Leaflet: information for the user

Nemea 200 mg tablets

Clozapine

Read this leaflet carefully before starting to take the medicine, as it contains important information for you.

- Keep this leaflet, as you may need to read it again.

- If you have any doubts, consult your doctor or pharmacist.

- This medicine has been prescribed only for you, and you must not give it to other people, even if they have the same symptoms as you, as it may harm them.

- If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

1. What Nemea is and for what it is used

2. What you need to know before starting to take Nemea

3. How to take Nemea

4. Possible side effects

5. Storage of Nemea

6. Contents of the pack and additional information

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

Nemea is used for the treatment of patients with schizophrenia when the use of other medications has not been effective. Schizophrenia is a mental disorder that involves disturbances in thought, emotional reactions, and behavioral disturbances. You can only use this medication if you have already tried at least two other neuroleptic medications, including one of the new atypical neuroleptic medications for treating schizophrenia, and these medications do not respond, or cause severe adverse reactions that cannot be treated.

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

This medication is a Special Medical Control (ECM), meaning that the use of clozapine should be monitored by a specialized doctor. Follow carefully 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 medication (listed in section 6).

- if it will not be possible to perform blood tests periodically.

- if you have ever been told that you have a low blood count (e.g., leucopenia or agranulocytosis), especially if it was caused by other medications. This does not apply if you had a low white blood cell count caused by previous chemotherapy.

- if you previously had to stop taking Nemea because it caused 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 bone marrow disease.

- if you have uncontrolled epilepsy (seizures or attacks).

- if you have had severe mental disorders caused by alcohol or other medications (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 (yellow discoloration of the skin and eyes, feeling unwell, and loss of appetite).

- if you have any other severe liver disease.

- if you have paralytic ileus (intestinal obstruction, your intestine does not function correctly and you have severe constipation).

- if you are using any medication that prevents your bone marrow from functioning correctly.

- if you are using any medication that reduces the number of white blood cells in your blood.

Inform your doctor and do not take Nemea if any of the above circumstances apply.

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 be life-threatening.

Before starting treatment with Nemea, inform 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 related to blood clot formation.

- glaucoma (elevated eye pressure).

- diabetes. In patients with or without a medical history of diabetes mellitus (see section 4), elevated blood glucose levels (sometimes significantly) have been reported.

- prostate problems or difficulty urinating.

- any heart, kidney, or liver disease.

- chronic constipation or taking medications that cause constipation (such as anticholinergics).

- galactose intolerance, Lapp-Lactase deficiency, or glucose-galactose malabsorption.

- controlled epilepsy.

- intestinal diseases.

- inform your doctor if you have ever had abdominal surgery.

- if you have had a 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 high blood pressure, cardiovascular problems, or problems with blood vessels in the brain.

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

- if you have signs offlu, fever, symptoms similar to the flu, sore throat, or any other infection. You will need to have an urgent blood test to see if these symptoms are related to the medication.

- if you have a sudden increase in body temperature, muscle stiffness that can lead to altered consciousness (neuroleptic malignant syndrome), as this may be a severe adverse reaction that requires immediate treatment.

- if you haverapid and irregular heart rate, even when at rest,palpitations, breathing problems, chest pain, or unusual fatigue. Your doctor will need to check your heart and, if necessary, refer you to a cardiologist immediately.

- if you havenausea (feeling of dizziness), vomiting (feeling dizzy)and/orloss of appetite. Your doctor will need to examine your liver.

- if you havesevere constipation. Your doctor will need to treat you to prevent other complications.

Medical examinations and blood tests

Before starting treatment with Nemea, your doctor will ask 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 completing 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 must stop treatment with Nemea immediately. Your white blood cells should return to normal values.

- Blood tests should be done for 4 weeks after completing 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 necessary for you or if you have any special concerns.

If you have liver abnormalities, you will have periodic tests of liver function during treatment with Nemea.

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

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

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

If you need to undergo surgery or if you are unable to walk for a long period for any reason, inform your doctor that you are taking Nemea. You may be at risk of developing a blood clot (blood clot in a vein).

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)

Elderly patients may be more susceptible to the following adverse effects during treatment with Nemea: mild headache or dizziness after changing position, nausea, rapid heart rate, urinary retention, and constipation.

Inform your doctor or pharmacist if you have a disease called dementia.

Other medications and Nemea

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication. You may need to take different amounts of your medications or different medications.

Do not take Nemea with other medications that prevent the correct functioning of the bone marrow and/or reduce the number of blood cells produced by the body, such as:

- carbamazepine, a medication used to treat epilepsy.

