LEPONEX 100 mg TABLETS

Introduction

Package Leaflet: Information for the Patient

Leponex 100 mg Tablets

Clozapine

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack and other information

1. What is Leponex and what is it used for
2. What you need to know before you take Leponex
3. How to take Leponex
4. Possible side effects
5. Storing Leponex
6. Contents of the pack and other information

1. What is Leponex and what is it used for

The active substance of Leponex is clozapine, which belongs to a group of medicines called antipsychotics (also known as neuroleptics) used to treat specific mental disorders, such as psychosis.

Leponex is used to treat patients with schizophrenia when other medicines have not worked. Schizophrenia is a mental illness that involves disorders of thought, emotional reactions, and behavioral disorders. You can only use this medicine if you have already tried at least two other neuroleptic medicines, including one of the new atypical neuroleptics to treat schizophrenia, and these medicines have not responded, or have caused severe adverse reactions that cannot be treated.

Leponex is also indicated to treat thought disorders, emotional reactions, and severe behavioral disorders that occur in Parkinson's disease, when other treatments have not been effective.

2. What you need to know before you take Leponex

Do not take Leponex if:

• you are allergic (hypersensitive) to clozapine or any of the other components of Leponex (listed in section 6).
• it will not be possible to perform periodic blood tests on you.
• you have ever been told that you have a low white blood cell count (e.g., leucopenia or agranulocitosis), especially if it was caused by other medicines. This does not apply if you have had a low white blood cell count caused by previous chemotherapy.
• you have previously had to stop using Leponex because it caused you severe adverse reactions (e.g., agranulocitosis or heart problems).
• you are being or have been treated with long-acting depot injections of antipsychotics.
• you have or have had a bone marrow disease.
• you have uncontrolled epilepsy (seizures or attacks).
• you have had severe mental disorders caused by alcoholic beverages or other medicines (e.g., narcotics).
• you have episodes of loss of consciousness and a strong sensation of difficult-to-control sleepiness.
• you have circulatory collapse that can occur as a result of a severe state of shock.
• you have any severe kidney disease.
• you have myocarditis (inflammation of the heart muscle).
• you have any other severe heart disease.
• you have symptoms or active liver disease such as jaundice (yellowing of the skin and eyes, feeling unwell, and loss of appetite).
• you have any other severe liver disease.
• you have paralytic ileus (intestinal obstruction, your intestine does not work properly, and you have severe constipation).
• you use any medicine that prevents your bone marrow from working properly.
• you use any medicine that reduces the number of white blood cells in your blood.

Tell your doctor and do not take Leponex if any of the above circumstances apply to you.

Leponex should not be administered 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 minimize the risk of severe adverse reactions that can be life-threatening.

Before starting treatment with Leponex,tell your doctor if you have or have had any of the following circumstances:

• blood clots or family history of blood clots, as this type of medicine has been associated with the formation of blood clots.
• glaucoma (high eye pressure).
• diabetes. In patients with or without a medical history of diabetes mellitus (see section 4), elevated blood glucose levels have been reported (sometimes considerably).
• prostate problems or difficulty urinating.
• any heart, kidney, or liver disease.
• chronic constipation or are taking medicines that cause constipation (such as anticholinergics).
• galactose intolerance, Lapp-lactase deficiency, or glucose-galactose malabsorption.
• controlled epilepsy.
• large intestine diseases.
• abdominal surgery.
• a heart disease or family history of abnormal heart conduction called "prolongation of the QT interval".
• risk of having a stroke, for example, if you have very high blood pressure, cardiovascular problems, or problems in the blood vessels of the brain.

Immediately before taking the next dose of Leponex tablets, inform your doctor if:

• you have signs of cold, fever, flu-like symptoms, sore throat, or any other infection. You will need to have an urgent blood test to see if these symptoms are related to the medicine.
• you have a sudden increase in body temperature, muscle stiffness that can lead to altered consciousness (neuroleptic malignant syndrome), as it may be a severe adverse reaction that requires immediate treatment.
• you have rapid and irregular heartbeat, even when you are at rest, palpitations, breathing problems, chest pain, or unusual tiredness. Your doctor should perform a heart check and, if necessary, refer you immediately to a cardiologist.
• you have nausea (feeling sick), vomiting (feeling sick)and/or loss of appetite. Your doctor should examine your liver.
• you have severe constipation. Your doctor should treat you to avoid other complications.

