Yentreve - patient leaflet, side effects, dosage

B. PACKAGE LEAFLET

Package leaflet: information for the user

YENTREVE 40 mg hard gastro-resistant capsules

YENTREVE 20 mg hard gastro-resistant capsules Duloxetine (as 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 of the side effects talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.

What is in this leaflet :

• 1. What YENTREVE is and what it is used for

• 2. What you need to know before you take YENTREVE

• 3. How to take YENTREVE

• 4. Possible side effects

• 5. How to store YENTREVE

• 6. Contents of the pack and other information

1. What YENTREVE is and what it is used for

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

YENTREVE is a medicine to be taken by mouth to treat Stress Urinary Incontinence (SUI) in women.

Stress urinary incontinence is a medical condition in which patients have accidental loss or leakage of urine during physical exertion or activities such as laughing, coughing, sneezing, lifting, or exercise.

YENTREVE is believed to work by increasing the strength of the muscle that holds back urine when you laugh, sneeze, or perform physical activities.

The efficacy of YENTREVE is reinforced when combined with a training program called Pelvic Floor Muscle Training (PFMT).

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)

• – have liver disease

• – have severe kidney disease

• – are taking or have taken within the last 14 days, another medicine known as a monoamine oxidase inhibitor (MAOI) (see ‘Other medicines and YENTREVE’)

• – are taking fluvoxamine which is usually 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 be taking YENTREVE.

Warnings and Precautions

The following are reasons why YENTREVE may not be suitable for you. Talk to your doctor before you take Yentreve if you:

• – are taking medicines to treat depression (see ‘Other medicines and YENTREVE’)

• – are taking St. John’s Wort, a herbal treatment (Hypericum perforatum )

• – have kidney disease

• – have had seizures (fits)

• – have had mania

• – suffer from bipolar disorder

• – have eye problems, such as certain kinds of glaucoma (increased pressure in the eye)

• – have a history of bleeding disorders (tendency to develop bruises), especially if you are pregnant (see ‘Pregnancy and breast-feeding‘)

• – are at risk of low sodium levels (for example if you are taking diuretics, especially if you are elderly)

• – are currently being treated with another medicine which may cause liver damage.

• – are taking other medicines containing duloxetine (see ‘Other medicines and YENTREVE’)

YENTREVE may cause a sensation of restlessness or an inability to sit or stand still. You should tell your doctor if this happens to you.

Medicines like Yentreve (so called SSRIs/SNRIs) may cause symptoms of sexual dysfunction (see section 4). In some cases, these symptoms have continued 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 ingredient (duloxetine) is used as an antidepressant medicine. If you are depressed and/or have anxiety disorders you can sometimes have thoughts of harming or killing yourself. These may be increased when first starting antidepressants, since these medicines all take time to work, usually about two weeks but sometimes longer.

You may be more likely to think like this if you:

• – have previously had thoughts about killing or harming yourself

• – are a young adult. Information from clinical trials has shown an increased risk of suicidal behaviour in adults aged less than 25 years with psychiatric conditions who were treated with an antidepressant

If you have thoughts of harming or killing yourself at any time, contact your doctor or go to a hospital straight away.

You may find it 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 behaviour.

Children and adolescents under 18 years of age

YENTREVE should not be used for 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 behaviour and anger) when they take this class of medicines. Also, the long-term safety effects concerning growth, maturation, and cognitive and behavioural development of YENTREVE in this age group have not yet been demonstrated.

Other medicines and YENTREVE

Please tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including medicines obtained without a prescription.

Your doctor should decide whether you can take YENTREVE with other medicines. Do not start or stop taking any medicines, including those bought without a prescription and herbal remedies, before checking with your doctor.

