Aiupil

Leaflet accompanying the packaging: Information for the user

Ayupil, 12.5 mg, orally disintegrating tablets

Ayupil, 25 mg, orally disintegrating tablets

Ayupil, 100 mg, orally disintegrating tablets

Ayupil, 200 mg, orally disintegrating tablets

Clozapine

You should carefully read the contents of the leaflet before taking the medicine, as it contains important information for the patient.

• You should keep this leaflet, so that you can read it again if you need to.
• If you have any doubts, you should consult a doctor or pharmacist.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any possible side effects not listed in this leaflet, they should tell their doctor or pharmacist. See section 4.

Table of contents of the leaflet

• 1. What is Ayupil and what is it used for
• 2. Important information before taking Ayupil
• 3. How to take Ayupil
• 4. Possible side effects
• 5. How to store Ayupil
• 6. Contents of the pack and other information

1. What is Ayupil and what is it used for

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

2. Important information before taking Ayupil

When not to take Ayupil

• if the patient has been diagnosed with an allergy (hypersensitivity) to clozapine or to any of the other ingredients of Ayupil (listed in section 6)
• if it is not possible to perform regular blood tests on the patient
• if the patient has ever had a low white blood cell count in the blood (e.g., leukopenia or agranulocytosis), especially if it was caused by taking medicines, except in cases of a low white blood cell count in the blood related to previous chemotherapy

with the exception of cases of a low white blood cell count in the blood related to previous chemotherapy

• if the patient has previously stopped taking Ayupil due to severe side effects (e.g., agranulocytosis or heart disorders)
• if the patient is or has been treated with depot antipsychotic injections
• if the patient has or has had bone marrow depression
• if the patient has uncontrolled epilepsy (seizures or other types of epilepsy)
• if the patient has acute mental disorders caused by alcohol or drugs (e.g., narcotics)
• if the patient has impaired consciousness and increased drowsiness
• if the patient has circulatory collapse, which may be the result of severe shock
• if the patient has severe kidney dysfunction
• if the patient has myocarditis
• if the patient has other severe heart diseases
• if the patient has symptoms 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 dysfunction
• if the patient has paralytic ileus (the patient's intestine does not work properly and the patient has severe constipation)
• if the patient is taking any medicines that suppress normal bone marrow function
• if the patient is taking any medicines that reduce the number of white blood cells in the blood

If any of the above points apply to the patient, they should tell their doctor and not take Ayupil.
Ayupil should not be taken by 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 side effects that can be life-threatening.

Before the patient starts taking Ayupil, they should tell their doctor if they have or have had:

• -blood clots, because medicines like this one have been associated with the formation of blood clots
• -glaucoma (increased pressure in the eye)
• -diabetes (high, sometimes significantly high, blood glucose levels, occurring in patients with diabetes or without diabetes in their medical history) (see section 4.4)
• -prostate problems or difficulty urinating
• -heart, kidney, or liver disease
• -chronic constipation or taking medicines that cause constipation (such as anticholinergic medicines)
• -controlled epilepsy
• -colon disease
• -previous abdominal surgery
• -heart disease or a family history of abnormal heart conduction, known as QT prolongation
• -risk of stroke, e.g., if the patient has high blood pressure, cardiovascular problems, or problems with blood vessels in the brain

The patient should immediately tell their doctor before taking the next dose of Ayupil if they:

• experience symptoms of a cold, fever, flu-like symptoms, sore throat, or any infection. The doctor may recommend urgent blood tests if these symptoms are related to the medicine
• experience a sudden increase in body temperature, muscle stiffness, which can lead to loss of consciousness (symptoms of malignant neuroleptic syndrome) and require immediate treatment as a severe side effect
• experience rapid and irregular heartbeat, even at rest, palpitations, difficulty breathing, chest pain, or unexplained fatigue. The doctor will check the patient's heart function and, if necessary, refer them to a cardiologist immediately
• experience nausea, vomiting, and (or) loss of appetite. The doctor will check the patient's liver function
• experience constipation, abdominal pain, abdominal tenderness, fever, bloating, and (or) bloody diarrhea. A consultation with the doctor is necessary.

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.