- certain antibiotics: chloramphenicol, sulfonamides such as cotrimoxazole.

- certain pain medications: analgesics of the pyrazolone group such as phenylbutazone.

- penicillamine, a medication used to treat rheumatoid arthritis inflammation.

- cytotoxic agents, medications used in chemotherapy.

- long-acting depot injections of antipsychotic medications.

These medications increase your risk of developing agranulocytosis (low white blood cell count).

Taking Nemea with other medications may affect the correct action of Nemea and/or the other medications. Inform your doctor if you intend to take, are taking (even if the 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.

- benzodiazepines and other medications used to treat anxiety or sleep disorders.

- narcotics and other medications that can affect your 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 to treat colds and allergies such as hay fever (seasonal allergic rhinitis).

- anticholinergic medications, used to relieve stomach upset, 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 heart rate.

- 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 or viral infections (such as protease inhibitors, used to treat HIV/AIDS).

- atropine, a medication that may be used in eye drops or cough and cold preparations.

- adrenaline, a medication used in emergency situations.

- hormonal contraceptives (birth control pills).

This list is not exhaustive. Your doctor and pharmacist have more information about medications that should be taken with caution or avoided while taking Nemea. They also know if the medications you are taking belong to any of the listed groups. Inform them.

Taking Nemea with food, drinks, and alcohol

Do not drink alcohol during treatment with Nemea.

Inform your doctor if you smoke and how often you take beverages containing caffeine (coffee, tea, cola). Sudden changes in your smoking or caffeine habits may also change the effects of Nemea.

Pregnancy and breastfeeding

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

The following symptoms may appear in newborn babies, from 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 need to contact your doctor.

Some women taking medications for mental illnesses have irregular or no menstrual periods. If this has happened to you, your menstrual periods will return to normal when your medication is replaced by Nemea. This means you should use effective birth control.

Do not breastfeed your baby during treatment with Nemea. Clozapine, the active ingredient in Nemea, can pass into breast milk and affect the baby.

Driving and operating machinery

Nemea may cause drowsiness, dizziness, and seizures, especially at the beginning of treatment. Therefore, you should avoid driving or operating machinery while experiencing these symptoms.

Nemea may cause symptoms such as drowsiness, dizziness, or visual disturbances, and decrease your reaction time. These effects, as well as the underlying disease, may impair your ability 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 medication.

Nemea contains lactose

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

To reduce the risk of seizures, drowsiness, or hypotension as much as possible, your doctor will need to gradually increase the dose.Follow exactly the administration instructions for this medication 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 your doctor has indicated.

If you are a patient 60 years of age or older, your doctor may have you start treatment with a lower dose and gradually increase your dose more slowly, 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 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 begins 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 to reach 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 may increase (particularly seizures). Always take the minimum dose that is effective for you. Most patients must take part of the dose in the morning and the other 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 the 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 initial normal dose of clozapine is 12.5 mg (half of a 25 mg tablet) at night. Swallow the tablet with the help of a glass of water. Your doctor will gradually increase the dose in amounts of 12.5 mg, with a maximum of two increases per week, to reach a maximum dose of up to 50 mg by the end of the second week. Dose increases 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. Only in exceptional cases can doses above 50 mg per day be increased. 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 Toxicological 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 breathing, 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 there is little time left for the next dose, do not take the missed dose and take the next dose at the time it is due.

Do not take a double dose to compensate for the missed doses. If you have stopped taking Nemea for two or more days, do not start treatment without first consulting your doctor.

If you interrupt treatment with Nemea

Do not stop treatment with Nemea without asking your doctor, as you may experience withdrawal symptoms. These symptoms include sweating, headache, nausea (feeling dizzy), vomiting (feeling dizzy), and diarrhea.If you experience any of these symptoms, consult your doctor immediately. These symptoms may be followed by more severe symptoms unless you are treated immediately. Your initial symptoms may recur. If you have to interrupt treatment, it is recommended to gradually reduce 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 have 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, it should be restarted 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.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

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

Inform your doctor immediately before taking the next Nemea tablet:

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

-if you havesevere constipation. Your doctor will need to treat you to prevent other complications.

Common(affects up to 1 in 10 patients):

if you have signs ofcold, 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 medicine.

-if you have seizures.

Rare(affects 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 may be a serious side effect that requires immediate treatment.

Uncommon(affects 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 havenausea (feeling of dizziness), vomiting (feeling dizzy)and/orloss of appetite. Your doctor will need to examine your liver.

