Package leaflet: Information for the user

Leponex 25 mg tablets

clozapine
Please read this leaflet carefully before taking this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not pass it on to others, even if they have the same symptoms as you, because it may be harmful.
If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Leponex is and what it is used for

The active substance in Leponex is clozapine, which belongs to a group of medicines called
antipsychotics (medicines used to treat specific mental disorders such as
psychoses).
Leponex is used to treat people with schizophrenia who have not benefited from other
medicines.
Schizophrenia is a mental illness that affects the way a person thinks, feels, and behaves. You should use this medicine only after having tried at least two other antipsychotics for the treatment of schizophrenia, including one of the more recent atypical antipsychotics, and only if these medicines have not worked or have caused serious side effects that cannot be managed.
Leponex is also used to treat severe disturbances in thinking, emotions, and behaviour in people with Parkinson's disease who have not benefited from other medicines.

2. What you should know before taking Leponex

Do not take Leponex if

you are allergic (hypersensitive) to clozapine or to any of the other ingredients of Leponex (listed in section 6).
you are unable to undergo regular blood tests.
you have previously had a low white blood cell count (e.g. leucopenia or agranulocytosis), especially if caused by medications. This does not apply to you if the low white blood cell count was caused by previous chemotherapy treatment.
you previously had to stop taking Leponex due to serious side effects (e.g. agranulocytosis or heart problems).
you are or have been treated with long-acting depot antipsychotic injections.
you suffer from or have suffered from bone marrow disorders.
you suffer from uncontrolled epilepsy (epileptic seizures or convulsions).
you have an acute mental disorder caused by alcohol or drugs (e.g. narcotics).
you suffer from decreased level of consciousness and severe drowsiness.
you suffer from circulatory collapse, which may occur following severe shock.
you suffer from any severe kidney disease.
you suffer from myocarditis (inflammation of the heart muscle).
you suffer from any other serious heart disorder.
you have symptoms of acute liver disease such as jaundice (yellowing of the skin and eyes, nausea and loss of appetite).
you suffer from any other severe liver disease.
you suffer from paralytic ileus (your intestine does not function properly causing severe constipation).
you are taking any medication that impairs bone marrow function.
you are taking any medication that reduces the number of white blood cells in the blood. If you are in any of the situations described above, inform your doctor and do not take Leponex. Leponex must not be administered to unconscious persons or those in a coma.

Warnings and precautions
The precautionary measures described in this section are very important and must be
followed to minimize the risk of serious side effects that could be life-threatening.
Before treatment with Leponex, inform your doctor if you suffer from or have suffered from:

blood clot formation or a family history of blood clots, as medicines like this have been associated with blood clot formation.
glaucoma (increased eye pressure).
diabetes. High (sometimes even markedly high) blood sugar levels have been observed in patients with or without a history of diabetes mellitus (see section 4).
prostate problems or difficulty urinating.
any heart, kidney or liver disorder.
chronic constipation or if you are taking medications that cause constipation (such as anticholinergics).
galactose intolerance, lactase deficiency or glucose/galactose malabsorption syndrome.
controlled epilepsy.
disorders of the large intestine.
abdominal surgery.
a heart condition or family history of a cardiac conduction abnormality known as “QT interval prolongation”.
risk of stroke, for example if you have high blood pressure, cardiovascular disorders or problems with cerebral blood vessels.

Inform your doctor immediately before taking your next Leponex tablet if:

you develop signs of cold, fever, flu-like symptoms, sore throat or any type of infection. You will need to have a blood test urgently to determine whether your symptoms are related to the medicine.
you experience a sudden and rapid increase in body temperature, muscle rigidity which may lead to loss of consciousness (neuroleptic malignant syndrome): this may indicate a serious adverse reaction requiring immediate treatment.
you have a fast or irregular heartbeat, palpitations, shortness of breath, chest pain or unexplained fatigue. Your doctor will need to check your heart and, if necessary, refer you immediately to a cardiologist.
you experience nausea (feeling unwell), vomiting and/or loss of appetite. Your doctor will need to check your liver.
you develop severe constipation. Your doctor will need to treat this condition to prevent further complications.
you experience constipation, abdominal pain, intestinal tenderness, fever, bloating and/or bloody diarrhoea. Your doctor will need to examine you.

Clinical monitoring and haematological tests
Before starting treatment with Leponex, your doctor will take your medical history and perform a blood test to ensure that your white blood cell count is normal. This is important because your body needs white blood cells to fight infections.
Make sure you have regular blood tests before starting treatment, during treatment and after stopping treatment with Leponex.

Your doctor will tell you exactly when and where to have the tests. Leponex may only be taken if your blood cell count is normal.
Leponex can cause a severe decrease in white blood cells in the blood (agranulocytosis). Only regular blood tests can help your doctor determine whether you are at risk of developing agranulocytosis.
During the first 18 weeks of treatment, blood tests must be performed once a week. After this, blood tests must be performed at least once a month.
If your white blood cell count decreases, you must stop taking Leponex immediately. The white blood cell count must then return to normal.
After stopping treatment with Leponex, you must continue to have blood tests for another 4 weeks. Your doctor will also perform a general physical examination before starting treatment. Your doctor may also perform an electrocardiogram (ECG) to check your heart, but only if necessary or if you have specific concerns. If you have liver disorders, you must have regular liver function tests throughout your treatment with Leponex. If you have high blood sugar levels (diabetes), your doctor may need to monitor your blood sugar levels regularly. Leponex can cause changes in blood lipids. Leponex can cause weight gain. Your doctor may need to monitor your weight and blood lipid levels. If you already feel or Leponex causes you to feel dizzy, lightheaded or faint, be careful when standing up from a sitting or lying position, as this may increase your risk of falling.

If you are scheduled for surgery or for any reason are unable to walk for long periods, tell your doctor that you are taking Leponex. In these cases, you may be at risk of thrombosis (blood clot formation in the veins).
Children and adolescents under 16 years of age
If you are under 16 years of age, do not take Leponex, as there is insufficient information on its use in this age group.
Elderly patients (aged 60 years or older)
Elderly patients (aged 60 years or older) may be more likely to experience the following side effects during treatment with Leponex: weakness or lightheadedness upon changing position, dizziness, rapid heartbeat, difficulty urinating and constipation.
Inform your doctor or pharmacist if you suffer from a condition called dementia.
Other medicines and Leponex
Inform your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including those without a prescription or herbal preparations. It may be necessary to adjust the dose of these medicines or to take different medicines.
Do not take Leponex together with medicines that impair bone marrow function and/or reduce the number of blood cells produced by the body, such as:

carbamazepine, a medicine used for epilepsy.
certain antibiotics: chloramphenicol, sulfonamides such as co-trimoxazole.
certain painkillers: pyrazolone analgesics such as phenylbutazone.
penicillamine, a medicine used to treat rheumatoid arthritis.
cytotoxic drugs, medicines used for chemotherapy.
injections of long-acting depot antipsychotic medicines. These medicines increase the risk of developing agranulocytosis (lack of white blood cells).

Taking Leponex together with another medicine may affect the effect of Leponex and/or the other medicine. Inform your doctor if you intend to take, are currently taking (even if treatment is nearly finished) or have recently stopped taking any of the following medicines:

medicines for depression, such as lithium, fluvoxamine, tricyclic antidepressants, MAO inhibitors, citalopram, paroxetine, fluoxetine and sertraline.
other antipsychotic medicines used to treat mental disorders, such as perazine.
benzodiazepines and other medicines used to treat anxiety or sleep disorders.
narcotics and other medicines that may affect 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 clot formation.
antihistamines, medicines used for colds or allergies such as hay fever.
anticholinergic medicines, 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.
certain medicines used to treat gastric ulcers, such as omeprazole or cimetidine.
certain antibiotics, such as erythromycin and rifampicin.
certain medicines used to treat fungal infections (such as ketoconazole) or viral infections (such as protease inhibitors, used to treat HIV infections).
atropine, a medicine that may be present in certain eye drops or cough and cold preparations.
adrenaline, a medicine used in emergency situations.
hormonal contraceptives (birth control pills). This list is not exhaustive. Your doctor and pharmacist have more information about medicines to be taken with caution or avoided during treatment with Leponex, and know whether the medicine you are taking belongs to those listed. Discuss this with them.

Taking Leponex with food and drinks
Do not drink alcohol during treatment with Leponex.
Inform your doctor if you smoke and how frequently you consume caffeine-containing drinks (coffee, tea, Coca-Cola). Sudden changes in smoking or caffeine consumption habits may alter the effects of Leponex.
Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor before taking this medicine. Your doctor will discuss with you the benefits and potential risks of taking this medicine during pregnancy. Inform your doctor promptly if you become pregnant while taking Leponex.
The following symptoms have been observed in newborns of mothers who took Leponex during the third trimester (last three months of pregnancy): tremor, muscle stiffness and/or weakness, drowsiness, agitation, breathing difficulties and feeding problems. If your baby shows any of these symptoms, contact your doctor.
Some women taking certain medicines for mental disorders may not have periods or may have irregular periods. If this applies to you, your periods may return when switching from your current medicine to Leponex treatment. This means you must use adequate contraceptive measures.
Do not breastfeed while taking Leponex. Clozapine, the active substance in Leponex, may pass into breast milk and affect the baby.
Driving and using machines
Leponex may cause tiredness, drowsiness and seizures, especially at the beginning of treatment. You must not drive or operate machinery when you experience these symptoms.
Leponex contains lactose.
If your doctor has diagnosed you with an intolerance to certain sugars, consult him before taking Leponex.

3. How to take Leponex

To minimise the risk of low blood pressure, seizures, and drowsiness, your doctor must gradually increase the dose. Take Leponex exactly as instructed by your doctor. If you have any doubts, consult your doctor or pharmacist.
It is important that you do not change the dose or stop treatment with Leponex without first consulting your doctor. Continue taking the tablets unless otherwise advised by your doctor. If you are 60 years of age or older, your doctor may start you on a lower dose and increase it gradually, as certain side effects are more likely to occur (see section 2 “Before taking Leponex”).
If the dose prescribed for you cannot be achieved with this tablet, other strengths of this medicine are available.

Treatment of schizophrenia
The usual starting dose is 12.5 mg (half 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 well tolerated, your doctor will gradually increase the dose by 25–50 mg over the next 2–3 weeks until a daily dose of 300 mg is reached. Afterwards, if necessary, the daily dose may be increased by 50–100 mg every 3–4 days, or preferably at weekly intervals.
The effective daily dose is generally between 200 and 450 mg, divided into several single doses per day. Some individuals may require a higher dose. A daily dose of up to 900 mg is permitted. Higher daily doses (above 450 mg) may lead to an increased risk of side effects (particularly seizures). Always take the lowest effective dose for you. Most people take part of the dose in the morning and part in the evening. Your doctor will tell you exactly how to divide the daily dose. If your daily dose is only 200 mg, you may take this as a single dose in the evening. After taking Leponex for some time with good results, your doctor may attempt to reduce the dose. You should take Leponex for at least 6 months.

Treatment of severe thought disorders in patients with Parkinson’s disease
The usual starting dose is 12.5 mg (half a 25 mg tablet) in the evening. Swallow the tablet with water. Your doctor will gradually increase the dose by 12.5 mg at a time, with no more than 2 increases per week, until reaching a maximum dose of 50 mg by the end of the second week. Dose increases should be stopped or delayed if you feel weak, confused, or lightheaded. To avoid these symptoms, your blood pressure should be monitored during the first weeks of treatment.
The effective daily dose is generally between 25 and 37.5 mg, taken as a single dose in the evening. Only in exceptional cases should the daily dose exceed 50 mg. The maximum daily dose is 100 mg. Always take the lowest effective dose for you.

If you take more Leponex than you should
Contact your doctor immediately or seek urgent medical help if you think you have taken too many tablets, or if someone else has taken some of your tablets.
Symptoms of overdose include:
Drowsiness, fatigue, lack of energy, loss of consciousness, coma, confusion, hallucinations, agitation, slurred speech, joint stiffness, hand tremors, seizures (convulsions), increased saliva production, dilated pupils, vision disturbances, low blood pressure, collapse, rapid or irregular heartbeat, and difficult or shallow breathing.

If you forget to take Leponex
If you forget to take a dose, take it as soon as you remember. If it is almost time for your next dose, do not take the missed dose and take the next dose at the correct 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 Leponex for more than 48 hours.