• you experience constipation, abdominal pain, abdominal sensitivity, fever, abdominal distension, and/or diarrhea with blood. Your doctor will need to examine you.

Medical examinations and blood tests

Before starting treatment with Leponex, your doctor will ask you about your medical history and perform a blood test to ensure that your white blood cell count is normal. It is essential to know this, as you need white blood cells to fight infections.

Make sure you have regular blood tests before, during, and after finishing treatment with Leponex.

• Your doctor will inform you exactly when and where these tests will be performed. You can only take Leponex if you have a normal blood count.
• Leponex can cause a severe decrease in white blood cells in your blood (agranulocitosis). Only with regular blood tests can your doctor know if you are at risk of developing agranulocitosis.
• This test should be done weekly during the first 18 weeks of treatment with Leponex and then at least once a month.
• If there is a decrease in the number of white blood cells, you should stop treatment with Leponex immediately. Your white blood cells should return to normal values.
• Blood tests should be performed during 4 weeks after finishing treatment with Leponex.

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

If you have liver disorders, you will have periodic liver function tests throughout treatment with Leponex.

If you have high blood glucose levels (diabetes), your doctor may perform periodic checks of glucose levels.

Leponex may alter blood lipid levels. Leponex may cause weight gain. Your doctor may monitor your weight and lipid levels.

If you have a mild headache, dizziness, or weakness, or Leponex makes you feel this way, be careful when getting up from a sitting or lying position, as this can increase the risk of falls.

If you need to have surgery or if, for any reason, you cannot walk for a long period, tell your doctor that you are taking Leponex. You may be at risk of having a blood clot (thrombosis).

Children and adolescents under 16 years

If you are under 16 years old, you should not take Leponex, as there is not enough information available for its use in this age group.

Use in elderly patients (60 years and older)

Patient over 60 years may be more susceptible to the following adverse effects during treatment with Leponex: weakness or mild headache after changing position, dizziness, rapid heartbeat, urinary retention, and constipation.

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

Use of Leponex with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those obtained without a prescription or herbal remedies. You may need to take a different amount of your medicines or different medicines.

Do not take Leponex with other medicines that stop the proper functioning of the bone marrow and/or decrease the number of blood cells produced by the body,such as:

• carbamazepine, a medicine used in epilepsy.
• certain antibiotics: chloramphenicol, sulfonamides such as cotrimoxazole.
• certain painkillers: analgesics of the pyrazolone group 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 agranulocitosis (deficit of white blood cells in the blood).

Taking Leponex at the same time as other medicinesmay affect the proper action ofLeponex and/or theother medicines. Inform your doctor ifyou intend to take, ifyou are taking(even if treatment is about to finish) or if you have recently stopped takingany 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 disorders.
• narcotics and other medicines that 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 clotting.
• antihistamines, medicines used for colds and allergies, such as hay fever (seasonal allergic rhinitis).
• anticholinergic medicines, used to relieve stomach cramps, spasms, and dizziness.
• medicines used to treat Parkinson's disease.
• digoxin, a medicine used to treat heart problems.
• medicines used to treat rapid or irregular heartbeat.
• some medicines used to treat stomach ulcers, such as omeprazole or cimetidine.
• some antibiotics, such as erythromycin and rifampicin.
• some medicines used to treat fungal (such as ketoconazole) or viral infections (such as protease inhibitors, used to treat AIDS).
• atropine, a medicine that may be used in some eye drops or in preparations for cough and cold.
• adrenaline, a medicine used in emergency situations.
• hormonal contraceptives (birth control pills).

This list is not complete. Your doctor and pharmacist have more information about the medicines that should be administered with caution or should be avoided while taking Leponex. They also know if the medicines you are taking belong to any of the groups listed above. Discuss it with them.

Taking Leponex with food and drinks

During treatment with Leponex, do not drink alcohol.

Tell your doctor if you smoke and how often you take caffeine-containing drinks (coffee, tea, cola). A sudden change in your smoking or caffeine-containing drink habits can also change the effects of Leponex.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine. Your doctor will discuss with you the benefits and possible risks of using this medicine during pregnancy. Inform your doctor immediately if you become pregnant during treatment with Leponex.

