Duloxetine

Duloxetine also called duloxetine hydrochloride is a selective serotonin and norepinephrine reuptake inhibitor (SNRI) that is currently used to treat major depression, generalized anxiety disorder (GAD), fibromyalgia, pain and tingling caused by diabetic neuropathy (nerve damage that can develop in people who have diabetes) in adults and excessive worry and tension that disrupts daily life and lasts for 6 months or longer) in adults and children 7 years of age and older ¹. Duloxetine is also used to treat ongoing (chronic) bone or muscle pain such as lower back pain or osteoarthritis (joint pain or stiffness that may worsen over time) in adults. Duloxetine is also sometimes used to treat chemotherapy-induced peripheral neuropathy and stress urinary incontinence (leakage of urine during physical activity such as coughing, sneezing, laughing, and exercise) in women.

Duloxetine was approved for use in the United States in 2004 and is available in delayed-release (releases the medication in the intestine to prevent break-down of the medication by stomach acids) capsules of 20, 30 and 60 mg in multiple generic forms and under the brand name Cymbalta. The recommended dosage in adults is 40 to 60 mg daily, which can be raised to 120 mg daily based upon tolerance and clinical effects. Swallow the delayed-release capsules whole; do not split, chew, or crush them. Do not open the delayed-release capsules and mix the contents with liquids or sprinkle the contents on food. Your doctor may start you on a low dose of medication and increase your dose after one week.

When duloxetine is used to treat depression, it is usually taken once or twice a day with or without food. When duloxetine is used to treat generalized anxiety disorder (GAD), the pain of diabetic neuropathy, fibromyalgia, or ongoing bone or muscle pain, it is usually taken once a day with or without food. Take duloxetine at around the same time(s) every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take duloxetine exactly as directed. Do not take more or less of it, take it more often, or take it for a longer time than prescribed by your doctor.

Duloxetine may help control your symptoms but will not cure your condition. It may take 1 to 4 weeks or longer before you feel the full benefit of duloxetine. Continue to take duloxetine even if you feel well. Do not stop taking duloxetine without talking to your doctor. Your doctor will probably decrease your dose gradually. If you suddenly stop taking duloxetine, you may experience withdrawal symptoms such as nausea; vomiting; diarrhea; anxiety; dizziness; tiredness; headache; pain, burning, numbness, or tingling in the hands or feet; irritability; difficulty falling asleep or staying asleep; sweating; and nightmares. Tell your doctor if you experience any of these symptoms when your dose of duloxetine is decreased.

Common side effects of duloxetine are drowsiness, dyspepsia, nausea, headache, increased sweating, increased appetite, weight gain, urinary retention and sexual dysfunction. Rare, but potentially severe adverse events include suicidal thoughts and behaviors, mania, postural hypotension, syncope and falls, serotonin syndrome, seizures, severe skin rash, hypersensitivity reactions, hyponatremia, and glaucoma.

How does duloxetine work?

Duloxetine is a selective serotonin and norepinephrine reuptake inhibitor (SNRI) that works by increasing the amounts of serotonin and norepinephrine (noradrenaline), natural substances in your brain that help maintain mental balance and stop the movement of pain signals in your brain, by blocking the reuptake of serotonin and norepinephrine (noradrenaline) in your brain nerves cells synaptic clefts ¹, ², ³. Duloxetine works to treat various neuropathic and chronic pain states by increasing the activity of noradrenergic and serotonergic neurons in the descending spinal pathway on the dorsal horn. These descending neurons inhibit the activity of dorsal horn neurons, suppressing excessive input from reaching the brain. The hypothesis is that a deficiency in these inhibitory signals results in excess input reaching the brain, which gets perceived as pain ⁴.

In addition to its general SNRI properties, duloxetine also increases dopamine levels, specifically in the prefrontal cortex ¹. Due to the involvement of the prefrontal cortex in depression, the actions of duloxetine in this region also contribute to its efficacy in the treatment of depression. However, the mechanism of action does not involve the inhibition of dopamine transporters ⁵. The mechanism of action behind the increase in dopamine levels involves the inhibition of norepinephrine (noradrenaline) transporters. The norepinephrine (noradrenaline) transporters have a significant affinity for dopamine, resulting in the transporter’s ability to act on both dopamine and norepinephrine (noradrenaline). Therefore, inhibition of norepinephrine (noradrenaline) transporters can lead to an increase in dopamine. This increase in dopamine specifically occurs in the prefrontal cortex, where dopamine transporters are scarce, and reuptake relies more heavily on norepinephrine transporters ⁶.

