What They Are and How to Manage Them

Cymbalta (duloxetine) is a prescription drug that’s used to treat certain conditions, including depression. The drug can cause side effects that range from mild to serious, including some sexual side effects.

Cymbalta is used as a long-term treatment for several different conditions in adults, including:

• major depressive disorder
• generalized anxiety disorder (GAD)
• pain caused by diabetic neuropathy (nerve damage caused by diabetes)
• fibromyalgia (a condition that causes pain throughout the body)
• long-term musculoskeletal pain (pain in the bones, muscles, tendons, ligaments, and nerves)

Cymbalta is also approved to treat GAD and fibromyalgia in certain children.

The active ingredient in Cymbalta is duloxetine. (An active ingredient is what makes a drug work.) The drug comes as capsules that you swallow.

Keep reading to learn about the common, mild, and serious side effects that Cymbalta can cause. For a general overview of the drug, including details about its uses, see this article.

Some people may experience mild or serious side effects during Cymbalta treatment. Some side effects are more common than others.

Cymbalta’s more common side effects include:

• fatigue (lack of energy)
• nausea
• constipation
• reduced appetite
• sweating more than usual*
• dizziness

* To learn more about this side effect, see “Side effects explained” below.

Mild side effects have been reported with Cymbalta, many of which are also more common side effects of the drug. Cymbalta’s mild side effects include:

• sleepiness
• fatigue (lack of energy)
• nausea
• dry mouth
• constipation
• reduced appetite
• dizziness
• headache
• sexual side effects in females and males*
• sweating more than usual†
• trouble sleeping†
• headache
• belly pain

* In this article, we use the terms “female” and “male” to refer to someone’s sex assigned at birth. For information about the difference between sex and gender, see this article. For details on sexual side effects Cymbalta may cause, see “Sexual side effects in women and men” below.
† To learn more about this side effect, see “Side effects explained” below.

In most cases, these side effects should be temporary. Some may be easily managed, too. But if you have any symptoms that are ongoing or that bother you, talk with your doctor or pharmacist. And don’t stop using Cymbalta unless your doctor recommends it.

Cymbalta may cause mild side effects other than the ones listed above. See the Cymbalta medication guide for details.

Note: After the Food and Drug Administration (FDA) approves a drug, it tracks side effects of the medication. If you’d like to notify the FDA about a side effect you’ve had with Cymbalta, visit MedWatch.

Serious side effects from Cymbalta aren’t common, but they can happen. Serious side effects that have been reported with Cymbalta include:

• suicidal behaviors and thoughts*
• liver damage†
• eye problems†
• allergic reaction†‡
• fainting or dizziness when standing up
• blood pressure changes
• serotonin syndrome, a rare side effect of drugs that affect serotonin, a brain chemical
• low sodium levels
• urination problems
• severe skin reaction, such as Stevens-Johnson syndrome
• unusual bleeding or bruising

* Cymbalta has a boxed warning for this side effect. This is the most serious warning from the Food and Drug Administration (FDA). To learn more, see “Side effects explained” below.
† To learn more about this side effect, see “Side effects explained” below.
‡ An allergic reaction is possible after using Cymbalta. But this side effect wasn’t reported in studies.

If you develop serious side effects while taking Cymbalta, call your doctor right away. If the side effects seem life threatening or if you think you’re having a medical emergency, immediately call 911 or your local emergency number.

The most common side effects of Cymbalta in children may include:

• weight loss
• reduced appetite
• fatigue (lack of energy)
• nausea or vomiting
• diarrhea

Sexual side effects from taking Cymbalta are possible and may be more common in males than females.* In studies, sexual side effects were reported in a small percentage of males and females during Cymbalta treatment. Some of these side effects, such as erectile dysfunction, may be more likely to occur when taking a higher dosage of Cymbalta.

Males who took Cymbalta reported significantly more sexual side effects compared with those who took a placebo (a treatment that contains no active drug). The sexual side effects reported in males included:

• decrease in or loss of libido (sex drive)
• trouble becoming aroused
• erectile dysfunction
• difficulty reaching orgasm
• delayed ejaculation or being unable to ejaculate

Females who took Cymbalta also reported sexual side effects. But these side effects were similar to those experienced by females who received a placebo. Sexual side effects included:

• decreased libido (sex drive)
• trouble becoming aroused
• reduced vaginal lubrication
• difficulty reaching orgasm

Note that some males and females in this study reported improvements in sexual desire, performance, and satisfaction with Cymbalta treatment. This may be because the medication helped to reduce the symptoms of their condition. As a result, their sexual health may have also improved.

* In this article, we use the terms “female” and “male” to refer to someone’s sex assigned at birth. For information about the difference between sex and gender, see this article.

Some side effects of Cymbalta can affect your long-term health, but this isn’t common.

For example, liver failure is a rare but serious side effect of Cymbalta. Heavy alcohol use may increase the risk of liver failure. The liver damage that develops from this side effect doesn’t go away once a person stops taking Cymbalta.

You may be wondering if it’s safe to take Cymbalta long term. Studies have tested the drug’s safety for up to 6 months. A 2009 study has shown Cymbalta to be safe to use when taken for 12 months. Your doctor can tell you about their understanding of long-term Cymbalta use.

It’s a good idea to go over all of your medications with your doctor every so often. Together, you can discuss your condition and consider whether you should continue Cymbalta long term.

Keep reading to get answers to some frequently asked questions about Cymbalta’s side effects.

How long do Cymbalta’s side effects last?

How long side effects from Cymbalta last can vary. Some of the more common side effects are usually temporary, such as sleepiness, dizziness, and reduced appetite. These side effects typically ease within a few days or weeks after starting treatment.

Common side effects may get worse after your doctor increases your dosage, but this is usually temporary.

Other side effects are more likely to continue for as long as you’re taking the drug. Examples include sweating more than usual and sexual side effects. These side effects usually aren’t severe.

Cymbalta side effects can affect each person differently. For example, nausea may be a mild, temporary side effect for some people. For others it can be bothersome. In studies, a small percentage of people had to stop taking the drug due to nausea.