The following symptoms may appear in newborn babies of mothers who have used Leponex in the last trimester (the last three months of pregnancy): tremors, muscle stiffness and/or weakness, drowsiness, agitation, breathing problems, and difficulty feeding. If your baby develops any of these symptoms, you should contact your doctor.

Some women who take certain medicines for mental illnesses have irregular periods or do not have periods. If this has happened to you, your period will return to normal when your medication is replaced by Leponex. This means you should use effective contraceptives.

During treatment with Leponex, you should not breastfeed your baby. Clozapine, the active substance of Leponex, can pass into breast milk and affect the baby.

Driving and using machines

Leponex can cause tiredness, drowsiness, and seizures, especially at the start of treatment. Therefore, you should avoid driving or operating machinery while you have these symptoms.

Leponex can cause symptoms such as drowsiness, dizziness, or vision changes and reduce your reaction ability. These effects, as well as the illness itself, can make it difficult for you to drive vehicles or operate machinery. Therefore, do not drive, operate machinery, or engage in other activities that require special attention until your doctor assesses your response to this medicine.

Leponexcontains lactose.

If your doctor has told you that you have an intolerance to some sugars, contact your doctor before taking this medicine.

3. How to take Leponex

To minimize the risk of experiencing epileptic seizures, drowsiness, or hypotension, it is necessary for your doctor to gradually increase the dose. Follow your doctor's administration instructions for Leponex exactly. If in doubt, consult your doctor or pharmacist again.

It is essential that you do not change the dose or stop taking Leponex without first asking your doctor. Continue taking Leponex for the time your doctor has indicated.

If you are a patient 60 years or older, your doctor may start treatment with a lower dose and increase it more gradually, as you may be more susceptible to developing unexpected adverse reactions. (See section 2 "What you need to know before taking Leponex").

If you cannot achieve the prescribed dose with this tablet presentation, other presentations of this medication are available to achieve the prescribed dose.

Treatment of schizophrenia

Treatment is initiated with 12.5 mg (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 the help of a glass of water. If you tolerate it well, your doctor will gradually increase the dose in amounts of 25 or 50 mg over 2 to 3 weeks until reaching a daily dose of 300 mg. It may be necessary to continue increasing the dose in amounts of 50 or 100 mg twice a week, or preferably once a week.

The normal daily dose of clozapine is between 200 and 450 mg, divided into several doses per day. Some people may need higher doses. Doses of up to 900 mg per day are allowed. At daily doses above 450 mg, adverse reactions (particularly seizures) may increase. Always take the minimum dose that is effective for you. Most patients should take part of the dose in the morning and another part at night. Your doctor will tell you exactly how to divide your daily dose. If your daily dose does not exceed 200 mg, you can take it as a single dose at night. Once the treatment with Leponex is working well for some time, your doctor will try treatment with lower doses. You will need to take Leponex for at least 6 months.

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

The normal initial dose of clozapine is 12.5 mg (half a 25 mg tablet) at night. Swallow the tablet with the help of a glass of water. Your doctor will slowly increase the dose in amounts of 12.5 mg, with a maximum of two increases per week, until reaching a maximum dose of up to 50 mg at the end of the second week. Dose increments should be stopped or postponed if you feel weak, dizzy, or confused. To avoid such symptoms, your blood pressure will be measured during the first weeks of treatment.

The effective daily dose is between 25 and 37.5 mg, taken as a single dose at night. It can only be increased to doses above 50 mg per day in exceptional cases. The maximum dose is 100 mg per day. Always take the minimum that is effective for you.

If you take more Leponex than you should

If you think you have taken more Leponex than you should, or if someone has taken some of your tablets, inform your doctor or pharmacist immediately or call the Toxicology Information Service. Phone 91 562 04 20, indicating the medication and the amount taken.

The symptoms of overdose are:

Drowsiness, fatigue, lack of energy, unconsciousness, coma, confusion, hallucinations, agitation, incoherent speech, numbness in the limbs, tremors in the hands, seizures, increased saliva production, dilated pupils, blurred vision, low blood pressure, collapse, rapid or irregular heartbeat, shallow or difficult breathing.

If you forget to take Leponex

If you forget to take a dose, take the missed dose as soon as possible. If it is almost time for the next dose, do not take the missed dose and take the next dose at the scheduled time. Do not take a double dose to make up for the missed dose. If you have stopped taking Leponex for two or more days, do not start treatment again without consulting your doctor first.

