Package leaflet: Information for the user

Ayupil, 12.5 mg, orodispersible tablets
Ayupil, 25 mg, orodispersible tablets
Ayupil, 100 mg, orodispersible tablets
Ayupil, 200 mg, orodispersible tablets
Clozapine
Please read all of this leaflet carefully before 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 give it to others. It may harm them, even if their symptoms 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 leaflet

What Ayupil is and what it is used for
What you need to know before taking Ayupil
How to take Ayupil
Possible side effects
How to store Ayupil
Contents of the pack and other information

1. What Ayupil is and what it is used for

Ayupil contains the active substance clozapine.
Ayupil belongs to a group of medicines called antipsychotics (also known as neuroleptics) – medicines used to treat certain mental disorders such as psychosis.
Ayupil is used to treat patients with schizophrenia who have not responded to treatment with other medicines. Schizophrenia is a mental illness that causes disturbances in thinking, emotions, and behaviour.
Ayupil should only be used to treat patients who have already been treated with at least two different antipsychotic medicines, including one from the group of new atypical antipsychotics indicated for the treatment of schizophrenia, and who did not respond to these treatments or who experienced severe side effects that could not be managed.
Ayupil is also used to treat severe disturbances in thinking, emotions, and behaviour in patients with Parkinson's disease who do not respond to treatment with other medicines.

2. Important Information Before Using Ayupil

When not to use Ayupil

if the patient has a known hypersensitivity (allergy) to clozapine or to any of the other ingredients of Ayupil (listed in section 6)
if regular blood tests cannot be performed for the patient
if the patient has ever had a low white blood cell count (e.g. leukopenia or agranulocytosis), particularly caused by previous use of medications,
except in cases of low white blood cell count related to prior chemotherapy
if the patient previously discontinued Ayupil due to severe adverse reactions (e.g. agranulocytosis or cardiac disorders)
if the patient is or has been treated with long-acting (depot) injectable antipsychotic medications
if the patient has impaired bone marrow function
if the patient has uncontrolled epilepsy (seizures or other types of epileptic fits)
if the patient has acute psychiatric disturbances caused by alcohol or drugs (e.g. narcotics)
if the patient has reduced consciousness and marked drowsiness
if the patient has circulatory collapse, which may result from severe shock
if the patient has severe kidney function impairment
if the patient has myocarditis (inflammation of the heart muscle)
if the patient has other severe heart diseases
if the patient shows signs of active liver disease, such as jaundice (yellowing of the skin and whites of the eyes, nausea, loss of appetite)
if the patient has other severe liver function disorders
if the patient has paralytic ileus (the patient's intestine does not function properly and the patient has severe constipation)
if the patient is taking any medications that suppress normal bone marrow function
if the patient is taking any medications that reduce the number of white blood cells in the blood

If any of the above conditions apply to the patient, the patient must inform the doctor and must not use Ayupil.
Ayupil must not be used in patients who are unconscious or in a coma.

Warnings and Precautions
The safety issues mentioned in this section are very important. The patient must pay special attention to them in order to minimize the risk of severe, life-threatening adverse reactions.

Before starting treatment with Ayupil, the patient should inform the doctor if any of the following conditions are present or have occurred in the past:

(or in someone in their family) blood clots, because drugs such as this one have been associated with clot formation
glaucoma (increased pressure in the eye)
diabetes (elevated, sometimes significantly elevated, blood glucose levels, occurring in patients with or without a history of diabetes) (see section 4.4)
problems with the prostate gland or difficulty urinating
heart, kidney, or liver disease
chronic constipation or use of medications causing constipation (such as anticholinergic drugs)
controlled epilepsy
diseases of the large intestine
previous abdominal surgeries
heart disease or family history of cardiac conduction abnormalities, known as QT prolongation
risk of stroke, e.g. if the patient has high blood pressure, cardiovascular problems, or cerebrovascular issues

The patient must immediately inform the doctor before taking the next dose of Ayupil if:

symptoms of a cold, fever, flu-like symptoms, sore throat, or any infection occur. The doctor may recommend urgent blood count testing if these symptoms are related to the medication
sudden increase in body temperature or muscle rigidity occurs, which may lead to loss of consciousness (symptoms of neuroleptic malignant syndrome), a serious adverse reaction requiring immediate treatment
rapid or irregular heartbeat, palpitations, breathing difficulties, chest pain, or unexplained fatigue occur, even at rest. The doctor will assess heart function and, if necessary, refer the patient urgently to a cardiologist
nausea, vomiting, and/or loss of appetite occur. The doctor will check liver function
constipation, abdominal pain, abdominal tenderness, fever, bloating, and/or bloody diarrhea occur. A medical consultation is required.

Regular Medical Check-ups and Blood Tests
Before starting treatment with Ayupil, the doctor will take a medical history and order blood tests to confirm a normal white blood cell count. This is important because the patient's body needs white blood cells to fight infections.
Regular blood tests are essential before starting treatment, during treatment, and after discontinuation of Ayupil.

The doctor will clearly inform the patient when and where blood tests should be performed. Ayupil may only be used if the patient has a normal white blood cell count.
Ayupil may cause a significant decrease in the number of white blood cells in the blood (agranulocytosis). Only regular blood tests can detect whether the patient is at risk of developing agranulocytosis.
Blood tests should be performed weekly for the first 18 weeks of treatment. After that, tests should be performed at least once a month.
If a decrease in white blood cell count occurs, treatment with Ayupil must be stopped immediately. The white blood cell count should return to normal values.
Blood tests must continue for 4 weeks after discontinuation of Ayupil.
The doctor will also perform a medical examination before starting treatment with Ayupil. The doctor may order an electrocardiogram (ECG) to assess heart function if necessary for the patient or if the patient has specific concerns. If the patient has liver function disorders, regular liver function tests will be performed throughout the duration of Ayupil treatment. If the patient has high blood glucose levels (diabetes), the doctor may order regular glucose monitoring. Ayupil may alter blood lipid levels. Ayupil may cause weight gain. The doctor may monitor the patient's body weight and blood lipid levels.

If the patient currently experiences a feeling of emptiness in the head, dizziness, or fainting, or if Ayupil causes such symptoms, position changes from sitting or lying down should be made carefully, as these symptoms may increase the risk of falls.
If the patient is to undergo surgery or is immobilized for a prolonged period for other reasons, the use of Ayupil should be discussed with the doctor. There is a risk of thrombosis (blood clotting in veins).

Children and adolescents under 16 years of age
Patients under 16 years of age should not use Ayupil, as there is limited data on the use of the drug in this age group.

Elderly patients (aged 60 years and above)
In elderly patients (aged 60 years and above), the following adverse reactions may occur more frequently during treatment with Ayupil: fainting or feeling of emptiness in the head upon changing position, dizziness, rapid heartbeat, difficulty urinating, and constipation.
The patient should inform the doctor if they have a condition called dementia.

Ayupil and other medicines
The patient must inform the doctor or pharmacist about all medicines currently taken or recently used, as well as any medicines planned for use, including over-the-counter and herbal medicines. Dosage adjustments or changes in medication may be necessary.

Do not use Ayupil together with medicines that suppress normal bone marrow function and/or reduce the number of white blood cells produced by the body, such as:

carbamazepine, a medicine used in the treatment of epilepsy;
certain antibiotics: chloramphenicol, sulfonamides such as co-trimoxazole;
certain painkillers: pyrazolone derivative analgesics such as phenylbutazone;
penicillamine, a medicine used, among others, in the treatment of rheumatoid arthritis;
cytotoxic agents, medicines used in chemotherapy;
long-acting (depot) injectable antipsychotic medicines

These medicines increase the risk of developing agranulocytosis (lack of white blood cells).
Taking Ayupil together with other medicines may affect the action of Ayupil and/or other medicines. The patient should inform the doctor if they plan to take, are currently taking (even if treatment is ending), 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 and sleep disorders
narcotics and other medicines that may affect respiratory function
medicines used to treat 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 clots
antihistamines, medicines used to treat colds or allergies, such as hay fever
anticholinergic medicines, used to relieve stomach spasms and motion sickness
medicines used to treat Parkinson's disease
digoxin, a medicine used to treat heart conditions
medicines used to treat rapid or irregular heartbeat
certain medicines used to treat stomach ulcers, such as omeprazole or cimetidine
certain antibiotics, such as erythromycin and rifampicin
certain antifungal medicines (such as ketoconazole) or antiviral medicines (such as protease inhibitors used in the treatment of HIV infection)
atropine, a medicine that may be an ingredient in certain eye drops, cold remedies, or cough suppressants
adrenaline, a medicine used in emergency situations
hormonal contraceptives (birth control pills)

The above list is not exhaustive. The doctor or pharmacist has more information about medicines that should be used cautiously with Ayupil or avoided during treatment with Ayupil, and knows whether a medicine belongs to the mentioned groups. The patient should ask them.

Taking Ayupil with food, drink, and alcohol
Do not drink alcohol during treatment with Ayupil.
The patient should inform the doctor if they smoke tobacco and how often they drink beverages containing caffeine (coffee, tea, Coca-Cola). Sudden changes in smoking or caffeine-containing beverage habits may also alter the effects of Ayupil.

Pregnancy and breastfeeding
If the patient is pregnant, breastfeeding, suspects she may be pregnant, or plans to become pregnant, she should consult the doctor before using this medicine. The doctor will discuss the benefits and possible risks of using the medicine during pregnancy. The patient must inform the doctor immediately if she becomes pregnant during treatment with Ayupil.
Newborns of mothers who took antipsychotic medicines during the third trimester of pregnancy (last three months) may experience the following symptoms: tremors, muscle stiffness and/or weakness, drowsiness, agitation, breathing difficulties, and feeding problems. If the baby develops these symptoms, contact the doctor immediately.
Some women taking medicines for mental illnesses may have irregular or absent menstrual periods. As a result of switching from another treatment to Ayupil, normal menstruation may return. Therefore, women of childbearing age should use effective contraceptive methods.
Do not breastfeed during treatment with Ayupil. Clozapine, the active substance in Ayupil, may pass into breast milk and affect the infant.

Driving and operating machinery
Ayupil may cause fatigue, drowsiness, and seizures, especially during the initial period of treatment. Do not drive motor vehicles or operate machinery if the above symptoms occur.

Ayupil contains aspartame (E951)
Ayupil 12.5 mg contains 1.55 mg of aspartame per tablet, equivalent to 18 mg/g.
Ayupil 25 mg contains 3.10 mg of aspartame per tablet, equivalent to 18 mg/g.
Ayupil 100 mg contains 12.4 mg of aspartame per tablet, equivalent to 18 mg/g.
Ayupil 200 mg contains 24.8 mg of aspartame per tablet, equivalent to 18 mg/g.
Aspartame is a source of phenylalanine. It may be harmful to patients with phenylketonuria. This is a rare genetic disorder in which phenylalanine accumulates in the body due to improper excretion.

3. How to use Ayupil

To minimise the risk of low blood pressure, seizures and drowsiness, the dose of Ayupil must be increased gradually by the doctor. Ayupil should always be taken exactly as directed by the doctor. If in doubt, consult the doctor or pharmacist.
It is very important not to change the dose or stop taking Ayupil without first consulting the doctor. Treatment should be continued for as long as the doctor recommends. In patients aged 60 years or older, the doctor may start treatment with lower doses and increase them gradually, as they are more likely to experience certain adverse effects (see section 2, Important information before taking Ayupil).
If the prescribed dose cannot be achieved with the available strength of the medicine, another strength of this medicine is available on the market to achieve the required dose.

Treatment of schizophrenia
The usual starting dose is 12.5 mg once or twice daily on the first day, followed by 25 mg once or twice daily on the second day.
Do not open the blister or bottle until you are ready to take the medicine. Immediately after opening the blister or bottle, remove the tablet with dry hands and place the entire orally disintegrating tablet on the tongue in the mouth. The tablet will rapidly disintegrate in saliva. The orally disintegrating tablet may be taken with or without liquid.
If the treatment is well tolerated, the doctor may then gradually increase the daily dose by 25 mg to 50 mg over 2–3 weeks to achieve a target dose of up to 300 mg per day. Thereafter, if necessary, the daily dose may be further increased by 50 mg to 100 mg at intervals of 3 to 4 days, or preferably once weekly.
The effective daily dose is usually between 200 mg and 450 mg, divided into several individual doses. Some patients may require higher doses. The maximum daily dose is 900 mg. At daily doses exceeding 450 mg, certain adverse effects (particularly seizures) may become more pronounced. The lowest effective dose for the patient should always be used. Most patients take part of the dose in the morning and part in the evening. The doctor will explain exactly how the daily dose should be divided. If the daily dose is only 200 mg, the patient may take it as a single dose in the evening. If the patient has been taking Ayupil for some time with good effect, the doctor may consider reducing the dose. The patient should take Ayupil for at least 6 months.

Treatment of severe disorders of thought, emotion and behaviour in patients with Parkinson’s disease
The usual starting dose is 12.5 mg in the evening.
Do not open the blister or bottle until you are ready to take the medicine. Immediately after opening the blister or bottle, remove the tablet with dry hands and place the entire orally disintegrating tablet on the tongue in the mouth. The tablet will rapidly disintegrate in saliva. The orally disintegrating tablet may be taken with or without liquid.
The doctor will then gradually increase the dose by 12.5 mg, no more frequently than twice a week, until a maximum daily dose of 50 mg is reached by the end of the second week. If the patient experiences fainting, dizziness or confusion, dose escalation should be delayed or paused. To avoid such symptoms, the patient’s blood pressure should be monitored during the first weeks of treatment.
The effective daily dose is usually 25 mg to 37.5 mg, taken as a single evening dose. Doses exceeding 50 mg per day should only be used in exceptional cases. The maximum daily dose is 100 mg. The lowest effective dose should always be used.

Taking more Ayupil than prescribed
If a patient takes more Ayupil than prescribed, or if someone else takes the medicine, contact a doctor immediately or go to the nearest hospital.
Symptoms of overdose include:
drowsiness, fatigue, lack of energy, loss of consciousness, coma, confusion (disorientation), hallucinations, agitation, delirium, limb rigidity, hand tremor, epileptic seizures (convulsions), excessive salivation, dilated pupils, blurred vision, hypotension, collapse, rapid or irregular heartbeat, shallow breathing or breathing difficulties.

If a dose of Ayupil is missed
If a dose is missed, take it as soon as possible. However, do not take the medicine if it is almost time for the next dose. In this case, take the next dose at the usual time. Do not take a double dose to make up for a missed dose. If the patient has forgotten to take the medicine for 48 hours or longer, contact the doctor immediately.

Stopping Ayupil treatment
Do not stop taking Ayupil without consulting the doctor, as withdrawal reactions may occur. These include: sweating, headache, nausea, vomiting and diarrhoea. If any of these symptoms occur, inform the doctor immediately. After these symptoms, more serious adverse effects may occur if the patient does not receive immediate treatment. The symptoms of the illness may also return. To discontinue treatment, it is recommended to gradually reduce the dose by 12.5 mg over one to two weeks. The doctor will advise the patient on how to reduce the dose. If immediate discontinuation of Ayupil is necessary, consult the doctor.
If the doctor decides to restart treatment with Ayupil and the patient took the last dose more than two days previously, the starting dose will be 12.5 mg.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Some adverse reactions may be serious and require immediate medical attention.
You should immediately tell your doctor before taking the next dose of Ayupil if the patient experiences any of the following symptoms:

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

severe constipation. The doctor will initiate treatment to prevent further complications
rapid heartbeat.

Common adverse reactions (affects less than 1 in 10 patients):

cold symptoms, fever, flu-like symptoms, sore throat or other infections. Blood tests should be urgently performed to determine whether symptoms are related to the medicine
seizures
sudden fainting or sudden loss of consciousness with muscle weakness (fainting).

Uncommon adverse reactions (affects less than 1 in 100 patients):

sudden increase in body temperature, muscle stiffness, which may lead to loss of consciousness (neuroleptic malignant syndrome); this may indicate serious adverse reactions requiring immediate treatment
feeling of emptiness in the head, dizziness or fainting upon changing position from lying to standing, which may increase the risk of falling.

Rare adverse reactions (affects less than 1 in 1,000 patients):

symptoms of respiratory tract infection or pneumonia, such as fever, cough, breathing difficulties, wheezing
severe, burning pain in the upper abdomen radiating to the back, accompanied by nausea and vomiting due to pancreatitis
fainting and muscle weakness due to a significant drop in blood pressure (circulatory collapse)
difficulty swallowing (may lead to food aspiration)
nausea, vomiting and/or loss of appetite. The doctor will check liver function
onset or worsening of existing obesity
sleep apnea with or without snoring.

Rare (affects less than 1 in 1,000) or very rare adverse reactions
(may affect less than 1 in 10,000 patients):

fast and irregular heartbeat, even at rest, palpitations, breathing difficulties, chest pain or unexplained fatigue. The doctor will check heart function and, if necessary, refer the patient immediately to a cardiologist

Very rare adverse reactions (affects less than 1 in 10,000 patients):

prolonged, painful erection of the penis, called priapism. If the erection lasts more than 4 hours, immediate treatment may be required to avoid further complications
sudden bleeding or appearance of bruises, which may indicate reduced platelet count
symptoms caused by uncontrolled blood sugar levels (such as nausea or vomiting, abdominal pain, excessive thirst, excessive urination, disorientation or confusion)
abdominal pain, cramps, bloating, vomiting, constipation and difficulty passing gas, which may indicate intestinal obstruction
loss of appetite, bloating, abdominal pain, yellowing of the skin, severe weakness and general malaise. These symptoms may indicate developing liver failure, which may lead to fulminant hepatic necrosis
nausea, vomiting, fatigue, weight loss, which may be symptoms of kidney inflammation.

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

pressure-like chest pain, feeling of tightness in the chest, pressure or sudden severe pain (chest pain which may radiate to the left arm, jaw, neck and upper abdomen), shortness of breath, sweating, weakness, dizziness, nausea, vomiting and palpitations (symptoms of a heart attack). In such cases, seek medical attention immediately
chest tightness, heaviness, pressure, sudden severe pain, burning sensation or choking sensation (symptoms of insufficient blood and oxygen supply to the heart muscle). The doctor will check the patient's heart function
sensation of irregular heartbeat: "thumping", "pounding" or "fluttering" in the chest (palpitations)
rapid and irregular heartbeat (atrial fibrillation). Palpitations, fainting, shortness of breath or chest discomfort may occasionally occur. The doctor must check the patient's heart function
symptoms of low blood pressure, such as dizziness, vertigo, fainting, blurred vision, excessive fatigue, cold and clammy skin or nausea
symptoms suggesting blood clots in the veins, particularly in the legs (symptoms include leg swelling, pain and redness); clots may travel through blood vessels to the lungs, causing chest pain and breathing difficulties
confirmed or suspected infection with accompanying fever or low body temperature, abnormally rapid breathing, rapid heartbeat, changes in reaction speed and consciousness, low blood pressure (sepsis)
profuse sweating, headache, nausea, vomiting and diarrhoea (symptoms of cholinergic syndrome)
significantly reduced urine output (a sign of kidney failure)
hypersensitivity reaction (swelling mainly affecting the face, lips and throat, as well as the tongue, which may cause itching and be painful)
loss of appetite, bloating, abdominal pain, yellowing of the skin, severe weakness and general malaise. This may indicate liver failure, when normal liver tissue is replaced by scar tissue, leading to loss of liver function, including life-threatening conditions (potentially fatal), liver damage (damage to liver cells, bile ducts, or both), liver transplantation
constipation, abdominal pain, abdominal tenderness, fever, bloating, bloody diarrhoea. These symptoms may indicate acute colonic dilation (acute intestinal dilation) or intestinal infarction/ischemia. Medical consultation is required
dull chest pain with shortness of breath, with or without cough
increase or onset of muscle weakness, muscle cramps, muscle pain. These symptoms may indicate muscle disorders (rhabdomyolysis). Medical consultation is required
dull chest pain or abdominal pain, with shortness of breath, with or without cough and fever

If any of the above points apply to the patient, you should tell the doctor before administering the next dose of Ayupil.

Other adverse reactions:

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

drowsiness, dizziness
excessive salivation.

Common adverse reactions (affects less than 1 in 10 patients):

high white blood cell count (leukocytosis), high count of a specific type of white blood cells (eosinophilia)
weight gain
blurred vision
headache, tremor, stiffness, motor restlessness, convulsions, muscle twitching, involuntary movements, inability to move, inability to remain still
changes in ECG recording
hypertension, fainting or feeling of emptiness in the head upon changing position
nausea, vomiting, loss of appetite, dryness of the oral mucosa
minor abnormalities in liver function tests
urinary incontinence, urinary retention
fatigue, fever, increased sweating, increased body temperature
speech disorders (e.g. slurred speech).

Uncommon adverse reactions (affects less than 1 in 100 patients):

absence of white blood cells in the blood (agranulocytosis)
speech disorders (e.g. stuttering).

Rare adverse reactions (affects less than 1 in 1,000 patients):

low red blood cell count (anaemia)
motor restlessness, agitation
confusion, delirium
arrhythmia, myocarditis or pericarditis, pericardial effusion
increased blood glucose levels, diabetes
pulmonary embolism (venous thromboembolic disease)
hepatitis, jaundice (liver disease causing yellowing of the skin/dark urine/itching)
increased levels of an enzyme called creatine phosphokinase in the blood.

Very rare adverse reactions (affects less than 1 in 10,000 patients):

increased platelet count with possible blood clotting in blood vessels
uncontrolled movements of lips/tongue and limbs, obsessive thoughts and repetitive compulsive behaviors (obsessive-compulsive symptoms)
skin reactions
swelling of the parotid gland (enlargement of salivary glands)
breathing difficulties
very high levels of triglycerides or cholesterol in the blood
heart muscle disease (cardiomyopathy), cardiac arrest
sudden unexplained death

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

changes in brain wave tests (electroencephalogram/EEG), restless legs syndrome (irresistible urge to move legs or arms, usually accompanied by discomfort during rest, especially in the evening or at night, with temporary relief during movement)
diarrhoea, stomach discomfort, heartburn, postprandial discomfort, colitis causing diarrhoea, abdominal pain, fever
feeling of muscle weakness, muscle cramps, muscle pain
nasal congestion
nocturnal enuresis
sudden, uncontrolled rise in blood pressure (pseudo-phaeochromocytoma syndrome)
uncontrolled body curvature to one side (pleurothotonus)
ejaculation disorders in men, in which semen enters the bladder instead of being expelled externally (dry orgasm or retrograde ejaculation)
rash, purple-red spots, fever or itching due to vasculitis, colitis causing diarrhoea
abdominal pain, fever, skin discoloration, facial rash in a butterfly pattern, joint pain, muscle pain, fever and fatigue (systemic lupus erythematosus).

In elderly patients with dementia treated with antipsychotic medicines, there is a slightly increased risk of death compared to patients not taking antipsychotic medicines.

Reporting of adverse reactions

If any adverse reactions occur, including any adverse reactions not listed in this leaflet, you should inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309,
e-mail: [email protected]
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store the medicine Ayupil

Keep this medicine out of sight and reach of children.
Do not use the Ayupil medicine after the expiry date stated on the blister pack and carton.
The expiry date refers to the last day of the stated month.
No special storage conditions are required for this medicine.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Ayupil contains
12.5 mg, orodispersible tablets

The active substance is clozapine. One tablet contains 12.5 mg of clozapine.
The other ingredients are mannitol (E 421), microcrystalline cellulose, colloidal anhydrous silica, crospovidone (type A), aspartame (E 951), peppermint flavour (containing maltodextrin, sodium starch octenyl succinate (E 1450) and glyceryl tricaprylate (E 1518)), iron oxide yellow (E 172) and magnesium stearate.

25 mg, orodispersible tablets

The active substance is clozapine. One tablet contains 25 mg of clozapine.
The other ingredients are mannitol (E 421), microcrystalline cellulose, colloidal anhydrous silica, crospovidone (type A), aspartame (E 951), peppermint flavour (containing maltodextrin, sodium starch octenyl succinate (E 1450) and glyceryl tricaprylate (E 1518)), iron oxide yellow (E 172) and magnesium stearate.

100 mg, orodispersible tablets

The active substance is clozapine. One tablet contains 100 mg of clozapine.
The other ingredients are mannitol (E 421), microcrystalline cellulose, colloidal anhydrous silica, crospovidone (type A), aspartame (E 951), peppermint flavour (containing maltodextrin, sodium starch octenyl succinate (E 1450) and glyceryl tricaprylate (E 1518)), iron oxide yellow (E 172) and magnesium stearate.

200 mg, orodispersible tablets

The active substance is clozapine. One tablet contains 200 mg of clozapine.
The other ingredients are mannitol (E 421), microcrystalline cellulose, colloidal anhydrous silica, crospovidone (type A), aspartame (E 951), peppermint flavour (containing maltodextrin, sodium starch octenyl succinate (E 1450) and glyceryl tricaprylate (E 1518)), iron oxide yellow (E 172) and magnesium stearate.

What Ayupil looks like and contents of the pack
12.5 mg orodispersible tablets
Ayupil 12.5 mg are yellow, round, flat orodispersible tablets with a diameter of approximately 6.5 mm. The tablets are engraved with "C7PN" on one side and "12.5" on the other side.

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

100 mg orodispersible tablets
Ayupil 100 mg are yellow, round, flat orodispersible tablets with a diameter of approximately 13 mm. The tablets are engraved with "C7PN" on one side and "100" on the other side.

200 mg orodispersible tablets
Ayupil 200 mg are yellow, round, flat orodispersible tablets with a diameter of approximately 16 mm. The tablets are engraved with "C7PN" on one side and "200" on the other side.

12.5 mg orodispersible tablets
PVC/PVDC/Aluminium blisters are available in cartons containing 7, 10, 14, 20, 28, 30, 40, 50, 56, 60, 84, 90, 98, 100, 250, 300 or 500 tablets.
Single-dose PVC/PVDC/Aluminium blisters are available in cartons containing 7, 10, 14, 20, 28, 30, 40, 50, 56, 60, 84, 90, 98, 100, 250, 300 or 500 tablets.
HDPE bottles containing 250 or 500 tablets are also available.

25 mg orodispersible tablets
PVC/PVDC/Aluminium blisters are available in cartons containing 7, 10, 14, 20, 28, 30, 40, 50, 56, 60, 84, 90, 98, 100, 250, 300 or 500 tablets.
Single-dose PVC/PVDC/Aluminium blisters are available in cartons containing 7, 10, 14, 20, 28, 30, 40, 50, 56, 60, 84, 90, 98, 100, 250, 300 or 500 tablets.
HDPE bottles containing 250 or 500 tablets are also available.

100 mg orodispersible tablets
PVC/PVDC/Aluminium blisters are available in cartons containing 7, 10, 14, 20, 28, 30, 40, 50, 56, 60, 84, 90, 98, 100, 250, 300 or 500 tablets.
Single-dose PVC/PVDC/Aluminium blisters are available in cartons containing 7, 10, 14, 20, 28, 30, 40, 50, 56, 60, 84, 90, 98, 100, 250, 300 or 500 tablets.
HDPE bottles containing 250 or 500 tablets are also available.

200 mg orodispersible tablets
PVC/PVDC/Aluminium blisters are available in cartons containing 7, 10, 14, 20, 28, 30, 40, 50, 56, 60, 84, 90, 98, 100, 250, 300 or 500 tablets.
Single-dose PVC/PVDC/Aluminium blisters are available in cartons containing 7, 10, 14, 20, 28, 30, 40, 50, 56, 60, 84, 90, 98, 100, 250, 300 or 500 tablets.
HDPE bottles containing 250 or 275 tablets are also available.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Synthon BV
Microweg 22
6545 CM Nijmegen
The Netherlands

Manufacturer
Synthon BV
Microweg 22
6545 CM Nijmegen
The Netherlands

Synthon Hispania S.L.
C/ Castelló, nº1
Pol. Las Salinas
Sant Boi de Llobregat
08830 Barcelona
Spain