If you’re experiencing troublesome side effects, you shouldn’t suddenly stop taking Cymbalta. It’s best to talk with your doctor first. If you and your doctor decide that you should stop the drug, they’ll guide you on how best to do so.

Do seniors have a higher risk for side effects from Cymbalta?

No, this doesn’t seem to be the case. In general, older adults (ages 65 years and older) have a higher risk for medication side effects compared with younger adults. But in studies of Cymbalta, older adults had similar side effects to those of younger adults.

Can Cymbalta cause weight gain?

Cymbalta doesn’t typically cause weight gain. In studies, weight gain wasn’t reported as a side effect.

In fact, weight loss is more likely than weight gain with Cymbalta. This is because the drug commonly causes reduced appetite and nausea.

These side effects may lead to weight loss, especially in children. Because of this, if your child is taking Cymbalta, their doctor will monitor your child’s weight and height during Cymbalta treatment.

If you have questions about weight changes with Cymbalta, talk with your doctor.

Will Cymbalta side effects differ depending on the strength I use (20 mg, 30 mg, or 60 mg)?

Some side effects of Cymbalta may be dependent on dose. Cymbalta comes in the following strengths: 20 milligrams (mg), 30 mg, and 60 mg. A higher strength of the drug might come with a higher risk of certain side effects.

Common dose-dependent side effects of Cymbalta include nausea, fatigue (lack of energy), constipation, dizziness, reduced appetite, and sweating more than usual.

Learn more about some of the side effects Cymbalta may cause.

Sweating more than usual

Sweating more than usual is a common side effect of Cymbalta. This side effect may be worse with higher doses of the drug. In addition, hot flashes (also called hot flushes) are a possible side effect of this medication.

Some people may notice increased sweating only in certain situations, such as when they’re active or during humid weather. Others may have increased sweating more often, including while trying to sleep.

What might help

Increased sweating isn’t a harmful side effect, but it may be uncomfortable. Here are a few tips that may help ease this side effect:

• Use a strong deodorant.
• Shower more often.
• Wear light fabrics
• Use a fan at night.

If this side effect continues to bother you, your doctor may suggest adjusting your dosage or switching to a different drug.

But if Cymbalta is particularly effective for your condition, you may not want to switch to a different drug. In this case, your doctor may suggest treatments for your sweating. Examples of drugs sometimes used to treat this side effect include:

• benztropine (Cogentin)
• cyproheptadine
• terazosin

If you have concerns about sweating more than usual with Cymbalta, talk with your doctor.

Eye problems

Eye problems aren’t a common side effect of Cymbalta. But this drug may increase the risk of serious eye problems, such as glaucoma (a buildup of pressure within the eye).

Cymbalta can cause a person’s pupils to dilate. This can trigger a serious eye problem, including vision loss, especially for someone who has closed-angle glaucoma. Symptoms can include:

• sudden vision changes
• eye pain
• eye redness
• swelling in or around your eye

What might help

If you have closed-angle glaucoma, you shouldn’t take Cymbalta. If you’re not sure whether you have this condition, consider visiting an eye doctor. The results of an eye exam can help you and your doctor decide if it’s safe for you to take Cymbalta.

If you develop any of the above symptoms while taking Cymbalta, you should seek medical attention. Urgent treatment is needed to help prevent permanent vision loss.

If you have questions about eye problems that Cymbalta may cause, talk with your doctor.

Liver damage

Although rare, Cymbalta can cause serious liver damage that could be fatal. The risk of this side effect may be higher with alcohol use. It could also be higher in people who already had liver problems before starting Cymbalta.

The following may indicate that there’s a problem with your liver:

• pain in the upper right part of your belly
• itching
• dark urine
• yellowing of your skin or whites of your eyes
• increased liver enzyme levels

What might help

To help prevent this side effect, talk with your doctor about any liver problems you’ve had. It’s also important to be honest about your alcohol consumption. Talk with your doctor about whether you’ve had problems with your liver or alcohol in the past.

If you develop any of the above symptoms, get emergency medical care right away.

Trouble sleeping

Insomnia (trouble falling asleep or staying asleep) can occur with Cymbalta. In studies, this side effect was more commonly reported in people taking the drug for long-term musculoskeletal pain. (This is pain in the bones, muscles, tendons, ligaments, and nerves. ) Waking up earlier than desired was also reported with Cymbalta.

Insomnia is also a common side effect reported in children taking Cymbalta.

What might help

Here are a few tips that may help to improve your sleep:

• Try to exercise regularly.
• Avoid caffeine after lunch.
• Practice good sleep hygiene.

If you’re having insomnia since starting Cymbalta, talk with your doctor. They may suggest the temporary use of a sleep aid, such as melatonin. Or they may adjust your dosage or discuss other treatment options with you.

Suicidal behaviors and thoughts

Cymbalta has a boxed warning for suicidal behaviors and thoughts. A boxed warning is the most serious warning from the Food and Drug Administration (FDA). It alerts doctors and patients about drug effects that may be dangerous.

Antidepressants such as Cymbalta may increase the risk of suicidal behaviors and thoughts in children and young adults ages 24 years or younger. This is a rare side effect. Studies show that the risk is higher after a person first starts treatment or increases their dose.

What might help

While taking Cymbalta, you should watch for any new behaviors, feelings, or thoughts. This is especially important in the first few weeks after starting Cymbalta or after your dose is adjusted.

Consider using a journal or app to make notes about your mood. You may want to ask your loved ones to let you know if they notice that you’re acting differently. Tell your doctor right away if you or someone else notices any changes in your behavior or moods.

Suicide prevention

If you think someone is at immediate risk of self-harm or hurting another person:

• Call 911 or your local emergency number.
• Stay with the person until help arrives.
• Remove any guns, knives, medications, or other things that may cause harm.
• Listen, but don’t judge, argue, threaten, or yell.

If you or someone you know is considering suicide, get help from a crisis or suicide prevention hotline. Try the National Suicide Prevention Lifeline at 800-273-8255.