Uncommon(affects up to 1 in 1,000 patients)orvery rare(affects up to 1 in 10,000 patients):

-if you haverapid and irregular heartbeat, even when at rest,palpitations, breathing problems, chest painorunusual fatigue. Your doctor will need to check your heart and, if necessary, immediately refer you to a cardiologist.

Very rare(affects 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 prevent further complications.

Unknown(the frequency cannot be estimated from the available data):

- if you feel a crushing pain in the chest, sensation of oppression, 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). Go immediately for emergency medical treatment.

- if you feel pressure in the chest, heaviness, oppression, constriction, burning, or asphyxia (signs of insufficient blood and oxygen flow to the heart). Your doctor will need to 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 you have drastically reduced urine production (signs of kidney failure).

- if you notice an allergic reaction (swelling mainly on 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 side effects:

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

Drowsiness, dizziness, rapid heartbeat, increased saliva production.

Common(affects 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 cell in the blood (eosinophilia), weight gain, blurred vision, headache, tremor, stiffness, restlessness, agitation, convulsions, sudden movements, abnormal movements, inability to initiate movement, inability to stay still, changes in the heart's electrocardiogram (ECG), high blood pressure, weakness or mild headache after changing position, sudden loss of consciousness, nausea (feeling of dizziness), vomiting (feeling 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).

Rare(affects up to 1 in 100 patients):

Low white blood cell count in the blood (agranulocytosis), speech disorder (e.g. stuttering).

Uncommon(affects up to 1 in 1,000 patients):

High red blood cell count in the blood (anemia), restlessness, agitation, confusion, delirium, circulatory collapse, irregular heartbeat, inflammation of the heart muscle (myocarditis) or of the membrane surrounding the heart muscle (pericarditis), accumulation of fluid around the heart (pericardial effusion), difficulty swallowing (e.g. food does not move through the correct channel), high blood sugar levels, diabetes mellitus, blood clotting in the lungs (pulmonary embolism), inflammation of the liver (hepatitis), liver disease that causes yellow skin/dark urine/itching, inflammation of the pancreas that causes pain in the upper abdomen, high levels of a certain enzyme in the blood called creatine phosphokinase.

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

Increased number of platelets in the blood with possible blood vessel coagulation, decreased number of platelets in the blood, involuntary movements of the mouth/lips and tongue, obsessive thoughts and repetitive compulsive behaviors (obsessive-compulsive symptoms), skin reactions, facial swelling (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 stomach cramps caused by intestinal obstruction (ileus paralytic), abdominal swelling, abdominal pain, severe liver damage (fulminant hepatic necrosis), kidney inflammation, sudden unexpected death.

Unknown(the frequency cannot be estimated from the available data):

Liver damage including fatty liver disease, cell death, liver toxicity, liver damage that leads 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 ducts in the liver, or both) and liver transplant, changes in the brain wave recording (electroencephalogram/EEG), diarrhea, stomach discomfort, burning, stomach discomfort after eating, muscle weakness, muscle spasms, muscle pain, nasal congestion, nocturnal enuresis, sudden and uncontrolled increase in blood pressure (pseudopheochromocytoma), involuntary contraction that causes the body to curve to one side (pleurototonos), if you are a man, sexual dysfunction, in which semen enters the bladder instead of ejaculating through the penis (dry orgasm or retrograde ejaculation), hives, red-purple spots, fever, or itching due to inflammation of blood vessels, inflammation of the colon 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 cases of death in patients taking antipsychotics compared to those not taking them has been reported.

Reporting of side effects

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

Keep this medication out of the 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 there are signs that it has been tampered with.

Medications should not be disposed of through drains or in the trash. Dispose of the packaging and medications you no longer need at the SIGRE collection point at the pharmacy. Ask your pharmacist how to dispose of the packaging and medications you no longer need. This will help protect the environment.

Composition of Nemea

- The active ingredient is clozapine.

- The other components are: lactose monohydrate, microcrystalline cellulose, povidone, sodium glycinate of potato type A, magnesium stearate.

Appearance of the product and content of the container

The 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 pack contains 40 tablets.

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

Holder of the marketing authorization and responsible for manufacturing

Holder

Adamed Laboratories, S.L.U.

C/ de las Rosas de Aravaca, 31, 2nd floor

28023 Aravaca (Madrid).

Tel.: 91 357 11 25

Fax: 91 307 09 70

e-mail: [email protected]

Responsible for manufacturing

Farmalider, S.A.

c/ Aragoneses, 2

28108 Alcobendas (Madrid) – Spain

Tel.: +34 91 661 23 35

Fax: +34 91 661 04 42

Email:[email protected]

Date of the last review of this leaflet:June 2017.

The detailed information of this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es/