NEMEA 200 mg TABLETS

Introduction

Package Leaflet: Information for the User

Nemea 200 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 get 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 Nemea and what is it used for
2. What you need to know before you take Nemea
3. How to take Nemea
4. Possible side effects
5. Storing Nemea
6. Contents of the pack and other information

1. What is Nemea and what is it used for

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

Nemea 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.

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

2. What you need to know before you take Nemea

This medicine is subject to special medical control (Special Control Medical, SCM), i.e., the use of clozapine should be monitored by a specialized doctor. Carefully follow all the instructions given by your doctor.

Do not take Nemea:

• if you are allergic to clozapine or any of the other components of this medicine (listed in section 6).
• if it will not be possible to perform periodic blood tests on you.
• if you have ever been told that you have a low blood count (e.g., leukopenia or agranulocytosis), 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.

-if you have previously had to stop using Nemea because it caused you severe adverse reactions (e.g., agranulocytosis or heart problems).

• if you are being or have been treated with long-acting depot injections of antipsychotics.
• if you have or have had a bone marrow disease.
• if you have uncontrolled epilepsy (seizures or attacks).
• if you have had severe mental disorders caused by alcoholic beverages or other medicines (e.g., narcotics).
• if you have episodes of loss of consciousness and a strong feeling of sleep that is difficult to control.
• if you have circulatory collapse that can occur as a result of a severe shock state.
• if you have any severe kidney disease.
• if you have myocarditis (inflammation of the heart muscle).
• if you have any other severe heart disease.
• if you have symptoms or active liver disease such as jaundice (yellowing of the skin and eyes, feeling of discomfort, and loss of appetite).
• if you have any other severe liver disease.
• if you have paralytic ileus (intestinal obstruction, your intestine does not work correctly, and you have severe constipation).
• if you use any medicine that prevents your bone marrow from working correctly.
• if you use any medicine that reduces the number of white blood cells in your blood.

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

Nemea should not be administered to anyone who is unconscious or in a coma.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Nemea.

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 pose a threat to life.

Before starting treatment with Nemea, 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), high blood sugar levels have occurred (sometimes considerably).
• prostate problems or difficulty urinating.
• any heart, kidney, or liver disease.
• chronic constipation or taking medicines that cause constipation (such as anticholinergics).
• galactose intolerance, Lapp-lactase deficiency, or glucose-galactose malabsorption.
• controlled epilepsy.
• large intestine diseases.
• tell your doctor if you have ever had abdominal surgery.
• if you have had heart disease or a family history of abnormal heart conduction called "prolongation of the QT interval".
• if you are at 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 Nemea tablets, inform 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.
• if 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 effect that requires immediate treatment.
• if 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.
• if you have nausea (feeling of dizziness), vomiting (you are dizzy), and/or loss of appetite. Your doctor should examine your liver.
• if you have severe constipation. Your doctor should treat you to avoid other complications.

Medical examinations and blood tests

Before starting treatment with Nemea, 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 Nemea.

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

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 Nemea.

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

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

If Nemea causes you to have a mild headache, dizziness, or weakness, be careful when getting up from a sitting or lying position.

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 Nemea. 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 Nemea, 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 Nemea: 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 Nemea

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines. You may need to take a different amount of your medicines or different medicines.

Do not take Nemea with other medicines that prevent the correct 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 agranulocytosis (deficit of white blood cells in the blood).

Taking Nemea at the same time as other medicines may affect the correct action of Nemea and/or the other medicines. Inform 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.
• 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 medicines that should be administered with caution or should be avoided while taking Nemea. They also know if the medicines you are taking belong to any of the groups listed above. Discuss it with them.

Taking Nemea with food, drinks, and alcohol

During treatment with Nemea, do not drink alcohol.

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 Nemea.

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 Nemea.

The following symptoms may occur in newborn babies of mothers who have used Nemea 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 Nemea. This means you should use effective contraceptives.

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

Driving and using machines

Nemea 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.

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

Nemea contains lactose

This medicine contains lactose. If your doctor has told you that you have an intolerance to certain sugars, consult with them before taking this medicine.

3. How to take Nemea

To minimize the risk of suffering from epileptic seizures, drowsiness, or hypotension, it is necessary for your doctor to gradually increase the dose. Follow the administration instructions for this medication exactly as indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

It is essential that you do not change the dose or stop taking Nemea without first asking your doctor.

Continue taking Nemea for the time indicated by your doctor.

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 starting to take Nemea").

If with this tablet presentation you cannot reach the prescribed dose, 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 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 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 Nemea is working well for you for some time, your doctor will try treatment with lower doses. You will need to take Nemea 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. The 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. 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.

If you take more Nemea than you should

If you think you have taken more Nemea than you should, or if someone has taken some of your tablets, inform your doctor or pharmacist immediately or call the Toxicology Information Service, Telephone 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 difficulty breathing.

If you forget to take Nemea

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 missed doses. If you have stopped taking Nemea for two or more days, do not start treatment again without first consulting your doctor.

If you interrupt treatment with Nemea

Do not interrupt treatment with Nemea without asking your doctor, as you may have 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 Nemea and your last dose of Nemea 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, this medication 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 Nemea tablet:

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

• if you have severe constipation. Your doctor should treat you to avoid other complications.

Common(affect up to 1 in 10 patients):

if you have signs of cold, fever, flu-like symptoms, sore throat, or any other infection. An urgent blood test will be necessary to check if the symptoms you have are related to your medication.

• if you have epileptic seizures.

Uncommon(affect up to 1 in 100 patients):

• if you have 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.

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

• if you have signs of respiratory tract infection or pneumonia such as fever, cough, difficulty breathing, wheezing (noisy breathing).
• if you have 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):

• if you have a 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, immediately refer you to a cardiologist.

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

• if you are a man and experience persistent and painful erections of the penis. 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.

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

• if you feel a crushing chest pain, feeling of pressure, pressure, 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). Seek immediate emergency medical treatment.
• if you feel pressure in the chest, heaviness, pressure, constriction, burning, or shortness of breath (signs of insufficient blood and oxygen flow to the heart). Your doctor should evaluate your heart function.
• if you have 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.
• if you sweat profusely, have a headache, nausea, vomiting, and diarrhea (symptoms of cholinergic syndrome).
• if you notice that urine production has drastically decreased (signs of kidney failure).
• if you notice an allergic reaction (swelling mainly in the face, mouth, and throat, as well as on the tongue that can cause itching or be painful).

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

Other adverse effects:

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

Drowsiness, dizziness, rapid heartbeat, 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, sudden loss of consciousness, nausea (feeling dizzy), vomiting (being dizzy), 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(affect up to 1 in 100 patients):

Lack 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, circulatory collapse, irregular heartbeat, inflammation of the heart muscle (myocarditis) or the membrane surrounding the heart muscle (pericarditis), accumulation of fluid around the heart (pericardial effusion), difficulty swallowing (e.g., food does not pass through the proper passage), 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, pancreas inflammation that causes pain in the upper stomach, elevated levels in the blood of an enzyme called creatine phosphokinase.

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

Increased number of blood platelets with possible blood vessel clotting, decreased number of blood platelets, uncontrolled movements of the mouth/tongue and lips, obsessive thoughts and compulsive repetitive behaviors (obsessive-compulsive symptoms), skin reactions, swelling of the face (due to inflammation of the salivary glands), difficulty breathing, complications due to uncontrolled blood sugar levels (e.g., coma or ketoacidosis), very high levels of triglycerides or cholesterol in the blood, heart muscle disease (cardiomyopathy), cardiac arrest, severe constipation with abdominal pain and intestinal cramps caused by intestinal obstruction (paralytic ileus), abdominal swelling, abdominal pain, severe liver damage (fulminant hepatic necrosis), kidney inflammation, sudden unexpected death.

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

Liver disorders including fatty liver disease, liver cell death, liver damage/toxicity, liver disorders that lead to replacement of normal liver tissue with scar tissue, resulting in loss of liver function, 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, changes in brain wave recordings (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 (pleurothotonus), 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, 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).

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, www.notificaRAM.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medication.

5. Storage of Nemea

Keep this medication out of sight and reach of children.

Do not use Nemea after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

No special storage conditions are required.

Do not use this medication if the packaging is damaged or shows signs of tampering.

Medications should not be thrown down the drain or into the trash. Deposit the packaging and medications you no longer need in the SIGRE Point of the pharmacy. Ask your pharmacist how to dispose of the packaging and medications you no longer need. This way, you will help protect the environment.

6. Package contents and additional information

Composition of Nemea

• The active ingredient is clozapine.
• The other components are: lactose monohydrate, microcrystalline cellulose, povidone, sodium starch glycolate type A potato, magnesium stearate.

Appearance of the product and package contents

Nemea 200 mg tablets are yellow, oval, scored, with the mark "200" on one side. Each tablet contains 200 mg of clozapine.

PVC/PVDC/aluminum blister pack. Each package contains 40 tablets.

High-density polyethylene bottle. Each package contains 40 tablets.

Marketing authorization holder and manufacturer

Holder

Adamed Laboratorios, S.L.U.

C/ de las Rosas de Aravaca, 31, 2ª planta

28023 Aravaca (Madrid).

Phone: 91 357 11 25

Fax: 91 307 09 70

e-mail: infoesp@adamed.com

Manufacturer

Farmalider, S.A.

c/ Aragoneses, 2

28108 Alcobendas (Madrid) – Spain

Phone: +34 91 661 23 35

Fax: +34 91 661 04 42

Email: farmalider@farmalider.com

Date of the last revision of this prospectus:June 2017.

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