AGAVAN 100 mg TABLETS

Introduction

Package Leaflet: Information for the Patient

Agavan 100 mg Tablets EFG

clozapine

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

• Keep this package 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 symptoms 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 package leaflet. See section 4.

Contents of the Package Leaflet

1. What is Agavan and what is it used for
2. What you need to know before you take Agavan
3. How to take Agavan
4. Possible side effects
5. Storing Agavan
6. Package Contents and Further Information

1. What is Agavan and what is it used for

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

Clozapine 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 antipsychotic medicines, including one of the new atypical antipsychotics to treat schizophrenia, and these medicines have not responded, or have caused severe side effects that cannot be treated.

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

2. What you need to know before you take Agavan

Do not take clozapine if:

• you are allergic (hypersensitive) to clozapine or any of the other ingredients of Agavan (listed in section 6);
• it will not be possible to perform regular 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 had a low white blood cell count caused by previous chemotherapy;
• you have previously had to stop using clozapine 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 alcoholic beverages or other medicines (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 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 this medicine if any of the above circumstances apply to you.

This medicine should not be given to anyone who is unconscious or in a coma.

Warnings and Precautions

The safety measures mentioned in this section are very important. You must comply with them to minimize the risk of severe side effects that can be life-threatening.

Before starting treatment with clozapine, tell your doctor if you have or have had:

• blood clots or a 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), high blood sugar 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);
• controlled epilepsy;
• intestine disorders;
• abdominal surgery;
• a heart disease 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 in the blood vessels of the brain.

Immediately before taking the next dose of clozapine tablets, tell your doctor if:

• you have signs of a 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 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 side effect that requires immediate treatment;
• you have a rapid and irregular heartbeat, even when you are at rest, palpitations, breathing problems, chest pain, or unusual fatigue. Your doctor should check your heart and, if necessary, refer you immediately to a cardiologist;
• you have nausea (feeling sick), vomiting (being 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 tenderness, fever, abdominal distension, and/or bloody diarrhea. Your doctor will need to examine you.

Medical Exams and Blood Tests

Before starting treatment with clozapine, 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 clozapine.

• Your doctor will inform you exactly when and where these tests will be performed. You can only take clozapine if you have a normal blood count.
• Clozapine can cause a severe decrease in the number of 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 clozapine and then at least once a month.
• If there is a decrease in the number of white blood cells, you should stop treatment with clozapine immediately. Your white blood cells should return to normal values.

Blood tests should be performed during 4 weeks after finishing treatment with clozapine. 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 clozapine.

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

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

If you have a mild headache, dizziness, or weakness, or clozapine makes you feel this way, be careful when getting up from a sitting or lying position, as this can increase the possibility 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 clozapine. 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 clozapine, as there is not enough information available for its use in this age group.

Use in Elderly Patients (60 Years and Older)

Elderly patients (patients 60 years and older) may be more susceptible to the following side effects during treatment with clozapine: 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 Medicines and Agavan

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 clozapine with other medicines that stop the bone marrow from working properly and/or decrease the number of blood cells produced by the body, such as:

• carbamazepine, a medicine used in epilepsy;
• certain antibiotics: chloramphenicol, sulfonamides such as cotrimoxazole;
• certain pain relievers: 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 clozapine at the same time as other medicines can affect the correct action of clozapine and/or the other medicines. Tell your doctor if you intend to take, are taking (even if treatment is about to finish), or have recently stopped taking any of the following medicines:

• medicines used to treat depression, such as lithium, fluvoxamine, tricyclic antidepressants, MAO inhibitors, citalopram, paroxetine, fluoxetine, and sertraline;
• other antipsychotic medicines used to treat mental illnesses, such as perazine;
• benzodiazepines and other medicines used to treat anxiety or sleep 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;
• 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 medicines that should be administered with caution or should be avoided while taking clozapine. They also know if the medicines you are taking belong to any of the groups listed above. Discuss this with them.

Taking Agavan with Drinks and Alcohol

Do not drink alcohol during treatment with clozapine.

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

Pregnancy and Breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before taking this medicine.

Pregnancy

Your doctor will discuss with you the benefits and possible risks of using this medicine during pregnancy. Tell your doctor immediately if you become pregnant during treatment with clozapine.

The following symptoms may appear in newborn babies of mothers who have used clozapine 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 periods will return to normal when your medication is replaced with clozapine. This means you should use effective contraceptives.

Breastfeeding

Do not breastfeed your baby while taking clozapine. Clozapine, the active substance of clozapine, can pass into breast milk and affect your baby.

Driving and Using Machines

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

Clozapine can cause symptoms such as drowsiness, dizziness, or vision changes, and reduce your reaction ability. These effects, as well as your illness, 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.

This Medicine Contains Lactose

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

3. How to Take Agavan

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 this medication exactly. If in doubt, consult your doctor or pharmacist again.

It is essential that you do not change the dose or stop taking clozapine without first asking your doctor. Continue taking clozapine 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 your dose more gradually, as you may be more susceptible to developing some unexpected adverse reactions (see section 2 "What you need to know before taking Agavan").

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 or 50 mg over 2 to 3 weeks until reaching a dose of 300 mg per day. 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 may increase (particularly seizures). 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 clozapine treatment is working well for you over time, your doctor will try treatment with lower doses. You will need to take clozapine 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 by 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. 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

Oral route.

Swallow the tablet with water.

The tablets can be divided into equal doses.

