 30 to 60 minutes. The longer activing oral triptans include naratriptan and frovatriptan which have a slower onset of action but may be better tolerated. Intranasal formulations may have a more rapid onset of action as do subcutaneous administered forms. Brand names, year approved, tablet or wafer size, usual dose and maximum daily recommended doses are shown in the Table 1.

Comparing the clinical efficacy and harms of the different triptans has been an area of considerable interest to researchers and patients, but is complex because of the large variety of outcome measures that can be measured in studies ¹.

Early therapy is recommended in patients with recurrent migraine, and typically the dose is repeated in 2 to 4 hours if relief has not occurred. However, the total dosage should be limited to 2 to 3 doses per 24 hour period. Parenteral and intranasal administration is helpful in patients with nausea and vomiting. Chronic, long term use of triptans to prevent migraines has been studied, but is not currently approved. The seven triptans have similar side effect profiles which include “triptan sensations” characterized by tightening of the throat, chest, neck and limbs with paresthesias and hot or cold sensations. Triptans may also cause flushing, headache, somnolence and fatigue. Rare but potentially severe adverse events include medication overuse syndrome, cerebrovascular and cardiovascular events such as myocardial infarction and stroke, serotonin syndrome and anaphylaxis.

Table 1. Triptan medications

Footnotes:

* Also available as nasal spray, transdermal patch and solution for injection.
** Also available in orally disintegrating tablets and as nasal spray.

Triptan mechanism of action

Triptans work by binding to serotonin receptors in the brain, which leads to a reversal of blood vessel swelling. The triptans are serotonin agonists with high affinity for the 5-HT_1B and 5-HT_1D receptors which are found on smooth-muscle cells of blood vessels. Simulation of the 5-HT1D receptor results in constriction of intracranial blood vessels. The triptans may also block the release of vasoactive peptides from perivascular trigeminal neurons through their action at presynaptic 5-HT_1D receptors on nerve terminals.

Best triptan for migraine

There is no consistent evidence that one triptan has any particular advantage or disadvantage over another in any subgroup based on age, race, gender, prophylactic treatment, or menstruation-associated migraine ¹.

All triptans can help relieve migraines. Studies on the most commonly prescribed triptan, sumatriptan (50 mg), for example, show the following:

• Without sumatriptan, migraine pain went away within two hours in about 10 out of 100 people.
• With sumatriptan, the pain disappeared in the same time in 20 to 30 out of 100 people.

So an additional 10 to 20 out of 100 people had no pain two hours later. And the drug offered at least some pain relief in another 25 out of 100 people.

How quickly and effectively a drug works will also depend on the severity of the migraine, the dose of the drug and how it is administered. For instance, injections are faster and more effective than other forms of administration, but they also have more side effects.

Table 2. Triptan comparison summary of evidence

Triptan side effects

The possible side effects of triptans include drowsiness, unusual sensations such as tingling, weakness, heat or cold, and sometimes mild nausea as well. Using a suppository or injection might help avoid nausea. But triptans aren’t suitable for people who have cardiovascular (heart and blood vessel) diseases. This is because triptans can narrow the blood vessels and increase blood pressure, although this is rare.

Sumatriptan can cause adverse central nervous system events outside migraine attacks. It can cause mild sedative effects such as sleepiness or fatigue. It also causes a significant increase in the EEG alpha power as compared with the placebo. In a study measured by the Yale-Brown Scale, sumatriptan worsened the symptoms of patients with obsessive-compulsive disorder (OCD). Sumatriptan also can cause a transient rise in blood pressure, but the rise of blood pressure is the same as would be anticipated during moderate exercise. Subcutaneous injection administered by the physician results in transient stinging at the site of injection in most subjects; however, toleration is better when the subjects use the auto-injector. Sumatriptan can induce angle-closure glaucoma, but this is a rare event and should be treated correctly and promptly to prevent visual loss. A common adverse drug reaction of subcutaneous sumatriptan includes injection site reaction (bleeding, bruising, erythema). Intranasal sumatriptan leads to dysgeusia and nasal discomfort. Sumatriptan works earlier and more completely as compared to a combination of caffeine and ergotamine, but sumatriptan is associated with a higher rate of recurrent headaches. Rothner et al. reported a case of facial nerve palsy in a teenager using sumatriptan nasal spray. Hossein et al. described a recurrent paresis of the superior division of the oculomotor nerve occurring after subcutaneous administration of the drug. A thorough evaluation should be done of the patients who present with acute onset of a severe headache, and sumatriptan should be administered carefully since it could precipitate RCVS (Reversible cerebral vasoconstriction syndrome) or aggravate cerebral vasoconstriction. Vascular imaging should be performed after several days if sumatriptan-induced reversible vasoconstriction syndrome is suspected.

1. Helfand M, Peterson K. Drug Class Review: Triptans: Final Report Update 4 [Internet]. Portland (OR): Oregon Health & Science University; 2009 Jun. Results. Available from: https://www.ncbi.nlm.nih.gov/books/NBK47285[↩][↩]
2. Helfand M, Peterson K. Drug Class Review: Triptans: Final Report Update 4 [Internet]. Portland (OR): Oregon Health & Science University; 2009 Jun. Summary. Available from: https://www.ncbi.nlm.nih.gov/books/NBK47288[↩]

What is propylene glycol

Propylene glycol (1,2-dihydroxypropane or 1,2-propanediol or methyl glycol or trimethyl glycol) is a water soluble alcohol and it is a clear liquid used in antifreeze and deicing solutions for cars, airplanes, and boats; to make polyester compounds; and as solvent in the paint and plastics industries. Propylene glycol is a clear, colorless, slightly syrupy liquids at room temperature. It may exist in air in the vapor form, although propylene glycol must be heated or briskly shaken to produce a vapor. Propylene glycol is practically odorless and tasteless. Propylene glycol is also used to create artificial smoke or fog used in fire-fighting training and in theatrical productions.

Propylene glycol is used in pharmaceuticals, as a drug vehicle (for example as a U.S. Food and Drug Administration (FDA)-approved solvent for intravenous diazepam) and preservative. Propylene glycol is also used in personal lubricants, in semi-moist pet food and as a humectant for tobacco. Propylene glycol is currently authorized as a food additive (E 1520). In the food industry propylene glycol (E 1520) is used as a solvent for food colors and flavors, as a humectant, preservative and emulsifier ¹. Propylene glycol is used to absorb extra water and maintain moisture in certain medicines, cosmetics, or food products. The U.S. Food and Drug Administration (FDA) has classified propylene glycol as an additive that is “generally recognized as safe” for use in food, which means that it is acceptable for use in flavorings, drugs, and cosmetics, and as a direct food additive.

The Joint Food and Agriculture Organization of the United Nations (FAO)/World Health Organization (WHO) Expert Committee on Food Additives (JECFA) established an acceptable dietary intake of propylene glycol is 0 to 25 mg of propylene glycol for every kilogram (kg) of body weight for propylene glycol, which the European Food Safety Authority Panel on Contaminants in the Food Chain (CONTAM) endorses ². The lowest oral LD50 (lethal dose 50 is a dose where 50% of the test subjects die) values range between 18 and 23.9 grams (5 different species) and the reported dermal LD50 is 20.8 grams ³. Propylene glycol is not genotoxic. Its use as previous cargo would not give rise to any concerns regarding possible irritancy or allergenicity. There are no reactions of concern with edible fats and oils, nor are any anticipated impurities likely to be present at levels of toxicological relevance.

Propylene glycol can enter your bloodstream if you breathe air containing mists or vapors from this compound. Propylene glycol can also enter your bloodstream through your skin if you come in direct contact with it and do not wash it off. If you eat products that contain propylene glycol, it may enter your bloodstream. Exposure of the general population to propylene glycol is likely since many foods, drugs, and cosmetics contain it.

Propylene glycol breaks down in the body in about 48 hours. However, studies of people and animals show that if you have repeated eye, skin, nasal, or oral exposures to propylene glycol for a short time, you may develop some irritation.

Propylene glycol increases the amount of acid in your body. However, large amounts of propylene glycol are needed to cause this effect.

Propylene glycol breaks down at the same rate as ethylene glycol, although it does not form harmful crystals when it breaks down. Frequent skin exposure to propylene glycol can sometimes irritate the skin.

Propylene glycol induces remarkably fewer adverse effects in both humans and animals than does ethylene glycol ⁴. Data describing either human or animal effects after exposure to propylene glycol were not as prevalent as those found for ethylene glycol. Human data came from case reports of clinical studies, adverse reactions to medical treatment, or accidental exposure. Animal data generally support those effects, or lack thereof, observed in humans.

Propylene glycol is essentially nonirritating to the skin and mildly irritating to the eyes. Numerous studies support that propylene glycol is not a skin sensitizer. Repeated exposures of rats to propylene glycol in drinking water or feed did not result in adverse effects at levels up to 10% in water (estimated at about 10 g/kg body weight/day) or 5% in feed (dosage reported as 2.5 g/kg body weight/day) for periods up to 2 years. In cats, two studies of at least 90 days duration show that a species-specific effect of increased Heinz bodies was observed (NOAEL = 80 mg/kg body weight/day; LOAEL = 443 mg/kg body weight/day), with other hematological effects (decrease in number of erythrocytes and erythrocyte survival) reported at higher doses (6-12% in diet, or 3.7-10.1 g/cat/day). No Observed Adverse Effect Level (NOAEL) is the highest dose at which there was not an observed toxic or adverse effect. The Lowest Observed Adverse Effect Level (LOAEL) is the lowest dose at which there was an observed toxic or adverse effect. Propylene glycol did not cause fetal or developmental toxicity in rats, mice, rabbits, or hamsters (NOAELs range from 1.2 to 1.6 g/kg body weight/day in four species). No reproductive effects were found when propylene glycol was administered at up to 5% in the drinking water (reported as 10.1 g/kg body weight/day) of mice. Propylene glycol was not a genetic toxicant as demonstrated by a battery of in vivo (micronucleus, dominant lethal, chromosome aberration) and in vitro (bacterial and mammalian cells and cultures) studies. No increase in tumors was found in all tissues examined when propylene glycol was administered in the diet of rats (2.5 g/kg body weight/day for 2 years), or applied to the skin of female rats (100% propylene glycol; total dose not reported; 14 months) or mice (mouse dose estimated at about 2 g/kg body weight/week; lifetime). These data support a lack of carcinogenicity for propylene glycol.

Propylene glycol allergy

There is evidence from clinical studies that propylene glycol is a weak irritant and skin sensitizer (challenge with 2 % solution or stronger), and may increase the reaction to some contact allergens (i.e. adjuvant-like effect), if there is co-exposure, for example when propylene glycol is used as a vehicle ⁵. Oral or IV administration of propylene glycol may exacerbate dermatitis in some individuals ⁶. Taking into account that the worst case residue levels of propylene glycol in the oils and fats is considered to be 100 mg/kg, and additionally that propylene glycol is only a weak or very weak irritant, allergen or adjuvant, the European Food Safety Authority Panel on Contaminants in the Food Chain (CONTAM) Panel considers that there would be no significant risk for adverse reactions due to irritancy or allergy from the use of propylene glycol.

Retrospective analysis of cross-sectional data compiled by the North American Contact Dermatitis Group ⁷ from 1996 to 2006 /was examined/. RESULTS: Of 23,359 patients, 810 (3.5%) had allergic patch-test reactions to 30% propylene glycol, 12.8% of the reactions were of definite clinical relevance (positive reaction to a personal product containing propylene glycol), 88.3% were considered to be currently relevant (definite, probable, or possible relevance), and 4.2% of reactions were occupation related, most commonly to mechanical and motor vehicle occupations. Common sources of propylene glycol were personal care products (creams, lotions, and cosmetics, 53.8%), topical corticosteroids (18.3%), and other topical medicaments (10.1%). In patients positive only to PG (n = 135), the face was most commonly affected (25.9%), followed by a scattered or generalized pattern (23.7%).

To characterize relevant allergens and irritants associated with food in patients referred to the North American Contact Dermatitis Group ⁸ for patch testing retrospective analysis of cross-sectional data from the North American Contact Dermatitis Group from 2001 to 2004 was performed. Of 10,061 patch-tested patients, 109 (1.1%) had a total of 122 reactions associated with food. Approximately two-thirds of patients (66%) were female, and one-third (36%) were atopic. The hands were the most common sites of dermatitis (36.7%). There were 78 currently relevant (definite, probable, or possible) allergic reactions to North American Contact Dermatitis Group standard series allergens with a food source; the most common allergen was nickel (48.7%), followed by Myroxilon pereirae (balsam of Peru) (20.6%) and propylene glycol (6.4%) ⁸.

Contact dermatitis has been reported from propylene glycol exposure in a wide variety of topical preparations and ingestion of propylene glycol in sensitized individuals has produced flares of dermatitis ⁹. Skin irritation resulting from topical exposure is manifest as erythematous reactions restricted to sites of exposure. The irritation potential is enhanced after prolonged dermal exposure, under dermal occlusion, and in combination with triethanolamine-stearate, a cosmetic emulsifier. The nature of the skin reaction of propylene glycol-sensitive patients has been a matter of controversy. In one study primary irritant reactions to the skin and type IV delayed hypersensitivity reactions were observed following oral ingestion or topical application of propylene glycol. However, in most cases, the skin reaction was due to a primary irritation, not to an allergic reaction ⁹.

Results from human patch testing show no sensitization potential of propylene glycol after semi-occlusive or occlusive epicutaneous application to the skin of volunteers (in excess of 300 subjects in total). These studies demonstrate that propylene glycol is not irritating to skin or eye, nor does it cause sensitization by skin contact ¹⁰.

Patch-test in humans, 15 uL 100% propylene glycol/test chamber for 48 hr. Results: not irritating ¹¹.

In 6 human volunteers, pads containing /propylene glycol/ test substance were fixed to the forearm for 2 hr, observation time: 7 days. Results: not irritating ¹¹.

Cream containing 12% propylene glycol was tested on 204 persons. Results: not sensitizing ¹².

The irritant effects of propylene glycol was studied in humans (number of test subjects not indicated) using laser Doppler flowmetry ¹³. Propylene glycol was applied using three different methods: single open exposures to 1.0 mL propylene glycol on the ventral aspect of the thigh with and without occlusive patches for 5-15 min and repeated open exposure to 1.0 mL propylene glycol on the skin for 12 days. Blood flow at the test site was measured and used as an indication of irritation. propylene glycol, when administered under occlusive patches, caused weak erythema at the test site; the maximum reaction was measured 26 hr after exposure. Single open applications and repeated open exposure to propylene glycol did not cause any irritation reactions in this test ¹³.

A total of 866 patients with various dermatological conditions were patch tested (closed or covered patches) with 100% propylene glycol from April 1951 to April 1952 ¹³. The patches were applied to clinically normal skin, and test sites were examined 48 hr after patch application. Positive reactions were observed in 138 (15.7%) patients. Reactions ranged from simple erythema (+) to erythema with induration and vesiculations (++++). 89 of the 138 patients with positive reactions suffered from dermatitis venenata. A seasonal fluctuation in the incidence of positive reactions was also noted. The incidence was at a minimum when the climate was hot and humid (July, August, and September 1951 in New York City) and significantly greater during the cooler and less humid seasons. Of the 84 patients involved with simultaneous testing with several samples of propylene glycol from different sources, positive reactions were observed in 15. There were no differences in patient responses to different brands of propylene glycol 23 of the 138 patients with positive reactions to 100% propylene glycol were patch tested with aqueous propylene glycol. There were only 5 positive responses to 10% propylene glycol, and the application of 2.5% propylene glycol in water to 3 of the 23 patients resulted in one positive reaction. Additionally, 16 of the patients with positive reactions to 100% propylene glycol were also tested by simple inunction of the test substance. There was no evidence of an inflammatory response to the the rubbing of propylene glycol into the skin either shortly after application or 48 hr later ¹³.