Of note, duloxetine has no significant activity for muscarinic, cholinergic, alpha2-adrenergic, or H1 histaminergic receptors ¹.

Duloxetine special precautions

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For duloxetine, the following should be considered ⁷:

• tell your doctor and pharmacist if you are allergic to duloxetine, any other medications, or any of the ingredients in duloxetine delayed-release capsules. Ask your doctor or pharmacist for a list of the ingredients.
• tell your doctor or pharmacist if you are taking the following medications or have stopped taking them within the past two weeks: thioridazine or a monoamine oxidase (MAO) inhibitor, such as isocarboxazid (Marplan), linezolid (Zyvox); methylene blue; phenelzine (Nardil), selegiline (Emsam, Zelapar), and tranylcypromine (Parnate).
• your doctor will probably tell you not to take duloxetine. If you stop taking duloxetine, you should wait at least 5 days before you start to take an MAO inhibitor.
• some medications should not be taken with duloxetine. Other medications may cause dosing changes or extra monitoring when taken with duloxetine. Make sure you have discussed any medications you are currently taking or plan to take before starting duloxetine with your doctor and pharmacist. Before starting, stopping, or changing any medications while taking duloxetine, please get the advice of your doctor or pharmacist.
• the following nonprescription or herbal products may interact with duloxetine: St. John’s wort; tryptophan; proton pump inhibitors such as lansoprazole (Prevacid), omeprazole (Prilosec), pantoprazole (Protonix), and rabeprazole (Aciphex); cimetidine (Tagamet); aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (Advil, Motrin) and naproxen (Aleve, Naprosyn). Be sure to let your doctor and pharmacist know that you are taking these medications before you start taking duloxetine. Do not start any of these medications while taking duloxetine without discussing with your doctor.
• tell your doctor if you drink or have ever drunk large amounts of alcohol or if you use or have ever used street drugs or have ever overused prescription medications. Also tell your doctor if you have a low level of sodium in your blood; glaucoma (increased pressure in the eye that may cause loss of sight); if you have recently had a heart attack; or if you have or have ever had high blood pressure; seizures; coronary artery disease (blockage or narrowing of the blood vessels that lead to the heart); bleeding problems; any type of stomach problem such as slow stomach emptying; or heart, liver, or kidney disease. If you have diabetes, be sure to talk to your doctor about how serious your condition is so your doctor can decide if duloxetine is right for you.
• tell your doctor if you are pregnant, especially if you are in the last few months of your pregnancy, or if you plan to become pregnant or are breast-feeding. If you become pregnant while taking duloxetine, call your doctor. Duloxetine may cause problems in newborns following delivery if it is taken during the last months of pregnancy.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking duloxetine.
• you should know that duloxetine may make you drowsy, dizzy, or may affect your judgment, thinking or coordination. Do not drive a car or operate machinery until you know how this medication affects you.
• ask your doctor about the safe use of alcoholic beverages while you are taking duloxetine. Alcohol can increase the risk of serious side effects from duloxetine.
• you should know that duloxetine may cause dizziness, lightheadedness, and fainting when you get up too quickly from a lying position. This is more common when you first start taking duloxetine or with an increase in dose. To avoid this problem, get out of bed slowly, resting your feet on the floor for a few minutes before standing up.
• you should know that duloxetine may cause high blood pressure. You should have your blood pressure checked before starting treatment and regularly while you are taking this medication.
• you should know that duloxetine may cause angle-closure glaucoma (a condition where the fluid is suddenly blocked and unable to flow out of the eye causing a quick, severe increase in eye pressure which may lead to a loss of vision). Talk to your doctor about having an eye examination before you start taking this medication. If you have nausea, eye pain, changes in vision, such as seeing colored rings around lights, and swelling or redness in or around the eye, call your doctor or get emergency medical treatment right away.

Allergies

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

Children

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of duloxetine in children to treat anxiety in children 7 years of age and older. However, safety and efficacy have not been established in children younger than 7 years of age.

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of duloxetine in children to treat fibromyalgia in children 13 years of age and older. However, safety and efficacy have not been established in children younger than 13 years of age.

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

Elderly

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of duloxetine in the elderly. However, elderly patients may be more sensitive to the effects of duloxetine than younger adults, and are more likely to have hyponatremia (low sodium in the blood) and increase risk for falls, which may require caution in patients receiving duloxetine ⁸.

Pregnant women

Duloxetine is U.S. Food and Drug Administration (FDA) pregnancy category C, which means risk to fetal development cannot be ruled out. In animal reproductive studies, duloxetine demonstrated adverse effects on embryo/fetal development. Therefore, your doctor should only prescribe duloxetine if the potential benefits justify the potential risk to the fetus.

Breastfeeding Women

Duloxetine is excreted in breast milk and may produce effects in the nursing infant. Some studies show the relative infant dose of duloxetine to be 2.3%. Relative infant dose (RID) is the dose received via breast milk relative to the mother’s dose. A relative infant dose below 10% is acceptable when breastfeeding. Some sources recommend breastfeeding only if the relative infant dose is less than 5% if the mother is on psychotropic medication. Regardless, an infant breastfed by a mother receiving duloxetine requires monitoring for behavior changes, sleep disturbance, feeding changes, growth, and neurodevelopment ⁹.

Medical problems

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

• Alcohol abuse, history of or kidney disease, severe or liver disease (including cirrhosis): Duloxetine should not be used in patients with these conditions.
• Bipolar disorder (mood disorder with mania and depression), or risk of or bleeding problems or diabetes or digestion problems or glaucoma (angle-closure) or heart or blood vessel disease or hypertension (high blood pressure) or hyponatremia (low sodium in the blood) or mania, history of or seizures, history of or urinating problems (eg, urinary retention or trouble urinating): Use duloxetine with caution. Duloxetine may make these conditions worse.
• Kidney disease: Use duloxetine with caution. The effects may be increased because of slower removal of duloxetine from the body.

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 duloxetine, 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 duloxetine 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.

• Bromopride
• Isocarboxazid
• Linezolid
• Mavorixafor
• Methylene Blue
• Metoclopramide
• Ozanimod
• Phenelzine
• Procarbazine
• Rasagiline
• Safinamide
• Selegiline
• Thioridazine
• Tranylcypromine
• Viloxazine

Using duloxetine 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.

• Abciximab
• Abiraterone Acetate
• Abiraterone Acetate, Micronized
• Aceclofenac
• Acemetacin
• Alfentanil
• Almotriptan
• Amineptine
• Amitriptyline
• Amitriptylinoxide
• Amoxapine
• Amphetamine
• Amtolmetin Guacil
• Anagrelide
• Anileridine
• Apixaban
• Ardeparin
• Aripiprazole
• Asenapine
• Aspirin
• Atomoxetine
• Benzhydrocodone
• Benzphetamine
• Betrixaban
• Brexpiprazole
• Bromfenac
• Brompheniramine
• Bufexamac
• Buprenorphine
• Bupropion
• Buspirone
• Butorphanol
• Cangrelor
• Capmatinib
• Carbamazepine
• Carvedilol
• Celecoxib
• Certoparin
• Chlorpheniramine
• Chlorpromazine
• Choline Salicylate
• Cifenline
• Cilostazol
• Cimetidine
• Ciprofloxacin
• Citalopram
• Clomipramine
• Clonixin
• Clopidogrel
• Clozapine
• Cocaine
• Codeine
• Cyclobenzaprine
• Dacomitinib
• Deferasirox
• Desipramine
• Desvenlafaxine
• Deutetrabenazine
• Dexibuprofen
• Dexketoprofen
• Dextroamphetamine
• Dextromethorphan
• Dibenzepin
• Diclofenac
• Difenoxin
• Diflunisal
• Dihydrocodeine
• Diphenoxylate
• Dipyridamole
• Dipyrone
• Dixyrazine
• Dolasetron
• Donepezil
• Doxepin
• Doxorubicin
• Doxorubicin Hydrochloride Liposome
• Droxicam
• Edoxaban
• Eletriptan
• Eliglustat
• Encainide
• Enclomiphene
• Enoxacin
• Epoprostenol
• Eptifibatide
• Escitalopram
• Ethylmorphine
• Etodolac
• Etofenamate
• Etoricoxib
• Fedratinib
• Felbinac
• Fenfluramine
• Fenoprofen
• Fentanyl
• Fepradinol
• Feprazone
• Flecainide
• Floctafenine
• Flufenamic Acid
• Fluoxetine
• Fluphenazine
• Flurbiprofen
• Fluvoxamine
• Frovatriptan
• Gepirone
• Givosiran
• Granisetron
• Haloperidol
• Hydrocodone
• Hydromorphone
• Hydroxytryptophan
• Ibuprofen
• Iloperidone
• Iloprost
• Imipramine
• Indecainide
• Indomethacin
• Iobenguane I 123
• Iobenguane I 131
• Ketobemidone
• Ketoprofen
• Ketorolac
• Lasmiditan
• Levoketoconazole
• Levomilnacipran
• Levorphanol
• Lisdexamfetamine
• Lithium
• Lofepramine
• Lofexidine
• Lorcainide
• Lorcaserin
• Lornoxicam
• Loxoprofen
• Lumiracoxib
• Meclofenamate
• Mefenamic Acid
• Melitracen
• Meloxicam
• Meperidine
• Metaxalone
• Methadone
• Methamphetamine
• Methdilazine
• Methotrexate
• Methotrimeprazine
• Methoxyphenamine
• Metopimazine
• Metoprolol
• Mexiletine
• Milnacipran
• Mirtazapine
• Morniflumate
• Morphine
• Morphine Sulfate Liposome
• Nabumetone
• Nalbuphine
• Naproxen
• Naratriptan
• Nebivolol
• Nefazodone
• Nepafenac
• Nicergoline
• Nicomorphine
• Niflumic Acid
• Nimesulide
• Nimesulide Beta Cyclodextrin
• Nortriptyline
• Oliceridine
• Ondansetron
• Opipramol
• Opium
• Opium Alkaloids
• Oxaprozin
• Oxycodone
• Oxymorphone
• Oxyphenbutazone
• Pacritinib
• Palonosetron
• Papaveretum
• Parecoxib
• Paregoric
• Parnaparin
• Paroxetine
• Pentazocine
• Perazine
• Perphenazine
• Phenylbutazone
• Piketoprofen
• Pimozide
• Piperazine
• Pipotiazine
• Piritramide
• Piroxicam
• Pitolisant
• Pixantrone
• Prajmaline
• Pranoprofen
• Prasugrel
• Prochlorperazine
• Proglumetacin
• Promazine
• Promethazine
• Propafenone
• Propiomazine
• Propyphenazone
• Proquazone
• Protriptyline
• Quinidine
• Recainam
• Remifentanil
• Reviparin
• Risperidone
• Ritlecitinib
• Rivaroxaban
• Rizatriptan
• Rofecoxib
• Salicylic Acid
• Salsalate
• Selexipag
• Sertraline
• Sibutramine
• Sodium Salicylate
• St John’s Wort
• Sufentanil
• Sulfinpyrazone
• Sulindac
• Sulodexide
• Sumatriptan
• Tamoxifen
• Tapentadol
• Tenoxicam
• Thiethylperazine
• Thioproperazine
• Tianeptine
• Tiaprofenic Acid
• Ticagrelor
• Ticlopidine
• Tilidine
• Timolol
• Tirofiban
• Tolfenamic Acid
• Tolmetin
• Tolperisone
• Tolterodine
• Tramadol
• Trazodone
• Treprostinil
• Trifluoperazine
• Triflupromazine
• Trimipramine
• Tropisetron
• Tryptophan
• Valdecoxib
• Venlafaxine
• Vernakalant
• Vilazodone
• Vorapaxar
• Vortioxetine
• Warfarin
• Yohimbine
• Ziprasidone
• Zolmitriptan
• Zuclopenthixol

Duloxetine uses

Duloxetine hydrochloride is U.S. Food and Drug Administration (FDA) approved for use in the treatment of major depressive disorder, generalized anxiety disorder (GAD), fibromyalgia, chronic muscle and joint pain, and diabetic peripheral neuropathy ¹⁰, ¹¹, ¹². Duloxetine is used off-label (non-FDA approved) for chemotherapy-induced peripheral neuropathy and stress urinary incontinence in both men and women ¹².

Monitoring

Your doctor should check your blood pressure and vitals before initiating duloxetine hydrochloride therapy and routinely after that. Your doctor should also monitor you for suicidal ideation, especially when starting treatment, altering the dose, and after discontinuation of therapy. Your doctor should monitor you for worsening depression, behavioral changes such as mania, and withdrawal symptoms from abrupt discontinuation. Patients should be monitored for abnormal bleeding as duloxetine may impair platelet aggregation. Caution should be exercised when using anticoagulants or antiplatelet medications along with duloxetine therapy. Laboratory workup should include monitoring serum creatinine, blood urea nitrogen(BUN), transaminase levels, blood glucose levels, and HgbA1c in diabetic patients. Sodium levels require follow-up when prescribing duloxetine in the elderly population ¹².

Duloxetine dosage

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

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

For oral dosage form (delayed-release capsules):

• For treatment of anxiety
  • Adults: At first, 60 milligrams (mg) once a day. Some patients may start at 30 mg once a day for 1 week before increasing the dose to 60 mg once a day. Your doctor may increase your dose as needed. However, the dose is usually not more than 120 mg per day.
  • Older adults: At first, 30 mg once a day for 2 weeks before increasing the dose to 60 mg once a day. Your doctor may increase your dose as needed. However, the dose is usually not more than 120 mg per day.
  • Children 7 years of age and older: At first, 30 mg once a day for 2 weeks before increasing the dose to 60 mg once a day. Your doctor may increase your dose as needed. However, the dose is usually not more than 120 mg per day.
  • Children younger than 7 years of age: Use and dose must be determined by your doctor.
• For treatment of chronic muscle pain
  • Adults: 60 milligrams (mg) once a day. Some patients may start at 30 mg once a day for 1 week before increasing the dose to 60 mg once a day.
    • Low back pain: 30 mg can be given once daily for one week and increased up to 60 mg once daily as tolerated as an adjunct therapy. Maximum dose: 60 mg/day.
    • Knee pain: 30 mg can be given once daily for one week and increased up to 60 mg once daily as tolerated as an adjunct therapy.[6]
  • Children: Use and dose must be determined by your doctor.
• For treatment of depression
  • Adults: 40 milligrams (mg) per day (given as 20 mg two times per day) to 60 mg per day (given either once a day or as 30 mg two times per day). Your doctor may increase your dose as needed. However, the dose is usually not more than 120 mg per day.
  • Children: Use and dose must be determined by your doctor.
• For treatment of diabetic peripheral neuropathy
  • Adults: 60 milligrams (mg) once a day.
  • Children: Use and dose must be determined by your doctor.
• For treatment of fibromyalgia
  • Adults: 60 milligrams (mg) once a day. Some patients may start at 30 mg once a day for 1 week before increasing the dose to 60 mg once a day.
  • Children 13 years of age and older: At first, 30 mg once a day. Your doctor may increase your dose as needed. However, the dose is usually not more than 60 mg per day.
  • Children younger than 13 years of age: Use and dose must be determined by your doctor.

If you miss a dose of duloxetine, take 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. Do not double doses.

Duloxetine side effects

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

• nausea
• vomiting
• constipation
• diarrhea
• weight changes
• heartburn
• stomach pain
• decreased appetite
• dry mouth
• increased urination
• sweating or night sweats
• dizziness
• headache
• weight changes
• tiredness
• drowsiness
• muscle pain or cramps
• sexual problems in males; decreased sex drive, inability to get or keep an erection, or delayed or absent ejaculation
• sexual problems in females; decreased sex drive, or delayed orgasm or unable to have an orgasm
• uncontrollable shaking of a part of the body

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

• unusual bruising or bleeding
• pain in the upper right part of the stomach
• swelling of the abdomen
• itching
• yellowing of the skin or eyes
• dark colored urine
• loss of appetite
• extreme tiredness or weakness
• confusion
• unsteady walking that may cause falling
• flu-like symptoms
• agitation, fever, sweating, confusion, fast or irregular heartbeat, and severe muscle stiffness or twitching, loss of coordination, nausea, vomiting, or diarrhea
• seizures
• hallucinations (seeing things or hearing voices that do not exist)
• fever
• blisters or peeling skin
• rash
• hives
• difficulty breathing or swallowing
• swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
• hoarseness
• difficulty urinating.

Duloxetine may cause some teenagers and young adults to be agitated, irritable, or display other abnormal behaviors. Duloxetine may also cause some people to have suicidal thoughts and tendencies or to become more depressed. Some people may have trouble sleeping, get upset easily, have a big increase in energy, or start to act reckless. If you or your caregiver notice any of these unwanted effects, see your doctor right away. Let the doctor know if you or anyone in your family has bipolar disorder (manic-depressive) or has tried to commit suicide.

