YENTREVE 20 mg Hard Capsule

Зміст інструкції

1. YENTREVE 40 mg hard gastro-resistant capsules, 20 mg hard gastro-resistant capsules
   1. What is YENTREVE and what is it used for
   2. What you need to know before taking YENTREVE
   3. How to take YENTREVE
   4. Possible side effects
   5. How to store YENTREVE
   6. Package contents and other information

YENTREVE 40 mg hard gastro-resistant capsules, 20 mg hard gastro-resistant capsules

duloxetine (as hydrochloride)

Read this leaflet carefully before you start taking this medicine as it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist.

Contents of 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 is YENTREVE and what is it used for

YENTREVE contains the active ingredient 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 a loss or involuntary
emission of urine during physical effort or activities such as laughing, coughing, sneezing,
lifting weights or exercising.
It is believed that YENTREVE works by increasing the strength of the muscles that hold urine
when you laugh, sneeze or perform physical activities.
The effectiveness of YENTREVE is increased when it is combined with an exercise program
called Pelvic Floor Muscle Training (PFMT).

2. What you need to know before taking 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 a liver disease
• have a 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 commonly used to treat depression, ciprofloxacin or enoxacin which are used to treat some infections.

Tell your doctor if you have high blood pressure or a heart condition. Your doctor will tell you if you can
take YENTREVE.

Warnings and precautions
The reasons why YENTREVE may not be suitable for you are as follows. Talk to your doctor before
taking YENTREVE if:

• you are taking medicines to treat depression (see ‘Other medicines and YENTREVE’)
• you are taking St. John’s Wort ( Hypericum perforatum), a herbal medicinal product
• you have a kidney disease
• you have a history of seizures (convulsions)
• you have had a manic episode
• you suffer from bipolar disorder
• you have problems with your eyes, such as certain types of glaucoma (increased pressure inside the eye)
• you have a history of blood clotting disorders (tendency to bruise easily), especially if you are pregnant (see “Pregnancy and breastfeeding”)
• you are at risk of having low levels of sodium in your blood (for example if you are taking diuretics, especially if you are an elderly person)
• you are being treated with another medicine that can cause liver damage
• you are taking other medicines that contain duloxetine (see ‘Other medicines and YENTREVE’)

YENTREVE may cause a feeling of restlessness or inability to sit still or remain calm. If
this happens to you, you should tell your doctor.
Also, contact your doctor if:
You experience signs and symptoms of restlessness, hallucinations, loss of coordination, rapid heartbeat,
increased body temperature, rapid changes in blood pressure, overactive reflexes, diarrhea, coma, nausea, vomiting, you may be suffering from serotonin syndrome.
In its most severe form, serotonin syndrome can resemble neuroleptic malignant syndrome (NMS). The signs and symptoms of NMS can include a combination of fever, rapid heartbeat, sweating, severe muscle rigidity, confusion, increased muscle enzymes (determined by a blood test).
Medicines such as Yentreve (so-called selective serotonin reuptake inhibitors (SSRIs) and
serotonin-noradrenaline reuptake inhibitors (SNRIs)) can cause symptoms of sexual dysfunction (see
section 4). In some cases, persistence of these symptoms has been observed after discontinuation of
treatment.

Thoughts of suicide and worsening of depression and anxiety
Although YENTREVE is not indicated for the treatment of depression, its active ingredient
(duloxetine) is taken as an antidepressant medicine. If you are depressed and/or anxious, you may
sometimes have thoughts of harming yourself or of suicide. These thoughts may be increased when you
first start taking antidepressants, because these medicines require a period of time to be effective, usually about 2 weeks but
sometimes even longer.
You may be more likely to have these thoughts if you:

• have had thoughts of harming yourself or of suicide in the past
• are a young adult. Data from clinical studies have shown an increased risk of suicidal behaviour in adults under 25 years of age with psychiatric disorders who were treated with an antidepressant

