DULOXETINE ZENTIVA 60 mg HARD GASTRO-RESISTANT CAPSULES

2. What you need to know before you take Duloxetine Zentiva

Do not take Duloxetine Zentiva if:

• you are allergic to duloxetine or any of the other ingredients of this medicine (listed in section 6);
• you have liver failure;
• you have severe kidney disease;
• you are taking or have taken within the last 14 days another medicinal product called a monoamine oxidase inhibitor (MAOI) (see "Using Duloxetine Zentiva with other medicines");
• you are taking fluvoxamine, which is usually used to treat depression, ciprofloxacin or enoxacin, which are used to treat some infections.
• you are taking other medicines that contain duloxetine (see "Using Duloxetine Zentiva with other medicines")

Tell your doctor if you have high blood pressure or heart disease. Your doctor will decide if you can take Duloxetine Zentiva.

Warnings and precautions

Duloxetine Zentiva may not be suitable for you due to the following reasons. Tell your doctor before taking Duloxetine Zentiva if:

• you are using other medicines for depression (see "Using Duloxetine Zentiva with other medicines");
• you are taking St. John's Wort, a herbal remedy (Hypericum perforatum);
• you have any kidney disease;
• you have had seizures (fits);
• you have had mania;
• you have bipolar disorder;
• you have eye problems, such as certain types of glaucoma (increased pressure in the eye);
• you have had bleeding problems (a tendency to develop bruises), especially if you are pregnant (see "Pregnancy and breast-feeding");
• you are at risk of having low sodium levels (for example, if you are taking diuretics, especially if you are an elderly person);
• you are being treated with other medicines that may cause liver damage;
• you are taking any opioid medication such as those containing buprenorphine, tramadol, and pethidine. Using these medicines with Duloxetine Zentiva may cause serotonin syndrome, a potentially life-threatening condition (see "Using Duloxetine Zentiva with other medicines");
• you are taking other medicines that contain duloxetine (see "Taking Duloxetine Zentiva with other medicines").

Duloxetine Zentiva may cause a feeling of restlessness or an inability to sit or stand still. If this happens, you should tell your doctor.

Some medicines of the same class as Duloxetine Zentiva (called SSRIs/SNRIs) may cause symptoms of sexual dysfunction (see section 4). In some cases, these symptoms have persisted after stopping treatment.

Thoughts of suicide and worsening of your depression or anxiety disorder

If you are depressed and/or have an anxiety disorder, you may sometimes have thoughts of harming or killing yourself. These thoughts may be increased when you first start taking antidepressants, as all these medicines take time to work, usually about 2 weeks, but sometimes longer.

You are more likely to have these thoughts if:

• you have previously had thoughts of self-harm or suicide;
• you are a young adult. Information from clinical trials has shown an increased risk of suicidal behavior in adults aged less than 25 years with psychiatric conditions who were treated with an antidepressant.

Contact your doctor or go to the hospital immediately if you have any thoughts of self-harm or suicide.

It may be helpful to tell a relative or close friend that you are depressed or have an anxiety disorder and ask them to read this leaflet. You might ask them to tell you if they think your depression or anxiety is getting worse, or if they are worried about changes in your behavior.

Children and adolescents under 18 years

Duloxetine Zentiva is not normally given to children and adolescents under 18 years. Also, you should know that patients under 18 have an increased risk of side effects such as suicide attempt, suicidal thoughts, and hostility (predominantly aggression, oppositional behavior, and anger) when they take this class of medicine. Despite this, your doctor may prescribe duloxetine for patients under 18 because they decide that it is in the patient's best interest. If your doctor has prescribed duloxetine for a patient under 18 and you want to discuss this, please go back to your doctor. You should tell your doctor if any of the symptoms listed above occur or get worse in patients under 18 who are taking Duloxetine Zentiva. Also, in this age group, the long-term safety of duloxetine regarding growth, maturation, and cognitive and behavioral development has not yet been demonstrated.

Using Duloxetine Zentiva with other medicines

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

The main ingredient of Duloxetine Zentiva, duloxetine, is used in other medicines for other treatments: diabetic neuropathic pain, depression, anxiety, and urinary incontinence. You should avoid using more than one of these medicines at the same time. Check with your doctor if you are already using other medicines that contain duloxetine.

Your doctor will decide if you can take Duloxetine Zentiva with other medicines. Do not start or stop taking any medicines, including those bought without a prescription and herbal remedies, without first talking to your doctor.

You should also tell your doctor if you are taking any of the following medicines:

• Monoamine oxidase inhibitors (MAOIs): do not take Duloxetine Zentiva if you are taking, or have taken within the last 14 days, another antidepressant medicine called a monoamine oxidase inhibitor (MAOI). Examples of MAOIs include moclobemide (an antidepressant) and linezolid (an antibiotic). Taking an MAOI with many prescription medicines, including Duloxetine Zentiva, can cause serious side effects, even death. You must wait at least 14 days after stopping an MAOI before you can take Duloxetine Zentiva. Also, you must wait at least 5 days after stopping Duloxetine Zentiva before you can take an MAOI.
• Medicines that cause drowsiness: these include medicines prescribed by your doctor, such as benzodiazepines, strong painkillers, antipsychotics, phenobarbital, and antihistamines.
• Medicines that increase serotonin levels: triptans, tryptophan, selective serotonin reuptake inhibitors (SSRIs, such as paroxetine and fluoxetine), serotonin-norepinephrine reuptake inhibitors (SNRIs, such as venlafaxine), tricyclic antidepressants (such as clomipramine, amitriptyline), St. John's Wort, MAOIs (such as moclobemide and linezolid), and opioid medicines such as those containing buprenorphine, tramadol, and pethidine. These medicines increase the risk of side effects such as serotonin syndrome (see "Warnings and precautions"). If you notice any unusual symptoms while taking any of these medicines with Duloxetine Zentiva, you should tell your doctor.
• Oral anticoagulants or antiplatelet agents: medicines that thin the blood or prevent blood clotting. These medicines may increase the risk of bleeding.

Taking Duloxetine Zentiva with food, drinks, and alcohol

Duloxetine Zentiva can be taken with or without food. You should be cautious if you drink alcohol while being treated with duloxetine.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

• Tell your doctor if you become pregnant or are planning to become pregnant while being treated with Duloxetine Zentiva. You should only use Duloxetine Zentiva after discussing the potential benefits and risks with your doctor.

• Make sure your midwife and/or doctor know you are taking Duloxetine Zentiva. Other similar medicines (SSRIs) taken during pregnancy may increase the risk of a serious condition in babies, called persistent pulmonary hypertension of the newborn (PPHN), which makes the baby breathe faster and may turn blue. These symptoms usually start during the first 24 hours after the baby is born. If this happens to your baby, you should contact your midwife and/or doctor immediately.

• If you take Duloxetine Zentiva near the end of your pregnancy, your baby may have some symptoms when it is born. These usually start on the day the baby is born or during the first few days. These symptoms include being floppy, jittery, having difficulty feeding, having trouble breathing, and having seizures. If your baby has any of these symptoms when it is born, or if you are concerned about your baby's health, contact your doctor or midwife who will be able to advise you.

• If you take Duloxetine Zentiva near the end of your pregnancy, there is a greater risk of heavy vaginal bleeding shortly after giving birth, especially if you have had bleeding problems. Your doctor or midwife should know that you are taking duloxetine so that they can advise you.

• Data on the use of duloxetine in the first three months of pregnancy do not show an increased overall risk of birth defects in the baby. If you take duloxetine during the second half of your pregnancy, there may be a greater risk that your baby will be born early (6 additional premature babies per 100 women taking duloxetine in the second half of pregnancy), especially between 35 and 36 weeks of pregnancy.

• Tell your doctor if you are breast-feeding. Duloxetine Zentiva is not recommended during breast-feeding. Ask your doctor or pharmacist for advice.

Driving and using machines

While taking Duloxetine Zentiva, you may feel drowsy or dizzy. Do not drive or operate tools or machines until you know how the treatment affects you.

Duloxetine Zentiva contains sucrose

This medicine contains sucrose. If your doctor has told you that you have an intolerance to some sugars, contact them before taking this medicine.

3. How to take Duloxetine Zentiva

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Duloxetine Zentiva should be taken orally. You should swallow the capsule whole with water.

For depression and diabetic neuropathic pain:

The recommended dose of Duloxetine Zentiva is 60 mg once a day, but your doctor will prescribe the dose that is best for you.

For generalized anxiety disorder:

The usual starting dose of Duloxetine Zentiva is 30 mg once a day, after which most patients are moved to 60 mg once a day, but your doctor will prescribe the dose that is best for you. The dose may be adjusted up to 120 mg a day depending on your response to Duloxetine Zentiva.