Allergic reaction

Like most drugs, Cymbalta can cause an allergic reaction in some people. But this side effect wasn’t reported in studies.

Symptoms can be mild or serious and can include:

• skin rash
• itchiness
• flushing (temporary warmth, redness, or deepening of skin color)
• swelling under your skin, typically in your eyelids, lips, hands, or feet
• swelling of your mouth, tongue, or throat, which can make it hard to breathe

What might help

If you have mild symptoms of an allergic reaction, such as a mild rash, call your doctor right away. To manage symptoms, they may suggest an over-the-counter antihistamine you take by mouth, such as Benadryl (diphenhydramine). Or they may recommend a product you apply to your skin, such as hydrocortisone cream.

If your doctor confirms you had a mild allergic reaction to Cymbalta, they’ll decide if you should continue using it.

If you have symptoms of a severe allergic reaction, such as swelling or trouble breathing, call 911 or your local emergency number right away. These symptoms could be life threatening and require immediate medical care.

If your doctor confirms you had a serious allergic reaction to Cymbalta, they may have you switch to a different treatment.

Keeping track of side effects

During Cymbalta treatment, consider keeping notes on any side effects you’re having. You can then share this information with your doctor. This is especially helpful to do when you first start taking new drugs or using a combination of treatments.

Your side effect notes can include things such as:

• what dose of drug you were taking when you had the side effect
• how soon after starting that dose you had the side effect
• what your symptoms were from the side effect
• how it affected your daily activities
• what other medications you were also taking
• any other information you feel is important

Keeping notes and sharing them with your doctor will help your doctor learn more about how Cymbalta affects you. Your doctor can use this information to adjust your treatment plan if needed.

Cymbalta has several warnings that may affect whether you can safely use this drug to treat your condition.

Boxed warning: Suicidal behaviors and thoughts

Cymbalta has a boxed warning for suicidal behaviors and thoughts. A boxed warning is the most serious warning from the Food and Drug Administration (FDA).

Antidepressants such as Cymbalta may increase the risk of suicidal behaviors and thoughts in children and young adults ages 24 years or younger. After starting Cymbalta, you should watch for any new behaviors, feelings, or thoughts. Tell your doctor right away if you or your loved ones notice any changes in your behavior or moods.

To learn more, see “Side effects explained” above.

Other warnings

Cymbalta may not be right for you if you have certain medical conditions or other factors that affect your health. Talk with your doctor about your health history before you take Cymbalta. The list below includes factors to consider.

Liver or kidney problems. The liver and kidneys help clear Cymbalta from the body. In a person who has liver or kidney problems, Cymbalta levels could become too high in their body. This can worsen the drug’s side effects. In rare cases, Cymbalta may cause liver failure. People who already have liver problems may be at higher risk for this side effect. Before taking Cymbalta, tell your doctor about any liver or kidney problems you have.

Closed-angle glaucoma. Cymbalta can cause the pupils to dilate, which may worsen certain eye problems. If you have closed-angle glaucoma, vision loss could occur with Cymbalta. Talk with your doctor about other treatment options.

Heart or blood pressure conditions. Cymbalta may increase your blood pressure. If you already have high blood pressure or heart problems, taking Cymbalta could worsen your condition. Before starting this drug, tell your doctor about any heart or blood pressure problems you may have.

Slow stomach emptying. Cymbalta capsules are delayed-release. As such, they have a special coating that helps protect the drug against the acid in your stomach. If you have a condition that can slow stomach emptying, such as diabetes, the special coating may get destroyed. This could make Cymbalta less effective for treating your condition. Before taking Cymbalta, talk with your doctor about any medical conditions that you have.

Diabetes. If you have diabetes, Cymbalta may make it more difficult to manage your blood sugar levels. Before taking Cymbalta, talk with your doctor about a plan for managing your blood sugar levels.

Seizures. Cymbalta may increase the risk of seizures. But the drug hasn’t been studied in people with epilepsy (a seizure disorder). If you have a seizure disorder, your doctor may suggest another treatment option for your condition.

Bipolar disorder or mania. Cymbalta may bring on or worsen certain symptoms of bipolar disorder or mania. If you have bipolar disorder or mania, talk with your doctor about the risks involved in taking Cymbalta. If you aren’t sure whether you have either condition, your doctor may screen you for them before you take Cymbalta.

Low sodium levels. Cymbalta can cause low sodium levels. If you have problems with your sodium levels, talk with your doctor before you take Cymbalta.

Bleeding problems. Cymbalta may raise your risk for bruising or bleeding problems. If you have a condition that causes bleeding problems, taking this drug may worsen your condition. Before starting Cymbalta, tell your doctor about any current or past bleeding problems.

Allergic reaction. If you’ve had an allergic reaction to Cymbalta or any of its ingredients, you shouldn’t take Cymbalta. Ask your doctor what other medications are better options for you.

Alcohol and Cymbalta

Drinking alcohol isn’t recommended with Cymbalta, especially heavy alcohol consumption.

Alcohol may worsen some of Cymbalta’s common side effects, such as:

• nausea
• sleepiness
• dizziness

Heavy alcohol consumption while taking Cymbalta can increase your risk for serious liver problems and liver failure. This can be life threatening.

If you drink alcohol, talk with your doctor about whether it’s safe for you to do so while taking Cymbalta. You can also ask them how much alcohol is safe for you to drink.

Pregnancy and breastfeeding while taking Cymbalta

Cymbalta use isn’t recommended during pregnancy because its effects aren’t fully known. The drug may cause harm to a developing fetus.

If you’re pregnant or you’re considering a pregnancy, talk with your doctor. They’ll tell you about treatment options that may be safer during this time.

Cymbalta passes into breast milk, and the drug may affect a child who is breastfed. There have been reports of drowsiness and feeding problems in children breastfed by people taking Cymbalta.

If you’re breastfeeding or have plans to breastfeed, talk with your doctor. They can help you weigh the pros and cons of breastfeeding while taking this drug.