When 1,556 patients were patch tested with 100% propylene glycol, positive reactions were observed in 194 subjects ¹³. 4 patients had “true allergy” and the remainder had irritant reactions. Three groups of 42 patients with positive reactions to 100% propylene glycol were later tested with 3.2, 10, and 32 % propylene glycol, respectively, and the results were as follows: 3.2% propylene glycol (9 positive reactions), 10% propylene glycol (12 positive reactions), and 32% propylene glycol (20 positive reactions) ¹³.

Is propylene glycol safe?

The Scientific Committee on Food evaluated propylene glycol in 1996 and considered this substance as acceptable, noting that propylene glycol was a food additive with an ADI previously established by the Joint Food and Agriculture Organization of the United Nations (FAO)/World Health Organization (WHO) Expert Committee on Food Additives (JECFA) of 0-25 mg/kg body weight per day ¹⁴. In the 2003 Scientific Committee on Food evaluation of acceptable previous cargoes, propylene glycol was not further evaluated as it was already considered acceptable ¹⁵.

In 1993, the Scientific Committee on Food had also evaluated propylene glycol as a food additive, and concluded that “the uncertainty with regard to potential mutagenic effects at the germ cell level, the fact that most studies at the chromosomal level used limited protocols, that there is no in vitro assay for gene mutation in cultured mammalian cells as well as the absence of a carcinogenicity study in a second species leads the Committee to change the established full ADI into a temporary ADI of 25 mg/kg b.w.” ¹⁶. Propylene glycol is currently authorized as a food additive (E 1520).

The Joint Food and Agriculture Organization of the United Nations (FAO)/World Health Organization (WHO) Expert Committee on Food Additives (JECFA) at its 17th meeting in 1973 established an “Estimate of acceptable daily intake for man” of 0 to 25 mg/kg body weight for propylene glycol ¹⁷, following several previous evaluations, and specifications were also prepared ¹⁸. JECFA also evaluated propylene glycol as a flavoring substance in 2001. The evaluation was not finalised as further information was required whether propylene glycol is currently in use as a flavoring agent ¹⁹.

Propylene glycol was evaluated by the Scientific Committee on Food in 1978 as a substance intended for use in the manufacture of regenerated cellulose films ²⁰. The Committee considered the substance toxicologically acceptable for the use intended on the basis of the Joint Food and Agriculture Organization of the United Nations (FAO)/World Health Organization (WHO) Expert Committee on Food Additives (JECFA) acceptable daily intake of 0-25 mg/kg body weight per day. In 1984, propylene glycol was evaluated by the Scientific Committee on Food as a substance intended for use in materials in contact with food and considered acceptable on the basis of the JECFA acceptable daily intake.

The US Agency for Toxic Substances and Disease Registry (ATSDR) has prepared a toxicological profile on propylene glycol ²¹. There was insufficient information to establish an oral reference value.

Absorption, distribution, metabolism and elimination

According to JECFA ¹⁷, propylene glycol is rapidly absorbed after oral administration and appears in the blood-stream. After a dose of 8 mL/kg body weight (equivalent to 8,284 mg/kg body weight) had been administered to dogs approximately 24 hours were required for complete elimination from the blood-stream. Conversion to lactic acid has been shown to be the normal metabolic pathway, via two biochemical pathways ¹⁹. Phosphorylated propylene glycol can be converted to acetolphosphate, lactaldehyde phosphate, lactyl phosphate, and then lactic acid. Non-phosphorylated propylene glycol is successively oxidized to lactaldehyde, methylgloyoxal, and lactic acid ¹⁹. High doses are likely to be excreted largely unchanged in the urine ¹⁹.

Acute toxicity

As reported by JECFA, acute toxicity studies on propylene glycol have been carried out in rats, mice, rabbits and guinea pigs, providing LD50 (lethal dose 50 where 50% of the test subjects die) values of greater than 19,000 mg/kg body weight in all these species ¹⁷.

Subacute, subchronic toxicity studies

Short-term oral toxicity studies of propylene glycol in rats, rabbits and dogs have shown no adverse effects at levels approximating 10 % in the diet ¹⁶. Hematological effects have been seen at high dose levels in some species, notably cats. Cats appear to be uniquely sensitive to hematological effects of ingested propylene glycol, manifest as an increase of Heinz bodies in circulating erythrocytes ²².

Genotoxicity

Propylene glycol has been extensively evaluated in a range of genetic toxicity test systems. The existing studies provide convincing evidence that it is not genotoxic ¹⁹. Chronic toxicity studies and carcinogenicity as cited by JECFA ¹⁹, in a study in which rats were given propylene glycol in the diet at a concentration of 2.45 % or 4.9 % (equivalent to 900 and 1,800 mg/kg body weight per day) for 2 years no treatment-related adverse effects were found on growth, and histological examination revealed no treatment-related effects ²³. As cited by JECFA ¹⁹, in a study in which rats received propylene glycol in the diet at a concentration of 0, 310, 630, 1,300 or 2,500 mg/kg body weight per day for 2 years no treatment-related adverse effects on body weight gain, hematological, urinary, or clinical chemical end-points, or organ weights were found. The NOAEL was 1,300 mg/kg body weight per day ²⁴. No Observed Adverse Effect Level (NOAEL) is the highest dose at which there was not an observed toxic or adverse effect. As cited by JECFA ¹⁹, in a study in which dogs received propylene glycol in the diet at a concentration of 0, 2000, or 5000 mg/kg body weight per day for 2 years increased erythrocyte destruction was found at 5,000 mg/kg body weight per day. No significant treatment-related effects on hematological, clinical chemical, or urinary end-points, or on gross or histological appearance were found ²⁵.

Developmental and reproductive toxicity

In rats and mice, no adverse effects on reproductive performance were observed after oral treatment at doses as high as 10,000 mg/kg body weight per day during gestation of 1 generation or for multiple litters and 2 generations of mice ²⁶ or inhalation exposure to 112 ppm for 18 months ²⁷. Agency for Toxic Substances and Disease Registry (ATSDR) considered that further evaluation of the reproductive toxicity of propylene glycol was not necessary ²². As reported by JECFA, in a study to examine the potential of di(2-ethylhexyl)phthalate and its metabolites to cause testicular damage in rats after oral administration, a control group of six male Sprague Dawley rats were given propylene glycol orally at a dose of 2,000 mg/kg body weight per day for 5 days. Histopathological examination of testis, prostate and liver was done following
sacrifice on day 6. The testes of animals given propylene glycol were reported to contain occasional degenerated cells, most of which were in early meiotic prophase or undergoing meiotic division ²⁸. In another study cited by JECFA ²⁹, in which the effects of 15 chemicals, including propylene glycol, on differential ovarian follicle counts and reproductive performance were compared, propylene glycol was reported to have no effect on reproductive function ³⁰.

How might I be exposed to propylene glycol?

• You can be exposed to propylene glycol by eating food products, using cosmetics, or taking medicine that contains it.
• If you work in an industry that uses propylene glycol or products containing propylene glycol, you could be exposed by breathing or touching these substances.

Propylene glycol has been approved for use at certain levels in food (food additive E 1520), cosmetics, and pharmaceutical products. If you eat food products, use cosmetics, or take medicines that contain it, you will be exposed to propylene glycol, but these amounts are not generally considered harmful. People who work in industries that use propylene glycol may be exposed by touching these products or inhaling mists from spraying them. These exposures tend to be at low levels, however. Propylene glycol is used to make artificial smoke and mists for fire safety training, theatrical performances, and rock concerts. These artificial smoke products may also be used by private citizens. These products are frequently used in enclosed spaces, where exposure may be more intense.

Is there a medical test to determine whether I have been exposed to propylene glycol?

Propylene glycol is generally considered to be a safe chemical, and is not routinely tested for, unless specific exposure, such as to a medicine or cosmetic, can be linked with symptoms.

Since propylene glycol breaks down very quickly in the body, it is very difficult to detect, even though symptoms may be present.

How likely is propylene glycol to cause cancer?

The Department of Health and Human Services, the International Agency for Research on Cancer (IARC), and the EPA have not classified propylene glycol for carcinogenicity. Animal studies have not shown propylene glycol to be carcinogen.

No increase in tumors was observed after twice weekly applications of propylene glycol to the skin of Swiss mice for 120 weeks, at doses up to 2 mg ³¹. Based on this information, its long history of use in consumer products, and structural activity considerations, it is extremely unlikely that exposure to levels of propylene glycol near hazardous waste sites would influence the incidence of cancer in the population living in the vicinity.

Propylene glycol in medicinal products for children

Clinically, the weak evidence and the reliance on predominantly non-comparative data and case reports, severely limit the robustness of any recommendation regarding safe propylene glycol exposure levels in children. A variety of relevant aspects are to be considered when considering a safe dose of propylene glycol. These include patient characteristics such as (developmental) age, weight, health status, concomitant medication, administration route, pattern and duration of use.

In pre-term infants where metabolism and secretion mechanisms are yet immature, accumulation of propylene glycol can occur more easily, thus leading to an increased potential toxicity ³². Propylene glycol is used as excipient for a variety of medicinal products frequently applied in an intensive care unit (ICU) setting, where the patient collective will arguably display a variety of severe health conditions that could accentuate but also mask any adverse effects due to propylene glycol. In this regard, studies considered for this review have been conducted in an ICU setting. Finally, the hardly quantifiable impact of co-medication and its excipients (e.g. mannitol) or sources of propylene glycol other than those investigated could potentially distort the clinical picture and the interpretation of data, accordingly.

The current regulatory recommendations concerning propylene glycol have been made for oral intake via food products (FAO/WHO) or focus on the alcohol effect of propylene glycol only (European Medicines Agency – EMA).

Attempts to define a safety threshold for propylene glycol administration have not been utterly conclusive so far. For children, it was concluded that “a median propylene glycol exposure of 34 mg/kg/24h seems well tolerated and does not affect normal postnatal maturational changes in renal, metabolic and hepatic function” ³³. Determining a safe upper limit of propylene glycol exposure of 34 mg/kg/day might be a possible, rather conservative, approach. Importantly however, study specifics limit the generalizability of the proposed threshold: mainly (pre-term) infants in an ICU setting, short-term exposure (48h), use of historical controls, and assessment of selected endpoints only.

Based on the limited overall quality, non-clinical and clinical data available, the European Medicines Agency Committee considered that ³²:

• No recommendation on a safe dose for propylene glycol can be made based on the current available data;
• Correlations between propylene glycol exposure, patient characteristics and reported adverse events are not established;
• While there is a trend of increasing safety concerns with propylene glycol doses in excess of several hundred mg /kg/day in infants, the limitations of the available data do not allow for a definite conclusion;

The European Medicines Agency Committee therefore concluded that well designed clinical trials investigating the safety of propylene glycol exposure and reflective of common clinical use in terms of duration and quantity are needed to allow a better understanding of propylene glycol safety in children. Additional information from non-clinical juvenile studies assessing the toxicity and toxicokinetics of propylene glycol following repeated administration in the relevant species and age groups may be considered useful to assess the safety risks (particularly central nervous system toxicity) inherent to the formulation.

Propylene glycol uses

Propylene glycol (1,2-dihydroxypropane or 1,2-propanediol or methyl glycol or trimethyl glycol) is a clear liquid used in antifreeze and deicing solutions for cars, airplanes, and boats; to make polyester compounds; and as solvent in the paint and plastics industries. Propylene glycol is also used to create artificial smoke or fog used in fire-fighting training and in theatrical productions.

Uses of propylene glycol, with percent of demand, are:

1. Unsaturated polyester resins, 26 percent;
2. Antifreeze and de-icing fluids, 22 percent;
3. Food, drug and cosmetics uses, 18 percent;
4. Liquid detergents, 11 percent;
5. Functional fluids (inks, specialty anti-freeze, de-icing lubricants), 4 percent;
6. Pet foods, 3 percent;
7. Paints and coatings, 5 percent;
8. Tobacco, 3 percent;
9. Miscellaneous, including plasticizer use, 8 percent.

Propylene glycol is a synthetic liquid substance that absorbs water. Propylene glycol is used by the chemical, food, and pharmaceutical industries as an antifreeze when leakage might lead to contact with food. The Food and Drug Administration (FDA) has classified propylene glycol as an additive that is “generally recognized as safe” for use in food. It is used to absorb extra water and maintain moisture in certain medicines, cosmetics, or food products. It is a solvent for food colors and flavors, and in the paint and plastics industries.

Propylene glycol is used in pharmaceuticals, as a drug vehicle (for example as a U.S. Food and Drug Administration (FDA)-approved solvent for intravenous diazepam) and preservative. Propylene glycol is also used in personal lubricants, in semi-moist pet food and as a humectant for tobacco. Propylene glycol is currently authorized as a food additive (E 1520). In the food industry propylene glycol (E 1520) is used as a solvent for food colors and flavors, as a humectant, preservative and emulsifier ¹. Propylene glycol is used to absorb extra water and maintain moisture in certain medicines, cosmetics, or food products. The U.S. Food and Drug Administration (FDA) has classified propylene glycol as an additive that is “generally recognized as safe” for use in food.

Propylene glycol toxicity

Below are symptoms of propylene glycol antifreeze poisoning in different parts of the body.

Airways and lungs

• Rapid breathing
• No breathing

Bladder and kidneys

• Blood in urine
• No urine output or decreased urine output

Eyes, Ears, Nose, and Throat

• Blurred vision
• Blindness

Heart and blood

• Rapid heartbeat
• Low blood pressure

Muscles and joints

• Leg cramps

Nervous system

• Coma
• Convulsions
• Dizziness
• Fatigue
• Headache
• Slurred speech
• Stupor (lack of alertness)
• Unconsciousness
• Unsteady walk
• Weakness

Skin

• Blue lips and fingernails

Stomach and gastrointestinal tract

• Nausea and vomiting

Home Care

Seek medical help right away. DO NOT make a person throw up unless poison control or a health care provider tells you to.

Use standard first aid and CPR for signs of shock or no heartbeat (cardiac arrest). Call your local poison control center or your local emergency services number for more help. You can call for any reason, 24 hours a day, 7 days a week.

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. 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.

What to Expect at the Emergency Room

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

The healthcare provider will measure and monitor the person’s vital signs, including temperature, pulse, breathing rate, and blood pressure. The person may receive:

• Blood and urine tests
• Breathing support, including oxygen, tube through the mouth into the throat, and breathing machine
• Chest x-ray
• CT scan (advanced brain imaging)
• ECG (electrocardiogram or heart tracing)
• Intravenous fluids (through a vein)
• Medicines to reverse the effects of the poison
• Tube placed down the nose and into the stomach (sometimes)

Dialysis (kidney machine) treatment may be needed during recovery. This need may be permanent if kidney damage is severe.

Propylene glycol side effects

Non-asthmatic volunteers (n=27) were exposed to propylene glycol (propylene glycol) mist over 1 minute, during realistic training conditions ³⁴. Geometric mean concentration of propylene glycol was 309 mg/m³ (range 176-851 mg/³), with the highest concentrations in the afternoon. The medical investigation was performed both before and after the exposure (within 15 minutes). It included an estimate of tear film stability break up time, nasal patency by acoustic rhinometry, dynamic spirometry, and a doctor’s administered questionnaire on symptoms. After exposure to propylene glycol mist for 1 minute tear film stability decreased, ocular and throat symptoms increased, forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) was slightly reduced, and self rated severity of dyspnea was slightly increased. No effect was found for nasal patency, vital capacity (VC), FVC, nasal symptoms, dermal symptoms, smell of solvent, or any systemic symptoms. Those exposed to the higher concentrations in the afternoon had a more pronounced increase of throat symptoms, and a more pronounced decrease of tear film stability. In four subjects who reported development of irritative cough during exposure to propylene glycol, FEV1 was decreased by 5%, but FEV1 was unchanged among those who did not develop a cough. Those who developed a cough also had an increased perception of mild dyspnea. Short exposure to propylene glycol mist from artificial smoke generators in discotheques, theaters, and aviation emergency training may cause acute ocular and upper airway irritation in non-asthmatic subjects. A few may also react with cough and slight airway obstruction.