If you take more Agavan than you should

If you think you have taken more clozapine than you should, or if someone has taken any 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, or difficulty breathing.

If you forget to take Agavan

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 clozapine for two or more days, do not start treatment again without consulting your doctor first.

If you interrupt treatment with Agavan

Do not interrupt treatment with clozapine 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 clozapine and your last dose of clozapine was two days or more ago, you should start again with the initial dose of 12.5mg.

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

4. Possible adverse effects

Like all medications, Agavan can cause adverse effects, although not everyone will experience them.

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

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

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

• severe constipation. Your doctor should treat you to avoid other complications;
• rapid heartbeat.

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

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

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

• signs of cold, fever, flu-like symptoms, sore throat, or any other infection.You will need to have an urgent blood test to check if your symptoms are related to your medication;
• a sudden increase in your 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;
• dizziness, vertigo, 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):

• signs of respiratory tract infection or pneumonia such as fever, cough, difficulty breathing, wheezing;
• severe and 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 unwell), vomiting (being sick), and/or loss of appetite.Your doctor will need to examine your liver;
• interrupted breathing with or without snoring during sleep;
• signs of obesity or increased obesity.

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

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

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

• prolonged and painful erections of the penis, 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 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);
• abdominal pain, cramps, bloated abdomen, vomiting, constipation, and lack of gas passage, which can be signs and symptoms of intestinal obstruction;
• loss of appetite, bloated abdomen, abdominal pain, yellowing of the skin, severe weakness, and discomfort. These symptoms can be indicative of possible liver disease that can progress to sudden liver necrosis;
• nausea, vomiting, fatigue, weight loss, which can be symptoms of kidney inflammation.

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

• crushing 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), which can be fatal. 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 be fatal. Your doctor should evaluate your heart function;
• intermittent sensation in the chest in a "stabbing", "racing", or "quivering" 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, 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 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 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);
• loss of appetite, bloated abdomen, abdominal pain, yellowing of the skin, severe weakness, and discomfort. This can be indicative of possible liver damage that can lead to liver failure, including those 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 damage (rhabdomyolysis). Your doctor will need to examine you;
• acute chest or abdominal pain with difficulty breathing with or without cough or fever;
• During the use of clozapine, extremely intense and severe skin reactions have been reported, such as drug reaction with eosinophilia and systemic symptoms (DRESS).
• The adverse skin reaction can appear as rashes with or without blisters. There can be skin irritation, edema, and fever, and symptoms similar to those of the flu. The symptoms of DRESS syndrome 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 clozapine tablet.

Other adverse 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 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 unwell), vomiting (being sick), loss of appetite, dry mouth; minor anomalies in liver function tests;
• loss of bladder control, difficulty urinating;
• fatigue, fever, increased sweating, elevated body temperature;
• speech disorders (e.g., slurred words).

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

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

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

• 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);
• inflammation of the liver (hepatitis), liver disease that causes yellowing of the skin/dark urine/itching;
• high levels in the blood of an enzyme called creatine phosphokinase.

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

• increase in the number of blood platelets 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.

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

• changes in the brain wave record (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 (pseudopheochromocytoma);
• involuntary contraction that causes the body to curve 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);
• inflammation of the colon that causes diarrhea, abdominal pain, fever;
• rash, red-purple spots, fever, or itching due to inflammation of the blood vessels;
• 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 is 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 adverse effects, you can contribute to providing more information on the safety of this medication.

5. Storage of Agavan

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

Do not use this medicine after the expiry date which is stated on the outer packaging and on the blister after "CAD". The expiry date is the last day of the month indicated.

Do not store above 30°C.

Medicines should not be disposed of via wastewater or household waste. Place the packaging and any unused medicines in the SIGRE collection point at your pharmacy. If you are unsure, 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 Agavan

The active ingredient is clozapine.

Each tablet contains 100 mg of clozapine.

The other ingredients are: lactose monohydrate, corn starch, povidone, colloidal anhydrous silica, talc, and magnesium stearate.

Appearance of the Product and Package Contents

Biconvex, round tablets, pale yellow in color, 10 mm in diameter, and scored on one side.

Available in packs with PVC/PVdC-Al blisters containing 14, 28, 30, 40, 60, and 100 tablets.

Only some pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Aristo Pharma GmbH

Wallenroder Straße 8-10

13435 Berlin

Germany

Manufacturer

Aristo Pharma GmbH

Wallenroder Straße 8-10

13435 Berlin

Germany

Laboratorios Medicamentos Internacionales S.A. (Medinsa)

C/Solana 26

28850 Torrejon de Ardoz, Madrid

Spain

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

Aristo Pharma Iberia, S.L.

C/ Solana, 26

28850, Torrejón de Ardoz

Madrid, Spain

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

Germany Clozapin Aristo 100 mg Tabletten

Austria Clozapin Aristo 100 mg Tabletten

Czech Republic Clozapine Aristo 100 mg tablets

Denmark Clozapine Aristo 100 mg tablets

Spain Agavan 100 mg EFG tablets

France Clozapine Aristo 100 mg scored tablets

Italy Clozapina Aristo 100 mg tablets

Netherlands Clozapine Aristo 100 mg tablets

Norway Clozapine Aristo 100 mg tablets

Poland Clozapine Aristo 100 mg tablets

Portugal Clozapina Aristo 100 mg tablets

Sweden Clozapine Aristo 100 mg tablets

Date of the last revision of this leaflet:June 2022

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