LEPONEX 200 mg TABLETS

2. What you need to know before taking Leponex

Do not take Leponex if:

• you are allergic to clozapine or any of the other components of this medication (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 medications. 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 side effects (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 alcohol or other medications (e.g., narcotics);
• you have episodes of loss of consciousness and strong drowsiness that are difficult to control;
• you have circulatory collapse that can occur as a result of severe shock;
• you have 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 function properly, and you have severe constipation);
• you use any medication that prevents your bone marrow from functioning properly;
• you use any medication 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 side effects 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 a family history of blood clots, as this type of medication 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 taking medications that cause constipation (such as anticholinergics);
• galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption;
• controlled epilepsy;
• large intestine diseases;
• abdominal surgery;
• a heart condition or family history of abnormal heart conduction called "prolonged QT interval";
• risk of stroke, for example, if you have very high blood pressure, cardiovascular problems, or problems with the blood vessels in the brain.

Immediately before taking the next Leponex tablet, tell your doctor if:

• you have signs of cold, fever, flu-like symptoms, sore throat, or any other infection. You should have an urgent blood test to see if these symptoms are related to the medication;
• 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 side effect that requires immediate treatment;
• you have rapid and irregular heartbeat, even when at rest, palpitations, breathing problems, chest pain, or unusual fatigue. Your doctor should perform a heart check and, if necessary, refer you immediately to a cardiologist;
• you have nausea, vomiting, 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 tenderness, fever, feeling bloated, and/or bloody diarrhea. 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 your body needs 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 the blood (agranulocytosis). Only with regular blood tests can your doctor determine if you are at risk of developing agranulocytosis.
• This test should be performed 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 for another 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 elevated blood glucose levels (diabetes), your doctor may perform periodic glucose level checks.

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

If you experience 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 undergo surgery or if you cannot walk for an extended period, tell your doctor that you are taking Leponex. You may be at risk of developing thrombosis (blood clot in a vein).

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 old may be more susceptible to the following side 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.

Other medications and Leponex

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

Do not take Leponex with other medications that prevent the bone marrow from functioning properly and/or decrease the number of blood cells produced by the body, such as:

• carbamazepine, a medication used in epilepsy;
• certain antibiotics: chloramphenicol, sulfonamides, such as co-trimoxazole;
• certain pain medications: analgesics of the pyrazolone group, such as phenylbutazone;
• penicillamine, a medication used to treat rheumatic joint inflammation;
• cytotoxic agents, medications used in chemotherapy;
• long-acting depot injections of antipsychotic medications.

These medications increase your risk of developing agranulocytosis (deficit of white blood cells in the blood).

Taking Leponex at the same time as other medications may affect the proper action of Leponex and/or the other medications. Tell your doctor if you intend to take, are taking (even if treatment is about to end), or have recently stopped taking any of the following medications:

• medications used to treat depression, such as lithium, fluvoxamine, tricyclic antidepressants, MAO inhibitors, citalopram, paroxetine, fluoxetine, and sertraline;
• other antipsychotic medications used to treat mental illnesses, such as perazine;
• benzodiazepines and other medications used to treat anxiety or sleep disorders;
• narcotics and other medications that can affect breathing;
• medications used to control epilepsy, such as phenytoin and valproic acid;
• medications used to treat high or low blood pressure, such as adrenaline and noradrenaline;
• warfarin, a medication used to prevent blood clotting;
• antihistamines, medications used for colds and allergies, such as seasonal allergic rhinitis;
• anticholinergic medications, used to relieve stomach cramps, spasms, and dizziness;
• medications used to treat Parkinson's disease;
• digoxin, a medication used to treat heart problems;
• medications used to treat rapid or irregular heartbeat;
• some medications used to treat stomach ulcers, such as omeprazole or cimetidine;
• some antibiotics, such as erythromycin and rifampicin;
• some medications used to treat fungal (such as ketoconazole) or viral infections (such as protease inhibitors used to treat HIV infections);
• atropine, a medication that may be used in some eye drops or in cough and cold preparations;
• adrenaline, a medication used in emergency situations;
• hormonal contraceptives (birth control pills).