It is necessary to perform regular blood tests before starting treatment, during treatment, and after stopping treatment with Ayupil.

• -The doctor will inform the patient exactly when and where to have the blood tests done. Ayupil can only be taken 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 once a week for the first 18 weeks of treatment. Then, blood tests should be performed at least once a month.
• If the patient's white blood cell count decreases, treatment with Ayupil should be stopped immediately. The white blood cell count should return to normal.
• Blood tests should be performed for another 4 weeks after stopping treatment with Ayupil. The doctor will also perform a physical examination before starting treatment with Ayupil. The doctor may order an electrocardiogram (ECG) to check the patient's heart function if necessary. If the patient has liver dysfunction, regular liver function tests will be performed throughout the treatment with Ayupil. If the patient has high blood sugar levels (diabetes), the doctor may order regular blood glucose tests. Ayupil may cause changes in blood lipid levels. Ayupil may cause weight gain. The doctor may monitor the patient's weight and blood lipid levels.

If the patient experiences dizziness, lightheadedness, or fainting, or if the medicine causes these conditions, they should change positions carefully from sitting or lying down, as these symptoms can increase the risk of falls.
If the patient needs to undergo surgery or is immobilized for a longer period, they should discuss taking Ayupil with their doctor.
There is a risk of thrombosis (blood clotting in the veins).

Children and adolescents under 16 years of age

Patients under 16 years of age should not take Ayupil, as there is limited data on the use of the medicine in this age group.

Elderly patients (60 years of age and older)

In elderly patients (60 years of age and older), the following side effects may occur more frequently during treatment with Ayupil: fainting or lightheadedness when changing positions, dizziness, rapid heartbeat, difficulty urinating, and constipation.
The patient should tell their doctor if they have a condition called dementia.

Ayupil and other medicines

The patient should tell their doctor or pharmacist about all medicines they are currently taking, have recently taken, or plan to take, as well as over-the-counter medicines and herbal medicines. It may be necessary to change the dosage of the medicines or change the medicines.
Ayupil should not be taken 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 to treat epilepsy;
• certain antibiotics: chloramphenicol, sulfonamides, such as co-trimoxazole;
• certain painkillers: pyrazolone derivatives, such as phenylbutazone;
• penicillamine, a medicine used to treat rheumatoid arthritis;
• cytotoxic agents, medicines used in chemotherapy;
• depot antipsychotic injections

These medicines increase the risk of developing agranulocytosis (lack of white blood cells).
Taking Ayupil with other medicines may affect the action of Ayupil and (or) other medicines. The patient should tell their doctor if they plan to take, are taking (even if the treatment is ending), or have recently stopped taking 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 breathing
• medicines used to treat epilepsy, such as phenytoin and valproic acid
• medicines used to treat high and 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 cramps 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 medicines used to treat fungal or viral infections (such as ketoconazole or HIV protease inhibitors)
• atropine, a medicine that may be an ingredient in some eye drops, cold preparations, and cough medicines
• 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 with caution with Ayupil or should be avoided during treatment with Ayupil, and they know whether the medicine belongs to the listed groups. The patient should ask them about it.

Taking Ayupil with food, drink, and alcohol

The patient should not drink alcohol while taking Ayupil.
The patient should tell their doctor if they smoke and how often they drink caffeinated beverages (coffee, tea, cola). Sudden changes in smoking or caffeine consumption habits may also change the effects of Ayupil.

Pregnancy and breastfeeding

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a child, they should consult their doctor before taking this medicine. The doctor will discuss the benefits and possible risks of taking the medicine during pregnancy with the patient.
The patient should immediately tell their doctor if they become pregnant while taking Ayupil.
In newborns of mothers taking antipsychotic medicines in the last trimester of pregnancy (the last three months of their pregnancy), the following symptoms may occur: trembling, stiffness, and (or) muscle weakness, drowsiness, agitation, breathing difficulties, and feeding problems. If the child develops these symptoms, the patient should contact their doctor.
Some women taking antipsychotic medicines may have irregular periods or may not have them at all. When switching from another treatment to Ayupil, normal menstruation may return. Therefore, women of childbearing age should use effective contraception.
The patient should not breastfeed while taking Ayupil. Clozapine, the active substance of Ayupil, may pass into breast milk and affect the baby.

