NEMEA 25 mg ORALLY DISINTEGRATING TABLETS

Introduction

Package Leaflet: Information for the Patient

Nemea 25 mg orodispersible 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 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. Storage of Nemea
6. Contents of the pack and further information

1. What is Nemea and what is it used for

Nemea contains the active substance clozapine.

Nemea belongs to a group of medicines called antipsychotics (medicines 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 antipsychotic medicines, including one of the new atypical antipsychotics to treat schizophrenia, and these medicines did not work, or caused you severe side effects that cannot be treated.

Nemea 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 Nemea

Do not take Nemea:

• if you are allergic to clozapine or any of the other ingredients of this medicine (listed in section 6).
• if it will not be possible to have regular blood tests.
• if 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.
• if you previously had to stop using Nemea because it caused you severe side effects (e.g., agranulocitosis or heart problems).
• if you are being or have been treated with long-acting depot injections of antipsychotics.
• if you have or have had any bone marrow disease.
• if you have uncontrolled epilepsy (seizures or fits).
• if you have had severe mental disorders caused by alcohol or other medicines (e.g., narcotics).
• if you have episodes of loss of consciousness and strong drowsiness that is difficult to control.
• if you have circulatory collapse that can occur as a result of severe shock.
• if you have severe kidney disease.
• if you have myocarditis (inflammation of the heart muscle).
• if you have any other severe heart disease.
• if you have symptoms of active liver disease such as jaundice (yellowing of the skin and eyes, feeling unwell, and loss of appetite).
• if you have severe liver disease.
• if you have paralytic ileus (your intestine does not work properly and you have severe constipation).
• if you use any medicine that prevents your bone marrow from working properly.
• 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 applies to you.

Nemea 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 Nemea, tell your doctor if you have or have had any of the following:

• 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 if you are taking medicines that cause constipation (such as anticholinergics).
• controlled epilepsy.
• intestine disorders.
• abdominal surgery.
• a heart condition or family history of abnormal heart conduction called "prolonged QT interval".
• risk of having a stroke, for example, if you have very high blood pressure, cardiovascular problems, or problems in the blood vessels of the brain.

Immediately before taking the next dose of Nemea 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 fast and irregular heartbeat, even when you are at rest, palpitations, breathing problems, chest pain, or unusual tiredness. Your doctor should examine your heart 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, abdominal distension, and/or bloody diarrhea. Your doctor will need to examine you.

Medical examinations and blood tests

Before starting treatment with Nemea, your doctor will ask you about your medical history and have a blood test to make sure 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 tell 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 (agranulocitosis). Only with regular blood tests can your doctor know if you are at risk of developing agranulocitosis.
• This test should be done weekly for the first 18 weeks of treatment 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 for 4 weeks after finishing treatment with Nemea.

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

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

If you feel dizzy, lightheaded, or faint, or Nemea makes you feel this way, be careful when getting up from a sitting or lying position, as this can increase the risk of falls.

If you need to have surgery or if for any reason you cannot walk for a long period, tell your doctor that you are taking 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 old may be more susceptible to the following side effects during treatment with Nemea: fainting or dizziness after changing position, dizziness, fast heartbeat, difficulty urinating, 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 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 Nemea with other medicines that prevent your bone marrow from working properly and/or reduce the number of blood cells produced by your body, such as:

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

These medicines increase your risk of developing agranulocitosis (deficit of white blood cells in the blood).

Taking Nemea at the same time as other medicines may affect the proper action of Nemea and/or the other medicines. 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 medicines:

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

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

Taking Nemea with food and drinks

During treatment with Nemea, do not drink alcohol.

Tell your doctor if you smoke and how often you take beverages containing caffeine (coffee, tea, cola). Suddenly changing your smoking or caffeine habits can also change the effects of Nemea.

Pregnancy, breastfeeding, and fertility

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

Nemea contains aspartame (E951)

This medicine contains 3.10 mg of aspartame in each orodispersible tablet, equivalent to 18 mg/g.

Aspartame is a source of phenylalanine that may be harmful in cases of phenylketonuria (PKU), a rare genetic disorder in which phenylalanine accumulates because the body cannot eliminate it properly.

This medicine contains less than 1 mmol of sodium (23 mg) per dose, which is essentially "sodium-free".

3. How to take Nemea

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 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 it more gradually, as you may be more susceptible to developing unexpected adverse reactions. (See section 2 "What you need to know before taking 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 is initiated with 12.5 mg once or twice on the first day, followed by 25 mg once or twice on the second day.

Do not open the blister pack until you are ready to take it. Immediately after opening the blister pack or bottle, with dry hands, remove the tablet and place it on your tongue. The tablet disintegrates rapidly in saliva. The buccodispersable tablet can be taken with or without liquid.

If you tolerate it well, your doctor will gradually increase the dose in increments of 25-50 mg over 2 to 3 weeks until a dose of up to 300 mg per day is reached. It may be necessary to continue increasing the dose in increments 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 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 is only 200 mg, you can take it as a single dose at night. Once the treatment with Nemea has been working well 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 at night.

Do not open the blister pack until you are ready to take it. Immediately after opening the blister pack or bottle, with dry hands, remove the tablet and place it on your tongue. The tablet disintegrates rapidly in saliva. The buccodispersable tablet can be taken with or without liquid.

Your doctor will slowly increase the dose in increments of 12.5 mg, with a maximum of two increases per week, until a maximum dose of up to 50 mg is reached 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 usually 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 any 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 ingested.

The symptoms of overdose are:

Drowsiness, fatigue, lack of energy, unconsciousness, coma, confusion, hallucinations, agitation, incoherent speech, rigidity of the limbs, tremors in the hands, seizures, increased saliva production, dilation of the pupils, blurred vision, low blood pressure, collapse, rapid or irregular heartbeat, shallow or difficult 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 the missed dose. If you have stopped taking Nemea for more than 48 hours, contact your doctor immediately.

If you interrupt treatment with Nemea

Do not interrupt treatment with Nemea 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 may be followed by more severe ones unless you are treated immediately. Your initial symptoms may recur. If you need to interrupt treatment with Nemea, it is recommended to gradually decrease the dose in increments 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, they will start 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 Adverse Effects

Like all medications, this medication can produce adverse effects, although not all people suffer from them.

Some adverse effects can be serious and require immediate medical attention.Inform your doctor immediately before taking the next Nemea tablet if you experience any of the following circumstances:

Very Frequent(may affect more than 1 in 10 patients):

• severe constipation. Your doctor should treat you to avoid other complications.
• rapid heart rate.

Frequent(may affect up to 1 in 10 patients):

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

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

• 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, dizziness, or fainting when getting up from a sitting or lying position, as it can increase the possibility of falling.

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

• signs of respiratory tract infection or pneumonia such as fever, cough, difficulty breathing, wheezing (noisy breathing).
• burning pain, intense in the upper abdomen that extends 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.
• signs of obesity or increased obesity.
• interrupted breathing with or without snoring during sleep.

Rare(may affect up to 1 in 1,000 patients)or Very Rare(may affect up to 1 in 10,000 patients):

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

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

• persistent 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, excessive urination, disorientation, or confusion).
• abdominal pain, cramps, bloated abdomen, vomiting, constipation, and inability to pass gas, 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 alterations that lead to replacement of normal liver tissue with scar tissue, leading to loss of liver function, including those hepatic 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.
• nausea, vomiting, fatigue, weight loss, which can be symptoms of kidney inflammation.

Frequency Not Known(frequency cannot be estimated from available data):

• crushing chest pain, feeling of oppression, pressure, or constriction in the chest (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 lead to death. Seek immediate emergency medical treatment.
• pressure in the chest, heaviness, oppression, constriction, burning, or suffocation (signs of insufficient blood and oxygen flow to the heart) that can lead to death. Your doctor should evaluate your heart function.
• intermittent sensation in the chest of "stabbing", "pounding", or "fluttering" (palpitations).
• rapid and irregular heartbeats (atrial fibrillation). There may be occasional heart palpitations, fainting, difficulty breathing, or chest discomfort. Your doctor will need to evaluate your heart function.
• symptoms of low blood pressure such as dizziness, dizziness, 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 heart rate, altered reaction and consciousness, decreased blood pressure (sepsis).
• excessive sweating, headache, nausea, vomiting, and diarrhea (symptoms of 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 alterations that lead to replacement of normal liver tissue with scar tissue, leading to loss of liver function, including those hepatic 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, especially between meals, in the early morning, or after drinking acidic beverages; tarry stools, black or bloody stools; bloating, acidity, nausea, or vomiting, early feeling of fullness (ulceration of the stomach and/or intestine) that can lead to death.
• severe abdominal pain that worsens with movement, nausea, vomiting that includes vomiting blood (or liquid with the appearance of coffee grounds); the abdomen becomes rigid with sensitivity (rebound tenderness) that extends 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 cause 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 that can lead to death. Your doctor will need to examine you.
• sharp chest pain with difficulty breathing and with or without cough
• appearance or increase of muscle weakness, muscle spasms, muscle pain. This can indicate a possible muscle alteration (rhabdomyolysis). Your doctor will need to examine you.
• sharp 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 rash with eosinophilia and systemic symptoms (DRESS syndrome). The adverse skin reaction can appear as a rash with or without blisters. It can cause skin irritation, edema, fever, and flu-like symptoms. The symptoms of DRESS syndrome usually appear approximately between 2 and 6 weeks (possibly up to 8 weeks) after the start of treatment.

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

Other Adverse Effects:

Very Frequent(may affect more than 1 in 10 patients):

• drowsiness, dizziness
• increased saliva production

Frequent(may affect up to 1 in 10 patients):

• high levels of white blood cells in the blood (leukocytosis), high levels of a certain group of white blood cells in the blood (eosinophilia)
• weight gain
• blurred vision
• headache, tremor, 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, vomiting, 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., difficulty articulating words)

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

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

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

• low levels of red blood cells in the blood (anemia)
• restlessness, agitation
• confusion, delirium
• irregular heart rate, inflammation of the heart muscle (myocarditis) or the membrane that surrounds 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 patients):

• increase in the number of platelets in the blood with possible clotting in the blood vessels
• uncontrolled movements of the mouth/tongue and limbs, obsessive thoughts, and repetitive compulsive behaviors (obsessive-compulsive symptoms)
• skin reactions
• swelling in the front of the ear (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 available data):

• changes in the brain wave record (electroencephalogram/EEG), involuntary contraction that causes the body to curve to one side (pleurothotonos), 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)
• diarrhea, stomach discomfort, heartburn, stomach discomfort after eating, inflammation of the colon that causes diarrhea, abdominal pain, fever
• muscle weakness, muscle spasms, muscle pain, fever, and fatigue (lupus erythematosus)
• nasal congestion
• nocturnal enuresis
• sudden and uncontrollable increase in blood pressure (pseudopheochromocytoma)

-- 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 spots, butterfly-shaped rash on the face, joint pain, muscle pain
• fever or itching due to inflammation of the blood vessels
• change in skin color

In elderly patients with dementia, a small increase in the number of death cases 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, website: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medication.

5. Conservation of Nemea

Keep this medication out of sight and reach of children.

Do not use this medication after the expiration date that appears on the blister/pack and in the box. The expiration date is the last day of the month indicated.

This medication does not require special storage conditions.

Medications should not be thrown down the drain or into the trash. Deposit the containers and medications you no longer need in the SIGRE Point of the pharmacy. Ask your pharmacist how to dispose of the containers 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. Each tablet contains 25 mg of clozapine.
• The other components are: mannitol (E 421), microcrystalline cellulose, anhydrous colloidal silica, crospovidone (type A), aspartame (E 951), peppermint flavor (contains maltodextrin, sodium octenyl succinate starch (E 1450) and glycerol triacetate (E 1518)), yellow iron oxide (E 172), and magnesium stearate.

Appearance of the Product and Package Contents

Nemea 25 mg orodispersible tablets are yellow, round, flat, approximately 8 mm in diameter, and engraved with "C7PN" on one side and "25" on the other.

They are available in:

PVC/PVDC/Al blisters are available in packs containing 7, 10, 14, 20, 28, 30, 40, 50, 56, 60, 84, 90, 98, 100, 250, 300, or 500 tablets.

PVC/PVDC/Al unit-dose blisters are available in packs containing 7, 10, 14, 20, 28, 30, 40, 50, 56, 60, 84, 90, 98, 100, 250, 300, or 500 tablets.

HDPE bottles can contain 250 or 500 tablets.

Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Adamed Laboratorios, S.L.U.

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

28023 Madrid,

Spain

Manufacturers

Synthon BV

Microweg 22

6545 CM Nijmegen, Netherlands

or

Synthon Hispania, S.L.

Castello, 1, Polígono ”Las Salinas”

08830 Sant Boi de Llobregat (Barcelona), Spain

This medication is authorized in the member states of the European Economic Area with the following names:

Netherlands: Ayupine 12.5 mg, orodispersible tablets

Ayupine 25 mg, orodispersible tablets

Ayupine 50 mg, orodispersible tablets

Ayupine 100 mg, orodispersible tablets

Ayupine 200 mg, orodispersible tablets

Spain: Nemea 25 mg orodispersible tablets EFG

Nemea 100 mg orodispersible tablets EFG

Nemea 200 mg orodispersible tablets

Croatia: ZANIQ 12.5 mg orodispersible tablets

ZANIQ 25 mg orodispersible tablets

ZANIQ 100 mg orodispersible tablets

Date of the Last Revision of this Prospectus: March 2025

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