YENTREVE 40 mg hard gastro-resistant capsules

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).

DO NOT take YENTREVE if you:

• are allergic (hypersensitive) to duloxetine or any of the other ingredients of YENTREVE (see ?Further Information?)
• 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 ?Taking other medicines?)
• 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.

Take special care with YENTREVE

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

• are taking medicines to treat depression (see ?Taking other medicines?)
• 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)
• 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 ?Taking other medicines?)

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.

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 youhave 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 havean 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.

Use in 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.

Taking other medicines

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

The main ingredient of YENTREVE, duloxetine, is used in other medicines for other conditions:

• diabetic neuropathic pain, depression, anxiety and urinary incontinence Using more than one of these medicines at the same time should be avoided. Check with your doctor if you are already taking other medicines containing duloxetine.

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). 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), tricyclics (such as clomipramine, amitriptyline), pethidine, St John?s Wort and venlafaxine. 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: Medicines which thin the blood. These medicines might increase the risk of bleeding.

Taking YENTREVE with food and drink

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

Pregnancy and breast-feeding

Ask your doctor or pharmacist for advice before taking any 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.

• 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.

Important information about some of the ingredients of YENTREVE

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.

Always take YENTREVE exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.

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

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

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 without talking to your doctor.

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, sleep disturbances (vivid dreams, nightmares, inability to sleep), feeling restless or agitated, feeling anxious, feeling sick (nausea) or being sick (vomiting), tremor (shakiness), headaches, 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 product, ask your doctor or pharmacist.

Like all medicines, YENTREVE 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 (affects more than 1 user in 10)

• feeling sick (nausea), dry mouth, constipation and tiredness

Common side effects (affects 1 to 10 users in 100)

• anxiety, feeling agitated, less sex drive, having a poor quality of sleep
• headache, dizziness, feeling sleepy, tremor or numbness, including numbness or tingling of the skin
• flushing
• stomach pain, shivering, weakness
• being sick (vomiting), diarrhoea, heartburn
• increased sweating
• lack of appetite
• blurred eyesight
• vertigo

Uncommon side effects (affects 1 to 10 users in 1,000)

• throat inflammation
• feeling disorientated, having abnormal dreams, lack of motivation, grinding of teeth, changes in orgasm
• increased yawning
• tasting things differently than usual, nervousness, disturbance in attention
• muscle pain, muscle tightness or muscle spasm, contraction of the jaw muscle
• weight loss or weight gain, increased level of cholesterol in the blood
• burping, breaking wind, bad breath, indigestion or gastroenteritis
• inflammation of the liver that may cause abdominal pain, tiredness or yellow coloration of the skin
• tinnitus (perception of sound in the ear when there is no external sound), ear pain
• larger pupils (the dark centre of the eye) or visual disturbance
• feeling the heart pumping in the chest, fast or irregular heart beat
• fainting, increase in blood pressure,
• increased tendency to bruise, night sweats, cold sweats
• menopausal symptoms, abnormal periods, including heavy or prolonged periods
• allergic reactions, blisters
• decreased thyroid gland activity
• need to pass urine during the night, difficulty or inability to pass urine, pain on passing urine or abnormal urine odour
• dehydration,
• feeling hot/cold, thirst ? (itchy) rash
• passing bright red blood in your stools vomiting blood, or black tarry stools (faeces)
• chest pain

Rare side effects (affects 1 to 10 users in 10,000)

• increased level of sugar in the blood
• 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
• involuntary movements of the muscles, restless legs syndrome
• muscle twitching
• throat tightness or nose bleeds
• increased pressure in the eye (glaucoma)
• sensitivity to sunlight
• feeling dizzy (particularly when standing up too quickly), feeling cold in your fingers and/or toes
• abnormal manner of walking
• need to pass more urine then usual or urine flow decreased
• serious allergic reaction which causes difficulty in breathing or dizziness or hives
• experiencing hallucinations
• abnormal production of breast milk in men and women
• syndrome of inadequate secretion of anti-diuretic hormone (SIADH)
• mania (over activity, racing thoughts and decrease need for sleep), experiencing aggression and anger, suicidal thoughts or behaviour
• a sensation of restlessness or an inability to sit or stand still, ?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 or stiffness
• yellow colouration of the skin (jaundice), hepatic failure, Stevens-Johnson syndrome, sudden swelling of skin of mucosa (angioedema)

If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

Keep out of the reach and sight of children.

Do not use YENTREVE 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.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

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 sulphate, 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 blister packs of 28, 56, 98, 140 and 196 (2 x 98) capsules. YENTREVE 20 mg is available in blister 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 BV, Grootslag 1-5, NL-3991 RA Houten, 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:

BelgiëBelgiqueBelgien Eli Lilly Benelux S.A.N.V. TélTel 32-02 548 84 84 LuxembourgLuxemburg Eli Lilly Benelux S.A.N.V. TélTel 32-02 548 84 84

.. - . 359 2 491 41 40 Magyarország Lilly Hungária Kft. Tel 36 1 328 5100

eská republika Eli Lilly R, s.r.o. Tel 420 234 664 111 Malta Charles de Giorgio Ltd. Tel 356 25600 500

Danmark Eli Lilly Danmark AS Tlf 45 45 26 60 00 Nederland Eli Lilly Nederland B.V. Tel 31-0 30 60 25 800

Deutschland Lilly Deutschland GmbH Tel. 49-0 6172 273 2222 Norge Eli Lilly Norge A.S Tlf 47 22 88 18 00

Eesti Eli Lilly Holdings Limited Eesti filiaal Tel 372 6 817 280 Österreich Eli Lilly Ges.m.b.H. Tel 43-0 1 711 780

- .... 30 210 629 4600 Polska Eli Lilly Polska Sp. z o.o. Tel. 48 0 22 440 33 00

España Spaly Bioquímica, S.A. Tel 34-91 623 17 32 Portugal Lilly Portugal - Produtos Farmacêuticos, Lda Tel 351 21-4126600

France Lilly France S.A.S. Tel 33-0 1 55 49 34 34 România Eli Lilly România S.R.L. Tel 40 21 4023000

Ireland Eli Lilly and Company Ireland Limited Tel 353-0 1 661 4377 Slovenija Eli Lilly farmacevtska druba, d.o.o. Tel 386 01 580 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 SuomiFinland Oy Eli Lilly Finland Ab PuhTel 358-0 9 85 45 250

Phadisco Ltd 357 22 715000 Sverige Eli Lilly Sweden AB Tel 46-08 7378800

Latvija Eli Lilly Holdings Limited prstvniecba Latvij Tel 371 67364000 United Kingdom Eli Lilly and Company Limited Tel 44-0 1256 315000

Lietuva
Eli Lilly Holdings Limited atstovyb-
Tel. +370 (5) 2649600

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