Propylene glycol is estimated to be one-third as intoxicating as ethanol, with administration of large volumes being associated with adverse effects most commonly on the central nervous system, especially in neonates and children. Other adverse reactions reported, though generally isolated, include: ototoxicity; cardiovascular effects; seizures; and hyperosmolarity and lactic acidosis, both of which occur most frequently in patients with consumption of large quantities of propylene glycol or on administration to neonates, children under 4 years of age, pregnant women, and patients with hepatic or renal failure. Adverse effects may also occur in patients treated with disulfiram or metronidazole ³⁵.

There are numerous reports of propylene glycol-induced serum hyperosmolarity following the topical administration of silver sulfadiazine. Systemic absorption of propylene glycol resulting in hyperosmolarity occurred with topical application of silver sulfadiazine cream in 15 burn patients with burns over more than 35% of their body surface area ³⁶.

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What is calcium gluconate

Calcium gluconate also called D-gluconic acid calcium salt, is the calcium salt of gluconic acid or gluconate salt of calcium. Calcium gluconate is used to prevent or to treat calcium deficiencies. Calcium gluconate exists in both an anhydrous form (empirical formula C₁₂H₂₂O₁₄Ca) and as a monohydrate (empirical formula C₁₂H₂₂O₁₄CaH₂O). Each form is an odorless, white, free-flowing powder that is soluble in water, insoluble in alcohol and most organic solvents, and stable in air. Calcium gluconate has a variety of uses, including its use as a calcium replenisher in hypocalcemic states. Calcium as the gluconate salt helps to maintain calcium balance and prevent bone loss when taken orally. Calcium gluconate use in food in general as a source of calcium and the U.S. Food and Drug Administration (FDA) consider calcium gluconate as Generally Recognized as Safe (GRAS) ¹.

Calcium, the most abundant mineral in the body, is found in some foods, added to others, available as a dietary supplement, and present in some medicines (such as antacids). Calcium is required for vascular contraction and vasodilation, muscle function, nerve transmission, intracellular signaling and hormonal secretion, though less than 1% of total body calcium is needed to support these critical metabolic functions ². Serum calcium is very tightly regulated and does not fluctuate with changes in dietary intakes; the body uses bone tissue as a reservoir for, and source of calcium, to maintain constant concentrations of calcium in blood, muscle, and intercellular fluids ².

The remaining 99% of the body’s calcium supply is stored in the bones and teeth as calcium hydroxyapatite, where it supports their structure and function ². Bone itself undergoes continuous remodeling, with constant resorption and deposition of calcium into new bone. The balance between bone resorption and deposition changes with age. Bone formation exceeds resorption in periods of growth in children and adolescents, whereas in early and middle adulthood both processes are relatively equal. In aging adults, particularly among postmenopausal women, bone breakdown exceeds formation, resulting in bone loss that increases the risk of osteoporosis over time ².

Intestinal calcium absorption occurs through both an active, saturable, transcellular process and a non-saturable, passive process. Active transport is controlled by 1,25-dihydroxyvitamin D [1,25(OH)2D] or calcitriol, and passive transport is paracellular. Calcium absorption varies considerably throughout the lifespan, being higher during periods of rapid growth and lower in old age. Calcium absorption is affected by vitamin D status; it has been shown to be low in patients with vitamin D deficiency, but there is uncertainty about the serum concentration of 25-hydroxyvitamin D [25(OH)D] or calcidiol, that is required for optimal calcium absorption. Unabsorbed dietary calcium is lost in the feces. The main routes of obligatory (endogenous) calcium loss are urine, feces, and skin and sweat (dermal losses).

Table 1: Recommended Dietary Allowances (RDAs) for Calcium

Footnotes:

Recommended Dietary Allowance (RDA): Average daily level of intake sufficient to meet the nutrient requirements of nearly all (97%–98%) healthy individuals; often used to plan nutritionally adequate diets for individuals.

* Adequate Intake (AI)

National Academy of Sciences has recommended 1000 – 1300 mg per day as an adequate intake for adults, with an “upper limit” of 2500 mg per day to limit the potential for adverse effects that can be associated with excessive consumption of calcium, such as kidney stones, hypercalcemia, renal insufficiency, and the possibility of reduced absorption of other minerals.

If the dietary supply of calcium is insufficient to meet physiological requirements, calcium is resorbed from the skeleton to maintain blood concentrations within the range required for normal cellular and tissue functions. This causes a reduction in bone mass, which leads to osteopenia and osteoporosis, and an associated increased risk of fracture.

Excessively high levels of calcium in the blood known as hypercalcemia is defined by serum calcium concentrations > 2.75 mmol/L (11 mg/dL). Although very high calcium intakes have the potential to cause hypercalcemia ⁴, it is unlikely to occur with high intake of calcium from the diet alone but can be caused by high-dose calcium supplements, especially when accompanied by vitamin D supplements, as these can increase calcium absorption and hypercalcemia is most commonly associated with primary hyperparathyroidism or malignancy ².

Excessively high levels of calcium in the blood (hypercalcemia) can cause renal insufficiency, vascular and soft tissue calcification, hypercalciuria (high levels of calcium in the urine) and kidney stones ².

High calcium intake can cause constipation. It might also interfere with the absorption of iron and zinc, though this effect is not well established ². High intake of calcium from supplements, but not foods, has been associated with increased risk of kidney stones ². Some evidence links higher calcium intake with increased risk of prostate cancer, but this effect is not well understood, in part because it is challenging to separate the potential effect of dairy products from that of calcium ². Some studies also link high calcium intake, particularly from supplements, with increased risk of cardiovascular disease ⁴.

Milk, yogurt, and cheese are rich natural sources of calcium and are the major food contributors of this nutrient to people in the United States ². Nondairy sources include vegetables, such as Chinese cabbage, kale, and broccoli. Spinach provides calcium, but its bioavailability is poor. Most grains do not have high amounts of calcium unless they are fortified; however, they contribute calcium to the diet because they contain small amounts of calcium and people consume them frequently. Foods fortified with calcium include many fruit juices and drinks, tofu, and cereals. Selected food sources of calcium are listed in Table 2.

Table 2: Selected Food Sources of Calcium

Footnotes:

* DV = Daily Value. DVs were developed by the U.S. Food and Drug Administration to help consumers compare the nutrient contents among products within the context of a total daily diet. The DV for calcium is 1,000 mg for adults and children aged 4 years and older. Foods providing 20% of more of the DV are considered to be high sources of a nutrient, but foods providing lower percentages of the DV also contribute to a healthful diet. The U.S. Department of Agriculture’s (USDA’s) Nutrient Database site lists the nutrient content of many foods and provides comprehensive list of foods containing calcium arranged by nutrient content (https://ods.od.nih.gov/pubs/usdandb/Calcium-Content.pdf) and by food name (https://ods.od.nih.gov/pubs/usdandb/Calcium-Food.pdf).

** Calcium content varies slightly by fat content; the more fat, the less calcium the food contains.
*** Calcium content is for tofu processed with a calcium salt. Tofu processed with other salts does not provide significant amounts of calcium.

Calcium and Health

Many claims are made about calcium’s potential benefits in health promotion and disease prevention and treatment.

Bone health and osteoporosis

Bones increase in size and mass during periods of growth in childhood and adolescence, reaching peak bone mass around age 30. The greater the peak bone mass, the longer one can delay serious bone loss with increasing age. Everyone should therefore consume adequate amounts of calcium and vitamin D throughout childhood, adolescence, and early adulthood. Osteoporosis, a disorder characterized by porous and fragile bones, is a serious public health problem for more than 10 million U.S. adults, 80% of whom are women. Another 34 million have osteopenia, or low bone mass, which precedes osteoporosis. Osteoporosis is most associated with fractures of the hip, vertebrae, wrist, pelvis, ribs, and other bones ⁵. An estimated 1.5 million fractures occur each year in the United States due to osteoporosis ⁶.

When calcium intake is low or ingested calcium is poorly absorbed, bone breakdown occurs as the body uses its stored calcium to maintain normal biological functions. Bone loss also occurs as part of the normal aging process, particularly in postmenopausal women due to decreased amounts of estrogen. Many factors increase the risk of developing osteoporosis, including being female, thin, inactive, or of advanced age; smoking cigarettes; drinking excessive amounts of alcohol; and having a family history of osteoporosis ⁷.

Various bone mineral density (BMD) tests are available. The T-score from these tests compares an individual’s bone mineral density to an optimal bone mineral density (that of a healthy 30-year old adult). A T-score of -1.0 or above indicates normal bone density, -1.0 to -2.5 indicates low bone mass (osteopenia), and lower than -2.5 indicates osteoporosis ⁸. Although osteoporosis affects individuals of all races, ethnicities, and both genders, women are at highest risk because their skeletons are smaller than those of men and because of the accelerated bone loss that accompanies menopause. Regular exercise and adequate intakes of calcium and vitamin D are critical to the development and maintenance of healthy bones throughout the life cycle. Both weight-bearing exercises (such as walking, running, and activities where one’s feet leave and hit the ground and work against gravity) and resistance exercises (such as calisthenics and that involve weights) support bone health.

Supplementation with calcium plus vitamin D has been shown to be effective in reducing fractures and falls (which can cause fractures) in institutionalized older adults ⁹. However, among community-dwelling older adults over age 50, the benefits of supplementation with these nutrients on fracture resistance are much less clear. A recent systematic review of 26 randomized controlled trials found that calcium supplements, with or without vitamin D, modestly but significantly reduced the risk of total and vertebral fractures, but not fractures of the hip or forearm ¹⁰. But the four trials with the lowest risk of bias, involving a total of 44,505 individuals, showed no effect of supplementation on risk of fracture at any site. A related meta-analysis of calcium intake on bone mineral density found that calcium supplementation produced only a small, initial, and non-progressive increase in bone mineral density that was unlikely to result in a clinically significant reduction in the risk of bone fractures ¹¹. The U.S. Preventive Services Task Force concluded that the current evidence is insufficient to assess the balance of benefits and harms of combined vitamin D and calcium supplementation to prevent bone fractures in premenopausal women or in men ¹². For non-institutionalized postmenopausal women, the U.S. Preventive Services Task Force concluded that while current evidence was insufficient to assess the balance of benefits and harms of combined supplementation with vitamin D (at more than 400 IU/day) and calcium (at more than 1,000 mg/day) to prevent bone fractures, there was clearly no benefit in supplementing with smaller doses of these nutrients for this purpose.

In 1993, the U.S. Food and Drug Administration authorized a health claim related to calcium and osteoporosis for foods and supplements. In January 2010, this health claim was expanded to include vitamin D. Model health claims include the following: “Adequate calcium throughout life, as part of a well-balanced diet, may reduce the risk of osteoporosis” and “Adequate calcium and vitamin D as part of a healthful diet, along with physical activity, may reduce the risk of osteoporosis in later life” ¹³.

Cancer of the colon and rectum

Data from observational and experimental studies on the potential role of calcium in preventing colorectal cancer, though somewhat inconsistent, are highly suggestive of a protective effect ². Several studies have found that higher intakes of calcium from foods (low-fat dairy sources) and/or supplements are associated with a decreased risk of colon cancer ¹⁴. In a follow-up study to the Calcium Polyp Prevention Study, supplementation with calcium carbonate led to reductions in the risk of adenoma (a nonmalignant tumor) in the colon, a precursor to cancer ¹⁵, even as long as 5 years after the subjects stopped taking the supplement ¹⁶. In two large prospective epidemiological trials, men and women who consumed 700–800 mg per day of calcium had a 40%–50% lower risk of developing left-side colon cancer ¹⁷. But other observational studies have found the associations to be inconclusive ¹⁸.

In the Women’s Health Initiative, a clinical trial involving 36,282 postmenopausal women, daily supplementation with 1,000 mg of calcium and 400 International Units (IU) of vitamin D3 for 7 years produced no significant differences in the risk of invasive colorectal cancer compared to placebo ¹⁹. The authors of a Cochrane systematic review concluded that calcium supplementation might moderately help prevent colorectal adenomas, but there is not enough evidence to recommend routine use of calcium supplements to prevent colorectal cancer ²⁰. Given the long latency period for colon cancer development, long-term studies are needed to fully understand whether calcium intakes affect colorectal cancer risk.

Cancer of the prostate

Several epidemiological studies have found an association between high intakes of calcium, dairy foods or both and an increased risk of developing prostate cancer ²¹. However, others have found only a weak relationship, no relationship, or a negative association between calcium intake and prostate cancer risk ²². The authors of a meta-analysis of prospective studies concluded that high intakes of dairy products and calcium might slightly increase prostate cancer risk ²³.

Interpretation of the available evidence is complicated by the difficulty in separating the effects of dairy products from that of calcium. But overall, results from observational studies suggest that total calcium intakes >1,500 mg/day or >2,000 mg/day may be associated with increased prostate cancer risk (particularly advanced and metastatic cancer) compared with lower amounts of calcium (500–1,000 mg/day ²⁴. Additional research is needed to clarify the effects of calcium and/or dairy products on prostate cancer risk and elucidate potential biological mechanisms.

Cardiovascular disease

Calcium has been proposed to help reduce cardiovascular disease risk by decreasing intestinal absorption of lipids, increasing lipid excretion, lowering cholesterol levels in the blood, and promoting calcium influx into cells ². However, data from prospective studies of calcium’s effects on cardiovascular disease risk are inconsistent, and whether dietary calcium has different effects on the cardiovascular system than supplemental calcium is not clear. In the Iowa Women’s Health Study, higher calcium intake from diet and/or supplements was associated with reduced ischemic heart disease mortality in postmenopausal women ²⁵. Conversely, in a cohort of older Swedish women, both total and dietary calcium intakes of 1,400 mg/day and higher were associated with higher rates of death from cardiovascular disease and ischemic heart disease than intakes of 600–1,000 mg/day [85]. Other prospective studies have shown no significant associations between calcium intake and cardiac events or cardiovascular mortality ²⁶. Data for stroke are mixed, with some studies linking higher calcium intakes to lower risk of stroke, and others finding no associations or trends in the opposite direction ²⁶, ⁴.

Several studies have raised concerns that calcium from supplements might increase the risk of cardiovascular disease, including myocardial infarction and coronary heart disease ²⁷. For example, Xiao and colleagues ²⁸ reported that men who took more than 1,000 mg/day supplemental calcium had a 20% higher risk of total cardiovascular disease death than men who did not take supplemental calcium, but supplemental calcium intake in women was unrelated to cardiovascular disease mortality. A reanalysis of data from the Women’s Health Initiative found that calcium supplements (1,000 mg/day) taken with or without vitamin D (400 IU/day) increased the risk of cardiovascular events in women who were not taking calcium supplements when they entered the study ²⁹. While there is no established biological mechanism to support an association between calcium and cardiovascular disease, some scientists hypothesize that excessively high calcium intakes from supplements might override normal homeostatic controls of serum calcium levels and produce a temporary hypercalcemia ²⁹. Hypercalcemia is associated with increased blood coagulation, vascular calcification, and arterial stiffness, all of which raise cardiovascular disease risk ²⁹.

Many scientists question the strength of the available evidence linking supplemental calcium intake with cardiovascular disease risk, noting that no clinical trials were designed primarily to evaluate this potential relationship, so researchers have only considered cardiovascular disease outcomes in secondary analyses of trial data ³⁰. Based on a 2016 systematic review and meta-analysis of 4 randomized trials and 27 observational studies ³¹, the American Society for Preventive Cardiology and the National Osteoporosis Foundation concluded that there is “moderate-quality evidence” that calcium with or without vitamin D (from supplements or foods) “has no relationship (beneficial or harmful) with the risk for cardiovascular and cerebrovascular disease, mortality, or all-cause mortality in generally healthy adults” ³². They added that based on the evidence to date, “calcium intake from food and supplements that does not exceed the [UL] should be considered safe from a cardiovascular standpoint.”

Blood pressure and hypertension

Several clinical trials have demonstrated a relationship between increased calcium intakes and both lower blood pressure and risk of hypertension ³³, although the reductions are inconsistent. In the Women’s Health Study, calcium intake was inversely associated with risk of hypertension in middle-aged and older women ³⁴. However, other studies have found no association between calcium intake and incidence of hypertension ²⁶. The authors of a systematic review of the effects of calcium supplements for hypertension found any link to be weak at best, largely due to the poor quality of most studies and differences in methodologies ³⁵.

Calcium’s effects on blood pressure might depend upon the population being studied. In hypertensive subjects, calcium supplementation appears to lower systolic blood pressure by 2–4 mmHg, whereas in normotensive subjects, calcium appears to have no significant effect on systolic or diastolic blood pressure ²⁶.

Other observational and experimental studies suggest that individuals who eat a vegetarian diet high in minerals (such as calcium, magnesium, and potassium) and fiber and low in fat tend to have lower blood pressure ³⁶. The Dietary Approaches to Stop Hypertension (DASH) study was conducted to test the effects of three different eating patterns on blood pressure: a control “typical” American diet; one high in fruits and vegetables; and a third diet high in fruits, vegetables, and low-fat dairy products. The diet containing dairy products resulted in the greatest decrease in blood pressure ³⁷, although the contribution of calcium to this effect was not evaluated.

Preeclampsia

Preeclampsia is a serious medical condition in which a pregnant woman develops hypertension and proteinuria, usually after 20 weeks’ gestation ³⁸. It is a leading cause of maternal and neonatal morbidity and mortality, affecting about 5–8% of pregnancies in the United States and up to 14% of pregnancies worldwide ³⁸.

Studies suggest that calcium supplementation during pregnancy reduces the risk of preeclampsia, but the benefits may apply only to populations with inadequate calcium intakes ³⁹. For example, in a randomized clinical trial among 524 healthy women in India with mean baseline calcium intakes of only 314 mg/day, daily supplementation with 2,000 mg calcium starting between 12 and 25 weeks’ gestation and continuing until delivery significantly reduced the risk of preeclampsia, as well as preterm birth, compared to placebo ⁴⁰. Conversely, in a randomized trial of 4,589 healthy women in the United States, daily supplementation with 2,000 mg calcium from 13–21 weeks’ gestation through the remainder of pregnancy did not reduce the incidence of preeclampsia, pregnancy-induced hypertension, or other adverse perinatal outcomes compared to placebo [112]. The mean baseline calcium intake among these women, however, was about 1,100 mg/day. The authors of a 2014 Cochrane review of 13 clinical trials concluded that daily supplementation with 1,000 mg or more of calcium during pregnancy reduced the risk of preeclampsia by 55% ⁴¹. The reduction in risk was greatest for women at high risk of preeclampsia and those with low baseline calcium intakes (less than about 900 mg/day). For women with higher dietary calcium intakes, however, the reduction in preeclampsia risk was not statistically significant.

Several professional organizations recommend calcium supplements during pregnancy for women with low calcium intakes to reduce the risk of preeclampsia. For example, the American College of Obstetrics and Gynecology (ACOG) states that daily supplementation with 1,500–2,000 mg calcium may reduce the severity of preeclampsia in pregnant women who have calcium intakes less than 600 mg/day ⁴². Similarly, the World Health Organization (WHO) recommends 1,500–2,000 mg calcium for pregnant women with low dietary calcium intakes, particularly those at higher risk of gestational hypertension ³⁹. The WHO recommends dividing the total daily dose into three doses, preferably to be taken at mealtimes, and taking the supplements from 20 weeks’ gestation until delivery. The WHO also recommends separating calcium and prenatal iron supplements by several hours to minimize the inhibitory effects of calcium on iron absorption. But some researchers argue that this interaction has minimal clinical significance and suggest that providers not counsel patients to separate the supplements to simplify the supplement regimen and facilitate adherence ⁴³. The Canadian Hypertensive Disorders of Pregnancy Working Group ⁴⁴, the International Society for the Study of Hypertension in Pregnancy ⁴⁵, and the Society of Obstetric Medicine of Australia and New Zealand ⁴⁶ have all issued similar recommendations to ACOG and the WHO.

Kidney stones

Kidney stones in the urinary tract are most commonly composed of calcium oxalate. Some, but not all, studies suggest a positive association between supplemental calcium intake and the risk of kidney stones, and these findings were used as the basis for setting the calcium upper limit intake in adults ². In the Women’s Health Initiative, postmenopausal women who consumed 1,000 mg of supplemental calcium and 400 IU of vitamin D per day for 7 years had a 17% higher risk of kidney stones than subjects taking a placebo ⁴⁷. The Nurses’ Health Study also showed a positive association between supplemental calcium intake and kidney stone formation ⁴⁶. High intakes of dietary calcium, on the other hand, do not appear to cause kidney stones and may actually protect against developing them ⁴⁸. For most individuals, other risk factors for kidney stones, such as high intakes of oxalates from food and low intakes of fluid, probably play a bigger role than calcium intake ⁴⁹.

Weight management

Several studies have linked higher calcium intakes to lower body weight or less weight gain over time ⁵⁰. Two explanations have been proposed. First, high calcium intakes might reduce calcium concentrations in fat cells by decreasing the production of parathyroid hormone and the active form of vitamin D. Decreased intracellular calcium concentrations in turn increase fat breakdown and discourage fat accumulation in these cells ⁵¹. Secondly, calcium from food or supplements might bind to small amounts of dietary fat in the digestive tract and prevent its absorption ⁵¹. Dairy products, in particular, might contain additional components that have even greater effects on body weight than their calcium content alone would suggest ⁵².

Despite these findings, the results from clinical trials have been largely negative. For example, dietary supplementation with 1,500 mg/day of calcium (from calcium carbonate) for 2 years was found to have no clinically significant effects on weight in 340 overweight and obese adults as compared with placebo ⁵³. Three reviews of published studies on calcium from supplements or dairy products on weight management came to similar conclusions ⁵⁴. A meta-analysis of 13 randomized controlled trials published in 2006 concluded that neither calcium supplementation nor increased dairy product consumption had a statistically significant effect on weight reduction [136]. More recently, a 2009 evidence report from the Agency for Healthcare Research and Quality concluded that, overall, clinical trial results do not support an effect of calcium supplementation on weight loss ²⁶. Also, a 2012 meta-analysis of 29 randomized controlled trials found no benefit of an increased consumption of dairy products on body weight and fat loss in long-term studies ⁵⁴. Overall, the results from clinical trials do not support a link between higher calcium intakes and lower body weight or weight loss.

Calcium gluconate vs calcium chloride

10% Calcium Chloride injection is indicated for the treatment of hypocalcemia and conditions secondary to hypocalcemia (eg, tetany, seizures, arrhythmias); emergent treatment of severe hypermagnesemia, requiring a prompt increase in plasma calcium levels. Calcium chloride in water dissociates to provide calcium (Ca++) and chloride (Cl−) ions. They are normal constituents of the body fluids and are dependent on various physiological mechanisms for maintenance of balance between intake and output.

Based on the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care ⁵⁵, calcium chloride is an effective and recommended treatment to stabilize the myocardial cell membrane in patients with severe hyperkalemia (K+ >6.5 mEq/L with toxic ECG changes).

Based on the American Heart Association (AHA) Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care ⁵⁵, calcium chloride is effective and recommended for the treatment of malignant arrhythmias (including cardiac arrest) in patients with hypermagnesemia.

Based on the American Heart Association (AHA) Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care ⁵⁵ and the American Academy of Pediatrics Committee on Drugs, calcium chloride, although based on limited evidence, is an effective and recommended treatment in the setting of beta-blocker overdose (refractory to glucagon and high-dose inotropes/vasopressors).

Based on the American Heart Association (AHA) Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care ⁵⁵ and the American Academy of Pediatrics Committee on Drugs, calcium chloride, although based on limited evidence, is an effective and recommended treatment in the setting of calcium channel blocker overdose.

Calcium chloride injection also contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Premature neonates are particularly at risk because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which contain aluminum.

Calcium chloride is contraindications

Calcium chloride is contraindicated for cardiac resuscitation in the presence of ventricular fibrillation or in patients with the risk of existing digitalis toxicity.

Calcium chloride is not recommended in the treatment of asystole and electromechanical dissociation.

Calcium chloride dosage

10% Calcium Chloride injection consists of 1 gram of calcium chloride in a 10 mL vial, or 100 mg/mL. This concentration represents 27 mg or 1.4 mEq of elemental calcium per mL. Thus, one 10 mL syringe provides 270 mg of elemental calcium. The dosage recommendation in various references is given either as amount of calcium chloride or amount of elemental calcium, and often it is not specified. Ionized calcium concentrations should be measured, to assist in dosage adjustment.

10% Calcium Chloride injection is administered only by slow intravenous injection (not to exceed 1 mL/min), preferably in a central or deep vein.

The usual precautions for intravenous therapy should be observed. If time permits, the solution should be warmed to body temperature. The injection should be halted if the patient complains of any discomfort; it may be resumed when symptoms disappear. Following injection, the patient should remain recumbent for a short time.

The usual adult dosage in hypocalcemic disorders ranges from 200 mg to 1 g (2 to 10 mL) at intervals of 1 to 3 days depending on the response of the patient and/or results of serum ionized calcium determinations. Repeated injections may be required because of rapid excretion of calcium.

The pediatric dosage in hypocalcemic disorders ranges from 2.7 to 5.0 mg/kg hydrated Calcium Chloride (or 0.136 to 0.252 mEq elemental calcium per kg, or 0.027 to 0.05 mL of 10% Calcium Chloride injection per kg). No data from clinical trials is available about repeated dosages, though textbook references recommend repeat dosages q 4 to 6 hours.

Calcium gluconate uses

Parenteral calcium salts (ie, chloride, glubionate, gluceptate, and gluconate) are indicated in the treatment of hypocalcemia in conditions that require a rapid increase in serum calcium-ion concentration, such as in neonatal hypocalcemia due to “hungry bones” syndrome (remineralization hypocalcemia) following surgery for hyperparathyroidis, vitamin D deficiency; and alkalosis. Calcium gluconate have been used as adjunctive therapy for insect bites or stings, such as Black Widow Spider bites, and sensitivity reactions, especially when characterized by urticaria; and as an aid in the management of acute symptoms of lead colic, overdose of magnesium or certain heart medicines, and rickets. Calcium gluconate is also used for life support and life-threatening heart conditions. Parenteral calcuim gluconate and calcium gluceptate are also used for the prevention of hypocalcemia during exchange transfusions ⁵⁶.

Calcium gluconate is also used in sewage purification, industrial cleaning, metal surface treatment, textile bleach stabilizing, aluminum processing, and as a chelating agent in cement set retarding, cleaning products, personal care products, pharmaceuticals, coffee processing (anti-caking agent), and food and drugs (sequestering, buffering, and gelling agent). Calcium gluconate also has veterinary use for hypocalcemic conditions.

Calcium gluconate precautions and warnings

Calcium Gluconate Injection Contraindications

Calcium Gluconate Injection is contraindicated in:

• Hypercalcemia
• Neonates (28 days of age or younger) receiving ceftriaxone

Arrhythmias with concomitant cardiac glycoside use

Cardiac arrhythmias may occur if calcium and cardiac glycosides are administered together. Hypercalcemia increases the risk of digoxin toxicity. Administration of Calcium Gluconate Injection should be avoided in patients receiving cardiac glycosides. If concomitant therapy is necessary, Calcium Gluconate Injection should be given slowly in small amounts and with close ECG monitoring.

End-Organ damage due to intravascular ceftriaxone-calcium precipitates

Concomitant use of ceftriaxone and Calcium Gluconate Injection is contraindicated in neonates (28 days of age or younger) due to cases of fatal outcomes in neonates in which a crystalline material was observed in the lungs and kidneys at autopsy after ceftriaxone and calcium were administrated simultaneously through the same intravenous line. Concomitant administration can lead to the formation of ceftriaxone-calcium precipitates that may act as emboli, resulting in vascular spasm or infarction.

In patients older than 28 days of age, ceftriaxone and Calcium Gluconate Injection may be administered sequentially, provided the infusion lines are thoroughly flushed between infusions with a compatible fluid. Do not administer Ceftriaxone simultaneously with Calcium Gluconate Injection via a Y-site in any age group.

Tissue Necrosis and Calcinosis

Intravenous administration of Calcium Gluconate Injection and local trauma may result in calcinosis cutis due to transient increase in local calcium concentration. Calcinosis cutis can occur with or without extravasation of Calcium Gluconate Injection, is characterized by abnormal dermal deposits of calcium salts, and clinically manifests as papules, plaques, or nodules that may be associated with erythema, swelling, or induration. Tissue necrosis, ulceration, and secondary infection are the most serious complications.

A case report on an infant with severe asphyxia and persistent pulmonary hypertension as a newborn. The baby received prolonged intravenous calcium gluconate therapy for hypocalcemia ⁵⁷. At 5 weeks of age, multiple firm, indurated areas (armor-like lesions) were palpable in the subcutaneous tissues of the trunk, arms, legs, and face, particularly in skin folds. Roentgenographic study showed generalized soft-tissue calcifications throughout the body, extremities, and face. Calcinosis cutis occurs through a variety of pathogenetic mechanisms. Case reports on calcinosis cutis in infants are uncommon, and the calcifications are mostly localized. In this patient, they are generalized ⁵⁷.

If extravasation occurs or clinical manifestations of calcinosis cutis are noted, immediately discontinue intravenous administration at that site and treat as needed.

Hypotension, bradycardia, and cardiac arrhythmias with rapid administration

Rapid injection of Calcium Gluconate Injection may cause vasodilation, decreased blood pressure, bradycardia, cardiac arrhythmias, syncope and cardiac arrest. To avoid adverse reactions that may follow rapid intravenous administration, Calcium Gluconate Injection should be diluted with 5% dextrose or normal saline and infused slowly. If rapid intravenous bolus of Calcium Gluconate Injection is required, the rate of intravenous administration should not exceed 200 mg/minute in adults and 100 mg/minute in pediatric patients and ECG monitoring during administration is recommended

Aluminum Toxicity

Calcium Gluconate Injection contains aluminum, up to 400 mcg per liter, that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Premature neonates are particularly at risk because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which contain aluminum. Research indicates that patients with impaired kidney function, including premature neonates, who receive parenteral levels of aluminum at greater than 4 mcg/kg/day to 5 mcg/kg/day accumulate aluminum levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.

Drug Incompatibilities

• Do not mix Calcium Gluconate Injection with ceftriaxone. Concurrent use of intravenous ceftriaxone and Calcium Gluconate Injection can lead to the formation of ceftriaxone-calcium precipitates. Concomitant use of ceftriaxone and intravenous calcium-containing products is contraindicated in neonates (28 days of age or younger). In patients older than 28 days of age, ceftriaxone and calcium-containing products may be administered sequentially, provided the infusion lines are thoroughly flushed between infusions with a compatible fluid. Ceftriaxone must not be administered simultaneously with intravenous calcium-containing solutions via a Y-site in any age group.
• Do not mix Calcium Gluconate Injection with fluids containing bicarbonate or phosphate. Calcium Gluconate Injection is not physically compatible with fluids containing phosphate or bicarbonate. Precipitation may result if mixed.
• Do not mix Calcium Gluconate Injection with minocycline injection. Calcium complexes minocycline rendering it inactive.
• Vitamin D, vitamin A, thiazide diuretics, estrogen, calcipotriene and teriparatide administration may cause hypercalcemia. Monitor plasma calcium concentrations in patients taking these drugs concurrently.

Calcium gluconate in pregnancy

FDA Pregnancy Risk Category C: Adequate, well controlled human studies are lacking, and animal studies have shown risk to the fetus or are lacking as well. There is a chance of fetal harm if the drug is given during pregnancy; but the potential benefits may outweigh the potential risk ⁵⁸.

Risk summary

Limited available data with Calcium Gluconate Injection use in pregnant women are insufficient to inform a drug associated risk of adverse developmental outcomes. There are risks to the mother and the fetus associated with hypocalcemia in pregnancy.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Clinical Considerations

Disease-associated maternal risk: Maternal hypocalcemia can result in an increased rate of spontaneous abortion, premature and dysfunctional labor, and possibly preeclampsia.

Fetal/Neonatal adverse reactions: Infants born to mothers with hypocalcemia can have associated fetal and neonatal hyperparathyroidism, which in turn can cause fetal and neonatal skeletal demineralization, subperiosteal bone resorption, osteitis fibrosa cystica and neonatal seizures. Infants born to mothers with hypocalcemia should be carefully monitored for signs of hypocalcemia or hypercalcemia, including neuromuscular irritability, apnea, cyanosis and cardiac rhythm disorders.

Calcium gluconate in breastfeeding

Risk summary

Calcium is present in human milk as a natural component of human milk. It is not known whether intravenous administration of Calcium Gluconate Injection can alter calcium concentration in human milk. There are no data on the effects of Calcium Gluconate Injection on the breastfed infant, or on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Calcium Gluconate Injection and any potential adverse effects on the breastfed child from Calcium Gluconate Injection or from the underlying maternal condition.

Calcium gluconate for pediatric use

The safety and effectiveness of Calcium Gluconate Injection have been established in pediatric patients for the treatment of acute, symptomatic hypocalcemia.

Pediatric approval for Calcium Gluconate Injection, including doses, is not based on adequate and well-controlled clinical studies. Safety and dosing recommendations in pediatric patients are based on published literature and clinical experience.

Concomitant use of ceftriaxone and Calcium Gluconate Injection is contraindicated in neonates (28 days of age or younger) due to reports of fatal outcomes associated with the presence of lung and kidney ceftriaxone-calcium precipitates. In patients older than 28 days of age, ceftriaxone and Calcium Gluconate Injection may be administered sequentially, provided the infusion lines are thoroughly flushed between infusions with a compatible fluid. Calcium Gluconate Injection contains up to 400 mcg/L aluminum which may be toxic, particularly for premature neonates due to immature renal function. Parenteral administration of aluminum greater than 4 to 5 mcg/kg/day is associated with central nervous system and bone toxicity.

Calcium gluconate for geriatric use

In general dose selection for an elderly patient should start at the lowest dose of the recommended dose range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Calcium gluconate in people with kidney impairment

For patients with renal impairment, initiate Calcium Gluconate Injection at the lowest dose of the recommended dose ranges across all age groups. Monitor serum calcium levels every 4 hours.

Calcium Gluconate in people with liver impairment

Hepatic function does not impact the availability of ionized calcium after calcium gluconate intravenous administration. Dose adjustment in hepatically impaired patients may not be necessary.

Calcium gluconate dose

• Calcium gluconate is contraindicated in patients with hypercalcemia, ventricular fibrillation, and in digitalized patients. Some medicines can affect how calcium gluconate works. Tell your doctor if you are taking digoxin or antibiotics.
  

Calcium gluconate injection contains aluminum which may be toxic. Patients with impaired renal function, undergoing prolonged parenteral administration of calcium gluconate, should be monitored for clinical signs of aluminum toxicity. Clinicians should be aware these patients may achieve a level of aluminum accumulation capable of causing central nervous system and bone toxicity, as well as, tissue loading.

Ask a doctor or pharmacist if it is safe for you to take calcium gluconate if you have ever had:

• kidney disease;
• kidney stones;
• cancer;
• a parathyroid gland disorder; or
• high levels of calcium in your blood.

Ask a doctor before using calcium gluconate if you are pregnant or breast-feeding. Your dose needs may be different during pregnancy or while you are nursing.

Calcium can make it harder for your body to absorb certain medicines. If you take other medications, take them at least 2 hours before or 4 or 6 hours after you take calcium gluconate.

Other drugs may interact with calcium gluconate, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all your current medicines and any medicine you start or stop using.

Calcium Gluconate Injection Dosage and Administration

• Your doctor will prescribe your dose and schedule. This medicine is given through a needle placed in a vein.
• A nurse or other health provider will give you this medicine.

Calcium Gluconate Injection USP is a clear, colorless to slightly yellow, solution available in the following:

• Single dose vial: 1,000 mg per 10 mL (100 mg per mL)
• Single dose vial: 5,000 mg per 50 mL (100 mg per mL)
• Pharmacy bulk package: 10,000 mg per 100 mL (100 mg per mL)

Each mL of Calcium Gluconate Injection USP contains 9.3 mg (0.465 mEq) of elemental calcium.

Important Administration Instructions

• Calcium Gluconate Injection contains 100 mg of calcium gluconate per mL which contains 9.3 mg (i.e., 0.465 mEq) of elemental calcium.
• Dilute Calcium Gluconate Injection prior to use in 5% dextrose or normal saline and assess for potential drug or IV fluid incompatibilities.
• Inspect Calcium Gluconate Injection visually prior to administration.  The solution should appear clear and colorless to slightly yellow. Do not administer if there is particulate matter or discoloration.
• Use the diluted solution immediately after preparation.
• Administer Calcium Gluconate Injection intravenously via a secure intravenous line to avoid calcinosis cutis and tissue necrosis.
• Administer Calcium Gluconate Injection by bolus administration or continuous infusion:

For bolus intravenous administration:

• Dilute the dose of Calcium Gluconate Injection in 5% dextrose or normal saline to a concentration of 10-50 mg/mL prior to administration.  Administer the dose slowly and DO NOT exceed an infusion rate of 200 mg/minute in adults or 100 mg/minute in pediatric patients, including neonates.  Monitor patients, vitals and electrocardiograph (ECG) during administration.

For continuous intravenous infusion:

• Dilute Calcium Gluconate Injection in 5% dextrose or normal saline to a concentration of 5.8-10 mg/mL prior to administration.  Administer at the rate recommended in Table 3 and monitor patients, vitals, calcium and ECG during the infusion.
• Calcium Gluconate Injection is supplied in single-dose vials and pharmacy bulk packages.

Table 3. Dosing Recommendations in mg of Calcium Gluconate for Neonate, Pediatric, and Adult Patients

Serum Calcium Monitoring

• Measure serum calcium every 4 to 6 hours during intermittent infusions with Calcium Gluconate Injection and measure serum calcium every 1 to 4 hours during continuous infusion.

Dosage in Renal Impairment

For patients with renal impairment, initiate Calcium Gluconate Injection at the lowest dose of the recommended dose ranges for all age groups and monitor serum calcium levels every 4 hours.

Adult dose for hypocalcemia

Calcium gluconate intravenous:

• 500 to 2000 mg (5 to 20 mL) IV one time at a rate not to exceed 0.5 to 2 mL/min. The dose may be increased as needed. The usual daily dosage ranges from 1000 to 15,000 mg (10 to 150 mL) in divided doses or as a continuous infusion. Doses may be repeated every 1 to 3 days as needed and tolerated to normalize the serum calcium level.

Calcium gluconate oral:

• 500 to 2000 mg orally 2 to 4 times a day.

Adult dose for hypermagnesemia

1000 to 2000 mg (10 to 20 mL) IV one time at a rate not to exceed 0.5 to 2 mL/min. This dose may be repeated as necessary in severe cases of hypermagnesemia (where discontinuation of exogenous magnesium is inadequate) to temporarily reverse many of the toxic effects of magnesium in the central nervous system.

Adult dose for hyperkalemia

500 to 3000 mg (5 to 30 mL) IV one time at a rate not to exceed 0.5 to 2 mL/min. This dose may be repeated as necessary in cases of extreme hyperkalemia cardiotoxicity when P waves are absent, the QRS complexes are widened, and when continuous ECG monitoring is available. The use of calcium does not reduce the serum potassium level, but counteracts the effects of hyperkalemia on cardiac excitability.

Adult dose for exchange transfusion

300 mg (3 mL) IV one time with each 100 mL of citrated blood at a rate not to exceed 0.5 to 2 mL/min.

Adult dose for osteoporosis

1000 to 1500 mg/day orally in divided doses.

Pediatric dose for hypocalcemia

Neonatal:

Recommended daily allowance (RDA): (Dosage is in terms of elemental calcium):

• Oral: 400 mg/day
• Daily maintenance calcium:
• IV: 3 to 4 mEq/kg/day

Cardiac arrest in the presence of hyperkalemia or hypocalcemia, magnesium toxicity, or calcium antagonist toxicity: Dosage expressed in mg of calcium gluconate:

IV or intraosseous IO:

60 to 100 mg/kg/dose; may repeat in 10 minutes if necessary. If effective, consider IV infusion.

Hypocalcemia (dose depends on clinical condition and serum calcium level):

• IV: (Dose expressed in mg of calcium gluconate): 200 to 800 mg/kg/day as a continuous infusion or in 4 divided doses
• Oral: (Dosage expressed in mg of elemental calcium): 50 to 150 mg/kg/day in 4 to 6 divided doses
• Do not exceed 1 g/day

Dose expressed in mg of calcium gluconate:

• 500 to 1500 mg/kg/day in 4 to 6 divided doses

Hypocalcemia secondary to citrated blood infusion:

• IV: Give 0.45 mEq elemental calcium for each 100 mL citrated blood infused

Tetany: (Dose expressed in mg of calcium gluconate):

• IV: 100 to 200 mg/kg/dose over 5 to 10 minutes; may repeat after 6 hours or follow with an infusion with a maximum dose of 500 mg/kg/day

Dosing: Usual

Adequate intake (AI): (Dosage is in terms of elemental calcium):

Oral:

• 1 to 6 months: 210 mg/day
• 7 to 12 months: 270 mg/day
• 1 to 3 years: 500 mg/day
• 4 to 8 years: 800 mg/day
• 9 to 18 years: 1300 mg/day

Recommended daily allowance (RDA): (Dosage is in terms of elemental calcium):

Oral:

• 1 to 6 months: 400 mg/day
• 6 to 12 months: 600 mg/day
• 1 to 10 years: 800 mg/day
• 11 to 24 years: 1200 mg/day

Hypocalcemia (dose depends on clinical condition and serum calcium level):

Oral: (Dose expressed in mg of elemental calcium):

• Children: 45 to 65 mg/kg/day in 4 divided doses
• Dose expressed in mg of calcium gluconate: Infants and Children: 500 to 725 mg/kg/day in 3 to 4 divided doses

Hypocalcemia (dose depends on clinical condition and serum calcium level):

IV: (Dose expressed in mg of calcium gluconate):

• Infants and Children: 200 to 500 mg/kg/day as a continuous infusion or in 4 divided doses

Cardiac arrest in the presence of hyperkalemia or hypocalcemia, magnesium toxicity, or calcium antagonist toxicity:

IV, IO: (Dosage expressed in mg of calcium gluconate):

• Infants and Children: 60 to 100 mg/kg/dose (maximum: 3 g/dose); may repeat in 10 minutes if necessary; if effective, consider IV infusion.

Hypocalcemia secondary to citrated blood infusion:

• IV: Give 0.45 mEq elemental calcium for each 100 mL citrated blood infused

Tetany:

• IV: (Dose expressed in mg of calcium gluconate): Infants and Children: 100 to 200 mg/kg/dose; over 5 to 10 minutes; may repeat after 6 hours or follow with an infusion with a maximum dose of 500 mg/kg/day.

Daily maintenance calcium:

IV:

• Infants and Children 25 kg and less: 1 to 2 mEq/kg/day
• Children 25 to 45 kg: 0.5 to 1.5 mEq/kg/day
• Children greater than 45 kg: 0.2 to 0.3 mEq/kg/day or 10 to 20 mEq/day

Renal dose adjustments

Patients with renal dysfunction have an increased risk of hypercalcemia. Periodically checking the serum calcium level, especially if signs or symptoms of hypercalcemia are detected, is recommended.

Liver dose adjustments

Data not available

Dialysis

Calcium is removed by hemodialysis. To ensure a positive net calcium flux into the patient during dialysis, a dialysate calcium concentration of 3.0 to 3.5 mEq/L is usually required. Mid-dialysis hypercalcemia is not uncommon when this concentration is used.

Calcium is removed by peritoneal dialysis. The standard peritoneal dialysate contains 3.5 mEq/L of calcium (in 1.5% dextrose) to maintain a positive calcium balance and to prevent calcium losses. When higher concentrations of dextrose are used, the net calcium balance may be negative because of a greater convective removal of calcium during ultrafiltration, which counterbalances the diffusion of calcium from the dialysate to the patient.

Calcium gluconate side effects

Do not use calcium gluconate if you had an allergic reaction to calcium gluconate.

Call your doctor right away if you notice any of these side effects:

• Allergic reaction: Itching or hives, swelling in your face or hands, swelling or tingling in your mouth or throat, chest tightness, trouble breathing
• Feeling of warmth, tingling, or confusion
• Lightheadedness or fainting
• Slow or irregular heartbeat
• Little or no urinating
• Swelling, rapid weight gain
• High levels of calcium in your blood–nausea, vomiting, constipation, increased thirst or urination, muscle weakness, bone pain, confusion, lack of energy, or feeling tired.

If you notice these less serious side effects, talk with your doctor:

• Constipation, loss of appetite, nausea, vomiting, stomach pain
• Dry mouth, thirst, chalky taste in your mouth
• Increase in how much or how often you urinate
• Redness, swelling, irritation, or infection on the skin where the injection is given

Common side effects may include:

• upset stomach, gas; or
• constipation.

If you notice other side effects that you think are caused by calcium gluconate, tell your doctor.

Call your doctor for medical advice about side effects.

Calcium gluconate injection contains aluminum, up to 400 mcg per liter, that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Premature neonates are particularly at risk because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which contain aluminum. Research indicates that patients with impaired kidney function, including premature neonates, who receive parenteral levels of aluminum at greater than 4 mcg/kg/day to 5 mcg/kg/day accumulate aluminum levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.

Psychiatric

Psychiatric side effects have been reported rarely. They have included a single case of mania possibly associated with changes in cerebrospinal fluid and serum calcium following calcium gluconate administration.

A 35-year-old woman with an organic mental disorder associated with hypocalcemia and hypomagnesemia (secondary to short bowel syndrome) became noncompliant with her intramuscular injections of magnesium (Mg). Upon evaluation for progressive confusion and dysphoria, her serum Mg and calcium were found to be 0.3 mEq/L and 7.1 mg/dl, respectively. Intravenous Mg sulfate and calcium gluconate (6,000 mg) were given, with subsequent clearing of her sensorium. Within 12 hours the patient became manic and grandiose; associated Mg and calcium levels were 1.4 mEq/L and 8.2 mg/L, respectively. The symptoms of mania resolved without psychotropic medications and with discontinuation of calcium gluconate. This case report and other limited data suggest that mania can be precipitated by the rapid intravenous administration of calcium gluconate, particularly in persons who are predisposed to affective disorders.

Genitourinary

Genitourinary side effects have rarely included calcium nephrolithiasis. This effect has been reported more commonly with coadministration of loop diuretics.

Cardiovascular

A 51-year-old man with no history of cardiac disease was referred for calcium gluconate/pentagastrin testing for early detection of medullary thyroid carcinoma. He became pulseless and hypotensive within 15 seconds after receiving calcium gluconate 2 mg/kg and pentagastrin 0.5 mcg/kg. Atrial fibrillation and a ventricular rate response of 110/min ensued after a precordial thump. A complete evaluation for the cause of his atrial fibrillation was negative.

Cardiovascular side effects have included peripheral vasodilation, hypotension, syncope, vasospastic angina, serious cardiac arrhythmias, AV dissociation, and shock. Extreme caution is advised when parenteral calcium is given to a patient who has received digitalis since calcium may unmask digitalis intoxication. A single case of new atrial fibrillation has been reported.

Renal

Renal side effects have included significant increases in renal plasma flow, glomerular filtration rate, diuresis, natriuresis, and prostaglandin E2 and F1-alpha levels. However, the renal side effects do not appear to be clinically significant.

The renal effects of calcium gluconate include significant increases in renal plasma flow, glomerular filtration rate, diuresis, natriuresis, and prostaglandin E2 and F1-alpha levels. Data indicate that calcium gluconate infusions at subpressor doses have renal vasodilating, diuretic and natriuretic properties that appear to be facilitated by an increase in the renal production of prostaglandins.

Nervous system

Nervous system side effects have included tingling sensations, a “chalky” taste and a sense of oppression or “heat wave.”

Calcium gluconate antidote

There is no specific antidote for calcium salts poisoning. Calcium is rapidly cleared by hemodialysis. However, dialysis is rarely indicated unless the patient has renal failure.

A serum calcium concentration exceeding 2.6 mmol per liter (10.5 mg per 100 mL) is considered a hypercalcemic condition. Withholding additional administration of calcium and any other medications that may cause hypercalcemia usually resolves mild hypercalcemia in asymptomatic patients, when patient renal function is adequate ⁵⁹.

Most cases of hypercalcemia can be treated with saline hydration. Gastrointestinal or skin irritation is usually self-limited and does not require specific treatment beyond decontamination. There is no role for bisphosphonates or calcitonin in the treatment of hypercalcemia due to calcium salt exposure.

Management of severe toxicity

Most cases of hypercalcemia will resolve with hydration in patients with normal renal function. Hemodialysis can be used if emergent clearance is required of if the patient’s renal function is impaired. There is no role for bisphosphonates or calcitonin in the treatment of hypercalcemia due to calcium salt exposure.

When serum calcium concentration are greater than 2.9 mmol per liter (12 mg per 100 mL), immediate measures may be required with possible use of the following: Hydrating with intravenous 0.9% sodium chloride injection ⁵⁹. Forcing diuresis with furosemide or ethacrynic acid may be used to rapidly increase calcium and sodium excretion when saline overload occurs. Monitoring of potassium and magnesium serum concentrations and starting replacement early to prevent complications of therapy. ECG monitoring and the possible use of beta-adrenergic blocking agents to protect the heart against serious arrhythmias. Possibly including hemodialysis, calcitonin, and adrenocorticoids in the treatment. Determining serum calcium concentration at frequent intervals to guide therapy adjustments ⁵⁹.

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What is magnesium oxide

Magnesium is an abundant mineral in the body and magnesium is naturally present in many foods, added to other food products, available as a dietary supplement, and present in some medicines (such as antacids and laxatives). Magnesium oxide may be used for different reasons with some people using it as an antacid to relieve heartburn, sour stomach, or acid indigestion. Magnesium oxide also may be used as a laxative for short-term, rapid emptying of the bowel (before surgery, for example). Magnesium oxide should not be used repeatedly. Magnesium oxide also is used as a dietary supplement when the amount of magnesium in the diet is not enough. Magnesium oxide is available without a prescription.

Magnesium is a cofactor in more than 300 enzyme systems that regulate diverse biochemical reactions in the body, including protein synthesis, muscle and nerve function, blood glucose control, and blood pressure regulation ¹. Magnesium is required for energy production, oxidative phosphorylation, and glycolysis. Magnesium contributes to the structural development of bone and is required for the synthesis of DNA, RNA, and the antioxidant glutathione. Magnesium also plays a role in the active transport of calcium and potassium ions across cell membranes, a process that is important to nerve impulse conduction, muscle contraction, and normal heart rhythm ¹.

The total magnesium content of the human body is reported to be ~20 mmol/kg of fat-free tissue. In other words, total magnesium in the average 70 kg adult with 20% (w/w) fat is ~1000 to 1120 mmol or approximately 25 g magnesium, with 50% to 60% present in the bones and most of the rest in soft tissues ². About 99% of total body magnesium is located in bone, muscles and non-muscular soft tissue. Less than 1% of total magnesium is in blood serum, and these levels are kept under tight control. Magnesium excretion is mainly regulated by the kidney. About 100 mmol/L magnesium is filtered daily ³. Normal serum magnesium concentrations range between 0.75 and 0.95 millimoles (mmol)/L ⁴. Hypomagnesemia is defined as a serum magnesium level less than 0.75 mmol/L ⁵. Magnesium homeostasis is largely controlled by the kidney, which typically excretes about 120 mg magnesium into the urine each day ⁶. Urinary excretion is reduced when magnesium status is low ⁷.

Magnesium is widely distributed in plant and animal foods and in beverages (see Table 2). Green leafy vegetables, such as spinach, legumes, nuts, seeds, and whole grains, are good sources ¹. Water accounts for ~10% of daily magnesium intake ⁸, chlorophyll (and thus green vegetables such as spinach) is the major source of magnesium. Nuts, seeds and unprocessed cereals are also rich in magnesium. Legumes, fruit, fish and meat have an intermediate magnesium concentration. Some types of food processing, such as refining grains in ways that remove the nutrient-rich germ and bran, lower magnesium content substantially. Low magnesium concentrations are found in dairy products, except milk ⁹. In general, foods containing dietary fiber provide magnesium. Magnesium is also added to some breakfast cereals and other fortified foods. Some types of food processing, such as refining grains in ways that remove the nutrient-rich germ and bran, lower magnesium content substantially ⁷. Selected food sources of magnesium are listed in Table 2.

Tap, mineral, and bottled waters can also be sources of magnesium, but the amount of magnesium in water varies by source and brand (ranging from 1 mg/L to more than 120 mg/L) ¹⁰.

Approximately 30% to 40% of the dietary magnesium consumed is typically absorbed by the body ⁶.

Assessing magnesium status is difficult because most magnesium is inside cells or in bone ¹. The most commonly used and readily available method for assessing magnesium status is measurement of serum magnesium concentration, even though serum levels have little correlation with total body magnesium levels or concentrations in specific tissues ⁵. Other methods for assessing magnesium status include measuring magnesium concentrations in erythrocytes, saliva, and urine; measuring ionized magnesium concentrations in blood, plasma, or serum; and conducting a magnesium-loading (or “tolerance”) test. No single method is considered satisfactory ¹¹. Some experts ² but not others ¹ consider the tolerance test (in which urinary magnesium is measured after parenteral infusion of a dose of magnesium) to be the best method to assess magnesium status in adults. To comprehensively evaluate magnesium status, both laboratory tests and a clinical assessment might be required ⁵.

Table 1: Recommended Dietary Allowances (RDAs) for Magnesium

Footnote: *Adequate Intake (AI) = Intake at this level is assumed to ensure nutritional adequacy; established when evidence is insufficient to develop an Recommended Dietary Allowance (average daily level of intake sufficient to meet the nutrient requirements of nearly all (97%–98%) healthy individuals; often used to plan nutritionally adequate diets for individuals.).

Table 2: Selected food sources of magnesium

Footnotes: *DV = Daily Value. DVs were developed by the U.S. Food and Drug Administration (FDA) to help consumers compare the nutrient contents of products within the context of a total diet. The DV for magnesium is 400 mg for adults and children aged 4 and older. However, the FDA does not require food labels to list magnesium content unless a food has been fortified with this nutrient. Foods providing 20% or more of the DV are considered to be high sources of a nutrient.

Magnesium oxide supplement

Magnesium oxide supplement is available in a variety of forms, including magnesium oxide, magnesium citrate, and magnesium chloride ¹. The Supplement Facts panel on a dietary supplement label declares the amount of elemental magnesium in the product, not the weight of the entire magnesium-containing compound.

Absorption of magnesium from different kinds of magnesium supplements varies. Forms of magnesium that dissolve well in liquid are more completely absorbed in the gut than less soluble forms ⁶. Small studies have found that magnesium in the aspartate, citrate, lactate, and chloride forms is absorbed more completely and is more bioavailable than magnesium oxide and magnesium sulfate ¹³. One study found that very high doses of zinc from supplements (142 mg/day) can interfere with magnesium absorption and disrupt the magnesium balance in the body ¹⁴.

Magnesium oxide vs Magnesium citrate

Small studies have found that magnesium in the aspartate, citrate, lactate, and chloride forms is absorbed more completely and is more bioavailable than magnesium oxide and magnesium sulfate ¹³. Just like  magnesium oxide, magnesium citrate is also used to treats constipation, and empties the bowel before surgery or other medical procedures. Magnesium citrate is a low-volume osmotic laxative that is effective in small-volume bowel preparation. The 8-oz (237 mL) magnesium citrate solution consisted of magnesium carbonate (31%), citric acid (65%), and potassium citrate (3%), yielding 18.0 g of magnesium citrate (e.g., LoSo Prep; E-Z-Em).

Magnesium oxide uses

What is magnesium oxide used for

• Magnesium oxide is used to treat or prevent low magnesium levels.
• Magnesium oxide is used to treat heartburn and upset stomach.
• Magnesium oxide is used as laxative to relieve occasional constipation.

You should not use magnesium oxide if you are allergic to it.

Ask a doctor or pharmacist if it is safe for you to use magnesium oxide if you have other medical conditions, especially:

• kidney disease;
• heart disease;
• nausea, vomiting;
• a blockage in your intestines;
• low levels of calcium in your blood; or
• a sudden change in bowel habits for 2 weeks or longer.

It is not known whether magnesium oxide will harm an unborn baby. Ask a doctor before using this medicine if you are pregnant.

It is not known whether magnesium oxide passes into breast milk or if it could affect a nursing baby. Ask a doctor before using this medicine if you are breast-feeding.

Do not give this medicine to a child without medical advice.

Magnesium oxide should not be given to a child younger than 6 years old.

Magnesium benefits

Magnesium for ADHD

Attention deficit hyperactivity disorder (ADHD) is the most common psychiatric disorder in clinical samples of children and adolescents referring to child psychiatric clinics. Dietary factors can play a significant role in the etiology of attention deficit hyperactivity disorder (ADHD). Several studies reported that the magnesium level in children with ADHD is decreased in serum and erythrocytes and the Mg2+-ATPase activity is reduced ¹⁵. Treatment of magnesium deficiency can help in revealing hyperactivity in children [126,127,128,129,130]. Current treatments for ADHD, such as atomoxetine and stimulants, act through adrenergic and dopaminergic receptors. Magnesium interacts with the ADHD-related neurotransmitters (e.g., dopamine, serotonin) and inhibits N-methyl-d-aspartate (NMDA)-induced norepinephrine release. The results of several studies are promising that magnesium supplementation (e.g. 6 mg/kg BW per day) may be helpful in the treatment of ADHD ¹⁶. Unfortunately, until now there is still no double-blind randomized controlled clinical trial investigating the efficacy and safety of magnesium for treating ADHD.

Magnesium for osteoporosis

Magnesium is involved in bone formation and influences the activities of osteoblasts and osteoclasts ¹⁷. Magnesium also affects the concentrations of both parathyroid hormone and the active form of vitamin D, which are major regulators of bone homeostasis. Several population-based studies have found positive associations between magnesium intake and bone mineral density in both men and women ¹⁸. Other research has found that women with osteoporosis have lower serum magnesium levels than women with osteopenia and those who do not have osteoporosis or osteopenia ¹⁹. These and other findings indicate that magnesium deficiency might be a risk factor for osteoporosis ¹⁷.

Although limited in number, studies suggest that increasing magnesium intakes from food or supplements might increase bone mineral density in postmenopausal and elderly women ⁷. For example, one short-term study found that 290 mg/day elemental magnesium (as magnesium citrate) for 30 days in 20 postmenopausal women with osteoporosis suppressed bone turnover compared with placebo, suggesting that bone loss decreased ²⁰.

Diets that provide recommended levels of magnesium enhance bone health, but further research is needed to elucidate the role of magnesium in the prevention and management of osteoporosis.

Magnesium for migraines and headaches

Magnesium deficiency is related to factors that promote headaches, including neurotransmitter release and vasoconstriction ²¹. People who experience migraine headaches have lower levels of serum and tissue magnesium than those who do not.

However, research on the use of magnesium supplements to prevent or reduce symptoms of migraine headaches is limited. Three of four small, short-term, placebo-controlled trials found modest reductions in the frequency of migraines in patients given up to 600 mg/day magnesium ²¹. The authors of a review on migraine prophylaxis ²² suggested that taking 300 mg magnesium twice a day, either alone or in combination with medication, can prevent migraines.

In their evidence-based guideline update, the American Academy of Neurology and the American Headache Society concluded that magnesium therapy is “probably effective” for migraine prevention ²³. Because the typical dose of magnesium used for migraine prevention exceeds the Tolerable Upper Intake Level (maximum daily intake unlikely to cause adverse health effects), this treatment should be used only under the direction and supervision of a healthcare provider.

Magnesium for hypertension and cardiovascular disease

Hypertension is a major risk factor for heart disease and stroke. Studies to date, however, have found that magnesium supplementation lowers blood pressure, at best, to only a small extent. A meta-analysis of 12 clinical trials found that magnesium supplementation for 8–26 weeks in 545 hypertensive participants resulted in only a small reduction (2.2 mmHg) in diastolic blood pressure ²⁴. The dose of magnesium ranged from approximately 243 to 973 mg/day. The authors of another meta-analysis of 22 studies with 1,173 normotensive and hypertensive adults concluded that magnesium supplementation for 3–24 weeks decreased systolic blood pressure by 3–4 mmHg and diastolic blood pressure by 2–3 mmHg ²⁵. The effects were somewhat larger when supplemental magnesium intakes of the participants in the nine crossover-design trials exceeded 370 mg/day. A diet containing more magnesium because of added fruits and vegetables, more low-fat or non-fat dairy products, and less fat overall was shown to lower systolic and diastolic blood pressure by an average of 5.5 and 3.0 mmHg, respectively ²⁶. However, this Dietary Approaches to Stop Hypertension (DASH) diet also increases intakes of other nutrients, such as potassium and calcium, that are associated with reductions in blood pressure, so any independent contribution of magnesium cannot be determined.

Several prospective studies have examined associations between magnesium intakes and heart disease. The Atherosclerosis Risk in Communities study assessed heart disease risk factors and levels of serum magnesium in a cohort of 14,232 white and African-American men and women aged 45 to 64 years at baseline ²⁷. Over an average of 12 years of follow-up, individuals in the highest quartile of the normal physiologic range of serum magnesium (at least 0.88 mmol/L) had a 38% reduced risk of sudden cardiac death compared with individuals in the lowest quartile (0.75 mmol/L or less). However, dietary magnesium intakes had no association with risk of sudden cardiac death. Another prospective study tracked 88,375 female nurses in the United States to determine whether serum magnesium levels measured early in the study and magnesium intakes from food and supplements assessed every 2 to 4 years were associated with sudden cardiac death over 26 years of follow-up ²⁸. Women in the highest compared with the lowest quartile of ingested and plasma magnesium concentrations had a 34% and 77% lower risk of sudden cardiac death, respectively. Another prospective population study of 7,664 adults aged 20 to 75 years in the Netherlands who did not have cardiovascular disease found that low urinary magnesium excretion levels (a marker for low dietary magnesium intake) were associated with a higher risk of ischemic heart disease over a median follow-up period of 10.5 years. Plasma magnesium concentrations were not associated with risk of ischemic heart disease ²⁹. A systematic review and meta-analysis of prospective studies found that higher serum levels of magnesium were significantly associated with a lower risk of cardiovascular disease, and higher dietary magnesium intakes (up to approximately 250 mg/day) were associated with a significantly lower risk of ischemic heart disease caused by a reduced blood supply to the heart muscle ³⁰.

Higher magnesium intakes might reduce the risk of stroke. In a meta-analysis of 7 prospective trials with a total of 241,378 participants, an additional 100 mg/day magnesium in the diet was associated with an 8% decreased risk of total stroke, especially ischemic rather than hemorrhagic stroke ³¹. One limitation of such observational studies, however, is the possibility of confounding with other nutrients or dietary components that could also affect the risk of stroke.

A large, well-designed clinical trial is needed to better understand the contributions of magnesium from food and dietary supplements to heart health and the primary prevention of cardiovascular disease ³².

Magnesium for type 2 diabetes

Diets with higher amounts of magnesium are associated with a significantly lower risk of diabetes, possibly because of the important role of magnesium in glucose metabolism ³³. Hypomagnesemia might worsen insulin resistance, a condition that often precedes diabetes, or it might be a consequence of insulin resistance ³⁴. Diabetes leads to increased urinary losses of magnesium, and the subsequent magnesium inadequacy might impair insulin secretion and action, thereby worsening diabetes control ¹.

Most investigations of magnesium intake and risk of type 2 diabetes have been prospective cohort studies. A meta-analysis of 7 of these studies, which included 286,668 patients and 10,912 cases of diabetes over 6 to 17 years of follow-up, found that a 100 mg/day increase in total magnesium intake decreased the risk of diabetes by a statistically significant 15% ³⁵. Another meta-analysis of 8 prospective cohort studies that followed 271,869 men and women over 4 to 18 years found a significant inverse association between magnesium intake from food and risk of type 2 diabetes; the relative risk reduction was 23% when the highest to lowest intakes were compared ³⁶.

A 2011 meta-analysis of prospective cohort studies of the association between magnesium intake and risk of type 2 diabetes included 13 studies with a total of 536,318 participants and 24,516 cases of diabetes ³⁷. The mean length of follow-up ranged from 4 to 20 years. Investigators found an inverse association between magnesium intake and risk of type 2 diabetes in a dose-responsive fashion, but this association achieved statistical significance only in overweight (body mass index [BMI] 25 or higher) but not normal-weight individuals (BMI less than 25). Again, a limitation of these observational studies is the possibility of confounding with other dietary components or lifestyle or environmental variables that are correlated with magnesium intake.

Only a few small, short-term clinical trials have examined the potential effects of supplemental magnesium on control of type 2 diabetes and the results are conflicting ³⁸. For example, 128 patients with poorly controlled diabetes in a Brazilian clinical trial received a placebo or a supplement containing either 500 mg/day or 1,000 mg/day magnesium oxide (providing 300 or 600 mg elemental magnesium, respectively) ³⁹. After 30 days of supplementation, plasma, cellular, and urine magnesium levels increased in participants receiving the larger dose of the supplement, and their glycemic control improved. In another small trial in Mexico, participants with type 2 diabetes and hypomagnesemia who received a liquid supplement of magnesium chloride (providing 300 mg/day elemental magnesium) for 16 weeks showed significant reductions in fasting glucose and glycosylated hemoglobin concentrations compared with participants receiving a placebo, and their serum magnesium levels became normal ⁴⁰. In contrast, neither a supplement of magnesium aspartate (providing 369 mg/day elemental magnesium) nor a placebo taken for 3 months had any effect on glycemic control in 50 patients with type 2 diabetes who were taking insulin ⁴¹.

The American Diabetes Association states that there is insufficient evidence to support the routine use of magnesium to improve glycemic control in people with diabetes ³⁸. It further notes that there is no clear scientific evidence that vitamin and mineral supplementation benefits people with diabetes who do not have underlying nutritional deficiencies.

Magnesium oxide dosage

Use magnesium oxide exactly as directed on the label, or as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended.

Take magnesium oxide with a full glass of water.

When using magnesium oxide as a laxative, it may be best to take your dose at bedtime.

Magnesium oxide may be taken with food if it upsets your stomach.

Call your doctor if your symptoms do not improve after 7 days of treatment, or if symptoms get worse.

Store at room temperature away from moisture and heat.

Magnesium oxide can make it harder for your body to absorb other medicines you take by mouth. Avoid taking other medicines within 2 hours before or 2 hours after you take magnesium oxide. You may need to wait 4 hours to take your other medicines after taking magnesium oxide. Ask your doctor how to best schedule your medications.

Adult dose for dyspepsia

Uses: Acid indigestion, upset stomach

• 400 mg tablets: 1 tablet orally twice a day
• Maximum dose: 2 tablets per 24 hour period
• Duration of therapy: Up to 2 weeks

Comments:

• May have a laxative effect.

Adult dose for constipation

• Oral: Caplets (500 mg): 2 to 4 caplets orally daily with a full 8 ounce glass of liquid.
• Caplets may be taken all at bedtime or separately throughout the day.

Adult dose for vitamin/mineral supplementation during pregnancy/lactation

Recommended dietary intake:

• Women 19 to 30 years: 508 mg magnesium oxide (310 mg elemental magnesium) orally daily
• Women 31 years and older: 525 mg magnesium oxide (320 mg elemental magnesium) orally daily
• Men 19 to 30 years: 656 mg magnesium oxide (400 mg elemental magnesium) orally daily
• Men 31 years and older: 689 mg magnesium oxide (420 mg elemental) orally daily

Maximum magnesium oxide supplement dose: 574 mg magnesium oxide (350 mg elemental magnesium)

Pediatric dose for constipation

500 mg caplets:

• 12 years and older: 2 to 4 caplets orally daily, as a single dose or divided dose
• Maximum dose: 4 caplets per day
• Duration of therapy: 7 days or less

Comments:

-Bedtime is the preferred administration time for a single dose.
-Take with a full glass of water.

Pediatric dose for vitamin/mineral supplementation

Recommended dietary intakes:

• 14 to 18 years:
• Males: 672 mg magnesium oxide (410 mg elemental magnesium) per day
• Females: 590 mg magnesium oxide (360 mg elemental magnesium) per day

Maximum magnesium oxide supplement dose (both sexes): 574 mg magnesium oxide (350 mg elemental magnesium) per day

9 to 13 years: 394 mg magnesium oxide (240 mg elemental) per day

• Maximum magnesium oxide supplement dose: 574 mg magnesium oxide (350 mg elemental magnesium) per day

4 to 8 years: 213 mg magnesium oxide (130 mg elemental magnesium) per day

• Maximum magnesium oxide supplement dose: 180 mg magnesium oxide (110 mg elemental magnesium) per day

1 to 3 years: 131 mg magnesium oxide (80 mg elemental) per day

• Maximum magnesium oxide supplement dose: 107 mg magnesium oxide (65 mg elemental magnesium) per day

7 to 12 months: 123 mg magnesium oxide (75 mg elemental magnesium) per day

Birth to 6 months: 49 mg magnesium oxide (30 mg elemental magnesium) per day

Magnesium oxide side effects

Too much magnesium from food does not pose a health risk in healthy individuals because the kidneys eliminate excess amounts in the urine ⁴². However, high doses of magnesium from dietary supplements or medications often result in diarrhea that can be accompanied by nausea and abdominal cramping ⁷. Forms of magnesium most commonly reported to cause diarrhea include magnesium carbonate, chloride, gluconate, and oxide ⁴³. The diarrhea and laxative effects of magnesium salts are due to the osmotic activity of unabsorbed salts in the intestine and colon and the stimulation of gastric motility.

Very large doses of magnesium-containing laxatives and antacids (typically providing more than 5,000 mg/day magnesium) have been associated with magnesium toxicity ⁴⁴, including fatal hypermagnesemia in a 28-month-old boy ⁴⁵ and an elderly man ⁴⁶. Symptoms of magnesium toxicity, which usually develop after serum concentrations exceed 1.74–2.61 mmol/L, can include hypotension, nausea, vomiting, facial flushing, retention of urine, ileus, depression, and lethargy before progressing to muscle weakness, difficulty breathing, extreme hypotension, irregular heartbeat, and cardiac arrest ⁴⁷. The risk of magnesium toxicity increases with impaired renal function or kidney failure because the ability to remove excess magnesium is reduced or lost ⁴⁷.

Magnesium oxide may cause side effects. To avoid unpleasant taste, take the tablet with citrus fruit juice or carbonated citrus drink. Tell your doctor if either of these symptoms are severe or do not go away:

• cramping
• diarrhea

If you experience any of the following symptoms, call your doctor immediately:

• rash or hives
• itching
• dizziness or lightheadedness
• mood or mental changes
• unusual tiredness
• weakness
• nausea
• vomiting

Interactions with Medications

Several types of medications have the potential to interact with magnesium supplements or affect magnesium status. A few examples are provided below. People taking these and other medications on a regular basis should discuss their magnesium intakes with their healthcare providers.

Bisphosphonates

Magnesium-rich supplements or medications can decrease the absorption of oral bisphosphonates, such as alendronate (Fosamax®), used to treat osteoporosis ⁴⁸. Use of magnesium-rich supplements or medications and oral bisphosphonates should be separated by at least 2 hours.

Antibiotics

Magnesium can form insoluble complexes with tetracyclines, such as demeclocycline (Declomycin®) and doxycycline (Vibramycin®), as well as quinolone antibiotics, such as ciprofloxacin (Cipro®) and levofloxacin (Levaquin®). These antibiotics should be taken at least 2 hours before or 4–6 hours after a magnesium-containing supplement ⁴⁹.

Diuretics

Chronic treatment with loop diuretics, such as furosemide (Lasix®) and bumetanide (Bumex®), and thiazide diuretics, such as hydrochlorothiazide (Aquazide H®) and ethacrynic acid (Edecrin®), can increase the loss of magnesium in urine and lead to magnesium depletion ⁵⁰. In contrast, potassium-sparing diuretics, such as amiloride (Midamor®) and spironolactone (Aldactone®), reduce magnesium excretion ⁵⁰.

Proton pump inhibitors

Prescription proton pump inhibitor (PPI) drugs, such as esomeprazole magnesium (Nexium®) and lansoprazole (Prevacid®), when taken for prolonged periods (typically more than a year) can cause hypomagnesemia. In cases that FDA reviewed, magnesium supplements often raised the low serum magnesium levels caused by PPIs. However, in 25% of the cases, supplements did not raise magnesium levels and the patients had to discontinue the PPI. FDA advises healthcare professionals to consider measuring patients’ serum magnesium levels prior to initiating long-term PPI treatment and to check magnesium levels in these patients periodically.

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What is potassium chloride

Potassium is a mineral that is found in many foods and potassium is also an electrolyte that is vital to cell metabolism and is needed for several functions of your body, especially the beating of your heart. Potassium chloride is a mineral used to replenish potassium within your body. Potassium chloride (KCl) is used to prevent or to treat low blood levels of potassium (hypokalemia). Potassium levels can be low as a result of a disease or from taking certain medicines e.g. when thiazide diuretics or corticosteroids, or after a prolonged illness with diarrhea or vomiting or diets poor in potassium. Potassium chloride supplement may irritate your stomach and other side effects generally only occur with higher dosages. Acute oral potassium chloride toxicity is rare because large single doses induce nausea and vomiting, and because potassium chloride is rapidly excreted in the absence of any pre-existing kidney damage. Symptoms of acute poisoning after ingestion of potassium chloride are usually mild. Potassium chloride oral overdoses manifests in neuromuscular signs in the form of hyperkalemia, general muscular weakness and ascending paralysis, listlessness, vertigo, mental confusion, hypotension, acute cardiovascular changes with ECG abnormalities, and heart block. Gastrointestinal symptoms manifest as nausea, vomiting, paralytic ileus, and local mucosal necrosis, which may lead to perforation. There are several case reports of accidental IV (intravenous) or intraperitoneal administrations of potassium chloride. Symptoms of acute poisoning after parenteral administration are similar to symptoms after oral exposure but can appear more promptly and be more severe. A case report of a subcutaneous injection of potassium chloride reports chemical burns and skin lesions.

Potassium chloride (KCl) consists of odorless white crystals or crystalline powder or white granular powder or colorless crystals, with a strong saline taste.

Potassium chloride (KCl) is also used in the treatment of cumulative digitalis poisoning; and as a component of lethal injections. Potassium chloride is also used in the fertilizer industry as potash and in buffer solutions for photography. Potassium chloride has been identified as being used in hydraulic fracturing as a clay stabilizer.

You get most of the potassium you need from the foods that you eat, the usual dietary intake of potassium is 50 to 100 millimole (mmol) per day and most people have an adequate intake of potassium. Your body uses what it requires and your kidneys eliminate the rest in the urine. Your body tries to keep the blood potassium level within a very narrow range. Levels are mainly controlled by aldosterone, a hormone produced by the adrenal glands in the kidneys.

Potassium is absorbed via passive diffusion, primarily in the small intestine ¹. About 90% of ingested potassium is absorbed and used to maintain its normal intracellular and extracellular concentrations ². Potassium is excreted primarily in the urine, some is excreted in the stool, and a very small amount is lost in sweat. The kidneys control potassium excretion in response to changes in dietary intakes, and potassium excretion increases rapidly in healthy people after potassium consumption, unless body stores are depleted ³. The kidneys can adapt to variable potassium intakes in healthy individuals, but a minimum of 5 mmol (about 195 mg) potassium is excreted daily in urine ⁴. This, combined with other obligatory losses, suggests that potassium balance cannot be achieved with intakes less than about 400–800 mg/day.

The total amount of potassium in the adult body is about 45 millimole (mmol)/kg body weight (about 140 g for a 175 pound adult; 1 mmol = 1 milliequivalent [mEq] or 39.1 mg potassium) ⁴. Most potassium resides intracellularly, and a small amount is in extracellular fluid ¹. The intracellular concentration of potassium is about 30 times higher than the extracellular concentration, and this difference forms a transmembrane electrochemical gradient that is maintained via the sodium-potassium (Na+/K+) ATPase transporter ¹. In addition to maintaining cellular tonicity, this gradient is required for proper nerve transmission, muscle contraction, and kidney function.

The intracellular concentration of potassium is approximately 150 to 160 millimole (mmol) per liter. The normal adult plasma concentration is 3.6 to 5.0 mmol per liter. An active ion transport system maintains this gradient across the plasma membrane.

Because the blood concentration of potassium is so small, minor changes can have significant consequences. If potassium levels are too low or too high, there can be serious health consequences; a person may be at risk for developing shock, respiratory failure, or heart rhythm disturbances. An abnormal potassium level can alter the function of the nerves and muscles; for example, the heart muscle may lose its ability to contract.

Potassium helps transport nutrients into cells and removes waste products out of cells. Potassium is also important in muscle function, helping to transmit messages between nerves and muscles.

Potassium, along with other electrolytes such as sodium, chloride, and bicarbonate (total CO2), helps regulate the amount of fluid in your body and maintains a stable acid-base balance. Potassium is present in all body fluids, but most potassium is found within the cells. Only a small amount is present in fluids outside the cells and in the liquid part of the blood (called serum or plasma).

A potassium test is used to detect abnormal concentrations of potassium, including high potassium (hyperkalemia) and low potassium (hypokalemia). It is often used as part of an electrolyte panel or basic metabolic panel for a routine physical.

Potassium urine concentrations must be evaluated in association with blood levels. The body normally eliminates excess potassium, so the concentration in the urine may be elevated because it is elevated in the blood. It may also be elevated in the urine when the body is losing too much potassium; in this case, the blood level would be normal to low. If blood potassium levels are low due to insufficient intake, then urine concentrations will also be low.

• Decreased urinary potassium levels may be due to certain drugs such as NSAIDs, beta blockers, and lithium or due to the adrenal glands producing too little of the hormone aldosterone.
• Increased urinary potassium levels may be due to kidney disease, eating disorders such as anorexia, or muscle damage.

High potassium levels (hyperkalemia) may be seen in conditions such as:

• Kidney disease
• Addison disease
• Injury to tissue
• Infection
• Diabetes
• Dehydration
• Consuming too much potassium (for example, fruits are particularly high in potassium, so excessive intake of fruits or juices may contribute to high potassium)
• In patients on intravenous (IV) fluids, excessive IV potassium
• Certain drugs can also cause high potassium in a small percent of people; among them are non-steroidal anti-inflammatory drugs (NSAIDs), ACE inhibitors, beta blockers (such as propanolol and atenolol), angiotensin-converting enzyme inhibitors (such as captopril, enalapril, and lisinopril), and potassium-sparing diuretics (such as triamterene, amiloride, and spironolactone).

Low potassium levels (hypokalemia) may be seen in conditions such as:

• Diarrhea and vomiting
• Conn syndrome (hyperaldosteronism)
• A complication of acetaminophen overdose
• In diabetes, the potassium level may fall after someone takes insulin, particularly if the person has not managed his or her diabetes well.
• Low potassium is commonly due to “water pills” (potassium-wasting diuretics); if someone is taking these, their healthcare provider will check their potassium level regularly.
• Additionally, certain drugs such as corticosteroids, beta-adrenergic agonists such as isoproterenol, alpha-adrenergic antagonists such as clonidine, antibiotics such as gentamicin and carbenicillin, and the antifungal agent amphotericin B can cause loss of potassium.

The usual dietary intake of potassium by the average adult is 50 mEq to 100 mEq per day. Potassium depletion sufficient to cause hypokalemia usually requires the loss of 200 mEq or more mEq of potassium from the total body store.

Potassium depletion will occur whenever the rate of potassium loss through renal excretion and/or loss from the gastrointestinal tract exceeds the rate of potassium intake. Such depletion usually develops as a consequence of therapy with diuretics, primary or secondary hyperaldosteronism, diabetic ketoacidosis, or inadequate replacement of potassium in patients on prolonged parenteral nutrition. Depletion can develop rapidly with severe diarrhea, especially if associated with vomiting. Potassium depletion due to these causes is usually accompanied by a concomitant loss of chloride and is manifested by hypokalemia and metabolic alkalosis.

Potassium depletion may produce weakness, fatigue, disturbances or cardiac rhythm (primarily ectopic beats), prominent U-waves in the electrocardiogram, and in advanced cases, flaccid paralysis and/or impaired ability to concentrate urine.

If potassium depletion associated with metabolic alkalosis cannot be managed by correcting the fundamental cause of the deficiency, e.g., where the patient requires long-term diuretic therapy, supplemental potassium in the form of high-potassium food or Potassium Chloride may be able to restore normal potassium levels.

In rare circumstances (e.g., patients with renal tubular acidosis) potassium depletion may be associated with metabolic acidosis and hyperchloremia. In such patients potassium replacement should be accomplished with potassium salts other than the chloride, such as potassium bicarbonate, potassium citrate, potassium acetate, or potassium gluconate.

Treatment for low potassium may include the use of potassium chloride supplements and increasing the amount of potassium-rich foods in the diet, such as bananas, beef or spinach. Treatment for high potassium may include the use of diuretics, kidney dialysis, or insulin injections.

Potassium chloride medication

You should NOT use potassium chloride if you are allergic to it, or if:

• you have high levels of potassium in your blood (hyperkalemia); or
• you take a “potassium-sparing” diuretic (water pill) such as amiloride, spironolactone, or triamterene.

To make sure potassium chloride medicine is safe for you, tell your doctor if you have ever had:

• kidney disease;
• cirrhosis or other liver disease;
• an adrenal gland disorder;
• a large tissue injury such as a severe burn;
• severe dehydration;
• diabetes;
• heart disease or high blood pressure;
• stomach or intestinal bleeding;
• a blockage in your stomach or intestines; or
• chronic diarrhea (such as ulcerative colitis, Crohn’s disease).

It is not known whether potassium chloride medicine will harm an unborn baby. Your dose needs may be different during pregnancy. Tell your doctor if you are pregnant or breast-feeding.

Do not give this medicine to a child without medical advice.

How should I take potassium chloride?

Take potassium chloride exactly as prescribed by your doctor. Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose.

Read and carefully follow any Instructions for Use provided with your medicine. Ask your doctor or pharmacist if you do not understand these instructions.

Take potassium chloride with a full glass of water. Take the medicine with food or just after a meal.

Measure liquid medicine with the dosing syringe provided, or with a special dose-measuring spoon or medicine cup. If you do not have a dose-measuring device, ask your pharmacist for one.

Do not crush, chew, or suck on a tablet or capsule. Sucking on the pill could irritate your mouth or throat.

Call your doctor if you have trouble swallowing a potassium chloride capsule or tablet. You may be able to dissolve the tablet in water, or mix the medicine from a capsule with soft food. Carefully follow your doctor’s instructions.

Mix the powder form of this medicine with at least 4 ounces (one-half cup) of cold water or fruit juice before taking. Drink the mixture slowly, over 5 to 10 minutes in all. To make sure you get the entire dose, add a little more water to the same glass, swirl gently and drink right away.

To be sure this medicine is helping your condition, you may need frequent blood tests. You may not notice any change in your symptoms, but your blood work will help your doctor determine how long to treat you with potassium chloride. Your heart function may need to be checked using an electrocardiograph or ECG (sometimes called an EKG). Even if you have no symptoms, tests can help your doctor determine if this medicine is effective.

Your treatment may include a special diet. Follow the diet plan created for you by your doctor or nutrition counselor. Get familiar with the list of foods you should eat or avoid to help control your condition.

Potassium-rich foods include: squash, baked potatoes (skin on), spinach, lentils, broccoli, Brussels sprouts, zucchini, kidney or navy beans, raisins, watermelon, orange juice, bananas, cantaloupe, and low-fat milk or yogurt. Consume only the daily amounts recommended by your doctor or nutrition counselor.

Some tablets are made with a shell that is not absorbed or melted in the body. Part of this shell may appear in your stool. This is normal and will not make the medicine less effective.

Store at room temperature away from moisture and heat. Keep the medication in a closed container.

Potassium in food

What is potassium chloride used for?

Potassium chloride (KCl) is used as prevention and treatment of potassium deficiency, e.g. when thiazide diuretics or corticosteroids are used in case of excessive vomiting or diarrhea, or diets poor in potassium; in the treatment of cumulative digitalis poisoning; and as a component of lethal injections. Potassium chloride (KCl) is also used in the fertilizer industry as potash and in buffer solutions for photography. Potassium chloride has been identified as being used in hydraulic fracturing as a clay stabilizer.

Potassium chloride tablets replace potassium in your body. Potassium chloride tablets are used to prevent and treat low blood levels of potassium (this is also called hypokalemia). Potassium levels can become low if you have had a prolonged bout of either diarrhea or vomiting, have been taking diuretics (water pills), or with some diseases.

• For the treatment of patients with hypokalemia with or without metabolic alkalosis, in digitalis intoxication, and in patients with hypokalemic familial periodic paralysis. If hypokalemia is the result of diuretic therapy, consideration should be given to the use of a lower dose of diuretic, which may be sufficient without leading to hypokalemia.
• For the prevention of hypokalemia in patients who would be at particular risk if hypokalemia were to develop, e.g., digitalized patients or patients with significant cardiac arrhythmias.

The use of potassium salts in patients receiving diuretics for uncomplicated essential hypertension is often unnecessary when such patients have a normal dietary pattern and when low doses of the diuretic are used. Serum potassium should be checked periodically, however, and if hypokalemia occurs, dietary supplementation with potassium-containing foods may be adequate to control milder cases. In more severe cases, and if dose adjustment of the diuretic is ineffective or unwarranted, supplementation with potassium salts may be indicated.

Potassium chloride tablets should be taken with meals and with a glass of water or other liquid. This product should not be taken on an empty stomach because of its potential for gastric irritation.

Patients having difficulty swallowing whole tablets may try one of the following alternate methods of administration:

1. Break the tablet in half, and take each half separately with a glass of water.
2. Prepare an aqueous (water) suspension as follows:
   1. Place the whole tablet(s) in approximately 1/2 glass of water (4 fluid ounces).
   2. Allow approximately 2 minutes for the tablet(s) to disintegrate.
   3. Stir for about half a minute after the tablet(s) has disintegrated.
   4. Swirl the suspension and consume the entire contents of the glass immediately by drinking or by the use of a straw.
   5. Add another 1 fluid ounce of water, swirl, and consume immediately.
   6. Then, add an additional 1 fluid ounce of water, swirl, and consume immediately.

Aqueous suspension of potassium chloride that is not taken immediately should be discarded. The use of other liquids for suspending potassium chloride tablets,  is not recommended.

Potassium chloride dosage

You should NOT use potassium chloride if you have high levels of potassium in your blood (hyperkalemia), or if you also take a “potassium-sparing” diuretic.

• Contraindicated in renal failure. May cause potassium intoxication and life-threatening hyperkalemia in patients with renal insufficiency.
• Never give injectable potassium chloride undiluted.
• Do not infuse rapidly.
• Administer oral potassium with or after food to minimize gastric irritation.
• Take oral potassium with meals and a full glass of water or other liquids.
• TTake this medication as prescribed.
• Check with your physician at once if tarry stools or other signs of gastrointestinal bleeding are noticed.

To be sure potassium chloride is helping your condition, your blood may need to be tested often. Your heart rate may also be checked using an electrocardiograph or ECG (sometimes called an EKG) to measure electrical activity of the heart. This test will help your doctor determine how long to treat you with potassium. Do not miss any scheduled appointments.

Serious side effects of potassium include uneven heartbeat, muscle weakness or limp feeling, severe stomach pain, and numbness or tingling in your hands, feet, or mouth.

Do not stop taking this medicine without first talking to your doctor. If you stop taking this medicine suddenly, your condition may become worse.

Do not crush, chew, break, or suck on an extended-release tablet or capsule. Swallow the pill whole. Breaking or crushing the pill may cause too much of the drug to be released at one time. Sucking on a tablet can irritate your mouth or throat. Take potassium chloride with food or just after a meal.

Usual Adult Dose for Hypokalemia (low blood potassium)

Oral:

• 40 to 100 mEq per day, orally, in 2 to 5 divided doses
• Maximum single dose: 20 mEq per dose
• Maximum daily dose: 200 mEq

Parenteral (must be diluted prior to administration):

Dose and rate of administration are dependent on patient condition

• If serum potassium is 2.5 mEq/L or higher, rate should not exceed 10 mEq/hour, and manufacturers recommend that concentration not exceed 40 mEq/L

Maximum daily dose: 200 mEq

• If treatment is urgent (serum potassium less than 2 mEq/L and electrocardiographic changes and/or muscle paralysis), infuse cautiously at up to 40 mEq/hour with continuous cardiac monitoring

Maximum daily dose: 400 mEq

-In critical situations, may administer in saline rather than dextrose (dextrose may lower serum potassium)

Comments:

• Never give injectable potassium chloride undiluted.
• The usual adult dietary intake is 50 to 100 mEq potassium per day.
• Potassium depletion sufficient to cause hypokalemia usually requires the loss of 200 mEq or more of the total body stores of potassium.

Usual Adult Dose for Prevention of Hypokalemia (low blood potassium)

Oral:

Typical dose: 20 mEq, orally, daily

• Individualize dose based on serum potassium levels
• Divide dose if more than 20 mEq per day is used

Parenteral (must be diluted prior to administration):

Dose and rate of administration are dependent on patient condition

• If serum potassium is 2.5 mEq/L or higher, rate should not exceed 10 mEq/hour, and manufacturers recommend that concentration not exceed 40 mEq/L

Maximum daily dose: 200 mEq

Comments:

• Never give injectable potassium chloride undiluted
• The usual adult dietary intake is 50 to 100 mEq potassium per day.

Usual Pediatric Dose for Hypokalemia (low blood potassium)

Birth to 16 years:

Oral solution:

• Initial dose: 2 to 4 mEq/kg/day, orally, in divided doses
• Limit to 1 mEq/kg or 40 mEq per dose, whichever is lower

Maximum daily dose: 100 mEq

Parenteral (must be diluted prior to administration):

Dose and rate of administration are dependent on patient condition

• If serum potassium is 2.5 mEq/L or higher, rate should not exceed 10 mEq/hour, and manufacturers recommend that concentration not exceed 40 mEq/L

Maximum daily dose: 200 mEq

• If treatment is urgent (serum potassium less than 2 mEq/L and electrocardiographic changes and/or muscle paralysis), infuse cautiously at up to 40 mEq/hour with continuous cardiac monitoring

Maximum daily dose: 400 mEq

• In critical situations, may administer in saline rather than dextrose (dextrose may lower serum potassium)

Comments:

• Never give injectable potassium chloride undiluted

Usual Pediatric Dose for Prevention of Hypokalemia (low blood potassium)

Birth to 16 years:

Oral solution:

• Initial dose: 1 mEq/kg/day, orally
• Maximum daily dose: 3 mEq/kg/day

Intravenous (must be diluted prior to administration):

Dose and rate of administration are dependent on patient condition

• If serum potassium is 2.5 mEq/L or higher, rate should not exceed 10 mEq/hour, and manufacturers recommend that concentration not exceed 40 mEq/L

Maximum daily dose: 200 mEq

Comments:

• Never give injectable potassium chloride undiluted

Potassium chloride side effects

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• Diarrhea, stomach pain, muscle weakness, numbness or tingling in the hands, feet, or mouth, uneven heartbeat. Side effects are more likely if high dosages of potassium chloride are being taken.
• May not be suitable for some people including those with kidney failure, Addison’s disease, severe burns, or severe wounds.
• Should also not be taken by a person who is dehydrated or has high levels of potassium in their blood.
• May interact with several other medicines including digoxin, quinidine, ACE inhibitors, and several diuretics.
• Signs of a high potassium level (hyperkalemia): cardiac arrhythmias, cardiac arrest, slow heartbeat and heart block; listlessness, mental confusion; feeling weak (muscle weakness), lightheaded, or dizzy; feel like passing out; numbness or tingling (paresthesia) of the extremities; or shortness of breath; flaccid paralysis, cold skin, grey pallor, peripheral vascular collapse, fall in blood pressure and paralysis. Electrocardiogram (ECG) abnormalities include disappearance of the P-wave, widening and slurring of QRS complex, changes of the S-T segment, tall peaked T-waves. At extremely high concentrations (8 to 11 mmol/L) may cause death from cardiac depression, arrhythmias, or arrest.
• Chest pain or pressure.
• Signs of bowel problems like black, tarry, or bloody stools; fever; mucus in the stools; throwing up blood or throw up that looks like coffee grounds; very bad belly pain; or very bad hard stools (constipation) or loose stools (diarrhea).
• Very upset stomach or throwing up.
• Gastrointestinal ulceration may be caused by enteric-coated potassium chloride tablets.
• Delayed intestinal transit
• Nausea, vomiting, flatulence, abdominal pain/discomfort, diarrhea, obstruction, bleeding, ulceration, perforation, gastrointestinal hemorrhage, local irritation of the mucosa
• Swelling of belly.
• Local pain and inflammation may develop from intravenous or subcutaneous administration.
• Skin rash, urticaria and pruritus
• Neuromuscular symptoms may occur.

Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Potassium chloride overdose

Cardiac and related effects are the most important risks of potassium chloride overdose.

The administration of oral potassium salts to persons with normal excretory mechanisms for potassium rarely causes serious hyperkalemia. However, if excretory mechanisms are impaired or if potassium is administered too rapidly intravenously, potentially fatal hyperkalemia can result.

It is important to recognize that hyperkalemia is usually asymptomatic and may be manifested only by an increased serum potassium concentration (6.5 mEq to 8 mEq/L) and characteristic electrocardiographic changes (peaking of T-waves, loss of P-waves, depression of S-T segment, and prolongation of the QT-interval).

Late manifestations include muscle paralysis and cardiovascular collapse from cardiac arrest (9 mEq to 12 mEq/L).

Treatment measures for hyperkalemia include the following:

Basic life support measures are essential in severely poisoned patients:

• establish IV-line, obtain blood sample for electrolytes, BUN, glucose and arterial blood gas analysis;
• continuous ECG monitoring should be started for arrhythmias and electrolyte changes;
• cardiac dysrhythmias should be controlled with an appropriate drug regimen;
• emesis or gastric lavage should be performed as soon as possible.

Reduce the plasma concentration of potassium by infusion of sodium bicarbonate, glucose plus insulin, or dialysis. These regimes shift potassium into cells; they do not increase its elimination. Infusion of calcium salts may be necessary to correct ECG changes. Use of exchange resins, hemodialysis, or peritoneal dialysis.

In treating hyperkalemia, it should be noted that in patients who have been stabilized on digitalis, too rapid a lowering of the serum potassium concentration can produce digitalis toxicity.

The extended-release potassium chloride feature means that absorption and toxic effects may be delayed for hours. Consider standard measures to remove any unabsorbed drug.

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3. Stone MS, Martyn L, Weaver CM. Potassium intake, bioavailability, hypertension, and glucose control. Nutrients 2016;8.[↩]
4. Preuss HG, Clouatre DL. Sodium, chloride, and potassium. In: Erdman JW, Macdonald IA, Zeisel SH, eds. Present Knowledge in Nutrition. 10th ed. Washington, DC: Wiley-Blackwell; 2012:475-92.[↩][↩]