Driving and operating machinery

Ayupil may cause drowsiness, dizziness, and seizures, especially during the initial treatment period. The patient should not drive vehicles or operate machinery if they experience these symptoms.

Ayupil contains aspartame (E951)

Ayupil 12.5 mg contains 1.55 mg of aspartame per tablet, which corresponds to 18 mg/g.
Ayupil 25 mg contains 3.10 mg of aspartame per tablet, which corresponds to 18 mg/g.
Ayupil 100 mg contains 12.4 mg of aspartame per tablet, which corresponds to 18 mg/g.
Ayupil 200 mg contains 24.8 mg of aspartame per tablet, which corresponds 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 its improper elimination.

3. How to take Ayupil

In order to minimize the risk of low blood pressure, seizures, and drowsiness, it is necessary for the doctor to gradually increase the doses of Ayupil. Ayupil should always be taken according to the doctor's instructions. If the patient has any doubts, they should consult their doctor or pharmacist.
It is very important not to change the dose or stop taking Ayupil without consulting the doctor first. The patient should continue treatment for as long as the doctor recommends. In patients over 60 years of age, the doctor may start treatment with a lower dose and gradually increase it, as it is more likely that they will experience certain side effects (see section 2 Important information before taking Ayupil).
If the prescribed dose cannot be achieved with this strength of the medicine, another strength of the medicine is available on the market that will allow the required dose to be achieved.

Treatment of schizophrenia

The usual recommended starting dose is 12.5 mg once or twice a day on the first day, and then 25 mg once or twice a day 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, take out the tablet with dry hands and place the entire orally disintegrating tablet on the tongue. The tablet will dissolve quickly in saliva. The orally disintegrating tablet can be taken with or without a liquid.
Provided that 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 300 mg per day. Then, if necessary, the daily dose can be further increased by 50 mg to 100 mg at intervals of 3 to 4 days or, preferably, once a week.
The effective daily dose is usually between 200 mg and 450 mg, divided into several single doses. Some patients may need higher doses. The maximum daily dose is 900 mg. At doses above 450 mg per day, it is possible to exacerbate some side effects (in particular, seizures). The patient should always take the smallest effective dose of the medicine. Most patients take part of the dose in the morning and part in the evening. The doctor will explain how to divide the daily dose. If the daily dose is only 200 mg, the patient can take it as a single dose in the evening. If the patient has been taking Ayupil for some time with good results, the doctor may try to reduce the dose. The patient should take Ayupil for at least 6 months.

Treatment of severe disturbances in thinking, emotions, and behavior in patients with Parkinson's disease

The usual recommended 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, take out the tablet with dry hands and place the entire orally disintegrating tablet on the tongue. The tablet will dissolve quickly in saliva. The orally disintegrating tablet can be taken with or without a liquid.
Then, the doctor will gradually increase the dose by 12.5 mg, no faster than twice a week, to achieve a maximum dose of 50 mg per day by the end of the second week. If the patient experiences fainting, lightheadedness, or confusion, the dose increase should be delayed or suspended. To avoid these symptoms, the patient's blood pressure should be checked in the first weeks of treatment.
The effective daily dose is usually between 25 mg and 37.5 mg, taken as a single dose in the evening.
Taking doses higher than 50 mg per day should only be done in exceptional cases. The maximum daily dose is 100 mg. The patient should always take the smallest effective dose of the medicine.

Taking a higher dose of Ayupil than recommended

If the patient takes a higher dose of Ayupil than recommended or takes the medicine by mistake, they should immediately contact their doctor or go to the nearest hospital.
Symptoms of overdose include: drowsiness, fatigue, lack of energy, loss of consciousness, coma, confusion, delirium, agitation, hallucinations, stiffness of the limbs, trembling of the hands, seizures (convulsions), excessive salivation, dilated pupils, blurred vision, low blood pressure, shock, rapid or irregular heartbeat, shallow breathing or difficulty breathing.

Missing a dose of Ayupil

If the patient misses a dose of Ayupil, they should take it as soon as possible. However, they should not take the medicine if it is almost time for the next dose. In this case, they should take the next dose at the usual time. The patient should not take a double dose to make up for the missed dose. If the patient forgets to take Ayupil for 48 hours or more, they should contact their doctor immediately.

Stopping treatment with Ayupil

The patient should not stop taking Ayupil without consulting their doctor, as they may experience withdrawal reactions. These include: sweating, headache, nausea, vomiting, and diarrhea. If the patient experiences any of these symptoms, they should immediately tell their doctor. After these symptoms, more severe side effects may occur if the patient does not receive immediate treatment. The symptoms of the disease may also return. To stop treatment, it is recommended to gradually reduce the dose by 12.5 mg over a period of one to two weeks.
The doctor will advise the patient on how to reduce the dose of Ayupil. If it is necessary to stop taking Ayupil immediately, the patient should consult their doctor.
If the doctor decides to restart treatment with Ayupil and the patient has taken the last dose of Ayupil more than two days ago, the starting dose will be 12.5 mg.
If the patient has any further doubts about taking this medicine, they should consult their doctor or pharmacist.

4. Possible side effects

Like all medicines, Ayupil can cause side effects, although not everybody gets them.

Some side effects can be severe and require immediate medical attention. The patient should immediately tell their doctor before taking the next dose of Ayupil if they experience any of the following symptoms:

Ayupil:

Very commonside effects (affect more than 1 in 10 people):

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

Commonside effects (affect less than 1 in 10 people):

• symptoms of a cold, fever, flu-like symptoms, sore throat, or other infections. The doctor should urgently perform a blood test to check if the symptoms are related to the medicine
• seizures
• sudden fainting or loss of consciousness with muscle weakness (fainting).

Uncommonside effects (affect less than 1 in 100 people):

• sudden increase in body temperature, muscle stiffness, which can lead to loss of consciousness (malignant neuroleptic syndrome), as it may indicate the development of severe side effects that require immediate treatment
• feeling of emptiness in the head, dizziness, or fainting when changing positions, which can increase the risk of falls.

Rareside effects (affect less than 1 in 1,000 people):

• symptoms of respiratory tract infection or pneumonia, such as fever, cough, difficulty breathing, wheezing
• severe, burning pain in the upper abdomen that radiates to the back, with accompanying nausea and vomiting, caused by pancreatitis
• fainting and muscle weakness due to significantly low blood pressure (circulatory collapse)
• difficulty swallowing (which can cause food to be inhaled)
• nausea, vomiting, and (or) loss of appetite. The doctor will check the patient's liver function
• development or worsening of existing obesity
• sleep apnea with snoring or without snoring.

Rare(affect less than 1 in 1,000 people) or very rareside effects (may affect less than 1 in 10,000 people):

• rapid and irregular heartbeat, even at rest, palpitations, difficulty breathing, chest pain, or unexplained fatigue. The doctor will check the patient's heart function and, if necessary, refer them to a cardiologist immediately

Very rareside effects (may affect less than 1 in 10,000 people):

• prolonged, painful erection of the penis, known as priapism. If the erection lasts for more than 4 hours, immediate treatment may be necessary to prevent further complications
• sudden bleeding or bruising, which may be symptoms of a low 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 be symptoms of intestinal obstruction
• loss of appetite, bloating, abdominal pain, jaundice, severe weakness, and poor health. These symptoms may indicate the development of liver failure, which can lead to fulminant liver necrosis
• nausea, vomiting, fatigue, weight loss, which may be symptoms of kidney inflammation.

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

• chest pain, feeling of tightness in the chest, pressure, or sudden severe pain (chest pain that may radiate to the left arm, jaw, neck, and upper abdomen), shortness of breath, sweating, weakness, feeling of dizziness, nausea, vomiting, and palpitations (symptoms of a heart attack). In these cases, the patient should immediately contact their doctor
• pressure in the chest, feeling of heaviness, pressure, sudden severe pain, or burning (symptoms of inadequate blood flow and oxygen to the heart muscle). The doctor will check the patient's heart function
• feeling of irregular heartbeat: "thumping", "pounding", or "fluttering" in the chest (palpitations)
• rapid and irregular heartbeat (atrial fibrillation). Occasionally, palpitations, fainting, shortness of breath, or chest discomfort may occur. The doctor must check the patient's heart function
• -symptoms of low blood pressure, such as dizziness, lightheadedness, fainting, blurred vision, excessive fatigue, cold and clammy skin, or nausea
• symptoms of blood clots in the veins, especially in the legs (symptoms include swelling, pain, and redness of the leg); blood clots can travel through the blood vessels to the lungs, causing chest pain and difficulty breathing
• -confirmed or suspected infection with accompanying fever or low body temperature, rapid breathing, rapid heartbeat, changes in reaction rate and consciousness, low blood pressure (sepsis)
• -excessive sweating, headache, nausea, vomiting, and diarrhea (symptoms of cholinergic syndrome)
• -significantly reduced urine output (symptom of kidney failure)
• -allergic reaction (swelling mainly of the face, lips, and throat, as well as the tongue, which can cause itching and be painful)
• -loss of appetite, bloating, abdominal pain, jaundice, severe weakness, and poor health. This may indicate liver failure, where normal liver tissue is replaced by scar tissue, leading to loss of liver function, including a life-threatening condition (which can lead to death), liver damage (damage to liver cells, bile ducts, or both), liver transplant
• -constipation, abdominal pain, abdominal tenderness, fever, bloating, and bloody diarrhea. These symptoms may indicate acute colonic distension (acute intestinal distension) or intestinal infarction (intestinal necrosis). A consultation with the doctor is necessary
• -dull chest pain with shortness of breath, with or without cough
• -muscle weakness, muscle cramps, muscle pain. These symptoms may indicate muscle disorders (rhabdomyolysis). A consultation with the doctor is necessary
• -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, they should tell their doctor before taking the next dose of Ayupil.

Other side effects:

Very commonside effects (affect more than 1 in 10 people):

• -drowsiness, dizziness
• -excessive salivation.

Commonside effects (affect less than 1 in 10 people):

• -high white blood cell count in the blood (leukocytosis), high count of a certain type of white blood cell in the blood (eosinophilia)
• -weight gain
• -blurred vision
• -headache, trembling, stiffness, restlessness, muscle spasms, involuntary movements, inability to perform a movement, inability to remain still
• -changes in ECG recording
• -high blood pressure, fainting, or lightheadedness when changing positions,
• -nausea, vomiting, loss of appetite, dry mouth,
• -minor abnormalities in liver function tests,
• -urinary incontinence, urinary retention,
• -fatigue, fever, increased sweating, increased body temperature
• -speech disorders (e.g., slurred speech).

Uncommonside effects (affect less than 1 in 100 people):

• -low white blood cell count in the blood (agranulocytosis)
• -speech disorders (e.g., stuttering).

Rareside effects (affect less than 1 in 1,000 people):

• -low red blood cell count in the blood (anemia)
• -restlessness, agitation
• -confusion, delirium
• -arrhythmia, myocarditis, or pericarditis, pericardial effusion,
• -high blood glucose levels, diabetes,
• -pulmonary embolism (venous thromboembolism)
• -hepatitis, jaundice (liver disease that causes yellowing of the skin/ dark urine/ itching)
• -increased levels of the enzyme creatine phosphokinase in the blood.

Very rareside effects (affect less than 1 in 10,000 people):

• -increased platelet count with possible blood clotting in blood vessels
• -uncontrolled movements of the lips, tongue, and limbs, and obsessive-compulsive symptoms
• -skin reactions
• -swelling of the parotid gland (enlargement of the 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 the available data):

• -changes in brain wave tests (electroencephalogram/EEG), restless legs syndrome (an irresistible urge to move the legs or arms, usually accompanied by a feeling of discomfort, typically in the evening or at night, with temporary relief during movement).
• -diarrhea, discomfort in the stomach, heartburn, discomfort in the stomach after eating, inflammation of the colon causing diarrhea, abdominal pain, fever
• -muscle weakness, muscle cramps, muscle pain,
• -stuffy nose,
• -bedwetting,
• -sudden, uncontrolled increase in blood pressure (pseudo-pheochromocytoma syndrome)
• -uncontrolled bending of the body to one side (pleurothotonus)
• -ejaculation disorders in men, during which semen enters the bladder instead of being expelled outside the penis (dry orgasm or retrograde ejaculation)
• -rash, purple-red spots, fever, or itching due to vasculitis, inflammation of the colon causing 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, treated with antipsychotic medicines, there is a slightly increased risk of death compared to patients not taking antipsychotic medicines.

Reporting side effects

If the patient experiences any side effects, including any side effects not listed in the leaflet, they should tell their doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring, 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: ndl@urpl.gov.pl
Side effects can also be reported to the marketing authorization holder.
By reporting side effects, it is possible to gather more information on the safety of the medicine.

5. How to store Ayupil

The medicine should be stored out of sight and reach of children.
Ayupil should not be taken after the expiry date stated on the blister and carton.
The expiry date refers to the last day of the month.
There are no special precautions for storing the medicine.
Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the pack and other information

What Ayupil contains

12.5 mg, orally disintegrating tablets

• The active substance of Ayupil is clozapine. One tablet contains 12.5 mg of clozapine.
• The other ingredients 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.

25 mg, orally disintegrating tablets

• The active substance of Ayupil is clozapine. One tablet contains 25 mg of clozapine.
• The other ingredients 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.

100 mg, orally disintegrating tablets

• The active substance of Ayupil is clozapine. One tablet contains 100 mg of clozapine.
• The other ingredients 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.

200 mg, orally disintegrating tablets

• The active substance of Ayupil is clozapine. One tablet contains 200 mg of clozapine.
• The other ingredients 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.

How the Ayupil medicine looks like and what the packaging contains

12.5 mg orally disintegrating tablets
Ayupil 12.5 mg yellow, round, flat orally disintegrating tablets with a diameter of approximately 6.5
mm. The tablets have the inscription "C7PN" on one side and "12.5" on the other.
25 mg orally disintegrating tablets
Ayupil 25 mg yellow, round, flat orally disintegrating tablets with a diameter of approximately 8
mm. The tablets have the inscription "C7PN" on one side and "25" on the other.
100 mg orally disintegrating tablets
Ayupil 100 mg yellow, round, flat orally disintegrating tablets with a diameter of approximately 13
mm. The tablets have the inscription "C7PN" on one side and "100" on the other.
200 mg orally disintegrating tablets
Ayupil 200 mg yellow, round, flat orally disintegrating tablets with a diameter of approximately 16
mm. The tablets have the inscription "C7PN" on one side and "200" on the other.
12.5 mg orally disintegrating tablets
PVC/PVDC/Aluminum blister packs are available in boxes containing 7, 10, 14, 20, 28, 30, 40,
50, 56, 60, 84, 90, 98, 100, 250, 300 or 500 tablets.
Single-dose PVC/PVDC/Aluminum blister packs are available in boxes 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 available.
25 mg orally disintegrating tablets
PVC/PVDC/Aluminum blister packs are available in boxes containing 7, 10, 14, 20, 28, 30, 40,
50, 56, 60, 84, 90, 98, 100, 250, 300 or 500 tablets.
Single-dose PVC/PVDC/Aluminum blister packs are available in boxes 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 available.
100 mg orally disintegrating tablets
PVC/PVDC/Aluminum blister packs are available in boxes containing 7, 10, 14, 20, 28, 30, 40,
50, 56, 60, 84, 90, 98, 100, 250, 300 or 500 tablets.
Single-dose PVC/PVDC/Aluminum blister packs are available in boxes 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 available.
200 mg orally disintegrating tablets
PVC/PVDC/Aluminum blister packs are available in boxes containing 7, 10, 14, 20, 28, 30, 40,
50, 56, 60, 84, 90, 98, 100, 250, 300 or 500 tablets.
Single-dose PVC/PVDC/Aluminum blister packs are available in boxes 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 available.
Not all packaging sizes may be available on the market.

Marketing Authorization Holder

Synthon BV
Microweg 22
6545 CM Nijmegen
Netherlands

Manufacturer

Synthon BV
Microweg 22
6545 CM Nijmegen
Netherlands
Synthon Hispania S.L.
C/ Castelló, nº1
Pol. Las Salinas
Sant Boi de Llobregat
08830 Barcelona
Spain

Date of last update of the leaflet: