Document: Clozapine Mylan tablet ENG PL change

• Clozapine Mylan tablet PL
• Clozapine Mylan tablet ENG PL

---

PACKAGE LEAFLET

Package leaflet: Information for the patient

Clozapine Mylan 25 mg tablets

Clozapine Mylan 100 mg tablets

clozapine

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.

What is in this leaflet

1. What Clozapine Mylan is and what it is used for

2. What you need to know before you take Clozapine Mylan

3. How to take Clozapine Mylan

4. Possible side effects

5. How to store Clozapine Mylan

6. Contents of the pack and other information

1. What Clozapine Mylan is and what it is used for

The active ingredient of Clozapine Mylan is clozapine which belongs to a group of medicines called antipsychotics (medicines that are used to treat specific mental disorders such as psychosis).

Clozapine Mylan is used to treat people with schizophrenia in whom other medicines have not worked.

Schizophrenia is a mental illness which affects how you think, feel and behave. You should only use this medicine if you have already tried at least two other antipsychotic medicines, including one of the newer atypical antipsychotics, to treat schizophrenia, and these medicines did not work, or caused severe side effects that cannot be treated.

Clozapine Mylan is also used to treat severe disturbances in the thoughts, emotions and behaviour of people with Parkinson’s disease in whom other medicines have not worked.

2. What you need to know before you take Clozapine Mylan

Do not take Clozapine Mylan:

• if you are allergic to clozapine or any of the other ingredients of this medicine (listed in section 6).

• if you are not able to have regular blood tests.

• if you have ever been told you have a low white blood cell count (e.g. leucopenia or agranulocytosis), especially if this was caused by medicines. This does not apply if you have had low white blood cell count caused by previous chemotherapy.

• if you had to stop using clozapine previously because of severe side effects (e.g. agranulocytosis or heart problems).

• if you are being or have recently been treated with long-acting depot injections of antipsychotics.

• if you suffer from or have ever suffered from a disease of the bone marrow or use any medicine that stops your bone marrow from working properly.

• if you suffer from uncontrolled epilepsy (seizures or fits).

• if you have an acute mental illness caused by alcohol or drugs (e.g. narcotics).

• if you suffer from reduced consciousness and severe drowsiness.

• if you suffer from circulatory collapse which may occur as a result of severe shock.

• if you suffer from any severe kidney disease.

• if you suffer from any severe heart disease such as myocarditis (an inflammation of the heart muscle).

• if you have symptoms of active liver disease such as jaundice (yellow colouring of the skin and eyes, feeling sick and loss of appetite).

• if you suffer from any other severe liver disease.

• if you suffer from paralytic ileus (your bowel does not work properly and you have severe constipation).

• if you use any medicine that reduces the number of white cells in your blood.

If any of the above applies to you, tell your doctor and do not take Clozapine Mylan.

Clozapine Mylan must not be given to anyone who is unconscious or in a coma.

Warnings and precautions

The safety measures mentioned in this section are very important. You must comply with them to minimise the risk of serious life-threatening side effects.

Before you start treatment

Tell your doctor if you suffer from or have ever suffered from:

• blood clots or family history of blood clots, as medicines like these have been associated with formation of blood clots.

• glaucoma (increased pressure in the eye).

• diabetes or anyone in your family has suffered from diabetes. Elevated (sometimes considerably) blood sugar levels, has occurred in patients with or without diabetes mellitus in their medical history (see section 4).

• prostate problems or difficulty in urinating.

• any heart, kidney or liver disease.

• chronic constipation or if you are taking medicines which cause constipation (such as anticholinergics).

• controlled epilepsy.

• large intestine diseases.

Also tell your doctor if you:

• have ever had abdominal surgery.

• have had a heart disease or family history of abnormal conduction in the heart called “prolongation of the QT interval”.

• are at risk for having a stroke, for example if you have high blood pressure, heart problems or blood vessel problems in the brain.

During treatment

Tell your doctor immediately before taking the next Clozapine Mylan tablet:

• if you get signs of a cold, fever, flu-like symptoms, sore throat or any other infection. You will have to have an urgent blood test to check if your symptoms are related to your medicine.

• if you have a sudden rapid increase in body temperature, rigid muscles which may lead to unconsciousness (neuroleptic malignant syndrome) as you may be experiencing a serious side effect which requires immediate treatment.

• if you have fast and irregular heartbeat, even when you are at rest, palpitations, breathing problems, chest pain or unexplained tiredness. Your doctor will need to check your heart and if necessary refer you to a cardiologist immediately.

• if you experience nausea (feeling sick), vomiting (being sick) and/or loss of appetite. Your doctor will need to check your liver.

• if you have severe constipation. Your doctor will have to treat this in order to avoid further complications.

Medical check-ups and blood tests

Before you start taking Clozapine Mylan, your doctor will ask about your medical history and do a blood test to ensure that your white blood cells count is normal. It is important to find this out, as your body needs white blood cells to fight infections.

Make sure that you have regular blood tests before you start treatment, during treatment and after you stop treatment with Clozapine Mylan.

• Your doctor will tell you exactly when and where to have the tests. Clozapine may only be taken if you have a normal blood count.

• Clozapine can cause a serious decrease in the number of white cells in your blood (agranulocytosis). Only regular blood tests can tell the doctor if you are at risk of developing agranulocytosis.

• During the first 18 weeks of treatment, tests are needed once a week. Afterwards, tests are needed at least once a month.

• If there is a decrease in the number of white blood cells, you will have to stop clozapine treatment immediately. Your white blood cells should then return to normal.

• You will need to have blood tests for another 4 weeks after the end of clozapine treatment.

Your doctor will also do a physical examination before starting treatment. Your doctor may do an electrocardiogram (ECG) to check your heart, but only if this is necessary for you, or if you have any special concerns.

If you have a liver disorder you will have regular liver function tests as long as you continue to take clozapine.

If you suffer from high levels of sugar in the blood (diabetes) your doctor may regularly check your level of sugar in the blood.

Clozapine may cause alteration in blood lipids. Clozapine may cause weight gain. Your doctor may monitor your weight and blood lipid level.

If clozapine makes you feel light-headed, dizzy or faint, be careful when getting up from a sitting or lying position.

If you have to undergo surgery or if for some reason you are unable to walk around for a long time, discuss with your doctor the fact that you are taking clozapine. You may be at risk of thrombosis (blood clotting within a vein).

Children and adolescents under 16 years

If you are under 16 years of age you should not use Clozapine Mylan as there is not enough information on its use in that age group.

Elderly (aged 60 years and over)

Elderly (aged 60 years and over) may be more likely to have the following side effects during treatment with clozapine: faintness or light-headedness after changing position, dizziness, fast heartbeat, difficulty in passing urine, and constipation.

Tell your doctor or pharmacist if you suffer from a condition called dementia.

Other medicines and Clozapine Mylan

Tell your doctor or pharmacist if you are taking, have recently takenor might take any other medicines. This includes medicines obtained without a prescription or herbal therapies. You might need to take different amounts of your medicines or to take different medicines.

Do not take Clozapine Mylantogether with medicines that stop the bone marrow from working properly and/or decrease the number of blood cells produced by the body, such as:

• carbamazepine, a medicine used in epilepsy.

• certain antibiotics: chloramphenicol, sulphonamides such as co-trimoxazole.

• certain painkillers: pyrazolone analgesics such as phenylbutazone.

• penicillamine, a medicine used to treat rheumatic joint inflammation.

• cytotoxic agents, medicines used in chemotherapy.

• long-acting depot injections of antipsychotic medicines.

These medicines increase your risk of developing agranulocytosis (lack of white blood cells).

Taking Clozapine Mylan at the same time as another medicine may affect how well Clozapine Mylan and/or the other medicine works. Tell your doctor if you plan to take, if you are taking (even if the course of treatment is about to end) or if you have recently had to stop taking any of the following medicines:

• medicines used to treat depression such as lithium, fluvoxamine, tricyclic antidepressants, MAO inhibitors, citalopram, paroxetine, fluoxetine, and sertraline.

• other antipsychotic medicines used to treat mental illnesses, such as perazine.

• benzodiazepines and other medicines used to treat anxiety or sleep disturbances.

• narcotics and other medicines which can affect your breathing.

• medicines used to control epilepsy such as phenytoin and valproic acid.

• medicines used to treat high or low blood pressure such as adrenaline and noradrenaline.

• warfarin, a medicine used to prevent blood clots.

• antihistamines, medicines used for colds or allergies such as hay fever.

• anticholinergic medicines, which are used to relieve stomach cramps, spasms and travel sickness.

• medicines used to treat Parkinson’s disease.

• medicines which inhibit certain enzymes such as caffeine (used as painkiller), perazine ( medicine used to treat mental illness), fluvoxamine (used to treat depression), ciprofloxacin (antibiotic)

• digoxin, a medicine used to treat heart problems.

• medicines used to treat a fast or irregular heartbeat.

• hormonal contraceptives (birth control tablets), such as progesterone or combined oral contraceptives such as progesterone and oestrogen.

• some medicines used to treat stomach ulcers, such as omeprazole or cimetidine.

• some antibiotic medicines, such as erythromycin and rifampicin.

• some medicines used to treat fungal infections (such as ketoconazole) or viral infections (such as protease inhibitors, used to treat HIV infections).

• atropine, a medicine which may be used in some eye drops or cough and cold preparations.

• adrenaline, a medicine used in emergency situations.

This list is not complete. Your doctor and pharmacist have more information on medicines to be careful with or to avoid while taking this medicine. They will also know if the medicines you are taking belong to the listed groups.

Clozapine Mylanwith drink and alcohol

Do not drink alcohol during treatment with Clozapine Mylan.

Tell your doctor if you smoke and how often you have drinks containing caffeine (coffee, tea, cola).

Sudden changes in your smoking habits or caffeine drinking habits can also change the effects of this medicine.

Pregnancy, breast-feeding and fertility

Pregnancy

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. Your doctor will discuss with you the benefits and possible risks of using this medicine during pregnancy. Tell your doctor immediately if you become pregnant during treatment with this medicine.

The following symptoms may occur in new born babies, of mothers that have used clozapine in the last trimester (last three months of their pregnancy): shaking, muscle stiffness and/or weakness, sleepiness, agitation, breathing problems, and difficulty in feeding. If your baby develops any of these symptoms you may need to contact your doctor.

Some women taking some medicines to treat mental illnesses have irregular or no periods. If you have been affected in this way, your periods might return when your medicine is changed to clozapine. This means you should use effective contraception.

Breast-feeding

Do not breast-feed during treatment with clozapine. Clozapine may pass into your milk and affect your baby.

Driving and using machines

Clozapine Mylan might cause tiredness, drowsiness and seizures, especially at the beginning of treatment. You should not drive or operate machines while you have these symptoms.

Clozapine Mylan contains lactose

Clozapine Mylan contains lactose. If you have been told by your doctor that you have an intolerance to some sugars, discuss this with your doctor before taking this medicinal product.

3. How to take Clozapine Mylan

In order to minimise the risk of low blood pressure, seizures and drowsiness it is necessary that your doctor increases your dose gradually. Always take this medicine exactly as your doctorhas told you. Check with your doctor or pharmacist if you are not sure.

It is important that you do not change your dose or stop taking Clozapine Mylan without asking your doctor first. Continue taking the tablets for as long as your doctor tells you. If you are 60 years or older, your doctor may start you on a lower dose and increase it more gradually because you might be more likely to develop some unwanted side effects (see section 2 “Before you take Clozapine Mylan”).

Treatment of schizophrenia

The recommended starting dose is 12.5 mg (one half of a 25 mg tablet) once or twice on the first day followed by 25 mg once or twice on the second day. Swallow the tablet with water. If tolerated well, your doctor will then gradually increase the dose in steps of 25-50 mg over the next 2-3 weeks until a dose up to 300 mg per day is reached. Thereafter, if necessary, the daily dose may be increased in steps of 50 to 100 mg half-weekly or, preferably, at weekly intervals.

The effective daily dose is usually between 200 mg and 450 mg, divided into several single doses per day. Some people might need more. A maximum daily dose of up to 900 mg is allowed. Increased side effects (in particular seizures) are possible at daily doses over 450 mg. Always take the lowest effective dose for you. Most people take part of their dose in the morning and part in the evening. Your doctor will tell you exactly how to divide your daily dose. If your daily dose is only 200 mg, then you can take this as a single dose in the evening. Once you have been taking Clozapine Mylan with successful results for some time, your doctor may try you on a lower dose. You will need to take Clozapine Mylan for at least 6 months.

Treatment of severe thought disturbances in patients with Parkinson’s disease

The usual starting dose is 12.5 mg (one half of a 25 mg tablet) in the evening. Swallow the tablet with water. Your doctor will then gradually increase the dose in steps of 12.5 mg, not faster than two steps a week, up to a maximum dose of 50 mg by the end of the second week. Increases in the dosage should be stopped or postponed if you feel faint, light-headed or confused. In order to avoid such symptoms your blood pressure will be measured during the first weeks of treatment.

The effective daily dose is usually between 25 mg and 37.5 mg, taken as one dose in the evening. Doses of 50 mg per day should only be exceeded in exceptional cases. The maximum daily dose is 100 mg. Always take the lowest effective dose for you.

The tablet can be divided into equal doses.

Elderly

If you are elderly your doctor will start your therapy at a lower dose of 12.5 mg. Your doctor may gradually increase the dose up to maximum daily dose of 25 mg.

If you take more Clozapine Mylan than you should

If you think that you may have taken too many tablets, or if anyone else takes any of your tablets, contact a doctor immediately or call for emergency medical help.

The symptoms of overdose are:

Drowsiness, tiredness, lack of energy, unconsciousness, coma, confusion, hallucinations, agitation, incoherent speech, stiff limbs, trembling hands, increased or lack of reflexes, seizures (fits), increased production of saliva, widening of the black part of the eye, increased sensitivity to heat, blurred vision, low blood pressure, collapse, fast or irregular heartbeat, shallow or difficult breathing.

If you forget to take Clozapine Mylan

If you forget to take a dose, take it as soon as you remember. If it is almost time for your next dose, leave out the forgotten tablets and take the next dose at the right time. Do not take a double dose to make up for a forgotten dose. Contact your doctor as soon as possible if you have not taken any Clozapine Mylan for more than 48 hours.

If you stop taking Clozapine Mylan

Do not stop taking Clozapine Mylan without asking your doctor, because you might get withdrawal reactions.

These reactions include sweating, headache, nausea (feeling sick), vomiting (being sick) and diarrhoea. If you have any of the above signs, tell your doctor straight away. These signs may be followed by more serious side effects unless you are treated immediately. Your original symptoms might come back. A gradual reduction in dose in steps of 12.5 mg over one to two weeks is recommended, if you have to stop treatment. Your doctor will advise you on how to reduce your daily dose. If you have to stop Clozapine Mylan treatment suddenly, you will have to be checked by your doctor.

If your doctor decides to re-start the treatment with Clozapine Mylan and your last dose of Clozapine Mylan was over two days ago, this will be with the starting dose of 12.5 mg.

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.

Some side effects can be serious and need immediate medical attention:

Tell your doctor immediately, or go to the nearest hospital casualty department, if you notice any of the following:

Common (may affect up to 1 in 10 people):

Uncommon (may affect up to 1 in 100 people):

• signs of a cold, fever, flu-like symptoms, sore throat or any other infection. These may be signs of changes in the number or type of white blood cells (which help fight infections) which may lead to severe blood infection.

• a sudden rapid increase in body temperature, rigid muscles which may lead to unconsciousness (neuroleptic malignant syndrome) as you may be experiencing a serious side effect which requires immediate treatment.

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

• fast and irregular heartbeat, even when you are at rest, palpitations, breathing problems, chest pain or unexplained tiredness. These may be signs of heart rhythm changes (which may be seen on ‘ECG’ readings of the electrical activity of the heart) or enlargement of the heart muscle (cardiomyopathy) (very rare). They may also be signs of inflammation of the heart muscle (myocarditis) or the membrane surrounding the heart muscle (pericarditis) or fluid collection around the heart (pericardial effusion). Your doctor will need to check your heart and if necessary refer you to a cardiologist immediately.

• very slow, shallow (frequent, small breaths) or difficulty breathing, fainting and muscle weakness, which may be associated with heart problems (circulatory collapse).

• difficulty swallowing which may cause inhalation of food.

• respiratory tract infection or pneumonia such as fever, coughing, difficulty breathing, wheezing.

• extreme confusion, which may be associated with hallucinations (seeing, feeling or hearing things that are not there), increased or decreased activity and sleep problems (delirium).

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

• unexplained bruising, or you bleed for longer than normal. These may be signs of a decrease in the numbers of blood platelets (which help the blood to clot). You will have to have an urgent blood test to check if your symptoms are related to your medicine.

• blockage of the small or large intestine. Your doctor will have to treat this in order to avoid further complications. Very rarely this may lead severe constipation or an obstruction of the bowel (paralytic ileus).

• persistent painful erection of the penis. This is called priapism. If you have an erection which lasts more than 4 hours immediate medical treatment may be needed in order to avoid further complications.

Not known (cannot be estimated from the available data):

• crushing chest pain, sensation of chest tightness, pressure or squeezing (chest pain may radiate to the left arm, jaw, neck and upper abdomen), shortness of breath, sweating, weakness, light headedness, nausea, vomiting and palpitations (symptoms of heart attack). You should seek emergency medical treatment immediately. Very rarely this may lead to stopping of the heart beating (cardiac arrest).

• chest pressure, heaviness, tightness, squeezing, burning or choking sensation. These may be signs of insufficient blood flow and oxygen to the heart muscle. Your doctor will need to check your heart.

• blood clots in the veins, especially in the legs (symptoms include swelling, pain and redness in the leg), which may travel through blood vessels to the lungs causing chest pain and difficulty in breathing. These may be associated within an increase in numbers of blood platelets (which help the blood to clot).

• profuse sweating, headache, nausea, vomiting and diarrhoea (symptoms of cholinergic syndrome).

• severely decreased urine output, urine that may have blood in it or lower back pain (signs of kidney problems or failure).

• signs of allergic reaction such as swelling of the face, lips, tongue or throat which may cause difficulty in breathing and swallowing.

• rashes that may appear on the face, neck and scalp, joint pains and fever all of which may be signs of a problem with the body’s immune system (Systemic Lupus Erythematosus or SLE).

• a condition of rapidly increasing blood pressure which may lead to permanent organ damage (other signs may include faster heart beat, difficulty breathing, dizziness, vomiting, blurred vision).

• nausea (feeling sick), vomiting (being sick) and/or loss of appetite. These may be signs of liver problems, some of which may become serious, including inflammation of the liver, blockage of the bile duct, liver failure and in some cases the need for a liver transplant.

• nausea or vomiting, abdominal pain, excessive thirst, excessive urination, disorientation or confusion (signs of severe imbalance in the acid base and glucose balance in the body that can lead to coma).

Other side effects that may occur are:

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

Drowsiness, constipation, dizziness, increased production of saliva, increased heart rate.

Common (may affect up to 1 in 10 people):

High level of white blood cells (leukocytosis), high level of a specific type of white blood cell (eosinophilia), weight gain, blurred vision, headache, trembling, stiffness, restlessness, abnormal movements, inability to initiate movement, inability to remain motionless, high blood pressure, faintness or light-headedness after changing position, sudden loss of consciousness, nausea (feeling sick), vomiting (being sick), loss of appetite, dry mouth, fever, minor abnormalities in liver function tests, loss of bladder control, difficulty in passing urine, tiredness, increased sweating, raised body temperature, speech disorders (e.g. slurred speech).

Uncommon (may affect up to 1 in 100 people):

Other speech disorders (e.g. stuttering).

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

Low level of red blood cells (anaemia), restlessness, agitation, confusion, blood clot in the lungs (thromboembolism), inflammation of the liver (hepatitis), liver disease causing yellowing of the skin or eyes, dark urine and itching, raised levels of an enzyme called creatinine phosphokinase in the blood, reduced glucose tolerance which may be due to inability of the body to respond to a hormone called insulin, diabetes mellitus with symptoms such as extreme thirst whilst passing large volumes of urine, feel tired or very hungry.

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

Uncontrollable movements of mouth/tongue and limbs, obsessive thoughts and compulsive repetitive behaviours (obsessive compulsive symptoms), build up of hard faeces in your rectum which may be due to long term constipation (faecal impaction), skin reactions, swelling in front of the ear (enlargement of saliva glands), very high levels of triglycerides or cholesterol in the blood, sudden unexplained death.

Not known (frequency cannot be estimated from the available data)

Changes in brain wave machine readings (electroencephalogram/EEG), diarrhoea, stomach discomfort, heartburn, stomach discomfort after a meal, muscle weakness, muscle spasms, muscle pain, stuffy nose, nocturnal bedwetting, inflammation of blood vessels, inflammation of the lining of large intestine (which may include signs such as blood in the stool and severe abdominal pain), changes in skin colour, ejaculation problems, uncontrollable muscle spasms affecting the eyes, head, neck and body which may be due to prolonged exposure to certain class of medicines known as antipsychotics (medicines used to treat mental illness such as clozapine).

In elderly people with dementia, a small increase in the number of people dying has been reported for patients taking antipsychotics compared with those not taking antipsychotics.

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 [To be completed nationally].By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Clozapine Mylan

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 after “EXP”. The expiry date refers to the last day of that month.

This medicine does not require any special storage conditions.

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 Clozapine Mylancontains

Clozapine Mylan 100 mg tablets: Each tablet contains 100 mg clozapine.

What Clozapine Mylan looks like and contents of the pack

Clozapine Mylan 25 mg tablets: Pale yellow, round, flat tablet with bevelled edges marked with “CZ/25” on one side and “G/G” on the other side.

Clozapine Mylan 100 mg tablets: Pale, yellow, round, flat tablet with bevelled edges marked with “CZ/100” on one side and “G/G” on the other side.

Clozapine Mylan tablets are available in PVdC/PVC/Alu blister packs containing 14, 20, 28, 30, 50, 56, 60 and 100 tablets.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

[To be completed nationally]

Manufacturer

McDermott Laboratories Ltd. t/a Gerard Laboratories

35/36 Baldoyle Industrial Estate, Grange Road

Dublin 13

Ireland

Mylan Hungary Kft.

Mylan utca 1

2900 Komárom

Hungary

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

[To be completed nationally]

This leaflet was last revised in [To be completed nationally].

2016-07-06