Clozapine Tablets USP 50mg

Package Leaflet: Information for the user

Clozapine tablets USP 25mg
Clozapine tablets USP 50mg
Clozapine tablets USP 100mg

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:

What Clozapine is and what it is used for
What you need to know before you take Clozapine
How to take Clozapine
Possible side effects
How to store Clozapine
Contents of the pack and other information

What Clozapine is and what it is used for

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

Clozapine 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 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 Clozapine

Do not take Clozapine if you:

are allergic (hypersensitive) to clozapine or any of the other ingredients of Clozapine (listed in section 6).
are not able to have regular blood tests.
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.
had to stop using Clozapine previously because of severe side effects (e.g. agranulocytosis or heart problems).
are being or have been treated with long-acting depot injections of antipsychotics.
suffer from bone marrow disease or have ever suffered from bone marrow disease.
suffer from uncontrolled epilepsy (seizures or fits).
have an acute mental illness caused by alcohol or drugs (e.g. narcotics)
suffer from reduced consciousness and severe drowsiness.
suffer from circulatory collapse which may occur as a result of severe shock.
suffer from any severe kidney disease.
suffer from myocarditis (an inflammation of the heart muscle).
suffer from any other severe heart 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 paralytic ileus (your bowel does not work properly and you have severe constipation).
use any medicine that stops your bone marrow from working properly.
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. Clozapine 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 Clozapine, tell your doctor if you have or ever had:

blood clots or family history of blood clots, as medicines like these, have been associated with the formation of blood clots.
glaucoma (increased pressure in the eye).
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).
galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.
controlled epilepsy.
large intestine diseases.
abdominal surgery.
heart disease or family history of abnormal conduction in the heart called ?prolongation of the QT interval?.
the risk of 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 Clozapine 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.
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.
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.
experience nausea (feeling sick), vomiting (being sick) and/or loss of appetite. Your doctor will need to check your liver.
experience constipation, abdominal pain, abdominal tenderness, fever, bloating and/or bloody diarrhoea. Your doctor will need to examine you.

Medical check-ups and blood tests

Before you start taking Clozapine, 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.

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 you already suffer from feeling or if Clozapine makes you feel light-headed, dizzy or faint, be careful when getting up from a sitting or lying position as these may increase the possibility of falling.

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 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 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

Tell your doctor or pharmacist if you are taking, have recently taken or 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 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 Clozapine at the same time as another medicine may affect how well Clozapine 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.
digoxin, a medicine used to treat heart problems.
medicines used to treat a fast or irregular heartbeat.
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.
hormonal contraceptives (birth-control tablets).

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

Taking Clozapine with food and drink

Do not drink alcohol during treatment with Clozapine.

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 Clozapine.

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 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 Clozapine.

The following symptoms may occur in newborn 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.

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

Driving and using machines

Clozapine 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 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 Clozapine.

How to take Clozapine

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 Clozapine tablets exactly as your doctor has 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 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?).

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.

Treatment of schizophrenia

The usual starting dose is 12.5mg (one half of a 25mg tablet) once or twice on the first day followed by 25mg 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 25-50mg over the next 2-3 weeks until a dose up to 300mg per day is reached. Thereafter, if necessary, the daily dose may be increased in steps of 50 to 100mg half-weekly or, preferably, at weekly intervals.

The effective daily dose is usually between 200mg and 450mg, divided into several single doses per day. Some people might need more. A daily dose of up to 900mg is allowed.

Increased side effects (in particular seizures) are possible at daily doses over 450mg. 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 200mg, then you can take this as a single dose in the evening. Once you have been taking Clozapine with

successful results for some time, your doctor may try you on a lower dose. You will need to take Clozapine for at least 6 months.

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

The usual starting dose is 12.5mg (one half of a 25mg tablet) in the evening. Swallow the tablet with water. Your doctor will then gradually increase the dose in steps of 12.5mg, not faster than two steps a week, up to a maximum dose of 50mg 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 25mg and 37.5mg, taken as one dose in the evening. Doses of 50mg per day should only be exceeded in exceptional cases. The maximum daily dose is 100mg. Always take the lowest effective dose for you.

If you take more Clozapine 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, seizures (fits), increased production of saliva, widening of the black part of the eye, blurred vision, low blood pressure, collapse, fast or irregular heartbeat, shallow or difficult breathing.

If you forget to take Clozapine

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 for more than 48 hours.

If you stop taking Clozapine

Do not stop taking Clozapine 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 12.5mg 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 treatment suddenly, you will have to be checked by your doctor.

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

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

Possible side effects

Like all medicines, Clozapine 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 Clozapine tablet if you experience any of the following:

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

severe constipation. Your doctor will have to treat this in order to avoid further complications.
fast heartbeat

Common (affects up to 1 in 10 people):

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.
seizures.
sudden fainting or sudden loss of consciousness with muscle weakness (syncope).

Uncommon (affects up to 1 in 100 people):

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.
light-headedness, dizziness or fainting, when getting up from a sitting or lying position as it may increase the possibility of falling.

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

signs of respiratory tract infection or pneumonia such as fever, coughing, difficulty breathing, wheezing.
severe, burning, upper abdominal pain, extending to the back accompanied by nausea and vomiting due to inflammation of the pancreas.
fainting and muscle weakness due to a significant drop in blood pressure (Circulatory collapse).
difficulty in swallowing (which may cause inhalation of food).
nausea (feeling sick), vomiting (being sick) and/or loss of appetite. Your doctor will need to check your liver.
interruption in breathing with or without snoring during sleep
signs of becoming obese or increasing obesity

Rare (affects up to 1 in 1,000 people) or very rare (affects up to 1 in 10,000 people):

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.

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

persistent painful erection of the penis, if you are a man. This is called priapism. If you have an erection which lasts more than 4 hours of immediate medical treatment may be needed in order to avoid further complications.
spontaneous bleeding or bruising, which might be signs of a decrease in numbers of blood platelets.
symptoms due to uncontrolled blood sugar (such as nausea or vomiting, abdominal pain, excessive thirst, excessive urination, disorientation or confusion.
abdominal pain, cramping, swollen abdomen, vomiting, constipation and failure to pass gas which may be signs and symptoms of bowel obstruction.
loss of appetite, swollen abdomen, abdominal pain, yellowing of the skin, severe weakness and malaise. These symptoms may be signs that you are starting to develop a liver disorder that may advancement fulminant liver necrosis.
nausea, vomiting, fatigue, weight loss which may be symptoms of inflammation of the kidney.

Unknown (frequency cannot be estimated from the available data)

crushing chest pain, a 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, lightheadedness, nausea, vomiting and palpitations (symptoms of heart attack). You should seek emergency medical treatment immediately.
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.
intermittent ?thumping?, ?pounding? or ?fluttering? sensation in the chest (palpitations).
rapid and irregular heartbeats (atrial fibrillation). There may be occasional heart palpitations, fainting, shortness of breath, or chest discomfort. Your doctor will need to check your heart.
symptoms of low blood pressure such as light-headedness, dizziness, fainting, blurred vision, unusual fatigue, cold and clammy skin or nausea.
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.
proven or strongly suspected infection along with fever or low body temperature, abnormally rapid breathing, rapid heart rate, change in responsiveness and awareness, drop in blood pressure (sepsis).
profuse sweating, headache, nausea, vomiting and diarrhoea (symptoms of a cholinergic syndrome).
severely decreased urine output (a sign of kidney failure).
an allergic reaction (swelling mainly of the face, mouth and throat, as well as, the tongue, which may be itchy or painful).
loss of appetite, swollen abdomen, abdominal pain, yellowing of the skin, severe weakness and malaise. This may indicate possible 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.
constipation, abdominal pain, abdominal tenderness, fever, bloating, bloody diarrhoea. This may indicate possible megacolon (enlargement of the intestines) or intestinal infarction/ischaemia. Your doctor will need to examine you.
sharp chest pain with shortness of breath and with or without coughing
increased or new muscle weakness, muscle spasms, muscle pain. This may indicate possible muscle disorder (rhabdomyolysis). Your doctor will need to examine you.
sharp chest or abdominal pain with shortness of breath and with or without coughing or fever.

If any of the above apply to you, please tell your doctor immediately before taking the next Clozapine tablet.

Other side effects:

Very common (affects more than 1 in 10 people): Drowsiness, dizziness, increased production of saliva. Common (affects 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, convulsions, jerks, abnormal movements, inability to initiate movement, inability to remain motionless, changes in ECG heart machine, high blood pressure, faintness or light-headedness after changing position, 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), 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, irregular heartbeat, inflammation of the heart muscle (myocarditis) or the membrane surrounding the heart muscle (pericarditis), fluid collection around the heart (pericardial effusion), 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, 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, 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, very high levels of triglycerides or cholesterol in the blood, disorder of the heart muscle (cardiomyopathy), stopped heartbeat (cardiac arrest), sudden unexplained death.

Unknown (frequency cannot be estimated from the available data)

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, sudden, uncontrollable increase in blood pressure (pseudophaeochromocytoma), uncontrolled bending of the body to one side (pleurothotonus), ejaculatory disorder if you are a male, in which semen enters the bladder instead of ejaculating through the penis (dry orgasm or retrograde ejaculation), rash, purplish-red spots, fever or itching due to inflammation of blood vessel, inflammation of the colon resulting in diarrhoea, abdominal pain, fever, change in skin colour, ?butterfly? facial rash, joint pain, muscle pain, fever and fatigue (lupus erythematous), restless legs syndrome (irresistible urge to move your legs or arms, usually accompanied by uncomfortable sensations during periods of rest, especially in the evening or at night and temporarily relieved by movement).

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.

How to store Clozapine

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

Do not use Clozapine after the expiry date which is stated on the blister/bottle and the carton. The expiry date refers to the last day of that month.

This medicinal product 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.

Contents of the pack and other information

What Clozapine contains

The active substance is clozapine. Each tablet contains 25mg or 100mg clozapine.

The other ingredients are magnesium stearate, anhydrous colloidal silica, povidone K30, talc, maize starch, lactose monohydrate.

What Clozapine looks like and contents of the pack

Leponex tablets are available in PVC/PVDC/Aluminium or PVC/PE/PVDC/Aluminium blister packs containing 7, 14, 20, 28, 30, 40, 50, 60, 84, 98, 100, 500 (10×50) or 5000 (100×50) tablets,

PVC/PVDC/Aluminium or PVC/PE/PVDC/Aluminium perforated unit-dose blister packs containing 7×1, 14×1, 20×1, 28×1, 30×1, 40×1, 50×1, 60×1, 84×1, 98×1, 100×1, 500 (10x50x1) and 5000

(100x50x1) tablets, and in white plastic bottles containing 100 or 500 tablets. Not all pack sizes may be marketed.

Manufactured in India by:
TAJ LIFE SCIENCES PVT. LTD.
Unit No. 214, Old Bake House,
Bake House Lane, Fort,
Mumbai-400001
at: Ahmedabad- Gujarat, INDIA.
Ho.NO. +91 8448 444 095
Toll Free Phone: (1800-222-434 / 1800-222-825)