Duloxetine may decrease appetite and cause weight loss in children. Your child’s doctor will watch his or her growth carefully. See your child’s doctor if you have concerns about your child’s growth or weight while he or she is taking duloxetine. See your child’s doctor about the risks of giving duloxetine to your child.

Duloxetine may cause a serious condition called serotonin syndrome if taken together with some medicines. Do not use duloxetine with buspirone (Buspar®), fentanyl (Abstral®, Duragesic®), lithium (Eskalith®, Lithobid®), tryptophan, St. John’s wort, amphetamines, or some pain or migraine medicines (eg, meperidine, methadone, rizatriptan, sumatriptan, tramadol, Demerol®, Methadose®, Frova®, Imitrex®, Maxalt®, Relpax®, Ultram®, Zomig®). Check with your doctor first before using any other medicines with duloxetine.

Duloxetine may increase your risk for bleeding problems. Make sure your doctor knows if you are also taking other medicines that thin the blood, such as aspirin, non-steroidal anti-inflammatory drugs (NSAIDs) pain medicines (eg, ibuprofen, naproxen, Advil®, Aleve®, Celebrex®, or Motrin®) or warfarin (Coumadin®).

Serious skin reactions (eg, erythema multiforme, Stevens-Johnson syndrome) can occur during treatment with duloxetine. Check with your doctor right away if you have blistering, peeling, or loosening of the skin, chills, cough, diarrhea, itching, joint or muscle pain, red irritated eyes, red skin lesions, often with a purple center, sore throat, sores, ulcers, or white spots in the mouth or on the lips, or unusual tiredness or weakness while you are using duloxetine.

Do not suddenly stop taking duloxetine without checking first with your doctor. If you have been instructed to stop taking duloxetine, ask your doctor how to slowly decrease the dose. This will decrease your chance of having withdrawal symptoms such as dizziness, nausea, headaches, vomiting, increased sweating, irritability, nightmares, trouble with sleeping, or prickling or tingling feelings.

Duloxetine may affect blood sugar levels. If you are diabetic and notice a change in the results of your blood or urine sugar tests, check with your doctor.

Duloxetine may cause blurred vision, dizziness, drowsiness, trouble with thinking, or trouble with controlling body movements, which may lead to falls, fractures, or other injuries. Make sure you know how you react to duloxetine before you drive, use machines, or do anything else that could be dangerous if you are not alert or able to see clearly. You may also feel lightheaded or you may fall or faint when getting up suddenly from a lying or sitting position, so get up slowly. If these symptoms are bothering you or keeping you from doing your daily activities, tell your doctor right away.

You will need to measure your blood pressure before starting duloxetine and while you are using it. If you notice any change to your recommended blood pressure, call your doctor right away. If you have questions about this, talk to your doctor.

Hyponatremia (low sodium in the blood) may occur with duloxetine. Check with your doctor right away if you have confusion, decreased urine output, difficulty concentrating, fast or irregular heartbeat, headaches, memory problems, nausea or vomiting, swelling of the face, ankles, or hands, trouble breathing, or unusual tiredness or weakness.

Duloxetine may cause sexual problems. Check with your doctor right away if you have decreased interest in sexual intercourse, inability to have or keep an erection, or loss in sexual ability, desire, drive, or performance.

Avoid smoking while you are using duloxetine. If you have any questions about this, check with your doctor.

Duloxetine may cause other side effects. See your doctor if you have any unusual problems while taking duloxetine.

Duloxetine overdose

Fatal outcomes have occurred with duloxetine overdoses at as low as 1000 mg. Signs and symptoms of duloxetine overdose include serotonin syndrome, seizures, coma, somnolence, syncope, tachycardia, autonomic instability, diarrhea, and vomiting. Signs of serotonin syndrome include agitation, restlessness, disorientation, diaphoresis, hyperthermia, tachycardia, nausea, vomiting, tremor, muscle rigidity, hyperreflexia, myoclonus, dilated pupils, dry mucous membranes, and increased bowel sounds. Clonus and hyperreflexia are particularly common in serotonin syndrome.

There is no antidote to duloxetine overdose. If the patient is presenting with serotonin syndrome, cyproheptadine and cooling measures may be considered. Patients with abnormal vital signs need monitoring, and severe cases may warrant ICU-level of care ¹³, ¹⁴.

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