Many people find that Cymbalta is an effective treatment for their condition. When you’re considering Cymbalta as a treatment option, it’s a good idea to talk with your doctor about your risk for side effects. Here are some questions that you may want to ask:

• Do my medical conditions increase my risk for side effects with Cymbalta?
• Are there other ways to help me manage side effects from Cymbalta?
• Are there any lifestyle changes I can make that may help to reduce my need to take Cymbalta in the future?

To learn more about Cymbalta, see these articles:

• Cymbalta (duloxetine)
• Cymbalta Interactions: Alcohol, Medications, and Others
• Dosage Details for Cymbalta

To get information on different conditions and tips for improving your health, subscribe to any of Healthline’s newsletters. You may also want to check out the online communities at Bezzy. It’s a place where people with certain conditions can find support and connect with others.

Q:

My child has generalized anxiety disorder, and their doctor suggested Cymbalta treatment. I’m concerned about the drug’s suicide warning. How common or rare is this side effect, and how can it be avoided?

Anonymous patient

A:

The risk of suicidal behaviors and thoughts with Cymbalta use is rare. But Cymbalta does have a boxed warning for this side effect. A boxed warning is the most serious warning from the Food and Drug Administration (FDA).

When compared with a placebo (a treatment with no active drug), antidepressants such as Cymbalta were associated with increased suicidal behaviors and thoughts. This risk affected children and young adults ages 24 years and younger.

For more about this FDA boxed warning, see “Side effects explained” above.

If your child’s doctor prescribes Cymbalta, make sure to monitor your child for any changes in their behavior or mood. This is especially important when treatment with Cymbalta begins or the dosage is changed. Contact your child’s doctor right away if you notice any changes in your child’s behavior or mood.

The Healthline Pharmacist TeamAnswers represent the opinions of our medical experts. All content is strictly informational and should not be considered medical advice.

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Disclaimer: Healthline has made every effort to make certain that all information is factually correct, comprehensive, and up to date. However, this article should not be used as a substitute for the knowledge and expertise of a licensed healthcare professional. You should always consult your doctor or another healthcare professional before taking any medication. The drug information contained herein is subject to change and is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. The absence of warnings or other information for a given drug does not indicate that the drug or drug combination is safe, effective, or appropriate for all patients or all specific uses.

11 Cymbalta Side Effects You Should Know About

1

Withdrawal symptoms

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The goal with antidepressants is to reduce major symptoms and then taper off after about nine months, Saltz says.

But it can be hard to quit Cymbalta when the time comes, in large part due to withdrawal symptoms. One study found that dizziness, nausea, headaches, and paresthesia (commonly called “brain zaps,” or a sensation of electric shock in the brain) were common when going off the drug. Withdrawal symptoms lasted about two weeks on average.

The longer you’re on Cymbalta, the more likely it is to be an issue. And the risks of staying on the drug for the long-term are unknown. “What we do know is it is always important for everyone to taper off slowly [and under doctor supervision]. Abruptly stopping is much more likely to produce symptoms,” she says.

2

Suicidal thoughts

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People 24 and younger may experience thoughts of suicide on Cymbalta. According to the FDA, the risk is greatest in those under the age of 18 and elevated in people ages 18 to 24.

This may be because Cymbalta can worse or cause symptoms including anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, hypomania, and mania.

At the same time, suicide risk actually decreases in people 25 and over, particularly among people over the age of 65.

“Any of these drugs may increase suicidal thoughts in periods of time when there’s a big shift—when you’re starting or raising a dose,” says Saltz. “The numbers aren’t big, so we don’t know who will be affected.”

3

Low sex drive

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No getting around this one: Pretty much all antidepressants have the potential to zap your sex drive. In fact, low libido is one of the most common side effects of drugs like Cymbalta—although it doesn’t affect everyone.

If it does, your doctor might try decreasing your dose and/or your therapist may offer behavioral tricks to get around it. “Sometimes it goes away. Other times it may be intolerable, in which case it might not be a drug that’s good for you,” says Saltz.

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4

Fatigue or drowsiness

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If you find that you feel super-fatigued on Cymbalta, your doctor may suggest taking it at night before bed, when drowsiness isn’t a problem, or taking a divided dose, says Saltz.

While drugs like antihistamines don’t interact with SNRIs, your doctor will also advise you to skip them because, in combination, these two drugs can make you extra-drowsy.

5

High blood pressure

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With both SSRIs and SNRIs, increased blood pressure is possible. “Think of when you get a big adrenaline rush. You get basal restriction, which causes your blood pressure to go up,” says Saltz. A similar reaction can happen when you’re taking Cymbalta.

For most people, especially younger people, it’s not an issue. But if you already have borderline or high blood pressure, your doctor will want to keep an extra close eye on you.

6

Light-headedness

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Some people experience light-headedness or dizziness, especially when they first start Cymbalta. “It has to do with a shift in blood pressure. You’ll want to get up slowly from lying positions,” says Saltz. If it continues, or really bothers you, definitely check in with your doctor.

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7

Liver dysfunction

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Both medications and alcohol are metabolized—i.e. processed—by your liver, and consuming either in high levels can cause jaundice and other more serious liver problems. “Liver problems are pretty rare but bad,” says Saltz.

The risk rises if you drink alcohol while taking Cymbalta: One drink is more like two. Certain other drugs, including some OTC ones, can also potentially interact with Cymbalta and be hard on your liver. “That’s why it’s very important to discuss all other medications you’re taking with your doctor,” Saltz says.

8

Abnormal bleeding

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In very rare instances, taking aspirin, nonsteroidal anti-inflammatory drugs, warfarin, and other anti-coagulants while on Cymbalta can cause excessive bleeding. “Talk to doctor before you take those meds,” says Saltz.

9

Overdose or death

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One very rare but serious side effect of Cymbalta and other antidepressants is serotonin syndrome. “Raising serotonin levels a certain amount can be helpful, but a lot can cause toxicity and even kill you,” explains Saltz. If you experience fast heartbeat, loss of coordination, extremely restlessness, agitation, and/or hallucinations, tell your doctor right away, who will likely take you off of the medication immediately.

