YENTREVE 40 mg HARD GASTRO-RESISTANT CAPSULES

Introduction

Package Leaflet: Information for the User

YENTREVE 40mg hard gastro-resistant capsules

YENTREVE 20mg hard gastro-resistant capsules

Duloxetine (hydrochloride)

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack and other information:

1. What is YENTREVE and what is it used for
2. What you need to know before you take YENTREVE
3. How to take YENTREVE
4. Possible side effects
5. Storing YENTREVE
6. Contents of the pack and other information

1. What is YENTREVE and what is it used for

YENTREVE contains the active substance duloxetine. YENTREVE increases the levels of serotonin and noradrenaline in the nervous system.

YENTREVE is a medicine taken by mouth for the treatment of stress urinary incontinence (SUI) in women.

Stress urinary incontinence (SUI) is a disease in which patients have accidental losses or leaks of urine during physical exertion or after performing activities such as laughing, coughing, sneezing, lifting weights, or exercising.

It is believed that YENTREVE works by increasing the strength of the muscle that retains urine when laughing, sneezing, or performing physical activities.

The efficacy of YENTREVE is reinforced when combined with a program called pelvic floor muscle rehabilitation (PFMR).

2. What you need to know before you take YENTREVE

Do not take YENTREVE 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 failure
  • you are taking or have taken in the last 14 days another medicine known as a monoamine oxidase inhibitor (MAOI) (see "Using YENTREVE with other medicines")

• you are taking fluvoxamine, which is normally used to treat depression, ciprofloxacin, or enoxacin, which are used to treat some infections

Talk to your doctor if you have high blood pressure or heart disease. Your doctor will tell you if you should take YENTREVE.

Warnings and precautions

YENTREVE may not be suitable for you for the following reasons. Consult your doctor before taking YENTREVE if:

• you are using medicines to treat depression (see "Using YENTREVE with other medicines")
• you are taking St. John's Wort, a plant-based treatment (Hypericum perforatum)
• you have any kidney disease
• you have had seizures (epileptic fits)
• you have had mania
• you suffer from bipolar disorder
• you have eye problems such as some types of glaucoma (increased eye pressure)
• you have had bleeding problems (tendency to develop hematomas), especially if you are pregnant (see "Pregnancy and breastfeeding")
• you are at risk of having low sodium levels (e.g., 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 other medicines that contain duloxetine (see "Using YENTREVE with other medicines")

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

Some medicines in the same group as YENTREVE (called SSRIs/SNRIs) may cause symptoms of sexual dysfunction (see section 4). In some cases, these symptoms persist after stopping treatment.

Thoughts of suicide and worsening of depression or anxiety disorder.

Although YENTREVE is not indicated for the treatment of depression, its active substance (duloxetine) is used as an antidepressant medicine. If you are depressed and/or suffer from anxiety disorders, you may sometimes have thoughts of self-harm or suicide. These thoughts may be increased at the beginning of treatment with antidepressants, as all these medicines take time to work, usually a couple of weeks but sometimes longer.

It is more likely that you will have these thoughts if:

• you have previously had thoughts of self-harm or suicide
• you are a young adult. There is information from clinical trials that has shown an increased risk of suicidal behavior in adults under 25 years who suffer from a psychiatric disorder and are being treated with antidepressants

Contact your doctor or go directly to the hospital as soon as you have any thoughts of self-harm or suicide.

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

Children and adolescents under 18 years

YENTREVE should not be used in children and adolescents under 18 years. Additionally, you should know that patients under 18 years, when taking this type of medicine, have an increased risk of side effects such as attempted suicide, suicidal thoughts, and hostility (mainly aggression, oppositional behavior, and anger). Furthermore, in this age group, the long-term safety effects of YENTREVE related to growth, maturation, and cognitive and behavioral development have not yet been demonstrated.

Using YENTREVE with other medicines

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines, including those obtained without a prescription.

The main component of YENTREVE, duloxetine, is used in other medicines for other treatments:

• diabetic neuropathic pain, depression, anxiety, and urinary incontinence.

It should be avoided to use 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 YENTREVE with other medicines. Do not start or stop taking any medicine, including those obtained 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 YENTREVE if you are taking or have taken in the last 14 days another antidepressant medicine known as a monoamine oxidase inhibitor (MAOI). Examples of MAOIs include moclobemide (an antidepressant) and linezolid (an antibiotic). Taking an MAOI with many prescription medicines, including YENTREVE, can cause serious side effects, even life-threatening. You should wait at least 14 days after stopping treatment with an MAOI before taking YENTREVE. Similarly, you should wait at least 5 days after stopping treatment with YENTREVE before starting treatment with an MAOI.