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

Monoamine oxidase inhibitors (MAOIs): You should not take YENTREVE if you are taking or have recently taken (within the last 14 days) an antidepressant medicine called a monoamine oxidase inhibitor (MAOI). Examples of MAOIs include moclobemide (an antidepressant) and linezolid (an antibiotic). Taking a MAOI together with many prescription medicines, including YENTREVE, can cause serious or even life-threatening side effects. You must wait at least 14 days after you have stopped taking an MAOI before you can take YENTREVE. Also, you need to wait at least 5 days after you stop taking YENTREVE before you take a MAOI.

Medicines that cause sleepiness : These include medicines prescribed by your doctor including benzodiazepines, strong painkillers, antipsychotics, phenobarbital and sedative antihistamines.

Medicines that increase the level of serotonin : Triptans, tramadol, tryptophan, SSRIs (such as paroxetine and fluoxetine), 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 get any unusual symptom taking any of these medicines together with YENTREVE, you should see your doctor.

Oral anticoagulants or antiplatelet agents : Medicines which thin the blood or prevent the blood from clotting. These medicines might increase the risk of bleeding.

YENTREVE with food, drink and alcohol

YENTREVE may be taken with or without food. You should take extra care if you drink alcohol while taking YENTREVE.

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 you are trying to become pregnant, while you are taking YENTREVE. You should use YENTREVE only after discussing the potential benefits and any potential risks to your unborn child with your doctor.
• Make sure your midwife and/or doctor knows you are on YENTREVE. When taken during pregnancy, similar drugs (SSRIs) may increase the risk of a serious condition in babies, called persistent pulmonary hypertension of the newborn (PPHN), making the baby breathe faster and appear bluish. These symptoms usually begin 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 YENTREVE near the end of your pregnancy, your baby might have some symptoms when it is born. These usually begin at birth or within a few days of your baby being born. These symptoms may include floppy muscles, trembling, jitteriness, not feeding properly, trouble with breathing and fits. If your baby has any of these symptoms when it is born, or you are concerned about your baby’s health, contact your doctor or midwife who will be able to advise you.
• If you take YENTREVE near the end of your pregnancy there is an increased risk of excessive vaginal bleeding shortly after birth, especially if you have a history of bleeding disorders. Your doctor or midwife should be aware that you are taking duloxetine so they can advise you. early (6 additional premature infants for every 100 women who take YENTREVE in the second half of pregnancy), mostly between weeks 35 and 36 of pregnancy.
• Tell your doctor if you are breast-feeding. The use of YENTREVE while breastfeeding is not recommended. You should ask your doctor or pharmacist for advice.

Driving and using machines

YENTREVE may make you feel sleepy or dizzy. Do not drive or use any tools or machines until you know how YENTREVE affects you.

YENTREVE contains sucrose

YENTREVE contains sucrose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

YENTREVE contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per capsule, that is to say essentially ‘sodium-free’.

3. How to take YENTREVE

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

YENTREVE is for oral use. You should swallow your capsule whole with a drink of water.

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

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

Do not stop taking YENTREVE, or change your dose, without talking to your doctor. Treating your disorder properly is important to help you get better. If it is not treated, your condition may not go away and may become more serious and difficult to treat.

If you take more YENTREVE than you should

Call your doctor or pharmacist immediately if you take more than the amount of YENTREVE prescribed by your doctor. Symptoms of overdose include sleepiness, coma, serotonin syndrome (a rare reaction which may cause feelings of great happiness, drowsiness, clumsiness, restlessness, feeling of being drunk, fever, sweating or rigid muscles), fits, vomiting and fast heart rate.

If you forget to take YENTREVE

If you miss a dose, take it as soon as you remember. However, if it is time for your next dose, skip the missed dose and take only a single dose as usual. Do not take a double dose to make up for a forgotten dose. Do not take more than the daily amount of YENTREVE that has been prescribed for you in one day.

If you stop taking YENTREVE

DO NOT stop taking your capsules without the advice of your doctor even if you feel better. If your doctor thinks that you no longer need YENTREVE he or she will ask you to reduce your dose over 2 weeks.

