Package leaflet: Information for the user

Siloxezol 30 mg hard gastro‑resistant capsules

Siloxezol 60 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 side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1. What Siloxezol is and what it is used for

2. What you need to know before you take Siloxezol

3. How to take Siloxezol

4. Possible side effects

5. How to store Siloxezol

6. Contents of the pack and other information

1. What Siloxezol is and what it is used for

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

Siloxezol is used in adults to treat:

• depression

• generalised anxiety disorder (chronic feeling of anxiety or nervousness)

• diabetic neuropathic pain (often described as burning, stabbing, stinging, shooting or aching or like an electric shock. There may be loss of feeling in the affected area, or sensations such as touch, heat, cold or pressure may cause pain)

Siloxezol starts to work in most people with depression or anxiety within two weeks of starting treatment, but it may take 2‑4 weeks before you feel better. Tell your doctor if you do not start to feel better after this time. Your doctor may continue to give you Siloxezol when you are feeling better to prevent your depression or anxiety from returning

In people with diabetic neuropathic pain it can take some weeks before you feel better. Talk to your doctor if you do not feel better after 2 months.

2. What you need to know before you take Siloxezol

Do not take Siloxezol 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 Siloxezol’)

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

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

Talk to your doctor if you have high blood pressure or heart disease. Your doctor will tell you if you should be taking Siloxezol.

Warnings and precautions

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

• are taking other medicines to treat depression (see ‘Other medicines and Siloxezol’)

• 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 ‘Other medicines and Siloxezol’)

Siloxezol 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 your depression or anxiety disorder

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

Siloxezol should normally 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. Despite this, your doctor may prescribe Siloxezol for patients under 18 because he/she decides that this is in their best interests. If your doctor has prescribed Siloxezol for a patient under 18 and you want to discuss this, please go back to your doctor. You should inform your doctor if any of the symptoms listed above develop or worsen when patients under 18 are taking Siloxezol. Also, the long-term safety effects concerning growth, maturation, and cognitive and behavioural development of Siloxezol in this age group have not yet been demonstrated.

Other medicines and Siloxezol

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

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

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 Siloxezol 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 Siloxezol if you are taking, or have recently taken (within the last 14 days) another 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 Siloxezol, 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 Siloxezol. Also, you need to wait at least 5 days after you stop taking Siloxezol before you take a MAOI.

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

Siloxezol with food, drink and alcohol

Siloxezol may be taken with or without food. Care should be taken if you drink alcohol while you are being treated with Siloxezol.

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.

Driving and using machines

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

Siloxezol contains sucrose

Siloxezol 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.

3. How to take Siloxezol

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

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

For depression and diabetic neuropathic pain:

The usual dose of Siloxezol is 60 mg once a day, but your doctor will prescribe the dose that is right for you.

For generalised anxiety disorder:

The usual starting dose of Siloxezol is 30 mg once a day after which most patients will receive 60 mg once a day, but your doctor will prescribe the dose that is right for you. The dose may be adjusted up to 120 mg a day based on your response to Siloxezol.

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

Talk with your doctor about how long you should keep taking Siloxezol. Do not stop taking Siloxezol, 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 Siloxezol than you should

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

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 Siloxezol that has been prescribed for you in one day.

If you stop taking Siloxezol

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 Siloxezol he or she will ask you to reduce your dose over at least 2 weeks before stopping treatment altogether.

Some patients who stop taking Siloxezol suddenly have had symptoms such as:

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.

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 few weeks.

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

• headache, feeling sleepy

• feeling sick (nausea), dry mouth

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

• lack of appetite

• trouble sleeping, feeling agitated, less sex drive, anxiety, difficulty or failure to experience orgasm, unusual dreams

• dizziness, feeling sluggish, tremor, numbness, including numbness, pricking or tingling of the skin

• blurred eyesight

• tinnitus (hearing sound in the ear when there is no external sound)

• feeling the heart pumping in the chest,

• increased blood pressure, flushing

• increased yawning

• constipation, diarrhoea, stomach pain, being sick (vomiting), heartburn or indigestion, breaking wind

• increased sweating, (itchy) rash

• muscle pain, muscle spasm

• painful urination, frequent urination

• problems getting an erection, changes in ejaculation

• falls (mostly in elderly people), fatigue

• weight loss

Children and adolescents under 18 years of age with depression treated with this medicine had some weight loss when they first start taking this medicine. Weight increased to match other children and adolescents of their age and sex after 6 months of treatment.

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

• throat inflammation that causes a hoarse voice

• suicidal thoughts, difficulty sleeping, grinding or clenching the teeth, feeling disorientated, lack of motivation

• sudden involuntary jerks or twitches of the muscles, sensation of restlessness or an inability to sit or stand still, feeling nervous, difficulty concentrating, changes in sense of taste, difficulty controlling movement e.g. lack of coordination or involuntary movements of the muscles, restless legs syndrome, poor sleep quality

• large pupils (the dark centre of the eye), problems with eyesight

• feeling of dizziness or “spinning” (vertigo), ear pain

• fast and/or irregular heart beat

• fainting, dizziness, lightheadedness or fainting on standing up, cold fingers and/or toes

• throat tightness, nose bleeds

• vomiting blood, or black tarry stools (faeces), gastroenteritis, burping, difficulty swallowing

• inflammation of the liver that may cause abdominal pain and yellowing of the skin or whites of the eyes

• night sweats, hives, cold sweats, sensitivity to sunlight, increased tendency to bruise

• muscle tightness, muscle twitching

• difficulty or inability to pass urine, difficulty to start urinating, needing to pass urine during the night, needing to pass more urine than normal, having a decreased urine flow

• abnormal vaginal bleeding, abnormal periods, including heavy, painful, irregular or prolonged periods, unusually light or missed periods, pain in the testicles or scrotum

• chest pain, feeling cold, thirst, shivering, feeling hot, abnormal gait

• weight gain

• Siloxezol 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 1,000 people)

• serious allergic reaction which causes difficulty in breathing or dizziness with swollen tongue or lips, allergic reactions

• decreased thyroid gland activity which can cause tiredness or weight gain

• dehydration, 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, 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

• increased pressure in the eye (glaucoma)

• inflammation of the mouth, passing bright red blood in your stools, bad breath, 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)

• contraction of the jaw muscle

• abnormal urine odour

• menopausal symptoms, abnormal production of breast milk in men or women

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

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist.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 Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Siloxezol

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

Do not store above 25°C

Do not use this medicine after the expiry date which is stated on the carton and label 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 you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Siloxezol contains

The active substance is duloxetine

Each capsule contains 30 or 60 mg of duloxetine (as hydrochloride).

The other ingredients are:

Capsule content: sugar spheres (sucrose, maize starch), hypromellose phthalate (HP-55), hypromellose (E15 LV), triethyl citrate, hydroxypropyl cellulose, talc

Capsule shell 30 mg:gelatin,titanium dioxide (E171), Brilliant Blue FCF (E133), black iron oxide (E172), printing ink.,

Capsule shell 60 mg: gelatin, titanium dioxide (E171), black iron oxide (E172), printing ink

Printing ink contains: shellac, propylene glycol, black iron oxide (E172), potassium hydroxide.

What Siloxezol looks like and contents of the pack

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

Siloxezol is available in 2 strengths: 30 mg and 60 mg.

The 30 mg capsules have an opaque grey body imprinted with ‘DLX 30’ and an opaque blue cap imprinted with ‘DLX 30’, length 18.0 mm.

The 60 mg capsules have an opaque grey body imprinted with ‘DLX 60’ and an opaque white cap imprinted with ‘DLX 60’, length 20.4 mm.

Siloxezol is available in plastic (HDPE) containers with twist-off cap and desiccant in pack sizes of 28 capsules.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

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Manufacturer

Balkanpharma-Dupnitsa AD,

3 Samokovsko Shosse Str.,

Dupnitsa 2600,

Bulgaria

This medicinal product is authorised in the Member States of the EEA under the following names:

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This leaflet was last revised in 2015-12-03.

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