What are the potential side effects of taking duloxetine (Cymbalta)? Discover the common and serious side effects, how to manage them, and when to seek immediate medical attention.

Common Side Effects of Duloxetine (Cymbalta)

Duloxetine, also known by the brand name Cymbalta, is a medication used to treat various conditions such as depression, anxiety, and certain types of chronic pain. Like all medicines, duloxetine can cause side effects in some people, but most individuals experience no side effects or only minor ones.

The common side effects of duloxetine can occur in up to 1 in 10 people. These side effects often gradually improve as your body adjusts to the medication. Here are some of the common side effects and ways to manage them:

Difficulty Sleeping

If duloxetine is causing you difficulty sleeping, try taking it in the morning instead of at night.

Headaches

To manage headaches, make sure to rest, drink plenty of fluids, and avoid excessive alcohol consumption. You can also ask your pharmacist for a recommended painkiller. If the headaches persist for more than a week or are severe, speak to your doctor.

Feeling Dizzy

If duloxetine makes you feel dizzy when standing up, try getting up slowly or remain seated until you feel better. If you start to feel dizzy, lie down to prevent fainting, then sit until you feel stable. Avoid driving, cycling, or using tools or machinery if you feel dizzy.

Blurred Vision

Blurred vision can occur with duloxetine. Avoid driving, cycling, or using tools or machinery while this side effect is present. If the blurred vision lasts for more than a day or two, your doctor may need to adjust your treatment.

Constipation

To help with constipation, increase your intake of fiber-rich foods like fresh fruits, vegetables, and cereals, and drink plenty of water. Regular exercise can also help alleviate constipation.

Diarrhea

If you experience diarrhea, drink plenty of fluids to avoid dehydration. Signs of dehydration include decreased urination or dark, strong-smelling urine. Do not take any other medications to treat the diarrhea without first consulting a pharmacist or doctor.

Nausea or Vomiting

To manage nausea or vomiting, stick to simple meals and avoid rich or spicy foods. Take duloxetine in the morning with some food. Try small, frequent sips of water if you’re vomiting to prevent dehydration.

Dry Mouth

To help with dry mouth, chew sugar-free gum or suck on sugar-free sweets.

Sweating

Try wearing loose clothing, using a strong anti-perspirant, and keeping cool with a fan to manage excessive sweating. If these measures don’t help, you may need to try a different type of antidepressant.

Tiredness

Avoid driving, cycling, or using tools or machinery if you feel tired from duloxetine. Try taking the medication an hour before bedtime, and cut down on alcohol, as it can make tiredness worse. If the tiredness doesn’t go away after two weeks, consult your doctor.

Decreased Appetite and Weight Loss

This side effect should improve as your body adjusts to the medication. It may help to eat smaller, more frequent meals and consume foods you enjoy. If your appetite doesn’t improve or you lose a significant amount of weight, talk to your doctor.

Sexual Side Effects

Some people may experience a decreased interest in sex or difficulties with arousal or orgasm. If this side effect persists, speak to your doctor.

Serious Side Effects of Duloxetine (Cymbalta)

Serious side effects of duloxetine are rare, occurring in less than 1 in 100 people. If you experience any of the following, book an appointment with your doctor:

• Changes in your menstrual periods, such as heavy bleeding, spotting, or bleeding between periods

Call a doctor or NHS 111 immediately if you have:

• Hallucinations (seeing or hearing things that are not real) or aggressive behavior
• Feelings of euphoria, excessive enthusiasm or excitement, or restlessness
• Constant headaches, long-lasting confusion or weakness, or frequent muscle cramps (these can be signs of low sodium levels in your blood)
• Yellowing of the whites of your eyes or your skin (this may be less obvious on brown or black skin and can be signs of a liver problem)
• Eye pain or blurred vision
• Black or red poop, or blood in your vomit (these can be signs of bleeding from your gut)
• Coughed-up blood or blood in your pee
• Bleeding from your gums or unexplained bruises

Immediate Action Required

Call 999 or go to A&E immediately if you experience:

• Tightness in your chest or shortness of breath
• Any heavy bleeding

Managing Side Effects of Duloxetine (Cymbalta)

Most side effects of duloxetine are manageable, and many will improve as your body adjusts to the medication. However, if the side effects persist or you have any concerns, be sure to speak to your doctor or pharmacist for advice.

Seeking Medical Attention

If the advice provided does not help and a side effect is still bothering you or does not go away, it’s important to book an appointment with your doctor or speak to a pharmacist. They can provide further guidance on managing the side effects or explore alternative treatment options if necessary.

Conclusion

In summary, duloxetine (Cymbalta) can cause a range of side effects, but most are common and manageable. By understanding the possible side effects and how to cope with them, you can work with your healthcare team to ensure the safe and effective use of this medication. Remember to report any persistent or concerning side effects to your doctor or pharmacist.

Side effects of duloxetine – NHS

Like all medicines, duloxetine can cause side effects in some people. But most people have no side effects or only minor ones.

Some of the common side effects of duloxetine will gradually improve as your body gets used to it.

Common side effects

These common side effects of duloxetine can happen in up to 1 in 10 people. There are things you can do to help cope with them:

Difficulty sleeping

Try taking duloxetine first thing in the morning.

Headaches

Make sure you rest and drink plenty of fluids. Try not to drink too much alcohol. Ask your pharmacist to recommend a painkiller. Talk to your doctor if the headaches last longer than a week or are severe.

Feeling dizzy

If duloxetine makes you feel dizzy when you stand up, try getting up very slowly or stay sitting down until you feel better. If you begin to feel dizzy, lie down so you do not faint, then sit until you feel better. Do not drive, cycle or use tools or machinery if you feel dizzy.

Blurred vision

Avoid driving, cycling or using tools or machinery while this is happening. If it lasts for more than a day or two, your doctor may need to change your treatment.

Constipation

Try to get more fibre into your diet, such as fresh fruit and vegetables and cereals, and drink plenty of water. Try to exercise more regularly, for example by going for a daily walk or run.

Diarrhoea

Drink lots of fluids, such as water or squash, to avoid dehydration. Signs of dehydration include peeing less than usual or having dark, strong-smelling pee.

Do not take any other medicines to treat diarrhoea without speaking to a pharmacist or doctor.

If you take contraceptive pills and you have severe diarrhoea for more than 24 hours, your contraception may not protect you from pregnancy. Check the pill packet for advice.

Feeling or being sick (nausea or vomiting)

Stick to simple meals and do not eat rich or spicy food. Make sure you take duloxetine in the morning with some food. Try small, frequent sips of water if you’re being sick to avoid dehydration. Signs of dehydration include peeing less than usual or having dark, strong-smelling pee.

If you take contraceptive pills and you’re being sick, your contraception may not protect you from pregnancy. Check the pill packet for advice.

Dry mouth

Chew sugar-free gum or suck sugar-free sweets.

Sweating

Try wearing loose clothing, use a strong anti-perspirant, and keep cool using a fan if possible. If this does not help, you may need to try a different type of antidepressant.

Tiredness

Do not drive, cycle or use tools or machinery if you’re feeling this way. Try taking duloxetine 1 hour before bedtime. Cut down the amount of alcohol you drink as alcohol will make you feel more tired.

If the tiredness does not go away after 2 weeks, ask your doctor for advice.

Less appetite than usual and weight loss

This side effect should get better as your body gets used to the medicine. It may also help to eat smaller meals more often and eat foods you really enjoy. If your appetite does not improve or you lose a lot of weight, ask your doctor for advice.

Feeling less interested in sex, or having problems keeping an erection or reaching orgasm

Speak to your doctor if you get this side effect and it does not go away.

Speak to a doctor or pharmacist if the advice on how to cope does not help and a side effect is still bothering you or does not go away.

Serious side effects

Serious side effects are rare and happen in less than 1 in 100 people.

Book an appointment with your doctor if you get changes in your periods, such as heavy bleeding, spotting or bleeding between periods.

Call a doctor or call 111 straight away if you have:

• hallucinations (seeing or hearing things that are not real), or you become aggressive and angry
• feelings of euphoria, excessive enthusiasm or excitement, or feeling restless so that you cannot sit or stand still
• constant headaches, long-lasting confusion or weakness, or frequent muscle cramps – these can be signs of low sodium levels in your blood
• yellowing of the whites of your eyes, or your skin although this may be less obvious on brown or black skin – these can be signs of a liver problem
• eye pain or blurred vision
• black or red poo or blood in your vomit – these can be signs of bleeding from your gut
• coughed up blood or have blood in your pee
• bleeding from your gums, or bruises that appear without a reason or get bigger

Immediate action required: Call 999 or go to A&E now if you get:

• tightness in your chest or shortness of breath
• any heavy bleeding that you cannot stop, such as cuts or nosebleeds that do not stop within 10 to 15 minutes
• painful erections that last longer than 2 hours – this may happen even when you’re not having sex
• thoughts about harming yourself or ending your life

Find your nearest A&E

Serious allergic reaction

In rare cases, it’s possible to have a serious allergic reaction (anaphylaxis) to duloxetine.

Immediate action required: Call 999 now if:

• your lips, mouth, throat or tongue suddenly become swollen
• you’re breathing very fast or struggling to breathe (you may become very wheezy or feel like you’re choking or gasping for air)
• your throat feels tight or you’re struggling to swallow
• your skin, tongue or lips turn blue, grey or pale (if you have black or brown skin, this may be easier to see on the palms of your hands or soles of your feet)
• you suddenly become very confused, drowsy or dizzy
• someone faints and cannot be woken up
• a child is limp, floppy or not responding like they normally do (their head may fall to the side, backwards or forwards, or they may find it difficult to lift their head or focus on your face)

You or the person who’s unwell may also have a rash that’s swollen, raised, itchy, blistered or peeling.

These can be signs of a serious allergic reaction and may need immediate treatment in hospital.

Other side effects

These are not all the side effects of duloxetine. For a full list, see the leaflet inside your medicines packet.

Information:

You can report any suspected side effect using the Yellow Card safety scheme.

Visit Yellow Card for further information.

Page last reviewed: 14 February 2022

Next review due: 14 February 2025

Cymbalta Oral: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing

Warnings:

Antidepressant medications are used to treat a variety of conditions, including depression and other mental/mood disorders. These medications can help prevent suicidal thoughts/attempts and provide other important benefits. However, a small number of people (especially people younger than 25) who take antidepressants for any condition may experience worsening depression, other mental/mood symptoms, or suicidal thoughts/attempts. It is very important to talk with the doctor about the risks and benefits of antidepressant medication (especially for people younger than 25), even if treatment is not for a mental/mood condition.

Tell the doctor right away if you notice worsening depression/other psychiatric conditions, unusual behavior changes (including possible suicidal thoughts/attempts), or other mental/mood changes (including new/worsening anxiety, panic attacks, trouble sleeping, irritability, hostile/angry feelings, impulsive actions, severe restlessness, very rapid speech). Be especially watchful for these symptoms when a new antidepressant is started or when the dose is changed.

Warnings:

Antidepressant medications are used to treat a variety of conditions, including depression and other mental/mood disorders. These medications can help prevent suicidal thoughts/attempts and provide other important benefits. However, a small number of people (especially people younger than 25) who take antidepressants for any condition may experience worsening depression, other mental/mood symptoms, or suicidal thoughts/attempts. It is very important to talk with the doctor about the risks and benefits of antidepressant medication (especially for people younger than 25), even if treatment is not for a mental/mood condition.

Tell the doctor right away if you notice worsening depression/other psychiatric conditions, unusual behavior changes (including possible suicidal thoughts/attempts), or other mental/mood changes (including new/worsening anxiety, panic attacks, trouble sleeping, irritability, hostile/angry feelings, impulsive actions, severe restlessness, very rapid speech). Be especially watchful for these symptoms when a new antidepressant is started or when the dose is changed.

… Show More

Uses

Duloxetine is used to treat depression and anxiety. In addition, duloxetine is used to help relieve nerve pain (peripheral neuropathy) in people with diabetes or ongoing pain due to medical conditions such as arthritis, chronic back pain, or fibromyalgia (a condition that causes widespread pain).Duloxetine may improve your mood, sleep, appetite, and energy level, and decrease nervousness. It can also decrease pain due to certain medical conditions. Duloxetine is known as a serotonin-norepinephrine reuptake inhibitor (SNRI). This medication works by helping to restore the balance of certain natural substances (serotonin and norepinephrine) in the brain.

How to use Cymbalta

Read the Medication Guide and, if available, the Patient Information Leaflet provided by your pharmacist before you start using duloxetine and each time you get a refill. If you have any questions, ask your doctor or pharmacist.

Take this medication by mouth as directed by your doctor, usually 1 or 2 times a day with or without food. If you have nausea, it may help to take this drug with food. Swallow the capsule whole. Do not crush or chew the capsule or mix the contents with food or liquid. Doing so can release all of the drug at once, increasing the risk of side effects.

The dosage is based on your age, medical condition and response to treatment. To reduce your risk of side effects, your doctor may direct you to start this medication at a low dose and gradually increase your dose. Follow your doctor’s instructions carefully. Take this medication regularly to get the most benefit from it. To help you remember, take it at the same time(s) each day.

Keep taking this medication even if you feel well. Do not stop taking this medication without consulting your doctor. Some conditions may become worse when this drug is suddenly stopped. Also, you may experience symptoms such as dizziness, confusion, mood swings, headache, tiredness, diarrhea, sleep changes, and brief feelings similar to electric shock. Your dose may need to be gradually decreased to reduce side effects. Report any new or worsening symptoms right away.

Tell your doctor if your condition lasts or gets worse.

Side Effects

See also Warning section.

Nausea, dry mouth, constipation, loss of appetite, tiredness, drowsiness, or increased sweating may occur. If any of these effects last or get worse, tell your doctor promptly.

Dizziness or lightheadedness may occur, especially when you first start or increase your dose of this drug. To reduce the risk of dizziness, lightheadedness, or falling, get up slowly when rising from a sitting or lying position.

Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

This medication may raise your blood pressure. Check your blood pressure regularly and tell your doctor if the results are high.

Tell your doctor right away if you have any serious side effects, including: confusion, easy bleeding/bruising, decreased interest in sex, changes in sexual ability, muscle cramps/weakness, shaking (tremor), difficulty urinating, signs of liver problems (such as nausea that doesn’t stop, stomach/abdominal pain, vomiting, yellowing eyes/skin, dark urine).

Get medical help right away if you have any very serious side effects, including: black stools, vomit that looks like coffee grounds, seizure, eye pain/swelling/redness, widened pupils, vision changes (such as seeing rainbows around lights at night, blurred vision).

This medication may increase serotonin and rarely cause a very serious condition called serotonin syndrome/toxicity. The risk increases if you are also taking other drugs that increase serotonin, so tell your doctor or pharmacist of all the drugs you take (see Drug Interactions section). Get medical help right away if you develop some of the following symptoms: fast heartbeat, hallucinations, loss of coordination, severe dizziness, severe nausea/vomiting/diarrhea, twitching muscles, unexplained fever, unusual agitation/restlessness.

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing, skin blisters, mouth sores.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US – Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.

In Canada – Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Precautions

Before taking duloxetine, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: personal or family history of psychiatric disorders (such as bipolar/manic-depressive disorder), personal or family history of suicide attempts, bleeding problems, personal or family history of glaucoma (angle-closure type), high blood pressure, kidney disease, liver disease, seizure disorder, stomach problems (such as slow emptying of the stomach), use/abuse of alcohol.

This drug may make you dizzy or drowsy. Alcohol or marijuana (cannabis) can make you more dizzy or drowsy. Do not drive, use machinery, or do anything that needs alertness until you can do it safely. Avoid alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis).

If you have diabetes, duloxetine may affect your blood sugar. Check your blood sugar regularly as directed and share the results with your doctor. Your doctor may need to adjust your diabetes medication, exercise program, or diet.

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

Older adults may be more sensitive to the side effects of this drug, especially bleeding, dizziness, lightheadedness, or loss of coordination. Older adults may also be more likely to develop a type of salt imbalance (hyponatremia), especially if they are taking “water pills” (diuretics). Dizziness, lightheadedness, or loss of coordination can increase the risk of falling.

Children may be more sensitive to the side effects of this drug, especially loss of appetite and weight loss. Monitor weight and height in children who are taking this drug. See also Warning.

During pregnancy, this medication should be used only when clearly needed. When this medication is taken during the last 30 days of pregnancy, the mother may be at an increased risk of bleeding at birth. This medication may also harm an unborn baby. Babies born to mothers who have used this drug during the last 3 months of pregnancy may rarely develop withdrawal symptoms such as feeding/breathing difficulties, seizures, muscle stiffness, or constant crying. If you notice any of these symptoms in your newborn, tell the doctor promptly.

Since untreated mental/mood problems (such as depression, anxiety) can be a serious condition, do not stop taking this medication unless directed by your doctor. If you are planning pregnancy, become pregnant, or think you may be pregnant, immediately discuss the benefits and risks of using this medication during pregnancy with your doctor.

This drug passes into breast milk and may have undesirable effects on a nursing infant. Consult your doctor before breast-feeding.

Interactions

Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor’s approval.

Some products that may interact with this drug are: other drugs that can cause bleeding/bruising (including antiplatelet drugs such as clopidogrel, NSAIDs such as ibuprofen/naproxen, “blood thinners” such as dabigatran/warfarin).

Other medications can affect the removal of duloxetine from your body, which may affect how duloxetine works. Examples include cimetidine, viloxazine, certain quinolone antibiotics (such as ciprofloxacin, enoxacin), among others.

This medication can slow down the removal of other medications from your body, which may affect how they work. Examples of affected drugs include antiarrhythmic drugs (such as propafenone, flecainide, quinidine), antipsychotics (such as thioridazine), tricyclic antidepressants (such as desipramine, imipramine), among others.

Taking MAO inhibitors with this medication may cause a serious (possibly fatal) drug interaction. Avoid taking MAO inhibitors (isocarboxazid, linezolid, metaxalone, methylene blue, moclobemide, phenelzine, procarbazine, rasagiline, safinamide, selegiline, tranylcypromine) during treatment with this medication. Most MAO inhibitors should also not be taken for two weeks before and at least 5 days after treatment with this medication. Ask your doctor when to start or stop taking this medication.

The risk of serotonin syndrome/toxicity increases if you are also taking other drugs that increase serotonin. Examples include street drugs such as MDMA/”ecstasy,” St. John’s wort, certain antidepressants (including SSRIs such as fluoxetine/paroxetine, other SNRIs such as desvenlafaxine/venlafaxine), tryptophan, among others. The risk of serotonin syndrome/toxicity may be more likely when you start or increase the dose of these drugs.

Tell your doctor or pharmacist if you are taking other products that cause drowsiness including alcohol, marijuana (cannabis), antihistamines (such as cetirizine, diphenhydramine), drugs for sleep or anxiety (such as alprazolam, diazepam, zolpidem), muscle relaxants, and opioid pain relievers (such as codeine). Check the labels on all your medicines (such as allergy or cough-and-cold products) because they may contain ingredients that cause drowsiness. Ask your pharmacist about using those products safely.

Aspirin can increase the risk of bleeding when used with this medication. However, if your doctor has directed you to take low-dose aspirin for heart attack or stroke prevention (usually 81-162 milligrams a day), you should continue taking it unless your doctor instructs you otherwise.

Does Cymbalta interact with other drugs you are taking?

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Overdose

If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: severe drowsiness, fainting.

Do not share this medication with others.

Lab and/or medical tests (such as blood pressure, liver function) should be done while you are taking this medication. Keep all medical and lab appointments.

If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.

Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

Images

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This medicine is a white blue, oblong, capsule imprinted with “30 mg” and “LILLY 3240”.

Cymbalta 60 mg capsule,delayed release

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This medicine is a white blue, oblong, capsule imprinted with “30 mg” and “LILLY 3240”.

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CONDITIONS OF USE: The information in this database is intended to supplement, not substitute for, the expertise and judgment of healthcare professionals. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for you or anyone else. A healthcare professional should be consulted before taking any drug, changing any diet or commencing or discontinuing any course of treatment.

Simbalta: instruction, price, analogues | hard capsules, enteric Lilly S.A.

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duloxetine ((S)-(+)-N-Methyl-g-(1-naphthalenyloxy)-2-thiophenepropanamine) is a serotonin and norepinephrine reuptake inhibitor. It slightly inhibits dopamine uptake, has no significant affinity for histamine and dopamine, cholinergic and adrenergic receptors. The mechanism of the therapeutic action of duloxetine in depression is due to inhibition of serotonin and norepinephrine reuptake and, as a result, increased serotonergic and noradrenergic neurotransmission in the CNS. Duloxetine also normalizes pain threshold in some experimental models of neuropathic and inflammatory pain and reduces pain in a model of chronic pain. The analgesic effect of duloxetine is probably due to a slowdown in the transmission of nociceptive impulses in the CNS.

Duloxetine is well absorbed after oral administration. The maximum plasma concentration is reached 6 hours after taking the drug. Simultaneous ingestion of food slows down absorption, while the period of reaching the maximum concentration in the blood is lengthened from 6 to 10 hours, and absorption decreases (approximately 11%).

Duloxetine is highly bound to plasma proteins (greater than 90%).

Duloxetine is extensively metabolized in the body, metabolites are excreted primarily in the urine. Isoenzymes CYP 2D6 and CYP 1A2 catalyze the formation of the two main metabolites of duloxetine (glucuronide coupled to 4-hydroxy duloxetine, sulfate coupled to 5-hydroxy, methoxy duloxetine). The resulting metabolites do not have pharmacological activity.

The half-life of duloxetine is 12 hours. The mean plasma clearance of duloxetine is 101 l/h.

In patients with end-stage renal disease who are constantly on dialysis, there is a doubling of the concentration of duloxetine in the blood plasma and an increase in AUC compared with healthy individuals. Therefore, in patients with chronic renal failure, the drug is prescribed at a lower initial dose.

depression; diabetic neuropathy.

for depression and diabetic neuropathy is prescribed orally at a dose of 60 mg 1 time per day daily, regardless of food intake. Some patients may be recommended to prescribe the drug at a higher dose (up to a maximum of -120 mg / day in 2 divided doses). The possibility of prescribing at doses exceeding 120 mg / day has not been studied.

Initial dosage for patients with end-stage renal disease (creatinine clearance <30 mL/min) is 30 mg once daily.

Patients with cirrhosis of the liver are prescribed at a lower initial dose or with longer intervals between doses.

No dose adjustment is required in elderly or elderly patients. Duloxetine has not been studied in patients under 18 years of age.

hypersensitivity to duloxetine, concomitant therapy with MAO inhibitors.

during clinical trials, side effects such as constipation, nausea, dry mouth, dizziness, fatigue, insomnia and headache (≥10%) were observed. Less commonly (with a frequency of <10%, but ≥1%), tachycardia, dyspepsia, vomiting, decreased appetite, drowsiness, tremor, lethargy, sweating, feeling hot, yawning were observed. On the part of the reproductive system, ejaculation and erection disorders were observed (with a frequency of <10%, but ≥1%), decreased libido and anorgasmia. Rarely (<1%, but ≥0.1%), gastroenteritis, stomatitis, increased blood pressure, weight gain, muscle tension, taste and visual disturbances, agitation, urinary retention were observed.

Treatment with duloxetine in placebo-controlled clinical trials was associated with non-significant increases in ALT, AsAT, and CPK compared to placebo.

In clinical trials of duloxetine for the treatment of diabetic neuropathy, the mean duration of diabetes mellitus was approximately 11 years, mean initial fasting serum glucose was up to 163 mg/dl, and mean initial glycated hemoglobin was 7.80%. These studies noted a slight increase in initial fasting blood glucose after 12 weeks in patients treated with duloxetine, compared with placebo, at the usual regimen for 52 weeks. There were no changes in the rate of glycated hemoglobin, body weight of patients, lipid concentrations (Cholesterol, LDL, HDL, TG) or any side effects associated with diabetes mellitus.

The following side effects have been reported from post-marketing studies:

on the part of the organ of vision: very rarely (<0.01%) - glaucoma;

from the hepatobiliary system: very rarely (<0.01%) - hepatitis, jaundice;

from the immune system: very rarely (<0.01%) - anaphylactic reactions;

on the part of laboratory parameters: very rarely (<0. 01%) – increased activity of ALT, AST, alkaline phosphatase, bilirubin levels in the blood;

from the side of metabolism: very rarely (<0.01%) - hyponatremia;

on the part of the skin: rarely (0.01-0.1%) – rash; very rarely (<0.01%) - angioedema, Stevens-Johnson syndrome, urticaria;

from the side of the cardiovascular system: very rarely (<0.01%) - orthostatic hypotension and syncope (especially at the beginning of treatment).

patients at high risk of suicide during the treatment period should be under strict observation, since the possibility of suicidal attempts is not excluded before the onset of a pronounced remission.

Duloxetine hydrochloride has not been studied in patients under 18 years of age and should therefore not be used in this age group.

As with other CNS-active drugs, duloxetine should be used with caution in patients with a history of mania.

As with other CNS-active drugs, duloxetine should be used with caution in patients with a history of seizures.

Mydriasis has been reported in association with duloxetine, so duloxetine should be used with caution in patients with elevated intraocular pressure or at risk of developing acute narrow-angle glaucoma.

Increased plasma concentrations of duloxetine have been reported in patients with severe renal insufficiency (creatinine clearance <30 ml/min) or severe hepatic insufficiency. Such patients are advised to prescribe the drug at a lower initial dose.

In some patients, duloxetine leads to an increase in blood pressure. In patients with hypertension and / or other diseases of the cardiovascular system, monitoring of blood pressure is recommended.

In clinical studies, there was an increase in the activity of liver enzymes in the blood. In most patients treated with duloxetine, this increase was transient and resolved upon discontinuation of duloxetine treatment. A significant increase in liver enzyme activity (greater than 10 times normal) or liver damage with cholestasis, or a significant increase in enzyme activity in combination with liver damage, has rarely occurred, in some cases it has been associated with alcohol abuse.

Duloxetine was not mutagenic in experiments in vitro and in vivo .

In experiments, duloxetine at a dose of 45 mg/kg/day did not affect the reproductive function of male rats. In female rats, the use of duloxetine at a dose of 45 mg / kg / day was accompanied by such manifestations of reproductive toxicity as menstrual irregularities, a decrease in the birth rate index, survival rate, and slow growth of pups.

Adequate and well-controlled studies of the effect of the drug in pregnant women have not been conducted, so the use of the drug during pregnancy is not recommended.

Duloxetine is excreted in breast milk. The approximate daily dose in an infant is 0.14% of the dose for a nursing woman (in mg / kg). The safety of duloxetine use in a nursing infant has not been established, so breast-feeding while taking duloxetine is not recommended.

During the period of treatment with the drug, patients should refrain from potentially hazardous activities that require increased attention and speed of psychomotor reactions.

duloxetine should not be given concomitantly with MAO inhibitors or within at least 14 days after stopping treatment with MAO inhibitors. Due to the half-life of duloxetine, MAO inhibitors should also not be administered for at least 5 days after discontinuation of duloxetine treatment.

In clinical studies with the simultaneous administration of theophylline, a CYP1A2 substrate, with duloxetine at a dose of 60 mg 2 times a day, no significant changes in their pharmacokinetics were noted. These results indicate that duloxetine is unlikely to have a clinically significant effect on the metabolism of CYP1A2 substrates.

Since CYP1A2 is involved in the metabolism of duloxetine, concomitant use of duloxetine with active inhibitors of CYP1A2 may result in increased plasma concentrations of duloxetine. Fluvoxamine (at a dose of 100 mg 1 time per day), being an active inhibitor of CYP1A2, reduces the clearance of duloxetine from blood plasma by approximately 77%. In this regard, when prescribing duloxetine with CYP1A2 inhibitors (some quinolone antibacterial agents), it is advisable to prescribe duloxetine at a lower dose.

Duloxetine is a moderate inhibitor of CYP2D6. When prescribing duloxetine at a dose of 60 mg 2 times a day with a single dose of desipramine, which is a substrate of CYP2D6, the AUC of desipramine increases 3 times. Co-administration of duloxetine (at a dose of 40 mg 2 times a day) increases the stationary AUC of tolterodine (2 mg 2 times a day) by 71%, but does not affect the pharmacokinetics of the 5-hydroxyl metabolite. In this regard, when prescribing duloxetine with CYP2D6 inhibitors, which have a narrow therapeutic index, care must be taken.

Since CYP2D6 is involved in the metabolism of duloxetine, concomitant use of duloxetine with active inhibitors of CYP2D6 can lead to an increase in the concentration of duloxetine in the blood. Paroxetine (at a dose of 20 mg 1 time per day) reduces the clearance of duloxetine from blood plasma by approximately 37%. In this regard, caution should be exercised when prescribing duloxetine with CYP2D6 inhibitors.

When prescribing duloxetine in combination with other drugs that affect the central nervous system, especially with a similar mechanism of action, care should be taken.

Duloxetine binds to plasma proteins (>90%), so the administration of duloxetine to a patient who is taking other drugs that are highly bound to plasma proteins may lead to an increase in the free concentration of any of these drugs.

Clinical data on duloxetine overdose are limited. No cases of fatal overdose of duloxetine have been reported in pre-marketing clinical trials. There have been cases of overdose of the drug (up to 1400 mg), including in combination with other drugs, but they did not lead to death.

In animal experiments, the main manifestations of toxicity in case of overdose were noted from the side of the central nervous system and gastrointestinal tract. These included symptoms such as tremor, clonic convulsions, ataxia, vomiting, and anorexia.

No specific antidote known. Immediately after an overdose, gastric lavage and the appointment of activated charcoal are indicated. The airway should be secured. It is recommended to monitor the main vital signs, primarily cardiac activity, if necessary, symptomatic and supportive therapy. Duloxetine has a large volume of distribution, and therefore forced diuresis, hemoperfusion and exchange perfusion are ineffective in overdose.

at temperatures up to 30 °C in original packaging.

Duloxetine (Duloxetinum) – PsyAndNeuro.ru

30 mg capsule, delayed release(DR/EC)

60 mg capsule, delayed release(DR/EC)

30 mg capsule, delayed release(DR/EC)

Trade names in Russia

Simbalta, Duloxetine, Duloxetine Canon

Presentation

Capsules: 30 mg, 60 mg (14 capsules in a blister; 1, 2, 6 blisters per pack)

Contents 90 029

Antidepressant

Reverse inhibitor capture of serotonin and norepinephrine [2].

◊ Recommendations of the Ministry of Health of Russia

F32 Depressive episode

F33 Recurrent depression

F41.1 Generalized anxiety disorder

G63.2 Diabetic polyneuropathy (E10-E14+ with common fourth character .4)

M17 Gonarthrosis [arthrosis of the knee]

M54.5 Lower back pain

M79.1 Myalgia

R52.1 Persistent pain

◊ EMA Guidelines

• Anxiety Disorder
• Depression
• Diabetic neuropathy
• Neuralgia

◊ UK Medicines and Healthcare Products Regulatory Agency recommendations

• Depression
• Generalized anxiety disorder
• Diabetic polyneuropathy

◊ Off-label use

Stress urinary incontinence

9 0003 Depressive mood
• Lack of energy, motivation and interest
• Sleep disorder
• Anxiety
• Pain

Duloxetine is a potent serotonin and norepinephrine reuptake inhibitor and a less potent dopamine reuptake inhibitor. Duloxetine has no significant affinity for dopaminergic, adrenergic, cholinergic, histaminergic, opioid, glutamate and GABA receptors. It is believed that its antidepressant and analgesic actions are associated with the potentiation of serotonergic and noradrenergic activity in the CNS.

The mechanism of action of duloxetine in stress urinary incontinence has not yet been determined, but it is believed that it is associated with the potentiation of serotonin and norepinephrine activity in the spinal cord, which enhances the functioning of the urethral valves and, thereby, reduces urinary incontinence [3].

• Half-life 12 hours
• Absorption begins 2 hours after taking the drug. TCmax – 6 hours
• Metabolized by CYP2D6 and CYP1A2

◊ Dosage and dose adjustment

• Depression: 40-60 mg/day in 1-2 doses
• Start at 40 mg/day, in 2 divided doses; can be increased to 60 mg/day in 1-2 doses; maximum 120 mg/day
• Neuropathy and fibromyalgia: 60 mg/day in 1 dose
• Start at 30 mg/day, increase to 60 mg/day after a week
• GAD: 60 mg/day
• Start at 60 mg/day in 1 dose; maximum 120 mg/day
• No data on the effectiveness of doses above 60 mg/day
• Do not chew, do not crush, swallow whole [1].

◊ How fast it works

• Begins to work after 2-4 weeks;
• May be taken for many years to prevent relapse;
• If there is no effect after 6-8 weeks, increase the dose or switch to another drug;
• Neuropathic pain resolves within a week;
• Vasomotor symptoms during perimenopause in women with or without depression resolve within a week.

◊ Expected result

• Complete remission.
• After the disappearance of symptoms of depression, you should continue taking one year if it was the treatment of the first episode. If this is a re-episode treatment, treatment can be extended indefinitely.
• Use in the treatment of anxiety and chronic pain may be indefinite [1].

◊ If not working

• Change dose, switch to another drug, or add an ancillary drug;
• Connect psychotherapy;
• Review diagnosis for comorbid conditions;
• Patients with undiagnosed bipolar affective disorder may have poor response to treatment, in which case switching to a Mood Stabilizer [1].
• In the acute phase of a severe depressive disorder accompanied by psychotic or catatonic symptoms, as well as in patients with actual suicidal ideation, electroconvulsive therapy should be considered [5].

◊ How to stop taking

• Taper off gradually to avoid withdrawal.
• Taper scheme: dose reduced by 50% – 3 days, again reduced by 50% – 3 days, complete cessation. If withdrawal symptoms appear, increase the dose, wait for the withdrawal symptoms to subside, and continue to decrease [1].

◊ Treatment combinations

• Little data on augmentation
• Add other antidepressants with great care
• Combination with mirtazapine – “California rocket fuel” in the treatment of depression; important not to overlook bipolar disorder and suicidal ideation
• For fatigue, drowsiness, loss of concentration: modafinil [4].
• For bipolar depression, psychotic depression, resistant depression, resistant anxiety disorder: mood stabilizers, atypical antipsychotics
• For anxiety disorder: gabapentin, tiagabine

• Use caution if patient has had convulsions;
• Use caution if patient has bipolar disorder;
• Do not use if there is angle-closure glaucoma;
• Do not use if patient is a heavy drinker;
• Do not use if patient is taking thioridazine;
• Do not use if allergic to duloxetine [1].

◊ Patients with kidney disease

Not recommended for severe kidney disease [1].

◊ Patients with diseased liver

• Should not be used in liver failure of any degree;
• Increases the level of transaminases [1].

◊ Heart patients

With caution; Increases pressure [1].

◊ Elderly patients

Low dose preferred

◊ Children and adolescents 9 0065

• Not enough research, it is recommended to leave the application only to experts [1].
• It is necessary to check the patient’s condition regularly and personally, especially during the first weeks of treatment.
• Use with caution, bearing in mind the risk of undiagnosed bipolar affective disorder and suicidal tendencies.
• Inform adults of the risks.

◊ Pregnant women

• There have been no adequate studies of pregnant women [1].
• Not recommended for pregnant women, especially in the first trimester
• All risks should be weighed and compared

◊ Breastfeeding

• The drug passes into breast milk.
• If the infant shows signs of irritation or sedation, stop feeding or taking duloxetine
• However, postpartum treatment may be necessary and the risks should be weighed.

• Interaction with: safinamide, selegiline, procarbazine, isocarboxazid, eliglustat
• Combine with caution with TCAs
• Cannot be used with MAO inhibitors. After the end of the intake of MAO inhibitors, 14 days should pass. Start treatment with MAO inhibitors 7 days after the end of citalopram.
• Together with anticoagulants, probably increases the risk of bleeding [1].

Blood pressure monitor.

◊ Mechanism of side effects

Side effects are caused by increased serotonin and norepinephrine. Most side effects occur immediately after the start of treatment and go away over time.

◊ Side effects

• Nausea, diarrhea, decreased appetite
• Insomnia, sedation,
• Sweating
• 2 mm increase in blood pressure
• Difficulty urinating
• Dangerous side effects: convulsions, mania, suicidal ideation
• Weight gain: very rare
• Sedation: yes, but infrequently
• Sexual dysfunction: yes

◊ Dealing with side effects

1. Wait;
2. Reduce dose;
3. Add other medications or switch to another antidepressant [1].

◊ Long term use

Monitor blood pressure

◊ Habituation 900 65

No.

◊ Overdose

• Very rare cases of fatal overdose.
• Serotonin syndrome, sedation, vomiting, convulsions, coma

• Good for patients with somatic symptoms of depression;
• Good for depressed patients with lethargy;
• Good for atypical depression;
• Good for comorbid anxiety;
• Good for patients who have not responded to SSRIs [1].

• Not suitable for those with urological problems;
• Not suitable for elderly patients with diseased prostate.

• Duloxetine is more effective than others in patients whose depression is accompanied by pain [1]
• Has a neuroprotective effect in painful diabetic neuropathy [6]

1. Stephen Stahl “Prescriber’s Guide”, 6th edition, 2017

2. Neuroscience-Based Nomenclature (https://www.nbn2.com/taskforce)

3.