Some patients, who suddenly stop taking YENTREVE after more than 1 week of therapy, have had symptoms such as:

• dizziness, tingling feelings like pins and needles or electric shock-like feelings (particularly in the head), sleep disturbances (vivid dreams, nightmares, inability to sleep), fatigue, sleepiness, feeling restless or agitated, feeling anxious, feeling sick (nausea) or being sick (vomiting), shaking (tremor), headaches, muscle pain, feeling irritable, diarrhoea, excessive sweating or vertigo.

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 further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. These effects are normally mild to moderate and often disappear after a short time.

Very common side effects (may affect more than 1 in 10 people)

• feeling sick (nausea), dry mouth, constipation
• fatigue

Common side effects (may affect up to 1 in 10 people)

• lack of appetite
• trouble sleeping, feeling agitated, less sex drive, anxiety, difficulty sleeping
• headache, dizziness, feeling sluggish, feeling sleepy, tremor, numbness, including numbness, pricking or tingling of the skin
• blurred eyesight
• feeling of dizziness or “spinning” (vertigo)
• increased blood pressure, flushing
• diarrhoea, stomach pain, being sick (vomiting), heartburn or indigestion
• increased sweating
• weakness, shivering

Uncommon side effects (may affect up to 1 in 100 people)

• throat inflammation that causes a hoarse voice
• allergic reactions
• decreased thyroid gland activity which can cause tiredness or weight gain
• dehydration
• grinding or clenching the teeth, feeling disorientated, lack of motivation, difficulty or failure to experience orgasm, unusual dreams
• feeling nervous, difficulty concentrating, changes in sense of taste, poor sleep quality
• large pupils (the dark centre of the eye), problems with eyesight, eyes feel dry
• tinnitus (hearing sound in the ear when there is no external sound), ear pain
• feeling the heart pumping in the chest, fast and/or irregular heart beat
• fainting
• increased yawning
• vomiting blood, or black tarry stools (faeces), gastroenteritis, inflammation of the mouth, burping, difficulty swallowing, breaking wind, bad breath
• inflammation of the liver that may cause abdominal pain and yellowing of the skin or whites of

the eyes

abnormal vaginal bleeding, menopausal symptoms

chest pain, feeling cold, thirst, feeling hot

weight loss, weight gain

Yentreve may cause effects that you may not be aware of, such as increases in liver enzymes or blood levels of potassium, creatine phosphokinase, sugar, or cholesterol

Rare side effects (may affect up to 1 in 1000 people)

• serious allergic reaction which causes difficulty in breathing or dizziness with swollen tongue or lips
• low levels of sodium in the blood (mostly in elderly people; the symptoms may include feeling dizzy, weak, confused, sleepy or very tired, or feeling or being sick, more serious symptoms are fainting, fits or falls), syndrome of inappropriate secretion of anti-diuretic hormone (SIADH)
• suicidal behaviour, suicidal thoughts, mania (over activity, racing thoughts and decreased need for sleep), hallucinations, aggression and anger
• “Serotonin syndrome” (a rare reaction which may cause feelings of great happiness, drowsiness, clumsiness, restlessness, feeling of being drunk, fever, sweating or rigid muscles), fits, sudden involuntary jerks or twitches of the muscles, sensation of restlessness or an inability to sit or stand still, difficulty controlling movement e.g. lack of coordination or involuntary movements of the muscles, restless legs syndrome
• increased pressure in the eye (glaucoma)
• dizziness, lightheadedness or fainting on standing up, cold fingers and/or toes
• throat tightness, nose bleeds
• coughing, wheezing and shortness of breath which may be accompanied by a high temperature
• passing bright red blood in your stools, inflammation of the large intestine (leading to diarrhoea)
• liver failure, yellowing of the skin or whites of the eyes (jaundice)
• Stevens-Johnson syndrome (serious illness with blistering of the skin, mouth, eyes and genitals),

serious allergic reaction which causes swelling of the face or throat (angioedema), sensitivity to sunlight

• muscle twitching
• difficulty or inability to pass urine, needing to pass more urine than normal, having a decreased urine flow
• abnormal periods, including heavy, painful, irregular or prolonged periods, unusually light or missed periods, abnormal production of breast milk
• excessive vaginal bleeding shortly after birth (postpartum haemorrhage)
• falls (mostly in elderly people), abnormal gait

Very rare side effects (may affect up to 1 in 10,000 people)

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

5. How to store YENTREVE

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

Do not use this medicine after the expiry date which is stated on the carton.

