Patient leaflet - Duloxetine Milpharm 20 mg gastro-resistant capsules, hard

1. What Duloxetine is and what it is used for 2. What you need to know before you take

Duloxetine

3. How to take Duloxetine
4. Possible side effects
5. How to store Duloxetine
6. Contents of the pack and other information
1. What Duloxetine is and what it is used for

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

Duloxetine 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.

Duloxetine 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 Duloxetine is reinforced when combined with a training program called Pelvic Floor Muscle Training (PFMT).

2. What you need to know before you take Duloxetine

Do not take Duloxetine:

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 Duloxetine’)
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 Duloxetine.

Warnings and precautions

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

are taking medicines to treat depression (see
‘Other medicines and Duloxetine’)
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 Duloxetine’)

Medicines like Duloxetine (so called SSRIs/SNRIs) may cause symptoms of sexual dysfunction (see section 4). In some cases, these symptoms have continued after stopping treatment.

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

You should also contact your doctor:

If you experience signs and symptoms of restlessness, hallucinations, loss of coordination, fast heart beat, increased body temperature, fast changes in blood pressure, overactive reflexes, diarrhoea, coma, nausea, vomiting, as you might be suffering a serotonin syndrome.

In its most severe form, serotonin syndrome can resemble Neuroleptic Malignant Syndrome (NMS). Signs and symptoms of NMS may include a combination of fever, fast heart beat, sweating, severe muscle stiffness, confusion, increased muscle enzymes (determined by a blood test).

Thoughts of suicide and worsening of depression or anxiety disorder

Although Duloxetine 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

Duloxetine 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 Duloxetine in this age group have not yet been demonstrated.

Other medicines and Duloxetine

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

Some medicines may increase the side effects of Duloxetine and may sometimes cause very serious reactions. Do not take any other medicines whilst taking Duloxetine without first talking to your doctor, especially:

buprenorphine-containing medical products.
These medicines may interact with Duloxetine and you may experience symptoms such as involuntary, rhythmic contractions of muscles, including the muscles that control movement of the eye, agitation, hallucinations, coma, excessive sweating, tremor, exaggeration of reflexes, increased muscle tension, body temperature above 38°C. Contact your doctor when experiencing such symptoms.

The main ingredient of Duloxetine, 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 Duloxetine 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 Duloxetine 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 Duloxetine, 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 Duloxetine. Also, you need to wait at least 5 days after you stop taking Duloxetine 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 Duloxetine, 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.

Duloxetine with food, drink and alcohol

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

Pregnancy, breast-feeding and fertility

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 Duloxetine. You should use Duloxetine 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 Duloxetine. 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 Duloxetine 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 Duloxetine 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.

Available data from the use of Duloxetine during the first three months of pregnancy do not show an increased risk of overall birth defects in general in the child. If Duloxetine is taken during the second half of pregnancy, there may be an increased risk that the infant will be born early (6 additional premature infants for every 100 women who take Duloxetine 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 Duloxetine while breastfeeding is not recommended. You should ask your doctor or pharmacist for advice.

Driving and using machines

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

Duloxetine Capsules 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.

Sodium

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

3. How to take Duloxetine

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

The recommended dose of Duloxetine 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 Duloxetine, you may find it easier to take it at the same times every day.

Do not stop taking Duloxetine, 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 Duloxetine than you should

Call your doctor or pharmacist immediately if you take more than the amount of Duloxetine 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 Duloxetine

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 Duloxetine that has been prescribed for you in one day.

If you stop taking Duloxetine

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 Duloxetine he or she will ask you to reduce your dose over 2 weeks.

Some patients, who suddenly stop taking Duloxetine 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 any further questions on the use of this medicine, ask your doctor or pharmacist or nurse.

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: (may affect more than 1 in 10 people)

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

Common: (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: (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
(itchy) rash, night sweats, hives, cold sweats,
increased tendency to bruise
muscle pain, muscle tightness, muscle spasm,
contraction of the jaw muscle
difficulty to start urinating, painful urination,
needing to pass urine during the night, frequent urination, abnormal urine odour
abnormal vaginal bleeding, menopausal
symptoms
chest pain, feeling cold, thirst, feeling hot • weight loss, weight gain
Duloxetine 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: (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: (may affect up to 1 in 10,000 people)

inflammation of the blood vessels in 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 get any side effects, talk to your doctor, pharmacist or nurse.This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Yellow Card Scheme. Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Duloxetine

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

This medicine does not require any special storage conditions.

Do not use this medicine after the expiry date which is stated on the label, carton and bottle after EXP.The expiry date refers to the last day of that month.

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

6. Contents of the pack and other information

What Duloxetine contains

The active substance is duloxetine.
Each capsule contains 20 mg of duloxetine (as hydrochloride).
Each capsule contains 40 mg of duloxetine (as hydrochloride).
The other ingredients are
Capsule contents:
Sugar spheres, hypromellose, hydroxy propyl cellulose, crospovidone (Type B), talc, triethylcitrate, titanium dioxide, hypromellose phthalate
Capsule shell:
Cap: Iron oxide yellow (E172) (20 mg only), titanium dioxide, FD & C Blue (20 mg only), indigo carmine (40 mg only), gelatin, sodium lauryl sulfate.
Body: Iron oxide yellow (E172), iron oxide red (E172) (40 mg only), titanium dioxide, FD & C Blue (20 mg only), gelatin, sodium lauryl sulfate. Printing ink: Shellac, propylene glycol, iron oxide black (E172), potassium hydroxide.

What Duloxetine looks like and contents of the pack

Gastro-resistant capsule, hard

Duloxetine 20 mg gastro-resistant capsules, hard Green opaque /green opaque, size “4” hard gelatin capsules filled with white to off white pellets and imprinted with “DLX” on green opaque cap and "20" on green opaque body with black ink

Duloxetine 40 mg gastro- resistant capsules, hard Blue opaque /orange opaque, size “2” hard gelatin capsules filled with white to off white pellets and imprinted with "DLX" on blue opaque cap and "40" on orange opaque body with black ink

Duloxetine capsules are available in foil blister packs and HDPE bottle packs.

Pack sizes:

Blister packs: 14, 28, 56 and 98 capsules, hard HDPE bottle pack: 30, 98, 250 and 1000 capsules, hard

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Milpharm Limited

Ares Block, Odyssey Business Park

West End Road

Ruislip HA4 6QD

United Kingdom

Manufacturer

APL Swift Services (Malta) Limited

HF26, Hal Far Industrial Estate, Hal Far Birzebbugia, BBG 3000

Malta