If you stop taking Leponex
Do not stop treatment with Leponex without consulting your doctor, as you may experience withdrawal symptoms. These include sweating, headache, nausea, vomiting, and diarrhoea. If you experience any of these symptoms, contact your doctor immediately. These symptoms may be followed by more serious side effects if you do not receive prompt and appropriate treatment. The original symptoms may reappear. If you need to stop treatment, a gradual reduction of the dose in steps of 12.5 mg over one to two weeks is recommended. Your doctor will advise you on how to reduce your daily dose. If you need to stop treatment with Leponex suddenly, you should be monitored by your doctor. If your doctor decides to restart treatment with Leponex and more than two days have passed since your last dose, you must begin again with a dose of 12.5 mg.

If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, Leponex can cause side effects, although not everyone experiences them.
Some side effects can be serious and require immediate medical attention.
Contact your doctor immediately before taking your next Leponex tablet if you experience any of the following side effects:
Very common (occur in more than 1 in 10 patients):

Severe constipation. Your doctor will need to treat this condition to prevent further complications.
Fast heartbeat

Common (occur in up to 1 in 10 patients):

Signs of cold, fever, flu-like symptoms, sore throat, or any type of infection. You will need to urgently have a blood test to check whether your symptoms are related to the medicine.
Seizures
Sudden fainting or sudden loss of consciousness with muscle weakness (syncope)

Uncommon (occur in up to 1 in 100 patients):

Sudden and rapid increase in body temperature, muscle stiffness that may lead to loss of consciousness (neuroleptic malignant syndrome): this may be a serious side effect requiring immediate treatment.
Feeling of light-headedness, dizziness, or fainting when standing up from sitting or lying down, as this may increase the risk of falls.

Rare (occur in up to 1 in 1,000 patients):

Signs of respiratory tract infection or pneumonia such as fever, cough, difficulty breathing, wheezing.
Severe and burning abdominal pain in the upper abdomen spreading 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 swallowing (which may cause food aspiration).
Nausea, vomiting and/or loss of appetite. Your doctor will need to check your liver function.
Obesity or worsening of obesity
Breathing stops, with or without snoring, during sleep

Rare (occur in up to 1 in 1,000 patients) or very rare (occur in up to 1 in 10,000 patients):

Fast and irregular heartbeat, even at rest, palpitations, breathing problems, chest pain, or unexplained fatigue. Your doctor will need to check your heart and, if necessary, refer you immediately to a cardiologist.

Very rare (occur in up to 1 in 10,000 patients):

Painful and prolonged erection of the penis if you are a man: this condition is known as priapism. If an erection lasts longer than 4 hours, you may need immediate medical treatment to avoid further complications.
Spontaneous bleeding or bruising, which may be signs of a reduced number of platelets in the blood.
Symptoms due to uncontrolled blood sugar levels (such as nausea or vomiting, abdominal pain, excessive thirst, excessive urination, disorientation or confusion).
Abdominal pain, cramps, bloated abdomen, vomiting, constipation, inability to pass gas, which may be signs and symptoms of intestinal obstruction.
Loss of appetite, bloated abdomen, abdominal pain, yellowing of the skin, severe weakness and malaise. These symptoms may indicate the onset of a liver disorder that may lead to fulminant hepatic necrosis.
Nausea, vomiting, fatigue, weight loss, which may be symptoms of kidney inflammation.

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

Unbearable chest pain, feeling of pressure, tightness or constriction in the chest (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 a heart attack) which may lead to death. In this case, call for urgent medical assistance immediately.
Chest pressure, heaviness, tightness, constriction, burning, or choking sensation (signs of insufficient blood and oxygen supply to the heart muscle) which may lead to death. In this case, your doctor will need to check your heart.
Intermittent sensation in the chest of a "thump", a "punch", or an "abnormal beat" (palpitations).
Rapid and irregular heartbeats (atrial fibrillation). Occasional palpitations, fainting, shortness of breath, or chest discomfort may occur. In this case, your doctor will need to check your heart.
Symptoms of low blood pressure such as light-headedness, dizziness, fainting, blurred vision, unusual tiredness, cold and sweaty skin, or nausea.
Signs of blood clots in the veins, especially in the legs (symptoms include swelling, pain, and redness in the legs), with clots that may travel through blood vessels to the lungs and cause chest pain and breathing difficulties.
Proven or strongly suspected infection with fever or abnormally low body temperature, abnormally rapid breathing, fast heart rate, altered responsiveness and sensitivity, low blood pressure (sepsis).
Excessive sweating, headache, nausea, vomiting, and diarrhoea (symptoms of cholinergic syndrome).
Marked decrease in urine output (a sign of kidney failure).
Allergic reaction (swelling, especially of the face, mouth, and throat, and also swelling of the tongue, which may cause itching or pain).
Loss of appetite, bloated abdomen, abdominal pain, yellowing of the skin, severe weakness and malaise. This may indicate possible liver disorders involving replacement of normal liver tissue with scar tissue, leading to loss of liver function, including life-threatening liver events such as liver failure (which may lead to death), liver injury (damage to liver cells, bile ducts in the liver, or both), and liver transplants.
Burning pain in the upper abdomen, particularly between meals, early in the morning, or after drinking acidic beverages; tarry, black, or bloody stools; bloating, heartburn, nausea or vomiting, early feeling of fullness (intestinal ulceration of the stomach and/or intestine) which may lead to death.
Severe abdominal pain worsened by movement, nausea, vomiting including vomiting of blood (or coffee-ground-like liquid); the abdomen becomes rigid with rebound tenderness spreading from the perforation site throughout the abdomen; fever and/or chills (perforation of the stomach and/or intestine or intestinal rupture) which may lead to death.
Constipation, abdominal pain, abdominal tenderness, fever, bloating, diarrhoea with blood. This may indicate possible megacolon (enlargement of the intestine) or intestinal infarction/ischaemia/necrosis which may lead to death. In this case, your doctor will need to examine you.
Sudden chest pain with shortness of breath, with or without cough.
New or increased muscle weakness, muscle spasms, muscle pain. This may indicate a possible muscle disorder (rhabdomyolysis). In this case, your doctor will need to examine you.
Acute chest or abdominal pain with shortness of breath and with or without cough or fever.
Severe and very intense skin reactions have been reported during the use of Leponex, such as rash with eosinophilia and systemic symptoms (DRESS syndrome). The adverse skin reaction may appear as a rash with or without blisters. Skin irritation, swelling, fever, and flu-like symptoms may occur. Symptoms of DRESS syndrome usually appear approximately 2–6 weeks (potentially up to 8 weeks) after starting treatment.