Overdose can also be a problem. “Someone who purposely took a bottle might say they’re only antidepressants, but it’s very dangerous. And if your kid gets a hold of a bottle, call poison control and head to the ER right away,” says Saltz.

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10

Stomach pain

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Gastrointestinal symptoms like nausea, diarrhea, constipation, and heartburn are not as rare as overdose or death, but they’re obviously not as serious, either. Other milder symptoms include headaches, dry mouth, loss of appetite, and night sweats. “We try to figure out if they can be managed over time. They can go away, but they don’t always,” says Saltz.

One last word of warning: Be sure to let your doctor know if you have a family or personal history of bipolar disorder, because antidepressants may increase your likelihood of becoming manic. “If you experience periods of time of where you feel highly agitated and irritable or overly confident and sped up, ask your doctor,” says Saltz. “It’s not that you wouldn’t be prescribed an antidepressant, but you really want to be cautious. You’d be checked more frequently and might be put on a mood stabilizer instead.”

Colleen de Bellefonds

Colleen de Bellefonds is an American freelance journalist living in Paris, France, with her husband and dog, Mochi. She loves running, yoga, and wine, and is very particular about her baguettes. 

Simbalta capsules enteric 30mg №14

Composition

Each capsule contains:

for a dosage of 30 mg:

active substance: duloxetine hydrochloride equivalent to 30 mg duloxetine base,

excipients:

contents of capsule – hypromellose 11.2 mg, sucrose 18.1 mg, granulated sugar 40.6 mg, talc 23.6 mg, hypromellose acetate succinate 22.4 mg, triethyl citrate 4.5 mg, dye white (titanium dioxide, hypromellose) 14.9mg,

capsule shell – indigo carmine 0.11625 mg, titanium dioxide 1.77255 mg, sodium lauryl sulfate 0.06875 mg, gelatin i.e. up to 50 mg,

overprint – TekPrint SW-4028 green ink trace amounts.

for a dosage of 60 mg:

active substance: duloxetine hydrochloride equivalent to 60 mg duloxetine base,

excipients: 900 12

contents of capsule – hypromellose 22. 3 mg, sucrose 36.2 mg, granulated sugar 80.9 mg, talc 47.1 mg, hypromellose acetate succinate 44.6 mg, triethyl citrate 8.9 mg, white dye (titanium dioxide, hypromellose ) 29.6 mg,

capsule shell – indigo carmine 0.18006 mg, titanium dioxide 0.69848 mg, sodium lauryl sulfate 0.10763 mg, gelatin a.i. 76 mg, iron dye yellow oxide 0.13449 mg,

overprint – white ink TekPrint SW-0007P trace amounts.

Dosage form

Enteric capsules

Description

Capsules 30 mg : opaque, hard gelatin capsules (#3) consisting of a blue cap with green ink identification code 95 43 and white bodies with green ink dosage 30 mg.

Capsules 60 mg : opaque, hard gelatin capsules (#1) consisting of a blue cap with identification code 9 imprinted in white ink542 and green body with white ink 60 mg. The contents of the capsules are pellets from white to grayish-white.

Pharmacodynamics

Duloxetine is an antidepressant, a serotonin and norepinephrine reuptake inhibitor, and weakly inhibits dopamine uptake, without significant affinity for histaminergic, dopaminergic, cholinergic and adrenergic receptors. The mechanism of action of duloxetine in the treatment of depression is to suppress the reuptake of serotonin and norepinephrine, resulting in increased serotonergic and noradrenergic neurotransmission in the CNS.

Duloxetine has a central mechanism of pain suppression, which is primarily manifested by an increase in the threshold of pain sensitivity in pain syndrome of neuropathic etiology.

Pharmacokinetics

Absorption . Duloxetine is well absorbed when taken orally. Absorption begins 2 hours after taking the drug. The maximum concentration of the drug is reached 6 hours after priming. Food intake does not affect the maximum concentration of the drug, but increases the time to reach the maximum concentration from 6 to 10 hours, which indirectly reduces the degree of absorption (approximately 11%).

Distribution . The apparent volume of distribution is about 1640 liters. Duloxetine binds well to plasma proteins (> 90%), mainly to albumin and l-acid globulin, but liver or kidney disorders do not affect the degree of plasma protein binding.

Metabolism . Duloxetine is extensively metabolized and its metabolites are primarily excreted in the urine.

Both the CYP2D6 isoenzyme and the CYP1A2 isoenzyme catalyze the formation of two major metabolites (4-hydroxyduloxetine glucuronide, 5-hydroxy,6-methoxyduloxetine sulfate). Circulating metabolites do not have pharmacological activity.

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

Selected patient groups .

Gender : although pharmacokinetic differences between males and females have been identified (mean clearance of duloxetine is lower in females), these differences are not large enough to warrant dose adjustment based on sex.

Age : Although pharmacokinetic differences have been identified between middle-aged and elderly patients (AUC – area under the concentration-time curve is higher and the half-life of the drug is longer in the elderly), these differences are not enough to change the dose depending only on the age of patients.

Impaired renal function : in patients with severely impaired renal function (end-stage renal disease – chronic renal failure) on hemodialysis, the Cmax (maximum concentration) and average exposure (AUC) values ​​of duloxetine increased by 2 times. In this regard, the feasibility of reducing the dose of the drug in patients with clinically significant impaired renal function should be considered.

Impaired liver function : Patients with clinical signs of hepatic impairment may experience slow metabolism and excretion of duloxetine. Following a single dose of 20 mg duloxetine in 6 patients with cirrhosis of the liver with moderate hepatic impairment (Child-Pugh Class B), the half-life of duloxetine was approximately 15% longer than in healthy subjects of the corresponding sex and age with a five-fold increase in mean exposure . Despite the fact that the Cmax in patients with cirrhosis was the same as in healthy people, the elimination half-life was approximately 3 times longer.