If at any time you have thoughts of harming yourself or of suicide, contact your doctor or go
immediately to hospital.
You may find it helpful to tell a relative or close friend that you are depressed or anxious, 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 in children and adolescents under 18 years of age. Also, you
should know that patients under 18 years of age, when taking this type of medicine, have an
increased risk of undesirable effects such as suicide attempts, suicidal thoughts and
hostility (particularly aggressive behaviour, oppositional behaviour and anger). Furthermore, long-term safety effects of YENTREVE relating to growth, maturity and cognitive and behavioural development have not yet been demonstrated in this
age group.

Other medicines and YENTREVE
Tell your doctor or pharmacist if you are taking, have recently taken or might take
any other medicines, including those available without a prescription.
The main component of YENTREVE, duloxetine, is found in other medicines for other
conditions:

• diabetic neuropathic pain, depression, anxiety and urinary incontinence. The simultaneous use of more than one of these medicines should be avoided. Check with your doctor if you are already taking medicines that contain duloxetine.

Your doctor needs to decide whether you can take YENTREVE with your other medicines. Do not start or
stop taking any medicine, including those bought without a prescription
and herbal medicinal products, before consulting your doctor.
Also, tell your doctor if you are taking any of the following medicines:

Monoamine Oxidase Inhibitors (MAOIs): You must not take YENTREVE if you are taking, or have recently taken (within the last 14 days) a medicine for depression called a monoamine
oxidase inhibitor (MAOI). Examples of MAOI medicines include moclobemide (an
antidepressant) and linezolid (an antibiotic). Taking an 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 stopping taking an
MAOI before you can take YENTREVE. Also, you must wait at least 5 days after stopping taking YENTREVE before taking an MAOI.

Medicinesthat cause drowsiness:These include medicines prescribed by your doctor, such as
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-Noradrenaline Reuptake Inhibitors (SNRIs) (such as venlafaxine), tricyclic antidepressants
(such as clomipramine, amitriptyline), pethidine, St. John’s Wort (hypericum) and MAOIs (such as
moclobemide and linezolid). These medicines increase the risk of side effects; if you experience
any unusual symptoms while taking one of these medicines together with YENTREVE,
you should consult your doctor.

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

YENTREVE with food, drink and alcohol
YENTREVE can be taken independently of meals. You should be particularly careful if you drink
alcohol while taking YENTREVE.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, or are planning to become pregnant, ask your doctor or
pharmacist for advice before taking this medicine.

• Tell your doctor if you are pregnant, or planning 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 unborn child.
• Make sure your midwife and/or doctor knows that you are being treated with YENTREVE. Medicines similar to YENTREVE (SSRIs) when taken during pregnancy can increase the risk of a serious condition in newborns, called persistent pulmonary hypertension of the newborn (PPHN), which means the newborn has a fast breathing rate and a bluish skin colour. These symptoms usually appear during the first 24 hours after birth. If this happens to the newborn, contact your midwife or doctor immediately.
• If you take YENTREVE near the end of your pregnancy, your newborn may experience some symptoms shortly after birth. Generally these appear at birth or within a few days of birth. These symptoms can include floppy muscles, tremor, nervousness, difficulty feeding, a breathing disorder and seizures. If your newborn experiences any of these symptoms after birth, or you are concerned about the 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 delivery, particularly if you have a history of bleeding disorders. Your doctor or midwife should be informed that you are taking duloxetine so that they can advise you.
• Available data on the use of YENTREVE during the first 3 months of pregnancy do not show an increased risk of overall birth defects in the baby. If YENTREVE is taken during the second half of pregnancy there may be an increased risk that the baby may be born prematurely (6 more babies born prematurely per 100 women taking YENTREVE in the second part of pregnancy), mostly between weeks 35 and 36 of pregnancy.
• Tell your doctor if you are breastfeeding. The use of YENTREVE during breastfeeding is not recommended. Ask your doctor or pharmacist for advice.