Store in the original package to protect from moisture. Do not store above 30°C.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away of medicines you no longer use. These measures will help to protect the environment.

6. Contents of the pack and other information

What YENTREVE contains

The active substance is duloxetine.

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

The other ingredients are:

Capsule content : hypromellose, hypromellose acetate succinate, sucrose, sugar spheres, talc, titanium dioxide (E171), triethyl citrate (See end of section 2 for further information on sucrose).

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

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

What YENTREVE looks like and contents of the pack

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

YENTREVE is available in 2 strengths: 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 packs of 28, 56, 98, 140 and 196 (2 × 98) capsules.

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

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

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

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

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

Belgie/Belgiqu­e/Belgien Eli Lilly Benelux S.A./N.V. Tél/Tel: + 32-(0)2 548 84 84 Efc^rapufl Tn „Enu ^unu HegepnaHg“ E.B. – Etnrapua mea. + 359 2 491 41 40 Česká republika Eli Lilly ČR, s.r.o. Tel: + 420 234 664 111 Danmark Eli Lilly Danmark A/S Tlf: +45 45 26 60 00 Deutschland Lilly Deutschland GmbH Tel. + 49-(0) 6172 273 2222

Lietuva Eli Lilly Lietuva Tel. +370 (5) 2649600 Luxembourg/Lu­xemburg Eli Lilly Benelux S.A./N.V. Tél/Tel: + 32-(0)2 548 84 84 Magyarország Lilly Hungária Kft. Tel: + 36 1 328 5100 Malta Charles de Giorgio Ltd. Tel: + 356 25600 500 Nederland Eli Lilly Nederland B.V. Tel: + 31-(0) 30 60 25 800

Eesti Eli Lilly Nederland B.V. Tel: + 372 6 817 280	Norge Eli Lilly Norge A.S Tlf: +47 22 88 18 00
EMáSa OAPMAZEPB-AIAAY A.E.B.E. Tql: +30 210 629 4600	Österreich Eli Lilly Ges.m.b.H. Tel: + 43-(0) 1 711 780
España Spaly Bioquímica, S.A. Tel: + 34–91 623 17 32	Polska Eli Lilly Polska Sp. z o.o. Tel: +48 22 440 33 00
France Lilly France Tél: +33-(0) 1 55 49 34 34	Portugal Lilly Portugal – Produtos Farmacéuticos, Lda Tel: + 351 21–4126600
Hrvatska Eli Lilly Hrvatska d.o.o. Tel: +385 1 2350 999	Romania Eli Lilly Romania S.R.L. Tel: + 40 21 4023000
Ireland Eli Lilly and Company (Ireland) Limited Tel: +353-(0) 1 661 4377	Slovenija Eli Lilly farmacevtska družba, d.o.o. Tel: +386 (0)1 580 00 10
Ísland Icepharma hf. Sími + 354 540 8000	Slovenská republika Eli Lilly Slovakia s.r.o. Tel: + 421 220 663 111
Italia Eli Lilly Italia S.p.A. Tel: + 39– 055 42571	Suomi/Finland Oy Eli Lilly Finland Ab Puh/Tel: +358-(0) 9 85 45 250
Kúnpog Phadisco Ltd Tql: +357 22 715000	Sverige Eli Lilly Sweden AB Tel: + 46-(0)8 7378800
Latvija Eli Lilly (Suisse) S.A Pärstävnieciba Latvijä Tel: + 371 67364000	United Kingdom (Northern Ireland) Eli Lilly and Company (Ireland) Limited Tel: + 353-(0) 1 661 4377

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency web site:.

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