Indications for use

• depression
• pain form of peripheral diabetic neuropathy
• generalized anxiety disorder
• chronic pain syndrome of the musculoskeletal system (including due to fibromyalgia, chronic pain syndrome in the lower back and osteoarthritis of the knee)

Contraindications

Overdoses have been reported in clinical studies with up to 3000 mg of duloxetine taken alone or in combination with other drugs. At the same time, one of these cases ended in death. However, spontaneous (post-marketing) reports have described lethal acute overdoses, usually with combined use of several drugs, in which the dose of duloxetine was not more than 1000 mg. An overdose of duloxetine (isolated or combined) may be accompanied by the following symptoms: drowsiness, coma, clonic convulsions, serotonin syndrome, vomiting and tachycardia. In preclinical studies (in animals), the main signs of intoxication associated with overdose were related to disorders of the central nervous and digestive systems and included such manifestations as tremor, clonic convulsions, ataxia, vomiting and loss of appetite.

Overdose treatment. The specific antidote is not known, however, in the case of serotonin syndrome, corrective treatment with cyproheptadine and the use of methods for normalizing body temperature are possible. An adequate supply of fresh air must be ensured. Cardiac monitoring and vital signs are recommended, along with symptomatic and supportive treatment. Gastric lavage may be indicated if little time has passed since the drug was taken orally, or as part of symptomatic treatment. Activated charcoal may be used to limit absorption. Duloxetine is characterized by a large volume of distribution, and therefore the effectiveness of forced diuresis, hemoperfusion, exchange perfusion seems doubtful.

Use in pregnancy and lactation

Due to insufficient experience with the use of duloxetine during pregnancy, the drug should be used during pregnancy only if the potential benefit to the patient significantly outweighs the potential risk to the fetus. Patients should be warned that if pregnancy occurs or is planned during treatment with duloxetine, they should inform their physician.

Epidemiological evidence suggests that the use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy, especially in late pregnancy, may increase the risk of persistent pulmonary hypertension in the newborn. Despite the lack of studies on the relationship of persistent pulmonary hypertension in newborns and the use of SSRIs, a potential risk cannot be excluded, given the mechanism of action of duloxetine (serotonin reuptake inhibition).

As with other serotonergic drugs, withdrawal symptoms may occur in newborns if duloxetine is used by the mother late in pregnancy.

Withdrawal syndrome includes the following symptoms: low blood pressure, tremor, hyperexcitability syndrome, feeding difficulties, respiratory distress syndrome, convulsions. Most of the symptoms were observed during childbirth or in the first few days after childbirth.

Due to the fact that duloxetine passes into breast milk (the concentration in the fetus is approximately 0.14% of the concentration in the mother on the basis of mg / kg body weight), breast-feeding is not recommended during duloxetine therapy.

Interactions

Monoamine oxidase inhibitors (MAOIs). Due to the risk of developing serotonin syndrome, duloxetine should not be used in combination with MAOIs, and for at least 14 days after stopping MAOI treatment. Based on the length of the half-life of duloxetine, a break of at least 5 days after the end of duloxetine should be taken before taking an MAOI.

Reversible selective MAOIs such as moclobemide have a lower risk of serotonin syndrome. However, the concomitant use of a reversible MAOI and duloxetine is not recommended.

CYP1A2 isoenzyme inhibitors. Due to the fact that the CYP1A2 isoenzyme is involved in the metabolism of duloxetine, the simultaneous use of duloxetine with potential inhibitors of the CYP1A2 isoenzyme is likely to lead to an increase in the concentration of duloxetine. The potent CYP1A2 inhibitor fluvoxamine (100 mg once daily) reduced the mean plasma clearance of duloxetine by approximately 77%. Caution should be exercised when prescribing duloxetine with inhibitors of the CYP1A2 isoenzyme (eg, some quinolone antibiotics) and lower doses of duloxetine should be used.

Drugs affecting the central nervous system. Caution should be exercised when co-administering duloxetine with other drugs and agents that affect the central nervous system, especially those that have a similar mechanism of action, including alcohol. Simultaneous use with other drugs that have a serotonergic effect (for example, SNRIs, SSRIs, triptans and tramadol) can lead to the development of serotonin syndrome.

Serotonin syndrome. In rare cases, serotonin syndrome has been observed with concomitant use of SSRIs (eg, paroxetine, fluoxetine) and serotonergic drugs. Caution should be exercised when co-administering duloxetine with serotonergic antidepressants such as SSRIs, tricyclic antidepressants (clomipramine or amitriptyline), St. John’s wort, venlofaxine or triptans, tramadol, finidine, and tryptophan.

Drugs metabolized by the CYP1A2 isoenzyme. The simultaneous use of duloxetine (60 mg 2 times a day) did not significantly affect the pharmacokinetics of theophylline, which is metabolized by the CYP1A2 isoenzyme. Duloxetine is unlikely to have a clinically significant effect on the metabolism of CYP1A2 isoenzyme substrates.

Drugs metabolized by CYP2D6 isoenzyme . Duloxetine is a moderate inhibitor of the CYP2D6 isoenzyme. When taking duloxetine at a dose of 60 mg 2 times a day, along with a single dose of desipramine, a substrate of the CYP2D6 isoenzyme, the AUC of desipramine increases 3 times. Co-administration of duloxetine (40 mg twice daily) increased the steady state concentration of tolterodine (2 mg twice daily) by 71%, but had no effect on the pharmacokinetics of the 5-hydroxy metabolite. Thus, caution should be exercised when using duloxetine with drugs that are primarily metabolized by the CYP2D6 isoenzyme system and have a narrow therapeutic index.

CYP2D6 isoenzyme inhibitors. Since the CYP2D6 isoenzyme is involved in the metabolism of duloxetine, concomitant use of duloxetine with potential inhibitors of the CYP2D6 isoenzyme may lead to increased duloxetine concentrations. Paroxetine (20 mg once daily) reduced the mean clearance of duloxetine by approximately 37%. When using duloxetine with inhibitors of the CYP2D6 isoenzyme (for example, SSRIs), caution should be exercised.