If you interrupt treatment with Leponex

Do not interrupt treatment with Leponex without asking your doctor, as you may experience withdrawal symptoms. These symptoms include sweating, headache, nausea (feeling dizzy), vomiting (being dizzy), and diarrhea. If you experience any of these symptoms, consult your doctor immediately. These symptoms can be followed by more severe ones unless you are treated immediately. Your initial symptoms may recur. If you need to interrupt treatment, it is recommended to gradually decrease the dose in amounts of 12.5 mg over a period of 1 to 2 weeks. Your doctor will give you instructions on how to reduce your daily dose. If you need to interrupt your treatment suddenly, your doctor should examine you. If your doctor decides to restart treatment with Leponex and your last dose of Leponex was two days or more ago, you should start again with the initial dose of 12.5 mg.

If you have any other doubts about the use of this medication, ask your doctor or pharmacist.

4. Possible adverse effects

Like all medications, Leponex can cause adverse effects, although not all people experience them.

Some adverse effects can be serious and require immediate medical attention:

Tell your doctor immediately before taking the next Leponex tablet if you experience any of the following circumstances:

Very common(affect more than 1 in 10 patients):

• Severe constipation. Your doctor should treat you to avoid other complications.
• Rapid heartbeat.

Common(affect up to 1 in 10 patients):

• Cold-like symptoms, fever, flu-like symptoms, sore throat, or any other infection. An urgent blood test should be done to check if the symptoms you have are related to your medication.
• Seizures.
• Sudden fainting or loss of consciousness with muscle weakness (syncope).

Uncommon(affect up to 1 in 100 patients):

• A sudden increase in body temperature, muscle stiffness that can lead to altered consciousness (neuroleptic malignant syndrome), as it can be a serious adverse effect that requires immediate treatment.
• Mild headache, dizziness, or weakness when standing up from a sitting or lying position, as it can increase the risk of falls.

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

• Signs of respiratory tract infection or pneumonia such as fever, cough, difficulty breathing, wheezing (noisy breathing).
• Burning pain in the upper abdomen that spreads to the back accompanied by nausea and vomiting due to pancreas inflammation.
• Fainting and muscle weakness due to a significant drop in blood pressure (circulatory collapse).
• Difficulty swallowing (which can cause food inhalation).
• Nausea (feeling sick), vomiting (being sick), and/or loss of appetite. Your doctor will need to confirm your liver function.
• Signs of obesity or increased obesity.
• Interruption in breathing with or without snoring during sleep.

• Nausea (feeling dizzy), vomiting (being dizzy), and/or loss of appetite. Your doctor should examine your liver.

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

• Rapid and irregular heartbeat, even at rest, palpitations, breathing problems, chest pain, or unusual fatigue. Your doctor should have your heart checked and, if necessary, immediately refer you to a cardiologist.

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

• Persistent and painful erections, if you are a man. This is called priapism. If you have an erection that lasts more than four hours, you may need immediate medical treatment to avoid additional complications.
• Spontaneous bleeding or bruising, which could be signs of a decrease in platelet count in the blood.
• Symptoms due to uncontrolled blood sugar levels (such as nausea or vomiting, abdominal pain, excessive thirst, frequent urination, disorientation, or confusion).
• Abdominal pain, cramps, bloated abdomen, vomiting, constipation, and lack of gas passage, which can be signs and symptoms of intestinal obstruction.
• Lack of appetite, bloated abdomen, abdominal pain, yellowing of the skin, severe weakness, and discomfort. These symptoms can be indicative of starting to develop liver disease that can progress to sudden liver necrosis.
• Nausea, vomiting, fatigue, weight loss, which can be symptoms of kidney inflammation.

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

• Crushing chest pain, feeling of pressure, tightness, or constriction (chest pain may radiate to the left arm, jaw, neck, and upper abdomen), difficulty breathing, sweating, weakness, dizziness, nausea, vomiting, and palpitations (symptoms of a heart attack), which can cause death. Seek immediate emergency medical treatment.
• Pressure in the chest, heaviness, tightness, constriction, burning, or suffocation (signs of insufficient blood and oxygen flow to the heart), which can cause death. Your doctor should evaluate your heart function.
• Intermittent sensation in the chest in a "stabbing", "accelerated", or "agitated" manner (palpitations).
• Rapid and irregular heartbeats (atrial fibrillation). There may be occasional heart palpitations, fainting, difficulty breathing, or chest discomfort. Your doctor will need to check your heart.
• Symptoms of low blood pressure such as dizziness, fainting, blurred vision, unusual fatigue, cool and moist skin, or nausea.
  • Signs of blood clots in the veins, especially in the legs (symptoms including swelling, pain, and redness in the legs), which can move through the blood vessels to the lungs causing chest pain and difficulty breathing.
  • Confirmed or suspected infection, accompanied by fever or low body temperature, rapid breathing, rapid heartbeat, altered reaction capacity and consciousness, decreased blood pressure (sepsis).
  • Excessive sweating, headache, nausea, vomiting, and diarrhea (symptoms of the cholinergic syndrome).

• Drastic decrease in urine production (signs of kidney failure).
• Allergic reaction (swelling mainly in the face, mouth, and throat, as well as on the tongue that can be itchy or painful).
• Lack of appetite, bloated abdomen, abdominal pain, yellowing of the skin, severe weakness, and discomfort. This can be indicative of possible liver alterations leading to replacement of normal liver tissue with scar tissue, resulting in loss of liver function, including those liver events that lead to life-threatening consequences such as liver failure (which can lead to death), liver damage (damage to liver cells, bile duct in the liver, or both), and liver transplant.
• Burning pain in the upper abdomen, particularly between meals, early in the morning, or after drinking acidic beverages; black, tarry stools or stools with blood; bloating, heartburn, nausea, or vomiting, early feeling of fullness (intestinal ulceration of the stomach and/or intestine), which can lead to death.
• Severe abdominal pain worsened by movement, nausea, vomiting, even vomiting blood (or liquid that looks like coffee grounds); the abdomen becomes rigid with sensitivity (rebound) that spreads from the point of perforation throughout the abdomen; fever and/or chills (intestinal perforation of the stomach and/or intestine or intestinal rupture) that can lead to death.
• Constipation, abdominal pain, abdominal sensitivity, fever, bloating, diarrhea with blood. This can be a symptom of possible megacolon (expansion of the intestines) or intestinal ischemia/infarction/necrosis, which can lead to death. Your doctor will need to examine you.
• Appearance or increase of muscle weakness, muscle spasms, muscle pain. This can indicate possible muscle alteration (rhabdomyolysis). Your doctor will need to examine you.
• Sudden chest or abdominal pain with difficulty breathing with or without cough or fever.
• During the use of Leponex, extremely intense and severe skin reactions have been reported, such as drug reaction with eosinophilia and systemic symptoms (DRESS).

Skin reaction can appear as rashes with or without blisters. Skin irritation, edema, and fever, and flu-like symptoms may occur. DRESS syndrome symptoms usually appear approximately 2 to 6 weeks (possibly up to 8 weeks) after treatment begins.

If any of the above cases apply to you, inform your doctor immediately before taking the next Leponex tablet.

Other adverse effects:

Very common(affect more than 1 in 10 patients):

Drowsiness, dizziness, increased saliva production.

Common(affect up to 1 in 10 patients):

High levels of white blood cells in the blood (leukocytosis), high levels of a certain type of white blood cells in the blood (eosinophilia), weight gain, blurred vision, headache, tremors, stiffness, restlessness, agitation, seizures, sudden movements, abnormal movements, inability to initiate movement, inability to remain still, changes in the electrocardiogram (ECG) test of the heart, high blood pressure, weakness or mild headache after changing position, nausea (feeling dizzy), vomiting (being dizzy), loss of appetite, dry mouth, minor abnormalities in liver function tests, loss of bladder control, difficulty urinating, fatigue, fever, increased sweating, elevated body temperature, speech disorders (e.g., slurred words).

Uncommon(affect up to 1 in 100 patients):

Deficit of white blood cells in the blood (agranulocytosis), speech disorder (e.g., stuttering).

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

High levels of red blood cells in the blood (anemia), restlessness, agitation, confusion, delirium, irregular heartbeat, inflammation of the heart muscle (myocarditis) or the membrane surrounding the heart muscle (pericarditis), accumulation of fluid around the heart (pericardial effusion), high blood sugar levels, diabetes mellitus, blood clotting in the lungs (thromboembolism), liver inflammation (hepatitis), liver disease that causes yellowing of the skin/dark urine/itching, elevated levels in the blood of an enzyme called creatine phosphokinase.