If you experience any of the reactions described above, please consult your doctor immediately before taking another Leponex tablet.

Other side effects:
Very common (occur in more than 1 in 10 patients):
Drowsiness, dizziness, increased saliva production.

Common (occur in up to 1 in 10 patients):
Elevated white blood cell levels (leucocytosis), elevated levels of specific types of white blood cells (eosinophilia), weight gain, blurred vision, headache, tremor, stiffness, restlessness, seizures, spasms, abnormal movements, inability to initiate movements, inability to remain still, changes in electrocardiogram (ECG) pattern, high blood pressure, weakness or light-headedness upon changing position, nausea (feeling sick), vomiting, loss of appetite, dry mouth, slightly abnormal liver function tests, loss of bladder control, difficulty urinating, fatigue, fever, increased sweating, increased body temperature, speech disorders (e.g. slurred speech).

Uncommon (occur in up to 1 in 100 patients):
Lack of white blood cells in the blood (agranulocytosis), speech disorders (e.g. stuttering).

Rare (occur in up to 1 in 1,000 patients):
Low levels of red blood cells in the blood (anaemia), inability to rest, agitation, confusion, delirium, irregular heartbeat, inflammation of the heart muscle (myocarditis) or of the membrane surrounding the heart muscle (pericarditis), fluid accumulation around the heart (pericardial effusion), elevated blood sugar levels, diabetes mellitus, blood clots in the lungs (thromboembolism), liver inflammation (hepatitis), liver disorders causing yellowing of the skin/dark urine/itching, increased blood levels of an enzyme called creatine phosphokinase.

Very rare (occur in up to 1 in 10,000 patients):
Increased number of platelets in the blood with possible formation of clots in blood vessels, uncontrollable movements of the mouth, tongue, and lips, obsessive thoughts and repetitive compulsive behaviours (obsessive/compulsive symptoms), skin reactions, swelling of the front part of the ears (enlargement of the salivary glands), breathing difficulties, very high levels of cholesterol and triglycerides in the blood, heart muscle disease (cardiomyopathy), cessation of heartbeat (cardiac arrest), unexplained sudden death.

Not known (frequency cannot be estimated from the available data):
Changes observed on electroencephalogram (EEG), diarrhoea, stomach discomfort, heartburn, stomach discomfort after meals, muscle weakness, muscle spasms, muscle pain, nasal congestion, bedwetting at night, sudden and uncontrolled increase in blood pressure (pseudopheochromocytoma), involuntary curvature of the body to one side (pleurothotonus), in males, ejaculation disorders where semen enters the bladder instead of being ejaculated through the penis (dry orgasm or retrograde ejaculation), skin rash, red-purple spots, fever or itching due to inflammation of blood vessels, inflammation of the colon causing diarrhoea, abdominal pain, fever, skin colour changes, butterfly-shaped facial rash, joint pain, muscle pain, fever, and fatigue (lupus erythematosus). Restless legs syndrome (irresistible urge to move the legs or arms, usually accompanied by unpleasant sensations during periods of rest, especially in the evening or at night, and temporarily relieved by movement).

In elderly patients with dementia, a small increase in the number of deaths has been reported among patients taking antipsychotics compared to those who did not.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist.
You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Leponex

Keep this medicine out of the sight and reach of children.
Do not use Leponex after the expiry date stated on the bottle or blister pack and on the outer carton. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Leponex contains

The active substance in Leponex is clozapine. Each tablet contains 25 mg of clozapine.
The other components are magnesium stearate, anhydrous colloidal silica, povidone (K 30), talc, maize starch, lactose monohydrate.

Description of the appearance of Leponex and pack sizes
Leponex tablets are yellow, round, flat tablets with bevelled edges, marked with the letters “L/O” separated by a scored line on one side and “CLOZ” on the opposite side.
Leponex tablets are available in PVC/PVDC/aluminium or PVC/PE/PVDC/aluminium blisters containing 7, 14, 20, 28, 30, 40, 50, 60, 84, 98, 100, 500 (10x50) or 5000 (100x50) tablets; unit-dose divisible blisters in PVC/PVDC/aluminium or PVC/PE/PVDC/aluminium containing 7x1, 14x1, 20x1, 28x1, 30x1, 40x1, 50x1, 60x1, 84x1, 98x1, 100x1, 500 (10x50x1) and 5000 (100x50x1) tablets; and in white plastic bottles containing 100 or 500 tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Viatris Healthcare Limited
Damastown Industrial Park
Mulhuddart
Dublin 15
DUBLIN
Ireland

Manufacturer
McDermott Laboratories Limited
T/A Gerard Laboratories
T/A Mylan Dublin
Unit 35/36 Baldoyle Industrial Estate
Grange Road
Dublin 13
Ireland
Mylan Hungary Kft.
Mylan utca 1.
Komárom, 2900
Hungary
Madaus GmbH
Lütticher Straße 5
53842 Troisdorf
Germany

This medicinal product is authorised in the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:
Austria Leponex 25 mg Tabletten
Belgium Leponex 25 mg tabletten/Leponex 25 mg Tabletten/Leponex 25 mg comprimés
Denmark Leponex
Finland Leponex 25 mg tabletti
France Leponex 25 mg comprimé sécable
Germany Leponex 25 mg Tabletten
Greece Leponex 25 mg Δισκία
Iceland Leponex 25 mg töflur
Ireland Clozaril 25 mg tablets
Italy Leponex 25 mg compresse
Luxembourg Leponex 25 mg comprimés
Norway Leponex 25 mg tabletter
Netherlands Leponex 25 mg, tabletten
Portugal Leponex 25 mg comprimidos
United Kingdom (Northern Ireland) Clozaril 25 mg tablets
Spain Leponex 25 mg comprimidos
Sweden Leponex 25 mg tabletter

Package leaflet: Information for the user

Leponex 100 mg tablets

clozapine
Please read this leaflet carefully before taking this medicine because it contains
important information for you

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as yours, because it could be harmful.
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

What Leponex is and what it is used for
What you need to know before taking Leponex
How to take Leponex
Possible side effects
How to store Leponex
Package contents and other information

1. What Leponex is and what it is used for

The active substance of Leponex is clozapine, which belongs to a group of medicines called antipsychotics (medicines used to treat specific mental disorders such as psychosis).
Leponex is used to treat people with schizophrenia who have not benefited from other medicines.
Schizophrenia is a mental illness that affects the way a person thinks, feels, and behaves. This medicine should be used only after having tried at least two other antipsychotics for the treatment of schizophrenia, including one of the more recent atypical antipsychotics, and only if these medicines have not worked or have caused severe side effects that cannot be managed.
Leponex is also used to treat severe disturbances of thought, emotions, and behaviour in people with Parkinson's disease who have not benefited from other medicines.

2. What you need to know before taking Leponex

Do not take Leponex if:

you are allergic (hypersensitive) to clozapine or to any of the other ingredients of Leponex (listed in section 6).
you are unable to undergo regular blood tests.
you have previously had a low white blood cell count (e.g. leucopenia or agranulocytosis), especially if caused by medications. This does not apply to you if the low white blood cell count was due to prior chemotherapy treatment.
you previously had to stop taking Leponex due to serious side effects (e.g. agranulocytosis or heart problems).
you are or have been treated with long-acting depot antipsychotic injections.
you suffer from or have suffered from bone marrow disorders.
you have uncontrolled epilepsy (epileptic seizures or convulsions).
you have an acute mental disorder caused by alcohol or drugs (e.g. narcotics).
you suffer from decreased level of consciousness and severe drowsiness.
you have circulatory collapse, which may occur following severe shock.
you suffer from any severe kidney disease.
you have myocarditis (inflammation of the heart muscle).
you suffer from any other serious heart disorder.
you have symptoms of acute liver disease such as jaundice (yellowing of the skin and eyes, nausea, and loss of appetite).
you suffer from any other severe liver disease.
you have paralytic ileus (your intestine does not function properly, causing severe constipation).
you are taking any medication that impairs bone marrow function.
you are taking any medication that reduces the number of white blood cells in the blood. If you are in any of the situations described above, inform your doctor and do not take Leponex. Leponex must not be administered to unconscious persons or those in a coma.

Warnings and precautions
The precautionary measures described in this section are very important and must be
followed to minimize the risk of serious adverse effects that could endanger your life.
Before starting treatment with Leponex, inform your doctor if you suffer from or have suffered from:

blood clot formation or a family history of blood clots, as such medicines have been associated with blood clot formation.
glaucoma (increased eye pressure).
diabetes. Elevated blood sugar levels (sometimes markedly) have been observed in patients with or without a history of diabetes mellitus (see section 4).
prostate problems or difficulty urinating.
any heart, kidney, or liver disorder.
chronic constipation or if you are taking medications that cause constipation (such as anticholinergics).
galactose intolerance, lactase deficiency, or glucose-galactose malabsorption syndrome.
controlled epilepsy.
disorders of the large intestine.
abdominal surgery.
a heart disorder or family history of a cardiac conduction abnormality known as “QT interval prolongation”.
risk of stroke, for example if you have high blood pressure, cardiovascular disorders, or cerebrovascular problems.

Inform your doctor immediately before taking your next dose of Leponex if:

you develop signs of cold, fever, flu-like symptoms, sore throat, or any type of infection. You will need an urgent blood test to determine whether your symptoms are related to the medicine.
you experience a sudden and rapid increase in body temperature, muscle rigidity that may lead to loss of consciousness (neuroleptic malignant syndrome): this may indicate a serious adverse reaction requiring immediate treatment.
you have a fast or irregular heartbeat, palpitations, difficulty breathing, chest pain, or unexplained fatigue. Your doctor will need to examine your heart and, if necessary, refer you immediately to a cardiologist.
you experience nausea (feeling unwell), vomiting, and/or loss of appetite. Your doctor will need to check your liver function.
you develop severe constipation. Your doctor will need to treat this condition to prevent further complications.
you experience constipation, abdominal pain, intestinal tenderness, fever, bloating, and/or bloody diarrhoea. Your doctor will need to examine you.

Clinical monitoring and haematological tests
Before starting treatment with Leponex, your doctor will review your medical history and perform a blood test to ensure your white blood cell count is normal. This is important because your body needs white blood cells to fight infections.
Make sure you have regular blood tests before starting treatment, during treatment, and after stopping
treatment with Leponex.

Your doctor will tell you exactly when and where to have the tests. Leponex may only be taken if your blood cell count is normal.
Leponex can cause a severe reduction in the number of white blood cells in the blood (agranulocytosis). Only regular blood tests can help your doctor determine if you are at risk of developing agranulocytosis.
During the first 18 weeks of treatment, blood tests must be performed weekly. After that, blood tests must be performed at least once a month.
If your white blood cell count decreases, you must stop taking Leponex immediately. Your white blood cell count must return to normal.
After stopping treatment with Leponex, you must continue to have blood tests for another 4 weeks. Your doctor will also perform a general physical examination before starting treatment. Your doctor may also perform an electrocardiogram (ECG) to check your heart, but only if necessary or if you have specific concerns. If you have liver disorders, you will need regular liver function tests for as long as you are taking Leponex. If you have high blood sugar levels (diabetes), your doctor may need to monitor your blood sugar levels regularly. Leponex may cause changes in blood lipid levels. Leponex may cause weight gain. Your doctor may need to monitor your weight and blood lipid levels.
If you already feel or Leponex causes dizziness, lightheadedness, or faintness, be cautious when standing up from a sitting or lying position, as this may increase your risk of falling.
If you are undergoing surgery or for any reason are unable to walk for prolonged periods, inform your doctor that you are taking Leponex. In these cases, you may be at risk of thrombosis (blood clot formation in veins).

Children and adolescents under 16 years of age
If you are under 16 years of age, do not take Leponex, as there is insufficient information on its use in this age group.

Elderly (aged 60 years or older)
Elderly patients (aged 60 years or older) may be more likely to experience the following side effects during treatment with Leponex: weakness or lightheadedness upon changing position, dizziness, rapid heartbeat, difficulty urinating, and constipation.
Inform your doctor or pharmacist if you have a condition called dementia.

Other medicines and Leponex
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including over-the-counter medicines or herbal preparations. It may be necessary to adjust the dose of these medicines or switch to different ones.
Do not take Leponex together with medicines that impair bone marrow function and/or reduce the number of blood cells produced by the body, such as:

carbamazepine, a medicine used for epilepsy.
certain antibiotics: chloramphenicol, sulfonamides such as cotrimoxazole.
certain pain medicines: pyrazolone analgesics such as phenylbutazone.
penicillamine, a medicine used to treat rheumatoid arthritis.
cytotoxic drugs, medicines used in chemotherapy.
injections of long-acting depot antipsychotic medicines. These medicines increase the risk of developing agranulocytosis (lack of white blood cells).

Taking Leponex together with another medicine may affect the effect of Leponex and/or the other
medicine. Inform your doctor if you are planning to take, are currently taking (even if treatment is nearly
complete), or have recently stopped taking any of the following medicines:

medicines for depression, such as lithium, fluvoxamine, tricyclic antidepressants, MAO inhibitors, citalopram, paroxetine, fluoxetine, and sertraline.
other antipsychotic medicines used to treat mental disorders, such as perazine.
benzodiazepines and other medicines used to treat anxiety or sleep disorders.
narcotics and other medicines that may affect 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, used to relieve stomach cramps, spasms, and motion 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.
certain medicines used to treat gastric ulcers, such as omeprazole or cimetidine.
certain antibiotics, such as erythromycin and rifampicin.
certain antifungal (e.g. ketoconazole) or antiviral medicines (e.g. protease inhibitors used to treat HIV infection).
atropine, a medicine that may be present in certain eye drops or cough and cold preparations.
adrenaline, a medicine used in emergencies.
hormonal contraceptives (birth control pills). This list is not exhaustive. Your doctor and pharmacist have more information about medicines to be taken with caution or avoided during treatment with Leponex, and can advise whether any medicine you are taking belongs to those listed. Discuss this with them.

Taking Leponex with food and drink
Do not drink alcohol during treatment with Leponex.
Inform your doctor if you smoke and how frequently you consume caffeine-containing drinks (coffee, tea, Coca-Cola). Sudden changes in smoking or caffeine consumption habits may alter the effects of Leponex.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding, consult your doctor before taking this medicine. Your doctor will discuss with you the benefits and potential risks of taking this medicine during pregnancy. Inform your doctor promptly if you become pregnant while taking Leponex.
The following symptoms have been observed in newborns of mothers who took Leponex during the third trimester (last three months of pregnancy): tremor, muscle stiffness and/or weakness, drowsiness, agitation, breathing difficulties, and feeding problems. If your baby shows any of these symptoms, contact your doctor.
Some women taking certain medicines for mental disorders may have absent or irregular menstrual periods. If this applies to you, menstruation may resume when switching from your current medicine to Leponex. This means you should use appropriate contraceptive measures.
Do not breastfeed while taking Leponex. Clozapine, the active substance in Leponex, can pass into breast milk and affect the baby.

Driving and using machines
Leponex may cause fatigue, drowsiness, and seizures, especially at the beginning of treatment. You should not drive or operate machinery when you experience these symptoms.

Leponex contains lactose.
If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking Leponex.

3. How to take Leponex

To minimize the risk of low blood pressure, seizures, and drowsiness, your doctor must gradually increase the dose. Always take Leponex exactly as prescribed by your doctor. If you have any doubts, consult your doctor or pharmacist.
It is important that you do not change the dose or stop treatment with Leponex without first consulting your doctor. Continue taking the tablets unless otherwise instructed by your doctor. If you are 60 years of age or older, your doctor may start you on a lower dose and increase it gradually, as certain side effects may occur more frequently (see section 2 “Before taking Leponex”).
If the prescribed dose cannot be achieved with this tablet, other strengths of this medicine are available.

Treatment of schizophrenia
The usual starting dose is 12.5 mg (half a 25 mg tablet) once or twice daily on the first day, followed by 25 mg once or twice daily on the second day. Swallow the tablet with water. If well tolerated, your doctor will gradually increase the dose by 25–50 mg over the next 2–3 weeks until reaching a dose of 300 mg per day. Afterwards, if necessary, the daily dose may be increased by 50–100 mg every 3–4 days, or preferably at weekly intervals.
The effective daily dose is generally between 200 and 450 mg, divided into multiple daily doses. Some individuals may require a higher dose. A daily dose of up to 900 mg is allowed. Higher daily doses (above 450 mg) may lead to an increased risk of side effects (particularly seizures). Always take the lowest effective dose for you. Most people take part of the dose in the morning and part in the evening. Your doctor will tell you exactly how to divide the daily dose. If the daily dose is only 200 mg, you may take it as a single dose in the evening. After taking Leponex for some time with good results, your doctor may attempt to reduce the dose. You should take Leponex for at least 6 months.

Treatment of severe thought disorders in patients with Parkinson’s disease
The usual starting dose is 12.5 mg (half a 25 mg tablet) in the evening. Swallow the tablet with water. Your doctor will gradually increase the dose by 12.5 mg at a time, with no more than 2 increases per week, up to a maximum of 50 mg by the end of the second week. Dose increases should be stopped or delayed if you feel weak, confused, or lightheaded. To avoid these symptoms, you should monitor your blood pressure during the first weeks of treatment.
The effective daily dose is generally between 25 and 37.5 mg, taken as a single evening dose. Only in exceptional cases should the daily dose exceed 50 mg. The maximum daily dose is 100 mg. Always take the lowest effective dose for you.

If you take more Leponex than you should
Contact your doctor immediately or seek urgent medical help if you think you have taken too many tablets, or if someone else has taken some of your tablets.
Symptoms of overdose include:
Drowsiness, fatigue, lack of energy, loss of consciousness, coma, confusion, hallucinations, agitation, slurred speech, joint stiffness, hand tremor, seizures (convulsions), increased saliva production, dilation of the black part of the eye (pupils), vision disturbances, low blood pressure, collapse, rapid or irregular heartbeat, and difficulty breathing or shallow breathing.

If you forget to take Leponex
If you forget to take a dose, take it as soon as you remember. If it is almost time for your next dose, do not take the missed dose and take the next dose at the regular time. Do not take a double dose to make up for a missed one. Contact your doctor as soon as possible if you have not taken Leponex for more than 48 hours.

If you stop taking Leponex
Do not stop treatment with Leponex without consulting your doctor, as you may experience withdrawal symptoms. These symptoms include sweating, headache, nausea, vomiting, and diarrhea. If you experience any of these symptoms, contact your doctor immediately. These symptoms may be followed by more serious adverse effects if you do not receive prompt and appropriate treatment. The original symptoms may reappear. If you need to stop treatment, a gradual reduction of the dose by 12.5 mg increments over one to two weeks is recommended. Your doctor will advise you on how to reduce your daily dose. If you must stop treatment with Leponex suddenly, you should be monitored by your doctor. If your doctor decides to restart treatment with Leponex and more than two days have passed since your last dose, treatment should begin again with a dose of 12.5 mg.

If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, Leponex can cause side effects, although not everyone experiences them.
Some side effects can be serious and require immediate medical attention.
Contact your doctor immediately before taking your next tablet of Leponex if you experience any of the following side effects:

Very common (occur in more than 1 out of 10 patients):

Severe constipation. Your doctor will need to treat this condition to prevent further complications.
Fast heartbeat

Common (occur in up to 1 out of 10 patients):

Signs of cold, fever, flu-like symptoms, sore throat, or any type of infection. You will need to urgently have a blood test to determine whether your symptoms are related to the medicine.
Seizures
Sudden fainting or sudden loss of consciousness with muscle weakness (syncope)

Uncommon (occur in up to 1 out of 100 patients):

Sudden and rapid increase in body temperature, muscle rigidity that may lead to loss of consciousness (neuroleptic malignant syndrome): this may indicate a serious adverse reaction requiring immediate treatment.
Feeling of light-headedness, dizziness, or fainting when standing up from sitting or lying down, as this may increase the risk of falls.

Rare (occur in up to 1 out of 1,000 patients):

Signs of respiratory tract infection or pneumonia such as fever, cough, difficulty breathing, wheezing.
Severe abdominal pain and burning in the upper abdomen, radiating 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 swallowing (which may lead to food aspiration)
Nausea, vomiting, and/or loss of appetite. Your doctor will need to check your liver.
Obesity or worsening of obesity
Breathing interruptions, with or without snoring, during sleep

Rare (occur in up to 1 out of 1,000 patients) or very rare (occur in up to 1 out of 10,000 patients):

Fast and irregular heartbeat, even at rest, palpitations, breathing problems, chest pain, or unexplained fatigue. Your doctor will need to check your heart and, if necessary, refer you immediately to a cardiologist.

Very rare (occur in up to 1 out of 10,000 patients):

Painful and prolonged erection of the penis if you are a man: this condition is known as priapism. If you experience an erection lasting more than 4 hours, you may require immediate medical treatment to avoid further complications.
Spontaneous bleeding or bruising, which may be signs of a reduced platelet count in the blood.
Symptoms due to uncontrolled blood sugar levels (such as nausea or vomiting, abdominal pain, excessive thirst, excessive urination, disorientation or confusion).
Abdominal pain, cramps, bloated abdomen, vomiting, constipation, inability to pass gas, which may be signs and symptoms of intestinal obstruction.
Loss of appetite, bloated abdomen, abdominal pain, yellowing of the skin, severe weakness and malaise. These symptoms may indicate the onset of a liver disorder that could lead to fulminant hepatic necrosis.
Nausea, vomiting, fatigue, weight loss, which may be symptoms of kidney inflammation

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

Unbearable chest pain, feeling of pressure, tightness, or constriction in the chest (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 a heart attack) which may lead to death. In this case, call immediately for emergency medical assistance.
Chest pressure, heaviness, tightness, constriction, burning, or suffocating sensation (signs of insufficient blood and oxygen supply to the heart muscle) which may lead to death. In this case, your doctor will need to check your heart.
Intermittent sensation in the chest of a “thump”, a “punch”, or an “abnormal beat” (palpitations).
Rapid and irregular heartbeats (atrial fibrillation). Occasional palpitations, fainting, shortness of breath, or chest discomfort may occur. In this case, your doctor will need to check your heart.
Symptoms of low blood pressure such as light-headedness, dizziness, fainting, blurred vision, unusual tiredness, cold and sweaty skin, or nausea.
Signs of blood clots in the veins, especially in the legs (symptoms include leg swelling, pain, and redness), with clots that may travel through blood vessels to the lungs and cause chest pain and breathing difficulties.
Proven or strongly suspected infection with fever or abnormally low body temperature, abnormally rapid breathing, fast heart rate, changes in reactivity and sensitivity, low blood pressure (sepsis).
Excessive sweating, headache, nausea, vomiting, and diarrhoea (symptoms of cholinergic syndrome).
Marked decrease in urine output (a sign of kidney failure).
Allergic reaction (swelling, especially of the face, mouth, and throat, as well as swelling of the tongue, which may cause itching or pain).
Loss of appetite, bloated abdomen, abdominal pain, yellowing of the skin, severe weakness and malaise. This may indicate possible liver disorders involving replacement of normal liver tissue with scar tissue, leading to loss of liver function, including life-threatening liver events such as liver failure (which may lead to death), liver injury (damage to liver cells, bile ducts in the liver, or both), and liver transplants.
Burning pain in the upper abdomen, particularly between meals, early in the morning, or after drinking acidic beverages; tarry, black, or bloody stools; bloating, heartburn, nausea or vomiting, early feeling of fullness (intestinal ulceration of the stomach and/or intestine) which may lead to death.
Severe abdominal pain worsened by movement, nausea, vomiting including vomiting of blood (or coffee-ground-like material); the abdomen becomes rigid with rebound tenderness spreading from the perforation site throughout the abdomen; fever and/or chills (perforation of the stomach and/or intestine or intestinal rupture) which may lead to death.
Constipation, abdominal pain, abdominal tenderness, fever, bloating, diarrhoea with blood. This may indicate possible megacolon (enlargement of the intestine) or intestinal infarction/ischemia/necrosis which may lead to death. In this case, your doctor will need to examine you.
Sudden chest pain with shortness of breath, with or without cough
New or increased muscle weakness, muscle spasms, muscle pain. This may indicate a possible muscle disorder (rhabdomyolysis). In this case, your doctor will need to examine you.
Acute chest or abdominal pain with shortness of breath and with or without cough or fever.
Very severe and serious skin reactions have been reported during the use of Leponex, such as rash with eosinophilia and systemic symptoms (DRESS syndrome). The adverse skin reaction may appear as a rash with or without blisters. Skin irritation, edema, fever, and flu-like symptoms may occur. Symptoms of DRESS syndrome usually appear approximately 2–6 weeks (potentially up to 8 weeks) after starting treatment.

If you experience any of the reactions described above, please consult your doctor immediately before taking another tablet of Leponex.

Other side effects:

Very common (occur in more than 1 out of 10 patients):
Drowsiness, dizziness, increased saliva production.

Common (occur in up to 1 out of 10 patients):
Elevated white blood cell count (leucocytosis), elevated levels of specific types of white blood cells (eosinophilia), weight gain, blurred vision, headache, tremor, muscle stiffness, restlessness, seizures, spasms, abnormal movements, inability to initiate movements, inability to remain still, changes in electrocardiogram (ECG) pattern, high blood pressure, weakness or light-headedness upon changing position, nausea (feeling sick), vomiting, loss of appetite, dry mouth, slightly abnormal results in liver function tests, loss of bladder control, difficulty urinating, fatigue, fever, increased sweating, increased body temperature, speech disorders (e.g. slurred speech).

Uncommon (occur in up to 1 out of 100 patients):
Lack of white blood cells in the blood (agranulocytosis), speech disorders (e.g. stuttering).

Rare (occur in up to 1 out of 1,000 patients):
Low red blood cell count (anaemia), inability to rest, agitation, confusion, delirium, irregular heartbeat, inflammation of the heart muscle (myocarditis) or of the membrane surrounding the heart muscle (pericarditis), fluid accumulation around the heart (pericardial effusion), elevated blood sugar levels, diabetes mellitus, blood clots in the lungs (pulmonary embolism), liver inflammation (hepatitis), liver disorders causing yellowing of the skin/dark urine/itching, increased blood levels of an enzyme called creatine phosphokinase.

Very rare (occur in up to 1 out of 10,000 patients):
Increased number of platelets in the blood with possible blood clot formation in blood vessels, uncontrolled movements of the mouth, tongue, and lips, obsessive thoughts and repetitive compulsive behaviours (obsessive/compulsive symptoms), skin reactions, swelling of the front part of the ears (enlargement of the salivary glands), breathing difficulties, very high levels of cholesterol and triglycerides in the blood, heart muscle disease (cardiomyopathy), cessation of heartbeat (cardiac arrest), unexplained sudden death.

Not known (frequency cannot be estimated from available data):
Changes observed on electroencephalogram (EEG), diarrhoea, stomach discomfort, heartburn, stomach discomfort after meals, muscle weakness, muscle spasms, muscle pain, nasal congestion, bedwetting at night, sudden and uncontrollable increase in blood pressure (pseudopheochromocytoma), involuntary curvature of the body to one side (pleurothotonus), in males, ejaculation disorders, in which semen enters the bladder instead of being ejaculated through the penis (dry orgasm or retrograde ejaculation), skin rash, red-purple spots, fever or itching due to inflammation of blood vessels, inflammation of the colon causing diarrhoea, abdominal pain, fever, skin colour changes, butterfly-shaped facial rash, joint pain, muscle pain, fever and fatigue (lupus erythematosus). Restless legs syndrome (irresistible urge to move the legs or arms, usually accompanied by unpleasant sensations during periods of rest, especially in the evening or at night, and temporarily relieved by movement).

In elderly patients with dementia, a small increase in the number of deaths has been reported among patients taking antipsychotics compared to those who did not.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, consult your doctor or pharmacist.
You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Leponex

Keep this medicine out of the sight and reach of children.
Do not use Leponex after the expiry date stated on the bottle or blister pack and on the outer carton. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Leponex contains

The active substance in Leponex is clozapine. Each tablet contains 100 mg of clozapine.
The other components are magnesium stearate, anhydrous colloidal silica, povidone (K 30), talc, maize starch, lactose monohydrate.

Description of the appearance of Leponex and package contents
Leponex tablets are yellow, round, flat tablets with bevelled edges, marked with the letters “Z/A” separated by a scored line on one side and “CLOZ” on the other side.
Leponex tablets are available in PVC/PVDC/aluminum or PVC/PE/PVDC/aluminum blisters containing 7, 14, 20, 28, 30, 40, 50, 60, 84, 98, 100, 500 (10x50) or 5000 (100x50) tablets; unit dose divisible blisters in PVC/PVDC/aluminum or PVC/PE/PVDC/aluminum containing 7x1, 14x1, 20x1, 28x1, 30x1, 40x1, 50x1, 60x1, 84x1, 98x1, 100x1, 500 (10x50x1) and 5000 (100x50x1) tablets; and in white plastic bottles containing 100 or 500 tablets.
Not all pack sizes may be marketed.

Marketing Authorization Holder
Viatris Healthcare Limited
Damastown Industrial Park
Mulhuddart
Dublin 15
DUBLIN
Ireland

Manufacturer
McDermott Laboratories Limited
T/A Gerard Laboratories
T/A Mylan Dublin
Unit 35/36 Baldoyle Industrial Estate
Grange Road
Dublin 13
Ireland

Mylan Hungary Kft.
Mylan utca 1.
Komárom, 2900
Hungary

Madaus GmbH
Lütticher Straße 5
53842 Troisdorf
Germany

This medicinal product is authorized in the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:
Austria Leponex 100 mg Tabletten
Belgium Leponex 100 mg tabletten/Leponex 100 mg Tabletten/Leponex 100 mg comprimés
Denmark Leponex
Finland Leponex 100 mg tabletti
France Leponex 100 mg comprimé sécable
Germany Leponex 100 mg Tabletten
Greece Leponex 100 mg Δισκία
Iceland Leponex 100 mg töflur
Ireland Clozaril 100 mg tablets
Italy Leponex 100 mg compresse
Luxembourg Leponex 100 mg comprimés
Norway Leponex 100 mg tabletter
Netherlands Leponex 100 mg, tabletten
Portugal Leponex 100 mg comprimidos
United Kingdom (Northern Ireland) Clozaril 100 mg tablets
Spain Leponex 100 mg comprimidos
Sweden Leponex 100 mg tabletter