To help you remember to take Duloxetine Zentiva, it may be helpful to take it at the same times each day.

Discuss with your doctor how long you should take Duloxetine Zentiva. Do not stop taking Duloxetine Zentiva, or reduce the dose, without consulting your doctor. It is important to treat your condition properly to help you improve. If you do not treat your condition, it may not get better and may become more serious and more difficult to treat.

If you take more Duloxetine Zentiva than you should

Contact your doctor or pharmacist immediately if you take more than the amount of Duloxetine Zentiva prescribed by your doctor. Symptoms of overdose include drowsiness, coma, serotonin syndrome (a rare reaction that can cause intense happiness, drowsiness, clumsiness, restlessness, feeling drunk, sweating, or rigid muscles), seizures, vomiting, and rapid heartbeat.

If you forget to take Duloxetine Zentiva

If you forget to take a dose, take it as soon as you remember. However, if it is time for your next dose, skip the missed dose and take a single dose as usual. Do not take a double dose to make up for a forgotten dose. Do not take more than the prescribed amount of Duloxetine Zentiva in one day.

If you stop taking Duloxetine Zentiva

Do not stop taking your capsules without the advice of your doctor, even if you feel better. If your doctor thinks you no longer need to take Duloxetine Zentiva, they will tell you how to reduce your dose over at least 2 weeks before stopping treatment.

Some patients who stop taking Duloxetine Zentiva have had symptoms such as:

• dizziness, tingling, sensation of pins and needles or electric shock-like sensation (especially in the head), sleep disturbances (vivid dreams, nightmares, inability to sleep), fatigue, drowsiness, feeling restless or agitated, feeling anxious, nausea or vomiting, tremor, headache, muscle pain, feeling irritable, diarrhea, and excessive sweating or dizziness.

These symptoms are usually not serious and disappear within a few days, but if you have symptoms that are troublesome, you should ask your doctor for advice.

If you have any other questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them. These effects are usually mild to moderate and often disappear within a few weeks.

Very Common Adverse Effects(may affect more than 1 in 10 patients):

• headache, drowsiness;
• discomfort (nausea), dry mouth.

Common Adverse Effects(may affect up to 1 in 10 patients):

• loss of appetite;
• difficulty sleeping, feeling of agitation, decreased sexual desire, anxiety, difficulty or inability to have an orgasm, unusual dreams;
• dizziness, feeling of slowness, tremor, numbness, including numbness, itching or tingling of the skin;
• blurred vision;
• tinnitus (perception of sounds in the ear when there is no external sound);
• feeling of palpitations in the chest;
• increased blood pressure, flushing;
• increased yawning;
• constipation, diarrhea, stomach pain, vomiting, heartburn or indigestion, gas;
• increased sweating, rash;
• muscle pain, muscle spasms;
• painful urination, frequent urination;
• difficulty getting an erection, changes in ejaculation;
• falls (mostly in elderly people), fatigue;
• weight loss.

Children and adolescents under 18 years of age with depression treated with this medicine experienced a decrease in weight when they started taking this medicine. After 6 months of treatment, the weight increased to similar levels as other children and adolescents of the same age and sex.

Uncommon Adverse Effects(may affect up to 1 in 100 patients):

• inflammation of the throat that causes hoarseness;
• suicidal thoughts, difficulty sleeping, teeth grinding, feeling of disorientation, lack of motivation;
• spasms and sudden involuntary muscle movements, feeling of restlessness or inability to sit still, nervousness, difficulty concentrating, changes in taste, difficulty controlling movements, e.g., lack of coordination or involuntary muscle movements, restless legs syndrome, poor quality sleep;
• dilation of the pupils (the black dot in the center of the eye), vision problems;
• feeling of dizziness or vertigo, ear pain;
• rapid and/or irregular heartbeats;
• fainting, dizziness, feeling of dizziness or fainting when standing up, coldness in the fingers of the hands and/or feet;
• throat spasms, nosebleeds;
• vomiting blood, or black stools, gastroenteritis, belching, difficulty swallowing;
• liver inflammation that can cause abdominal pain and yellowing of the skin or the white part of the eyes;
• night sweats, rashes, cold sweats, sensitivity to sunlight, increased tendency to bruise;
• muscle stiffness, muscle spasms;
• difficulty or inability to urinate, difficulty starting urination, need to urinate at night, need to urinate more than usual, decreased urine flow;
• abnormal vaginal bleeding, abnormal menstrual periods, including heavy, painful, irregular, or prolonged menstruation, exceptionally light or absent menstruation, pain in the testicles or scrotum;
• chest pain, feeling of cold, thirst, chills, feeling of heat, alteration in gait;
• weight gain;
• Duloxetina Zentiva may cause effects that you may not be aware of, such as increased liver enzymes or potassium levels in the blood, creatine phosphokinase, sugar, or cholesterol.