Driving and using machines
YENTREVE may cause drowsiness or dizziness. Do not drive or use 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 medicine.

YENTREVEcontains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per capsule, i.e. essentially ‘sodium-free’.

3. How to take YENTREVE

Take this medicine following exactly the instructions of your doctor or pharmacist. If you have any doubts, ask your doctor or pharmacist.
YENTREVE is taken orally. Swallow the capsule without chewing, with the help of a glass of water.
The recommended dose of YENTREVE is 40 mg twice a day (in the morning and late afternoon or evening). Your doctor may decide to start 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, it may be easier for you to take it every day at the same time.
Do not stop taking YENTREVE, or change the dose, without talking to your doctor.
Appropriate treatment of the disorder is important to help you feel better. If left untreated, the disorder may not improve and may become more severe and difficult to treat.

If you take more YENTREVE than you should
Contact your doctor or pharmacist immediately if you have taken a quantity of YENTREVE greater than what your doctor has prescribed. Symptoms of overdose include drowsiness, coma, serotonin syndrome (a rare reaction that can cause feelings of great happiness, drowsiness, clumsiness, restlessness, feeling of drunkenness, fever, sweating or muscle rigidity), seizures, vomiting and increased heart rate.

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

If you stop taking YENTREVE
Even if you feel better, DO NOT stop taking the capsules without consulting your doctor. If the doctor believes you no longer need YENTREVE, they will ask you to gradually reduce the dose over a period of 2 weeks.
Some patients, who suddenly stop taking YENTREVE after more than 1 week of therapy, have experienced symptoms such as:

• dizziness, tingling sensations as from pinpricks or needle-like sensations or electric shock-like sensations (especially in the head), sleep disturbances (intense dreams, nightmares, inability to sleep), fatigue, drowsiness, feeling of restlessness or agitation, feeling of anxiety, nausea or unwellness (vomiting), being unsteady (tremor), headache, muscle pain, feeling of irritability, diarrhea, excessive sweating or dizziness. Usually these symptoms are not serious and disappear within a few days, but if you experience symptoms that are bothersome you should consult your doctor.

If you have any 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 everyone will experience them.
Normally these effects are mild to moderate and often disappear after a short time.

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

• feeling of unwellness (nausea), dry mouth, constipation
• fatigue

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

• loss of appetite
• difficulty falling asleep, feeling of agitation, decreased sexual desire, anxiety, difficulty in falling asleep
• headache, dizziness, feeling of sluggishness, feeling of drowsiness, tremor, numbness, including a sensation of tingling or pins and needles in the skin
• blurred vision
• feeling of dizziness or “spinning” (vertigo)
• increased blood pressure, hot flush
• diarrhea, stomach pain, nausea (vomiting), heartburn or indigestion
• increased sweating
• weakness, trembling

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

• inflammation of the throat causing a hoarse voice
• allergic reactions
• decreased activity of the thyroid gland which may determine fatigue or weight gain
• dehydration
• teeth grinding or forceful rubbing of the teeth, feeling of disorientation, lack of motivation, difficulty or inability to reach orgasm, unusual dreams
• feeling of nervousness, difficulty concentrating, alterations in the sense of taste, poor sleep quality
• pupil dilation (the dark center of the eye), visual disturbances, feeling of dry eyes
• tinnitus (perception of a sound in the ear in the absence of an external sound stimulus), ear pain
• feeling the heart beating in the chest, accelerated or irregular heartbeat
• fainting
• increased yawning
• emission of blood with vomiting, or presence of feces of a black, tarry color, gastroenteritis, inflammation of the mouth, belching, difficulty swallowing, accumulation of gas in the intestine, bad breath
• inflammation of the liver which can cause abdominal pain and yellowing of the skin or the whites of the eyes
• skin rash (with itching), night sweats, hives, cold sweats, increased tendency to develop bruises
• muscle pain, muscle stiffness, muscle spasm, contraction of the muscles of the mouth
• difficulty starting urination, painful urination, need to urinate during the night, frequent urination, altered smell of urine
• abnormal vaginal bleeding, symptoms of menopause
• chest pain, feeling of cold, thirst, feeling of heat
• weight loss, weight gain
• YENTREVE may cause effects of which you may not be aware, such as increases in liver enzymes or levels in the blood of potassium, creatine phosphokinase, sugars or cholesterol

Rare side effects (may affect up to 1 in 1,000 people)

• severe allergic reaction causing difficulty breathing or dizziness with swelling of the tongue and lips
• low levels of sodium in the blood (especially in elderly people; symptoms may include a feeling of dizziness, feeling weak, confused, sleepy or very tired, or feeling nauseous or being sick, more serious symptoms are loss of consciousness, seizures or falls), syndrome of inappropriate secretion of the antidiuretic hormone (SIADH)
• suicidal behavior, suicidal thoughts, mania (hyperactivity, racing thoughts and decreased need for sleep), hallucinations, aggressive behavior and anger
• “Serotonin Syndrome” (a rare reaction that can cause a feeling of great happiness, sleepiness, clumsiness, restlessness, feeling drunk, fever, sweating or muscle stiffness), seizures, sudden and involuntary spasms or contractions of the muscles, feeling of restlessness or inability to sit still or remain calm, difficulty in controlling

the movements such as lack of coordination or involuntary movements of the
muscles, restless legs syndrome

• increased pressure inside the eye (glaucoma)
• dizziness, feeling of emptiness in the head or of impending fainting when standing up, feeling of cold in the fingers of the hands and/or feet
• feeling of constriction in the throat, nosebleeds
• cough, wheezing and shortness of breath possibly accompanied by fever
• presence of bright red blood in the stool, inflammation of the large intestine (colon) (causing diarrhea)
• liver failure, yellowing of the skin or the whites of the eyes (jaundice)
• Stevens-Johnson Syndrome (serious disease with the appearance of blisters on the skin, mouth, eyes and genitals) severe allergic reaction causing swelling of the face and throat (angioedema), sensitivity to sunlight
• muscle contraction
• difficulty or inability to urinate, need to urinate more than usual, reduced urine flow
• abnormal menstrual cycles, including heavy, painful, irregular or prolonged cycles, unusually light or absent cycles, abnormal production of breast milk
• excessive bleeding from the vagina immediately after childbirth (postpartum hemorrhage)
• falls (especially in elderly people), abnormal gait

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

• Inflammation of the blood vessels of the skin (cutaneous vasculitis)

Frequency not known (cannot be estimated from the available data)

• signs and symptoms of a condition called "stress cardiomyopathy" which may include chest pain, shortness of breath, dizziness, fainting, irregular heartbeat.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, please tell your
doctor or pharmacist. You can also report side effects directly through the
national reporting system indicated in Annex V. By reporting side effects you can contribute to providing more information on the safety of this medicine.

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 pack.
Store in the original package to protect it from moisture. Do not store at a temperature
above 30 °C.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What YENTREVE contains
The active ingredientis duloxetine.
Each capsule contains 20 or 40 mg of duloxetine (as hydrochloride).
The otheringredients are:

Capsule contents: hypromellose, hypromellose acetate succinate, sucrose, sugar granules,
talc, titanium dioxide (E171), triethyl citrate.

(See the end of paragraph 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.

Description of the appearance of YENTREVE and package contents
YENTREVE is a hard, gastro-resistant capsule.
Each YENTREVE capsule contains granules of duloxetine hydrochloride with a coating to
protect them from stomach acidity.
YENTREVE is available in two strengths: 20 and 40 mg.
The 40 mg capsules are orange and blue in colour with ‘40 mg’ and the code ‘9545’ printed on them.
The 20 mg capsules are blue in colour with ‘20 mg’ and the code ‘9544’ printed on them.
YENTREVE 40 mg is available in packs of 28, 56, 98, 140 and 196 capsules (2 x 98).
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 further information on this medicine, contact the local representative of the Marketing
Authorisation Holder:

Lietuva
Eli Lilly Lietuva
Tel. +370 (5) 2649600

България
ТП "Ели Лили Недерланд" Б.В. - България
тел. + 359 2 491 41 40

België/Belgique/Belgien
Eli Lilly Benelux S.A./N.V.
Tél/Tel: + 32-(0)2 548 84 84

Luxembourg/Luxemburg
Eli Lilly Benelux S.A./N.V.
Tél/Tel: + 32-(0)2 548 84 84

Česká republika
Eli Lilly ČR, s.r.o.
Tel: + 420 234 664 111

Magyarország
Lilly Hungária Kft.
Tel: + 36 1 328 5100

Danmark
Eli Lilly Danmark A/S
Tlf: +45 45 26 60 00

Malta
Charles de Giorgio Ltd.
Tel: + 356 25600 500

Deutschland
Lilly Deutschland GmbH
Tel. + 49-(0) 6172 273 2222

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

Ελλάδα
ΦΑΡΜΑΣΕΡΒ-ΛΙΛΛΥ Α.Ε.Β.Ε.

Österreich
Eli Lilly Ges.m.b.H.
Τηλ: +30 210 629 4600 Tel: + 43-(0) 1 711 780

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

España
Spaly Bioquímica, S.A.
Tel: + 34-91-663 50 00

Portugal
Lilly Portugal - Produtos Farmacêuticos, Lda
Tel: + 351 21-4126600

Hrvatska
Eli Lilly Hrvatska d.o.o.
Tel: +385 1 2350 999

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 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

Κύπρος
Phadisco Ltd
Τηλ: +357 22 715000

Sverige
Eli Lilly Sweden AB
Tel: + 46-(0)8 7378800

United Kingdom (Northern Ireland)
Eli Lilly and Company (Ireland) Limited
Tel: + 353-(0) 1 661 4377
More detailed information on this medicine is available on the website of the European
Medicines Agency: http://www.ema.europa.eu .

Latvija
Eli Lilly (Suisse) S.A Pārstāvniecība Latvijā
Tel: + 371 67364000

ANNEX IV
SCIENTIFIC CONCLUSIONS AND JUSTIFICATION FOR THE VARIATION OF THE
MARKETING AUTHORISATION
Scientific conclusions
Considering the assessment of the Pharmacovigilance and Risk Assessment Committee
( Pharmacovigilance and Risk Assessment Committee, PRAC) of the Periodic Safety Update Report
( Periodic Safety Update Report, PSUR) for duloxetine, the PRAC’s scientific conclusions are as follows:
In light of the available literature data on neuroleptic malignant syndrome (Neuroleptic
malignant syndrome ,NMS)and stress cardiomyopathy (Takotsubo cardiomyopathy),
spontaneous reports, including in some cases a close temporal association, a de-challenge and/or re-
challenge positive, and considering a plausible mechanism of action, the PRAC considers that a
causal relationship between duloxetine and NMS and stress cardiomyopathy (Takotsubo cardiomyopathy) is
at least a reasonable possibility. The PRAC concluded that the product information of
medicines containing duloxetine should be amended accordingly.
Having examined the PRAC recommendation, the Committee for Human Medicinal Products
( Committee for Human Medicinal Products, CHMP) agrees with the overall conclusions and
with the justification of the recommendation.

Justification for the variation of the terms of the marketing authorisation
Based on the scientific conclusions on duloxetine, the CHMP considers that the benefit/risk
balance of the medicine containing duloxetine remains unchanged, subject to the proposed changes
to the product information.
The CHMP recommends the variation of the terms of the marketing authorisation.