Oral contraceptives and other steroid preparations. The results of studies in vitro indicate that duloxetine does not induce the catalytic activity of the CYP3A isoenzyme. No specific in vivo drug interaction studies have been performed with .

Anticoagulants and antithrombotic drugs. Due to the potential increased risk of bleeding associated with pharmacodynamic interactions, caution should be exercised when duloxetine is co-administered with anticoagulants or antithrombotic agents. In addition, the combined use of duloxetine and warfarin increased the value of the international normalized ratio (INR). However, concomitant use of duloxetine and warfarin under stable conditions in healthy volunteers in a clinical pharmacology study did not reveal a clinically significant change in the INR from the mean or change in the pharmacokinetics of the right- or left-handed isomer of warfarin.

Antacids and H antagonists ₂ -histamine receptors. Co-administration of duloxetine and aluminum- and magnesium-containing antacids or duloxetine and famotidine did not significantly affect the extent of absorption of duloxetine at a dose of 40 mg

CYP1A2 isoenzyme inducers. Population pharmacokinetic analysis showed that, compared with non-smokers, smokers had approximately 50% lower plasma concentrations of duloxetine.

Highly protein bound drugs. Duloxetine is highly bound to plasma proteins (&gt, 90%). Therefore, the administration of duloxetine to a patient who is taking another drug that is highly bound to plasma proteins may lead to an increase in the concentration of the free fractions of both drugs.

Dosage and administration

Inside. Capsules should be swallowed whole, without chewing or crushing. Do not add the drug to food or mix it with liquids, as this can damage the enteric coating of the pellets.

Depression. The initial and recommended maintenance dose is 60 mg once daily with or without food. In clinical studies, the safety of doses from 60 mg up to a maximum dose of 120 mg per day has been evaluated. However, there is no clinical evidence that patients who do not respond to the initial recommended dose experience any improvement with dose increases.

Response to therapy is usually observed 2-4 weeks after the start of treatment.

To avoid relapse after a response to antidepressant therapy is achieved, it is recommended to continue treatment for several months. In patients responding positively to duloxetine therapy with a history of recurring depression, further long-term therapy at a dose of 60 to 120 mg / day is possible.

Generalized anxiety disorder. The recommended starting dose in patients with generalized anxiety disorder is 30 mg daily, with or without food. In patients with insufficient response to therapy, the dose may be increased to 60 mg, the usual maintenance dose in most patients.

In patients with comorbid depression, the initial and maintenance dose is 60 mg daily (see also recommendations above). In clinical studies, doses up to 120 mg / day have been shown to be effective, in addition, such dosages have been evaluated for safety. Therefore, in patients with insufficient response to a dose of 60 mg, it may be appropriate to increase the dose to 90 mg or 120 mg. Dose escalation should be based on clinical response and tolerability.

To avoid relapse after a response to therapy, it is recommended to continue treatment for several months.

Painful form of peripheral diabetic neuropathy. The initial and recommended maintenance dose is 60 mg once daily with or without food. During clinical studies, the safety of doses from 60 mg to a maximum dose of 120 mg per day, divided into equal doses, was also evaluated. The plasma concentration of duloxetine is characterized by significant individual variability. Therefore, some patients who do not respond well to the 60 mg/day dose may improve with a higher dose.

Treatment response should be assessed after 2 months. Patients with poor initial response are unlikely to improve response after this time period.

Therapeutic effect should be evaluated regularly (at least once every three months).

Chronic pain syndrome of the musculoskeletal system (including due to fibromyalgia, chronic pain syndrome in the lower back and osteoarthritis of the knee). Initial treatment: The recommended dose of Cymbalta is 60 mg once daily. Therapy may be initiated at a dose of 30 mg for one week to allow patients to adjust to the drug before increasing the dose to 60 mg once daily. There is no evidence that higher doses provide additional benefit, even in patients who do not respond to therapy with the drug at a dose of 60 mg. Higher doses are associated with a higher incidence of adverse reactions. Continuation of Treatment: The efficacy of Cymbalta in the treatment of fibromyalgia has been demonstrated in placebo-controlled studies lasting up to 3 months. The efficacy of Cymbalta has not been established in longer-term studies, but the decision to continue treatment should be based on the individual patient’s response.

In patients with renal insufficiency: with a creatinine clearance of 30-80 ml / min, dose adjustment is not required, with a creatinine clearance of less than 30 ml / min, the use of the drug is contraindicated.

In patients with hepatic impairment: the drug should not be administered to patients with liver disease leading to liver failure.

Age : In elderly patients for the treatment of generalized anxiety disorder, an initial dose of 30 mg is recommended for two weeks prior to initiation of duloxetine at the target dose of 60 mg. In the future, it is possible to use the drug at a dose of more than 60 mg per day to achieve a good result. A systematic evaluation of the priming of the drug in a dose of more than 120 mg was not carried out. When using duloxetine for other indications, dose adjustment based on age is not required.

Recommended for use in patients 18 years of age. Duloxetine is not recommended for use in children under 18 years of age due to insufficient data on its safety and efficacy in this age group of patients.

Abrupt discontinuation of therapy: should be avoided. When treatment with duloxetine is discontinued, the dose should be gradually reduced over one to two weeks in order to reduce the risk of withdrawal. If severe withdrawal symptoms occur after a dose reduction or after treatment is stopped, then continuation of the previously prescribed dose may be considered. Subsequently, the doctor may continue to reduce the dose, but even more gradually.

Overdose

Cases of overdose have been reported in clinical trials with simultaneous oral administration of up to 3000 mg of duloxetine alone or in combination with other drugs. At the same time, one of these cases ended in death. However, spontaneous (post-marketing) reports have described lethal acute overdoses, usually with combined use of several drugs, in which the dose of duloxetine was not more than 1000 mg. An overdose of duloxetine (isolated or combined) may be accompanied by the following symptoms: drowsiness, coma, clonic convulsions, serotonin syndrome, vomiting and tachycardia. In preclinical studies (in animals), the main signs of intoxication associated with overdose were related to disorders of the central nervous and digestive systems and included such manifestations as tremor, clonic convulsions, ataxia, vomiting and loss of appetite.