This list is not complete. Your doctor and pharmacist have more information about medications that should be administered with caution or avoided while taking Leponex. They also know if the medications you are taking belong to any of the groups listed above. Discuss this 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 consume caffeine-containing beverages (coffee, tea, cola). Suddenly changing your smoking or caffeine consumption 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 medication. Your doctor will discuss the benefits and potential risks of using this medication during pregnancy with you. If you become pregnant during treatment with Leponex, inform your doctor immediately.

The following symptoms may occur 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 medications for mental illnesses have irregular or absent menstrual periods. If this has happened to you, your menstrual period will return to normal when your medication is replaced with 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 fatigue, drowsiness, and seizures, especially at the start of treatment. Therefore, you should avoid driving or operating machinery while experiencing these symptoms.

Leponex contains lactose.

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

3. How to take Leponex

Follow your doctor's or pharmacist's administration instructions for this medication exactly. If in doubt, consult your doctor or pharmacist again.

To minimize the risk of experiencing epileptic seizures, drowsiness, or low blood pressure, it is necessary for your doctor to gradually increase the dose.

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 over 60 years old, 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 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 to 50 mg over 2 to 3 weeks until you reach a daily dose of 300 mg. It may be necessary to continue increasing the dose in amounts of 50 to 100 mg twice a week, or preferably once a week.

The effective 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 part in the evening. 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 Leponex treatment is working well for you over 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

For the dose in psychotic disorders in Parkinson's disease, more suitable pharmaceutical forms are available.

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 you reach a maximum dose of up to 50 mg by the end of the second week. Dose increases should be interrupted 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 normally between 25 and 37.5 mg, taken as a single dose at night.

The dose can only be increased to more than 50 mg per day in exceptional cases. The maximum dose is 100 mg per day. Always take the minimum dose that is effective for you.

Method of administration

Leponex is administered orally.

The tablet can be divided into equal doses.

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, contact a doctor immediately or seek emergency medical help. You can also call the Toxicology Information Service. Telephone 91 562 04 20, indicating the medication and the amount ingested.

The symptoms of overdose are:

Drowsiness, fatigue, lack of energy, unconsciousness, coma, confusion, hallucinations, agitation, incoherent speech, numbness in the limbs, hand tremors, 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 more than 48 hours, 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, vomiting, and diarrhea. If you experience any of these symptoms, consult your doctor immediately. These symptoms can be followed by more severe ones unless you receive immediate treatment.Your initial symptoms may recur. If you need to interrupt treatment, it is recommended to gradually decrease the dose 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 treatment suddenly, your doctor should examine you.

If your doctor decides to restart treatment with Leponex and your last dose of Leponex was 2 days or more ago, you should start again with the initial dose of 12.5 mg.

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

4. Possible side effects

Like all medications, this medication can cause side effects, although not everyone will experience them.

Some side 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:

• Severe constipation. Your doctor should treat you to avoid other complications.
• Constipation, abdominal pain, abdominal tenderness, fever, feeling bloated, bloody diarrhea. This may indicate possible megacolon (enlargement of the intestine) or intestinal infarction/ischemia/necrosis, which can be fatal. Your doctor will need to examine you.

• Abdominal pain, cramps, bloated abdomen, vomiting, constipation, and lack of gas passage, which can be signs and symptoms of intestinal obstruction.
  • Burning pain in the upper abdomen, especially between meals, early in the morning, or after drinking acidic beverages; tarry stools, black or bloody stools; feeling bloated, heartburn, nausea, or vomiting, early feeling of fullness (ulceration of the stomach and/or intestine), which can be fatal.
  • 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 tenderness) that spreads from the point of perforation throughout the abdomen; fever and/or chills (perforation of the stomach and/or intestine or rupture of the intestine) that can be fatal.
  • Low white blood cell count in a blood test (agranulocytosis).
  • Signs of cold, fever, flu-like symptoms, sore throat, or any other infection. You should have an urgent blood test to see if these symptoms are related to the medication.
  • Confirmed or suspected infection, accompanied by fever or low body temperature, rapid breathing, rapid heartbeat, altered reaction and consciousness, decreased blood pressure (sepsis).
  • Signs of respiratory tract infection or pneumonia, such as fever, cough, difficulty breathing, wheezing (noisy breathing).
  • Seizures.
  • Rapid and irregular heartbeat, even at rest, palpitations, breathing problems, chest pain, or unusual fatigue. Your doctor should perform a heart check and, if necessary, refer you immediately to a cardiologist.
  • Chest pain, feeling of pressure, tightness, or heaviness (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) that can be fatal. Go to the doctor immediately for emergency treatment.
  • Heart muscle disease (cardiomyopathy), cardiac arrest (cardiac arrest).
  • Irrregular heartbeat, inflammation of the heart muscle (myocarditis) or the membrane surrounding the heart muscle (pericarditis), fluid accumulation around the heart (pericardial effusion).
  • Feeling of pressure, heaviness, tightness, burning, or suffocation in the chest (signs of insufficient blood and oxygen flow to the heart), which can be fatal. Your doctor should evaluate heart function.
  • Intermittent feeling in the chest of a "stabbing", "racing", or "agitated" nature (palpitations).
  • Rapid and irregular heartbeats (atrial fibrillation). There may be occasional heart palpitations, fainting, difficulty breathing, or chest discomfort. Your doctor should evaluate heart function.
  • Lack of appetite, bloated abdomen, abdominal pain, yellowing of the skin, severe weakness, and malaise. This may indicate possible liver damage leading to replacement of normal liver tissue with scar tissue, resulting in loss of liver function, including liver events that can lead to potentially fatal consequences, such as liver failure (which can be fatal), liver damage (damage to liver cells, bile ducts in the liver, or both), and liver transplant.
  • Sudden increase in body temperature, muscle stiffness that can lead to altered consciousness (neuroleptic malignant syndrome), as it can be a serious side effect that requires immediate treatment.

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

Other side effects:

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

Drowsiness, dizziness, increased saliva production.

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

High white blood cell count in the blood (leukocytosis), high levels of a certain type of white blood cell in the blood (eosinophilia), weight gain, blurred vision, headache, tremors, rigidity, restlessness, 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, dizziness or lightheadedness when changing position, dry mouth, minor abnormalities in liver function tests, loss of bladder control, difficulty urinating, fatigue, increased sweating, elevated body temperature, speech disorders (e.g., slurred speech), sudden loss of consciousness or fainting with muscle weakness (syncope).

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

Speech disorders (e.g., stuttering), dizziness, lightheadedness, or fainting when standing up from a sitting or lying position, as it can increase the risk of falls.

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

High red blood cell count in the blood (anemia), restlessness, agitation, confusion, delirium, high blood sugar levels, diabetes mellitus, blood clots 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, burning pain in the upper abdomen that radiates 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, vomiting, and/or loss of appetite. Your doctor should examine your liver for signs of obesity or increased obesity, interruption of breathing with or without snoring during sleep.

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

Increased number of platelets in the blood with possible coagulation in blood vessels, uncontrolled movements of the mouth/tongue and limbs, obsessive thoughts and compulsive repetitive behaviors (obsessive-compulsive symptoms), skin reactions, swelling in front of the ears (due to inflammation of the salivary glands), difficulty breathing, very high levels of triglycerides or cholesterol in the blood, sudden death of unknown cause, painful and persistent erection of the penis, if you are a man. This is called priapism. If you have an erection that lasts more than 4 hours, you may need immediate medical treatment to avoid additional complications, spontaneous bleeding or bruising, which could be signs of a decrease in the number of platelets in the blood, symptoms due to uncontrolled blood sugar levels (such as nausea or vomiting, abdominal pain, excessive thirst, frequent urination, disorientation, or confusion), nausea, vomiting, fatigue, and weight loss that can be symptoms of kidney inflammation.

Frequency not known (cannot be estimated from available data)

Changes in brain wave recording (electroencephalogram/EEG), diarrhea, stomach upset, heartburn, stomach upset after eating, muscle weakness, muscle spasms, muscle pain, nasal congestion, nocturnal enuresis, sudden and uncontrollable increase in blood pressure (pseudophochromocytoma), involuntary contraction that causes curvature of the body to one side (pleurothotonus), ejaculation disorder if you are a man, in which semen enters the bladder instead of being ejaculated through the penis (dry orgasm or retrograde ejaculation), rash, purple-red spots, fever, or itching due to inflammation of 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), symptoms of low blood pressure, such as dizziness, lightheadedness, fainting, blurred vision, unusual fatigue, cool and moist skin, or nausea, signs of blood clots in the veins, especially in the legs (symptoms that include swelling, pain, and redness of the legs), which can move through the blood vessels to the lungs, causing chest pain and difficulty breathing, excessive sweating, headache, nausea, vomiting, and diarrhea (symptoms of cholinergic syndrome), significant decrease in urine production (signs of kidney failure), allergic reaction (swelling mainly in the face, mouth, and throat, as well as on the tongue, which can be itchy or painful), chest pain with difficulty breathing, with or without cough, appearance or increase of muscle weakness, muscle spasms, muscle pain. This may indicate possible muscle damage (rhabdomyolysis). Your doctor will need to examine you; chest pain 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 syndrome). The adverse skin reaction may appear as a rash with or without blisters. Skin irritation, edema, and fever, and flu-like symptoms may occur. The symptoms of DRESS syndrome usually appear approximately 2 to 6 weeks (possibly up to 8 weeks) after starting treatment.

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 side effects

If you experience any side effects, consult your doctor or pharmacist, even if they are possible side effects not listed in this leaflet.

You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medication.

5. Storage of Leponex

• Keep this medication out of sight and reach of children.
• Do not use this medication after the expiration date shown on the blister pack and carton after EXP. The expiration date is the last day of the month indicated.
• This medication does not require special storage conditions.
• Medicines should not be disposed of through wastewater or household waste. Place the packaging and unused medicines in the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and medicines you no longer need. This will help protect the environment.

6. Container Content and Additional Information

Composition of Leponex 200 mg tabletsmg tablets

• The active ingredient is clozapine. Each tablet contains 200 mg of clozapine.
• The other components are magnesium stearate, anhydrous colloidal silica, povidone K30, talc, corn starch, and lactose monohydrate.

Appearance of the Product and Container Content

Light yellow, round, and biconvex tablet, with a cross-shaped notch on both sides of the tablet and with the engraving V C 7 on one side.

Diameter: approximately 13 mm.

Leponex 200 mg tablets are available in PVC/PE/PVdC-aluminum blisters with 20, 30, 40, 50, or 100 tablets, or in a single-dose perforated PVC/PE/PVdC-aluminum blister with 20 × 1, 30 × 1, 40 × 1, 50 × 1, and 100 × 1 tablets.

Only some package sizes may be marketed.

Marketing Authorization Holder

Viatris Healthcare Limited

Damastown Industrial Park

Mulhuddart, Dublin 15

Dublin

Manufacturer

Madaus GmbH

Lütticher Straße 5

53842 Troisdorf, Germany

Further information about this medicinal product can be obtained from the local representative of the marketing authorization holder:

Viatris Pharmaceuticals, S.L.

C/ General Aranaz, 86

28027 - Madrid

Spain

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

Belgium Leponex 200 mg tablets

Croatia Leponex 200 mg tablets

Czech Republic Leponex 200 mg tablets

Finland Leponex

Germany Leponex 200 mg tablets

Greece Leponex

Hungary Leponex 200mg tablets

Ireland Clozaril 200 mg tablets

Luxembourg Leponex 200 mg tablets

Spain Leponex 200 mg tablets

Slovenia Leponex 200 mg tablets

Date of the last revision of this leaflet:October 2024

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