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

Increased number of platelets in the blood with possible blood vessel clotting, uncontrolled movements of the mouth/tongue and lips, obsessive thoughts and repetitive compulsive behaviors (obsessive-compulsive symptoms), skin reactions, swelling of the face (due to inflammation of the salivary glands), difficulty breathing, very high levels of triglycerides or cholesterol in the blood, heart muscle disease (cardiomyopathy), cardiac arrest (cardiac arrest), sudden unexpected death.

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

Changes in brain wave recording (electroencephalogram/EEG), diarrhea, stomach discomfort, heartburn, stomach discomfort after eating, muscle weakness, muscle spasms, muscle pain, nasal congestion, nocturnal enuresis, sudden and uncontrollable increase in blood pressure (pseudopheochromocytoma), involuntary contraction that causes the body to bend to one side (pleurothotonos), if you are a man, ejaculation disorder, in which semen enters the bladder instead of ejaculating through the penis (dry orgasm or retrograde ejaculation), rash, red-purple spots, fever or itching due to inflammation of the blood vessels, colon inflammation that causes diarrhea, abdominal pain, fever, change in skin color, butterfly-shaped rash on the face, joint pain, muscle pain, fever, and fatigue (lupus erythematosus), restless legs syndrome (irresistible urge to move the legs or arms, usually accompanied by uncomfortable sensations during rest periods, especially in the afternoon or evening, and which is temporarily relieved by movement).

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

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that does not appear in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medication.

5. Storage of Leponex

• Keep this medicine out of the sight and reach of children.
• Do not use Leponex after the expiration date stated on the packaging after CAD. The expiration date is the last day of the month indicated.
• No special storage conditions are required.

Medicines should not be disposed of via wastewater or household waste. Deposit the packaging and any unused medicines at the SIGRE collection point in your pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and any unused medicines. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Leponex 100 mg tablets

• The active ingredient is clozapine. Each tablet contains 100 mg of clozapine.
• The other ingredients are magnesium stearate, anhydrous colloidal silica, povidone K30, talc, corn starch, and lactose monohydrate.

Appearance of the Product and Package Contents

Leponex tablets are yellow, round, flat, and have beveled edges, coded with "Z/A" with an angular notch on one side and "CLOZ" on the other side.

Leponex tablets are available in PVC/PVDC/Aluminum or PVC/PE/PVDC/Aluminum blister packs containing 7, 14, 20, 28, 30, 40, 50, 60, 84, 98, 100, 500 (10x50), or 5000 (100x50) tablets; and/or single-dose PVC/PVDC/Aluminum or PVC/PE/PVDC/Aluminum blister packs containing 7x1, 14x1, 20x1, 28x1, 30x1, 40x1, 50x1, 60x1, 84x1, 98x1, 100x1, 500 (10x50x1), and 5000 (100x50x1) tablets, and in a white plastic bottle containing 100 or 500 tablets.

Only some pack sizes may be marketed.

Other presentations:

Leponex 25 mg tablets in a pack of 40 tablets.

Marketing Authorization Holder

Viatris Healthcare Limited

Damastown Industrial Park

Mulhuddart, Dublin 15

Dublin

Ireland

Manufacturer

Mylan Hungary Kft.

Mylan utca 1

Komárom 2900

Hungary

or

McDermott Laboratories Limited

T/A Gerard Laboratories

T/A Mylan Dublin

Unit 35/36 Baldoyle Industrial Estate

Grange Road

Dublin 13

Ireland

or

Madaus GmbH

Lütticher Straße 5

53842 Troisdorf

Germany

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Viatris Pharmaceuticals, S.L.

C/ General Aranaz, 86

28027 Madrid

Spain

This medicine is authorized in the Member States of 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 Δισκ?α

Iceland Leponex 100 mg töflur

Ireland Clozaril 100 mg tablets

Italy Leponex 100 mg compresse

Luxembourg Leponex 100 mg

Netherlands Leponex 100 mg, tabletten

Norway Leponex 100 mg tabletter

Portugal Leponex 100 mg comprimidos

Spain Leponex 100 mg comprimidos

Sweden Leponex 100 mg tabletter

United Kingdom (Northern Ireland) Clozaril 100 mg tablets

Date of the last revision of this prospectus:August 2019

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) https://www.aemps.gob.es/