Medicines that cause drowsiness:This includes prescription medicines from your doctor, including benzodiazepines, strong painkillers, antipsychotics, phenobarbital, and sedating antihistamines.

Medicines that increase serotonin levels:Triptans, tramadol, 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), pethidine, St. John's Wort, and MAOIs (such as moclobemide and linezolid). These medicines increase the risk of side effects; if you notice any unusual symptoms when taking any of these medicines with YENTREVE, you should tell your doctor.

Oral anticoagulants or antiplatelet agents:Medicines that thin the blood or prevent blood clots. These medicines may increase the risk of bleeding.

Taking YENTREVE with food, drinks, and alcohol

YENTREVE can be taken with or without food. You should be careful if you drink alcohol while being treated with YENTREVE.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

• Tell your doctor if you become pregnant or plan to become pregnant while taking YENTREVE. You should only use YENTREVE after discussing with your doctor the potential benefits and any potential risk to the fetus.

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

• If you take YENTREVE towards the end of your pregnancy, your baby may have some symptoms when born. These symptoms usually start at birth or during the first few days after the baby's birth. Among these symptoms are weak muscles, tremors, restlessness, difficulty feeding, breathing problems, and seizures. If your baby has any of these symptoms when born or if you are concerned about your baby's health, contact your doctor or midwife, who can advise you.

• If you take YENTREVE towards the end of your pregnancy, there is a higher risk of excessive vaginal bleeding shortly after birth, especially if you have had bleeding problems. Your doctor or midwife should know that you are taking duloxetine so they can advise you.

• Tell your doctor if you are breastfeeding. It is not recommended to use YENTREVE during breastfeeding. Ask your doctor or pharmacist for advice.

Driving and using machines

During treatment with YENTREVE, you may feel drowsy or dizzy. Do not drive or operate tools or machines until you know how the treatment with YENTREVE affects you.

YENTREVE contains sucrose

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

3. How to take YENTREVE

Follow exactly the administration instructions of this medicine given by your doctor or pharmacist. Consult your doctor or pharmacist if you have any doubts.

YENTREVE should be taken by mouth. You should swallow the capsule whole with water.

The recommended dose of YENTREVE is one 40 mg capsule twice a day (in the morning and in the afternoon or evening). Your doctor may decide to start treatment with one 20 mg capsule twice a day for two weeks before increasing the dose to 40 mg twice a day.

To help you remember to take YENTREVE, it may be useful to take it at the same times every day.

Do not stop taking YENTREVE or change your dose without consulting your doctor. It is important to treat your disease properly to help you improve. If you do not treat it, your disease may not disappear and may become more serious and more difficult to treat.

If you take more YENTREVE than you should

Call your doctor or pharmacist immediately if you take more YENTREVE than prescribed by your doctor. Symptoms produced by an overdose include drowsiness, coma, serotonin syndrome (a rare reaction that can cause feelings of intense happiness, drowsiness, clumsiness, restlessness, feeling drunk, fever, sweating, or muscle stiffness), seizures, vomiting, and rapid heart rate.

If you forget to take YENTREVE

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 you normally would. Do not take a double dose to make up for missed doses. Do not take more YENTREVE than prescribed for you in one day.

If you stop taking YENTREVE

Do not stop taking your capsules without your doctor's advice, even if you feel better.If your doctor thinks you do not need to take YENTREVE anymore, they will tell you to reduce your dose over at least 2 weeks.

Some patients who have stopped taking YENTREVE after more than one week of treatment have presented with symptoms such as:

• dizziness, sensation of pins and needles or electric shock-like sensations (especially in the head), sleep disturbances (vivid dreams, nightmares, inability to sleep), fatigue, drowsiness, feeling of restlessness or agitation, feeling of anxiety, nausea or vomiting, tremors, headaches, muscle pain, feeling of irritability, diarrhea, and excessive sweating or dizziness

These symptoms are usually not serious and disappear within a few days. If you have symptoms that are bothersome, 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 disappear, often, in a short period of time.

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

• discomfort (nausea), dry mouth, constipation
• fatigue

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

• loss of appetite
• sleeping problems, feeling of agitation, decreased sexual desire, anxiety, difficulty sleeping
• headache, dizziness, drowsiness, tremors or feeling of numbness, including numbness or tingling in the skin
• blurred vision
• feeling of dizziness, "spins" (vertigo)
• increase in blood pressure, flushing
• diarrhea, stomach pain, vomiting, heartburn or indigestion
• increased sweating
• weakness, chills

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

• inflammation of the throat that causes hoarseness
• allergic reactions
• decreased activity of the thyroid gland that can cause fatigue or weight gain
• dehydration
• grinding of teeth, feeling of disorientation, lack of motivation, difficulty or inability to have an orgasm, unusual dreams
• nervousness, attention disorder, that foods taste differently than usual, poor quality rest
• dilation of the pupils (the black dot in the center of the eye) or vision changes, dry eyes
• tinnitus (perception of sound in the ear when there is no external sound), ear pain
• feeling of palpitations in the chest, rapid or irregular heartbeats
• fainting
• increased yawning
• vomiting blood, or black-colored stools, gastroenteritis, inflammation of the mouth, belching, difficulty swallowing, gas, bad breath
• inflammation of the liver that can cause abdominal pain or yellowing of the skin or the white part of the eyes
• rash (itching), night sweats, hives, cold sweats, increased tendency to bruise
• muscle pain, muscle tension or spasm, jaw muscle contractions
• difficulty starting urination, pain while urinating, need to urinate at night, frequent urination, abnormal urine odor
• abnormal vaginal bleeding, menopausal symptoms
• chest pain, feeling of cold, thirst, feeling of heat
• weight loss or weight gain
• YENTREVE 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, which can cause difficulty breathing or dizziness with swelling of the tongue or lips
• low sodium levels in the blood (mostly in elderly people; symptoms can include feeling of dizziness, weakness, confusion, sleepiness or excessive tiredness, nausea or vomiting, the most serious symptoms are fainting, seizures or falls), syndrome of inadequate secretion of antidiuretic hormone (SIADH)
• suicidal behavior, suicidal thoughts, mania (hyperactivity, accelerated thinking and decreased need for sleep), hallucinations, aggression and anger
• "Serotonin syndrome" (a rare reaction that can cause a feeling of intense happiness, drowsiness, clumsiness, restlessness, feeling of being drunk, fever, sweating or muscle stiffness), seizures, involuntary muscle movements, feeling of restlessness or inability to remain seated or still, difficulty controlling movements, e.g., lack of coordination or involuntary muscle movements, restless legs syndrome
• increased pressure in the eye (glaucoma)
• dizziness, drowsiness or fainting when standing up, cold fingers or toes
• throat spasms, nosebleeds
• Cough, wheezing and shortness of breath, which can be accompanied by high fever
• bright red blood in the stool, 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), sensitivity to sunlight
• muscle spasms
• difficulty or inability to urinate, need to urinate at night, decreased urine flow
• abnormal menstrual periods, including heavy, painful, irregular or prolonged menstruation, exceptionally light or absent menstruation, abnormal milk secretion
• excessive vaginal bleeding shortly after birth (postpartum hemorrhage)
• falls (mostly in elderly people), abnormal gait

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 YENTREVE

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

Do not use this medicine after the expiration date that appears on the packaging.

YENTREVE should be stored in its original packaging to protect it from moisture. Do not store the capsules above 30°C.

Medicines should not be thrown away through wastewater or household waste. Ask your pharmacist how to dispose of the packaging and medicines that you no longer need. This will help protect the environment.

6. Package Contents and Additional Information

Composition of YENTREVE

• The activeingredient is duloxetine.

Each capsule contains 20 or 40 mg of duloxetine (as hydrochloride).

• The otheringredients are:

Capsule content: hypromellose, succinate acetate of hypromellose, sucrose, sugar spheres, talc, titanium dioxide (E171) and triethyl citrate (For more information on sucrose, see the end of section 2).

Capsule body: gelatin, sodium lauryl sulfate, titanium dioxide (E171), carmine indigo (E132), red iron oxide, yellow iron oxide and edible black ink.

Edible black ink: synthetic black iron oxide (E172), propylene glycol and shellac.

Appearance of the Product and Package Contents

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

YENTREVE is available in 2 doses: 20 and 40 mg.

The 40 mg capsules are orange and blue and are printed with "40 mg" and the code "9545".

The 20 mg capsules are blue and are printed with "20 mg" and the code "9544".

YENTREVE 40 mg is available in blisters in packages of 28, 56, 98, 140 and 196 (2 x 98) capsules

YENTREVE 20 mg is available in blisters in packages of 28, 56 and 98 capsules.

Not all package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder:Eli Lilly Nederland B.V., Papendorpseweg 83, 3528 BJ Utrecht, Netherlands.

Manufacturer:Lilly S.A., Avda. de la Industria, 30. 28108 Alcobendas, Madrid, Spain.

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

Date of Last Revision of this Leaflet:

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