Overdose treatment. The specific antidote is not known, however, in the case of serotonin syndrome, corrective treatment with cyproheptadine and the use of methods for normalizing body temperature are possible. An adequate supply of fresh air must be ensured. Cardiac monitoring and vital signs are recommended, along with symptomatic and supportive treatment. Gastric lavage may be indicated if little time has passed since the drug was taken orally, or as part of symptomatic treatment. Activated charcoal may be used to limit absorption. Duloxetine is characterized by a large volume of distribution, and therefore the effectiveness of forced diuresis, hemoperfusion, exchange perfusion seems doubtful.

Special instructions

Exacerbation of manic/hypomanic state. As with similar CNS drugs, duloxetine should be used with caution in patients with a history of manic episodes.

Epileptic seizures. As with similar drugs that affect the central nervous system, duloxetine should be used with caution in patients with a history of epileptic seizures.

Mydriasis. Cases of mydriasis have been observed with duloxetine, so caution should be exercised when prescribing duloxetine to patients with elevated intraocular pressure or in individuals at risk of developing acute angle-closure glaucoma.

Increased blood pressure. In rare cases, there was a rise in blood pressure during the period of treatment with duloxetine. In patients with arterial hypertension and / or other cardiovascular diseases, it is recommended to measure blood pressure.

Impaired liver or kidney function. In patients with severe renal impairment (CC &lt, 30 ml / min) or severe hepatic insufficiency, an increase in the concentration of duloxetine in plasma is observed. If duloxetine is clinically warranted in such patients, lower initial doses of the drug should be used.

Suicidal behavior. The risk of committing suicide exists in all patients with depression and some other mental disorders. This danger may persist until the onset of remission. As a result, patients in whom the risk of committing suicide is highest should be under close medical supervision during pharmacotherapy. As well as the use of other drugs that have a mechanism of pharmacological action similar to duloxetine (SSRIs, SNRIs), the use of duloxetine during treatment, or upon its termination, in some cases was associated with the development of suicidal thoughts and suicidal behavior. The use of duloxetine in patients under 18 years of age has not been studied, and this drug is not intended for use in such patients. A causal relationship between the use of duloxetine and the occurrence of suicidal events in patients of this age group has not been established. At the same time, some analytical reviews of the results of a number of studies using antidepressants for the treatment of mental disorders indicate an increased risk of developing suicidal thoughts and / or suicidal behavior in children, adolescents and adults under 25 years of age compared with placebo. Physicians should encourage patients to report all disturbing thoughts and feelings at all times.

Increased risk of bleeding. SSRIs and SNRIs, including duloxetine, may increase the risk of bleeding, including gastrointestinal bleeding (see section Side effects). Therefore, duloxetine should be used with caution in patients taking anticoagulants and/or drugs that affect platelet function (eg, NSAIDs, aspirin) and in patients with a history of bleeding.

Hyponatremia. Cases of hyponatremia have been reported very rarely (in some cases, serum sodium was lower than 110 mmol/l). Most of these cases occurred in elderly patients, especially in combination with a recent history of altered fluid balance or in the presence of conditions predisposing to fluid balance changes.

Hyponatremia may present with non-specific symptoms (such as dizziness, weakness, nausea, vomiting, confusion, drowsiness, lethargy). Signs and symptoms in more severe cases included fainting, falls, and convulsions.

Monoamine oxidase inhibitors (MAOIs). Serious reactions, sometimes fatal, have been reported in patients taking a serotonin reuptake inhibitor in combination with a MAOI, including pyrexia, rigidity, myoclonus, peripheral disturbances with possible fluctuations in vital signs, and changes in mental status, including marked excitation with the transition to delirium and coma. These reactions have also been observed in patients who had their serotonin reuptake inhibitor discontinued shortly before MAOIs. In some cases, patients experienced symptoms characteristic of neuroleptic malignant syndrome. The effects of the combined use of duloxetine and MAOIs have not been evaluated in humans or animals. Therefore, given the fact that duloxetine is an inhibitor of both serotonin and norepinephrine reuptake, it is not recommended to take duloxetine in combination with an MAOI or for at least 14 days after stopping MAOI treatment. Based on the length of the half-life of duloxetine, a break of at least 5 days after the end of duloxetine should be taken before taking an MAOI.

Increased activity of liver enzymes. Some patients treated with duloxetine in clinical studies have experienced elevated liver enzymes. The observed abnormalities were usually transient and disappeared spontaneously or after duloxetine was discontinued. Serious elevations in liver enzymes (10 times or more above the upper limit of normal), as well as liver damage of cholestatic or mixed origin, were rare, and in some cases were associated with excessive alcohol consumption or previous liver disease. Caution is advised in the use of duloxetine in patients who consume significant amounts of alcohol, as well as those with existing liver disease.

Influence on the ability to drive vehicles and control mechanisms

Duloxetine may cause sedation, drowsiness and other side effects when taking duloxetine. In this regard, patients taking duloxetine should be careful when driving dangerous mechanical means, including a car.

Product form

Enteric capsules 30 mg or 60 mg.

Pharmacy conditions

Prescription

Storage conditions

Store at 15-30 C.

Keep out of the reach of children.

Shelf life

3 years. Do not use after expiration date.

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

• Pharmacological properties
• Simbalt’s testimony
• Application of Cymbalta
• Contraindications
• Side effects
• Special instructions
• Interactions
• Overdose
• Storage conditions
• Diagnosis
• Recommended alternatives
• Trade names

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, increased 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.

According to post-marketing studies, the following side effects were noted:

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;

from the skin side: 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 with a high risk of suicide during the treatment period should be under strict supervision, 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, the concomitant use of duloxetine with active CYP2D6 inhibitors 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.

Caution should be exercised when prescribing duloxetine in combination with other drugs that affect the central nervous system, especially those with a similar mechanism of action.

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.