Zaponex 25 mg Tablets    Leyden^ >eita

Zaponex 100 mg Tablets

Clozapine

Package leaflet: information for the user

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 Zaponex is and what it is used for

2.    What you need to know before you take Zaponex

3.    How to take Zaponex

4.    Possible side effects

5.    How to store Zaponex

6.    Contents of the pack and further information

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Q What Zaponex is and what it is used for

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

Zaponex 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.

Zaponex 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.

What you need to know before you take Zaponex

Do not take Zaponex if you:

•    are allergic (hypersensitive) to clozapine or any of the other ingredients of Zaponex (see section 6)

•    are not able to have regular blood tests

•    have ever been told you have a low white blood cell count (e.g. leukopenia 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.

•    suffer from bone marrow disease or have ever suffered from bone marrow disease

•    use any medicine that stops your bone marrow from working properly

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

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

•    suffer from uncontrolled epilepsy (seizures or fits)

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

•    suffer from myocarditis (an inflammation of the heart muscle)

•    suffer from any other severe heart disease

•    suffer from any severe kidney disease

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

•    suffer from any other severe liver disease

•    suffer from reduced consciousness and severe drowsiness

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

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

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

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

Zaponex 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 with Zaponex, 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. Elevated (sometimes considerably) blood sugar levels have 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)

•    galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption

•    controlled epilepsy

•    large intestine diseases

•    if you have ever had abdominal surgery

•    if you have had a heart disease or family history of abnormal conduction in the heart called "prolongation of the QT interval"

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

Tell your doctor immediately before taking the next Zaponex 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 Zaponex, your doctor will ask about your medical history and do a blood test to ensure that your white blood cell 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 Zaponex.

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

•    Zaponex 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. Between weeks 18 and 52, tests are needed at least every 2 weeks. 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 Zaponex 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 Zaponex 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 Zaponex. If you suffer from high levels of sugar in the blood (diabetes) your doctor may regularly check your level of sugar in the blood.

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

If Zaponex 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 Zaponex. 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 Zaponex as there is not enough information on its use in that age group.

Older people (aged 60 years and over)

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

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

Other medicines and Zaponex

Before you start taking Zaponex, please tell your doctor if you are taking or have recently taken any other medicines. This includes medicines obtained without a prescription or herbal therapies. You might need to take different amounts of your medicines or take different medicines.

Do not take Zaponex together 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 Zaponex may affect how well other medicines work or they might affect how well Zaponex works. Tell your doctor if you are 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

•    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

•    digoxin, a medicine used to treat heart problems

•    medicines used to treat a fast or irregular heart beat

•    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 Zaponex. They will also know if the medicines you are taking belong to the listed groups. Speak to them.

Taking Zaponex with food and drink

Do not drink alcohol during treatment with Zaponex.

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 Zaponex.

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.There are only limited data on the safe use of Zaponex during pregnancy. 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 Zaponex.

Pregnancy

The following symptoms may occur in newborn babies, of mothers that have used Zaponex 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.

Breast-feeding

Do not breast-feed during treatment with Zaponex. Clozapine, the active substance of Zaponex, may pass into your milk and affect your baby.

Women of childbearing potential

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 Zaponex. This means you should use effective contraception.

Driving and using machines

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

Zaponex 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 Zaponex.

Q How to take Zaponex

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 Zaponex tablets exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.

It is important that you do not change your dose or stop taking Zaponex without asking your doctor first. Continue taking the tablets for as long as your doctor tells you. If you are aged 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 Zaponex").

If the dose you are prescribed cannot be achieved with this strength tablet, other strengths of this medicinal product are available to achieve the dose.

Zaponex tablets can be divided into equal doses.

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 recommended daily dose is between 200 mg and 450 mg, divided into several single doses per day. Some people might need more. A 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 Zaponex with successful results for some time, your doctor may try you on a lower dose. You will need to take Zaponex for at least 6 months.

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

The recommended 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 recommended daily dose is 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.

If you take more Zaponex 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. Take this leaflet and any remaining tablets with you to show them.

The symptoms of overdose are:

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

If you forget to take Zaponex

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 Zaponex for more than 48 hours.

If you stop taking Zaponex

Do not stop taking Zaponex 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 Zaponex treatment suddenly, you will have to be checked by your doctor.

If your doctor decides to re-start the treatment with Zaponex and your last dose of Zaponex 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 product, ask your doctor or

pharmacist.

Q Possible side effects

Like all medicines, Zaponex can cause side effects, although not everybody gets

them.

Some side effects can be serious and need immediate medical attention: Tell your doctor immediately before taking the next Zaponex 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 experience 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.

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

•    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.

•    if you get signs of a respiratory tract infection or pneumonia such as fever, coughing, difficulty breathing, wheezing.

•    if you get signs of 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.

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

•    if you develop jaundice (yellowing of the skin or whites of the eyes) and darkening of urine (symptoms of liver inflammation or liver failure).

•    if you develop pain around the top of your stomach and/or jaundice and/or darkening of urine (symptoms of pancreas inflammation).

•    if you experience severely decreased urine output (sign of kidney failure).

•    if you experience seizures.

•    if you are a man and experience 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.

All possible side effects are listed under headings of frequency:

Very common (affects more than 1 in 10 people):

Drowsiness, dizziness, fast heartbeat, constipation, increased production of saliva. Common (affects up to 1 in 10 people):

Low level of white blood cells (leukopenia), 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 (akathisia), seizures, convulsions, jerks, 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, minor abnormalities in liver function tests, loss of bladder control, difficulty in passing urine, tiredness, fever, increased sweating, raised body temperature, speech disorders (e.g. slurred speech).

Uncommon (affects up to 1 in 100 people):

Lack of white blood cells (agranulocytosis), neuroleptic malignant syndrome (disorder with high fever, impaired consciousness and muscle stiffness), speech disorders (e.g. stuttering).

Rare (affects up to 1 in 1,000 people):

Low level of red blood cells (anaemia), restlessness, agitation, confusion, delirium, circulatory collapse, irregular heartbeat, inflammation of the heart muscle (myocarditis) or the membrane surrounding the heart muscle (pericarditis), fluid collection around the heart (pericardial effusion), difficulty in swallowing (e.g. food going down the wrong way), respiratory tract infection and pneumonia, high level of sugar in the blood, diabetes mellitus, blood clot in the lungs (thromboembolism), inflammation of the liver (hepatitis), liver disease causing yellowing of the skin/dark urine/itching, inflammation of the pancreas leading to severe upper stomach pain, raised levels of an enzyme called creatinine phosphokinase in the blood.

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

Increase in numbers of blood platelets with possible clotting in the blood vessels, decrease in numbers of blood platelets, uncontrollable movements of mouth/tongue and limbs, obsessive thoughts and compulsive repetitive behaviours (obsessive compulsive symptoms), skin reactions, swelling in front of the ear (enlargement of saliva glands), difficulty in breathing, complications due to uncontrolled blood sugar (e.g. coma or ketoacidosis), very high levels of triglycerides or cholesterol in the blood, disorder of the heart muscle (cardiomyopathy), stopped heartbeat (cardiac arrest), severe constipation with abdominal pain and stomach cramps caused by obstruction of the bowel (paralytic ileus), swollen abdomen, abdominal pain, severe liver damage (fulminant hepatic necrosis), inflammation of the kidneys, persistent painful erection of the penis (priapism), sudden unexplained death.

Unknown (frequency cannot be estimated from the available data):

Blood clots in the vein, profuse sweating, headache, nausea, vomiting and diarrhoea (symptoms of cholinergic syndrome), crushing chest pain, shortness of breath (symptoms of heart attack), chest pressure or heaviness (signs of insufficient blood flow and oxygen to the heart muscle), severely decreased urine output (sign of kidney failure), liver disorders including fatty liver disease, death of liver cells, liver toxicity/injury, liver disorders that involve replacement of normal liver tissue with scar tissue leading to loss of liver function, including those liver events leading to life-threatening consequences such as liver failure (which may lead to death), liver injury (injury of liver cells, bile duct in the liver, or both) and liver transplant, changes in brain waves machine (electroencephalogram/EEG), diarrhoea, stomach discomfort, heartburn, stomach discomfort after a meal, muscle weakness, muscle spasms, muscle pain, stuffy nose, nocturnal bedwetting.

In older people (aged 60 years and over) 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 the Yellow Card Scheme website www.mhra.gov.uk/yellowcard. By reporting side effects you can help provide more information on the safety of this medicine.

0 How to store Zaponex

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

Do not use Zaponex after the expiry date [EXP] which is stated on the outer carton box and on each blister or on the label of the container. The first two digits indicate the month and the last four digits indicate the year. The expiry date refers to the last day of that month.

Zaponex should be stored in its original package below 25°C.

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

0 Contents of the pack and further information

What Zaponex contains

The active substance is clozapine. Each tablet contains either 25 or 100 mg clozapine. The other ingredients are: lactose monohydrate, povidone, pregelatinised starch, maize starch, talc, colloidal anhydrous silica, magnesium stearate.

What Zaponex looks like and contents of the pack

The tablets are yellow and round, scored with a division mark on both sides and debossed with "CPN 25" or "CPN 100" on one side.

They are supplied in blister packs of 28, 30, 60, 84, 90 and 300 tablets or in plastic containers containing 500 tablets.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder:

Leyden Delta B.V., Neerbosscheweg 620, 6544 LL Nijmegen, The Netherlands. Manufacturer(s):

Synthon Hispania S.L., Castello, 1, Poligono Las Salinas, 08830 Sant Boi de Llobregat, Spain.

National registration number:

Zaponex 25 mg Tablets PL 32553/0001 Zaponex 100 mg Tablets PL 32553/0002

This leaflet was last revised in July 2015

Leyden Delta BV (NL)
Market	UK
Patient Leaflet	Zaponex 25 mg Tablets
	Zaponex 100 mg Tablets
	Clozapine
Dimensions	260 x 480 mm.
Laetus Code
Item Code	201501-Z
Software Application	QuarkXPress PP 9.5
Artwork version	5.3
Date	JUL 2015
Printing Color	Black
	Key-Lines
Typefont settings	Univers Condensed: 9 pnts.

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