Rare Adverse Effects(may affect up to 1 in 1,000 patients):

• severe allergic reactions that cause difficulty breathing or dizziness with swelling of the tongue or lips, allergic reactions;
• decreased activity of the thyroid gland, which can cause fatigue or weight gain;
• dehydration, low sodium levels in the blood (mainly in elderly people; symptoms may include feeling of dizziness, weakness, confusion, sleepiness, or excessive tiredness, nausea, or vomiting, the most severe symptoms are fainting, convulsions, or falls), syndrome of inadequate secretion of antidiuretic hormone (SIADH);
• suicidal behavior, mania (hyperactivity, accelerated thinking, and decreased need for sleep), hallucinations, aggression, and anger;
• "Serotonin syndrome" (a rare reaction that can cause feelings of intense happiness, drowsiness, clumsiness, restlessness, feeling of being drunk, fever, sweating, or muscle stiffness), convulsions;
• increased pressure in the eye (glaucoma);
• cough, wheezing, and shortness of breath, which may be accompanied by high fever;
• inflammation of the mouth, bright red blood in the stool, bad breath, inflammation of the large intestine (leading to diarrhea);
• liver failure, yellowing of the skin or the white part of the eyes (jaundice);
• Stevens-Johnson syndrome (a serious disease with blistering of the skin, mouth, eyes, and genitals), severe allergic reactions that cause swelling of the face or throat (angioedema);
• jaw muscle contractions;
• unusual urine odor;
• menopausal symptoms, abnormal milk production in men or women;
• excessive vaginal bleeding shortly after birth (postpartum hemorrhage).

Very Rare Adverse Effects(may affect up to 1 in 10,000 patients):

• inflammation of the blood vessels in the skin (cutaneous vasculitis).

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that is not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Duloxetina Zentiva

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiration date that appears on the box/blister after CAD. The expiration date is the last day of the month indicated.

Store below 30 °C. Store in the original packaging to protect it from moisture.

Do not throw away medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines that are no longer needed. This will help protect the environment.

6. Package Contents and Additional Information

What Duloxetina Zentiva contains

The active ingredient is duloxetine. Each capsule contains duloxetine hydrochloride equivalent to 30 mg and 60 mg of duloxetine.

The other ingredients are:

Capsule content: sucrose; corn starch; hypromellose; talc; hypromellose acetate succinate; triethyl citrate.

Capsule shell:

Duloxetina Zentiva 30 mg:

Capsule cap: indigo carmine (E132); titanium dioxide (E171); gelatin.

Capsule body: titanium dioxide (E171); gelatin.

Duloxetina Zentiva 60 mg:

Capsule cap: indigo carmine (E132); titanium dioxide (E171); gelatin. Capsule body: yellow iron oxide (E172); titanium dioxide (E171); gelatin.

How Duloxetina Zentiva is and what the package contains

Duloxetina Zentiva is a hard gastro-resistant capsule. Each Duloxetina Zentiva capsule contains duloxetine hydrochloride pellets with a coating to protect them from stomach acid.

Duloxetina Zentiva is available in 2 doses: 30 mg and 60 mg.

The 30 mg capsules are hard, opaque gelatin capsules, approximately 15.9 mm in length, with a white opaque body and a light blue opaque cap, containing white to light brownish-yellow spherical pellets.

The 60 mg capsules are hard, opaque gelatin capsules, approximately 19.4 mm in length, with an ivory opaque body and a light blue opaque cap, containing white to light brownish-yellow spherical pellets.

Duloxetina Zentiva 30 mg is available in packs of 7, 28, 56, 84, and 98 capsules.

Duloxetina Zentiva 60 mg is available in packs of 14, 28, 56, 84, and 98 capsules.

Not all pack sizes may be marketed.

Marketing Authorization Holder:

Zentiva, k.s.

U Kabelovny 130

102 37 Prague 10

Czech Republic

Manufacturer:

S.C. Zentiva S.A.

Theodor Pallady Nr 50

032266 Bucharest

Romania

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Date of the last revision of this leaflet:

Detailed information about this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu.