Simcloza

Package Leaflet: Information for the Patient

Symcloza, 25 mg, Tablets

Symcloza, 100 mg, Tablets

Symcloza, 200 mg, Tablets

Clozapine

Read the package leaflet carefully before taking the medicine, as it contains important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Table of Contents of the Leaflet

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

1. What is Symcloza and what is it used for

The active substance of Symcloza is clozapine, which belongs to a group of medicines called antipsychotics (medicines used to treat certain mental disorders, such as psychoses). Symcloza is used to treat patients with schizophrenia who do not respond to treatment with other medicines. Schizophrenia is a mental disorder that causes disturbances in thinking, emotions, and behavior. Symcloza is recommended only for the treatment of 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 have not responded to these medicines or have experienced severe side effects that could not be controlled. Symcloza 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 Symcloza

When not to take Symcloza

• if you are allergic to clozapine or any of the other ingredients of this medicine (listed in section 6);
• if you do not have the possibility of regular blood tests;
• if you have ever had a low white blood cell count in your blood (e.g., leukopenia or agranulocytosis), especially if it was caused by taking medicines, except for cases of low white blood cell count in the blood related to previously administered chemotherapy;
• if you have previously stopped taking Symcloza due to severe side effects (e.g., agranulocytosis or heart disorders);

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• if you are or have been treated with long-acting antipsychotic depot injections;
• if you have bone marrow depression;
• if you have uncontrolled epilepsy (seizures or other types of epilepsy);
• if you have acute mental disorders caused by alcohol or drugs (e.g., narcotics);
• if you have reduced consciousness and severe drowsiness;
• if you have circulatory collapse, which may be a consequence of severe shock;
• if you have severe kidney dysfunction;
• if you have myocarditis;
• if you have other severe heart diseases;
• if you have symptoms of active liver disease, such as jaundice (yellowing of the skin and whites of the eyes, nausea, and loss of appetite);
• if you have other severe liver dysfunction;
• if you have paralytic ileus (your intestine does not work properly and you have severe constipation);
• if you are taking any medicines that suppress bone marrow function;
• if you are taking any medicines that reduce the number of white blood cells in your blood.

If any of the above points apply to you, tell your doctor and do not take Symcloza. Symcloza must not be taken by patients who are unconscious or in a coma.

Warnings and precautions

Safety issues mentioned in this section are very important. You must pay special attention to them to minimize the risk of severe side effects that can be life-threatening.

Before you start taking Symcloza, tell your doctor if you have or have had:

• blood clots, as medicines like this have been associated with the formation of clots;
• glaucoma (increased pressure in the eye);
• diabetes; increased - sometimes significantly - glucose levels in the blood, occurring in patients with diabetes or without diabetes in their medical history (see section 4);
• prostate problems or difficulty urinating;
• heart, kidney, or liver disease;
• chronic constipation or taking medicines that cause constipation (such as anticholinergic medicines);
• lactose intolerance, lactase deficiency, or glucose-galactose malabsorption syndrome;
• controlled epilepsy;
• colon disease;
• previous abdominal surgery;
• if you have experienced heart disorders or abnormal heart conduction, known as "QT interval prolongation";
• if you are at risk of stroke, e.g., if you have: high blood pressure, heart and blood vessel problems, or problems with blood vessels in the brain.

Tell your doctor immediately before taking the next Symcloza tablet:

• if you experience symptoms of cold, fever, flu-like symptoms, sore throat, or any infection. Your doctor may recommend urgent blood tests to check if these symptoms are related to the medicine;

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• if you experience sudden increased temperature, muscle stiffness, which can lead to loss of consciousness (malignant neuroleptic syndrome), as this may indicate severe side effects that require immediate treatment;
• if you experience rapid and irregular heartbeat, even at rest, palpitations, difficulty breathing, chest pain, or severe fatigue. Your doctor will check your heart function and, if necessary, refer you to a cardiologist immediately;
• if you experience nausea, vomiting, and (or) loss of appetite. Your doctor will check your liver function;
• if you experience severe constipation. Your doctor will provide treatment to prevent further complications.

Medical check-ups and blood tests

Before starting treatment with Symcloza, your doctor will conduct a medical history and order blood tests to confirm a normal white blood cell count. This is important because your body needs white blood cells to fight infection.

Regular blood tests must be performed before starting treatment, during treatment, and after stopping treatment with Symcloza.

• Your doctor will inform you exactly when and where to have the tests done. Symcloza can only be taken if you have a normal white blood cell count.
• Symcloza may cause a significant decrease in the number of white blood cells in your blood (agranulocytosis). Only regular blood tests can confirm that you are at risk of developing agranulocytosis.
• Blood tests should be performed once a week for the first 18 weeks of treatment. Then, tests should be performed at least once a month.
• If your white blood cell count decreases, treatment with Symcloza must be stopped immediately. Your white blood cell count should return to normal.
• Blood tests should be performed for another 4 weeks after stopping treatment with Symcloza.

Your doctor will also perform a physical examination before starting treatment with Symcloza. Your doctor may order an electrocardiogram (ECG) to check your heart function if necessary, especially if you have concerns. If you have liver dysfunction, regular liver function tests will be performed throughout the treatment with Symcloza. If you have high blood sugar (diabetes), your doctor may order regular blood glucose tests. Symcloza may affect your lipid levels. Symcloza may cause weight gain. Your doctor may monitor your weight and lipid levels. If Symcloza causes you to feel dizzy, lightheaded, or faint, be careful when standing up from a sitting or lying position. If you need to undergo surgery or be immobilized for a longer period, discuss taking Symcloza with your 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 Symcloza, 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 Symcloza: fainting or feeling lightheaded when changing positions, dizziness, rapid heartbeat, difficulty urinating, and constipation. Tell your doctor if you have a condition called dementia.

Symcloza and other medicines

Tell your doctor or pharmacist about all medicines you are 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 your medicines or change your medicines.

Do not take Symcloza with medicines that suppress 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; antipsychotic depot injections. These medicines increase the risk of developing agranulocytosis (lack of white blood cells).

Taking Symcloza with other medicines may affect the action of Symcloza and (or) other medicines.

Tell your doctor if you 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 disorders, 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 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 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 infections (such as ketoconazole) or viral infections (such as protease inhibitors used to treat HIV infection);
• 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. Your doctor or pharmacist has more information about medicines that should be used with caution with Symcloza or should be avoided during treatment with Symcloza. Ask them about it.

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Symcloza with food and drink and alcohol

Do not drink alcohol while taking Symcloza. Tell your doctor if you smoke and how often you drink beverages containing caffeine (coffee, tea, cola). Sudden changes in smoking or caffeine consumption habits can also change the effects of Symcloza.

Pregnancy, breastfeeding, and fertility

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

Driving and using machines

Symcloza may cause drowsiness, dizziness, and seizures, especially during the initial treatment period. Do not drive or operate machinery if you experience these symptoms.

Symcloza contains lactose monohydrate

If you have been diagnosed with intolerance to some sugars, contact your doctor before taking the medicine.

3. How to take Symcloza

To minimize the risk of low blood pressure, seizures, and drowsiness, it is necessary for your doctor to gradually increase the dose of Symcloza. Symcloza should always be taken as directed by your doctor. If you have any doubts, consult your doctor or pharmacist. It is very important not to change the dose or stop taking Symcloza without consulting your doctor first. Continue treatment for as long as your doctor recommends. For patients over 60 years of age, the doctor may start treatment with smaller doses and gradually increase them, as it is more likely that certain side effects will occur (see section 2. Important information before taking Symcloza). If the tablets of this strength do not allow the patient to take the prescribed dose, tablets of a different strength are available.

Treatment of schizophrenia

The recommended initial dose is 12.5 mg (half a 25 mg tablet) once or twice a day on the first day, and then 25 mg once or twice a day on the second day. Swallow the tablet with water. If the treatment is well tolerated, the daily dose can then be gradually increased by 25 mg to 50 mg over 2-3 weeks to achieve a target dose of up to 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 200 mg or 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, some side effects may be more pronounced (especially seizures). Always use the smallest effective dose for the patient. Most patients take part of the dose in the morning and part in the evening. Your doctor will explain how to divide the daily dose. If you have been taking Symcloza for some time with good effect, your doctor may try to reduce the dose. You should take Symcloza for at least 6 months.

Treatment of severe disturbances in thinking in patients with Parkinson's disease

The recommended initial dose is 12.5 mg (half a 25 mg tablet) in the evening. Swallow the tablet with water. Then, your doctor will gradually increase the dose by 12.5 mg, no faster than twice a week, to a maximum dose of 50 mg per day by the end of the second week. If you experience fainting, dizziness, or confusion, the dose increase should be delayed or stopped. To avoid these symptoms, your doctor should check your blood pressure in the first weeks of treatment. The effective daily dose is usually 25 mg to 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. Always use the smallest effective dose of the medicine.

Overdose of Symcloza

If you or someone else has taken too many tablets, contact your doctor or call emergency services immediately. Symptoms of overdose: drowsiness, fatigue, lack of energy, loss of consciousness, coma, confusion (disorientation), hallucinations, agitation, chaotic speech, muscle stiffness, tremors, seizures (convulsions), excessive salivation, dilated pupils, blurred vision, low blood pressure, circulatory collapse, rapid or irregular heartbeat, palpitations, difficulty breathing, or severe fatigue.

Missing a dose of Symcloza

If you miss a dose, take it as soon as possible. However, do not take the medicine if it is almost time for your next dose. In this case, take the next dose at the usual time. Do not take a double dose to make up for the missed dose. If you forget to take Symcloza for 48 hours or longer, contact your doctor immediately.

Stopping treatment with Symcloza

Do not stop taking Symcloza without consulting your doctor, as withdrawal reactions may occur. These include: sweating, headache, nausea, vomiting, and diarrhea. If you experience any of these symptoms, tell your doctor immediately. After these symptoms, more severe side effects may occur if you do not receive immediate treatment. The symptoms of your illness may return. It is recommended to gradually reduce the dose by 12.5 mg over one to two weeks. Your doctor will inform you how to reduce the daily dose. If it is necessary to stop taking Symcloza immediately, consult your doctor. If your doctor decides to restart treatment with Symcloza and you have taken the last dose of Symcloza more than two days ago, the initial dose will be 12.5 mg. If you have any further doubts about taking this medicine, consult your doctor or pharmacist.

4. Possible side effects

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

Some side effects may be severe and require medical attention. Tell your doctor immediately before taking the next Symcloza tablet:

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

• if you experience severe constipation. Your doctor will provide treatment to prevent further complications.

Common(may affect up to 1 in 10 people):

• if you experience symptoms of cold, fever, flu-like symptoms, sore throat, or other infections. Urgent blood tests should be performed to check if these symptoms are related to the medicine;
• if you experience seizures.

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

• if you experience: sudden increased temperature, muscle stiffness, which can lead to loss of consciousness (malignant neuroleptic syndrome), as this may indicate severe side effects that require immediate treatment.

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

• if you have symptoms of respiratory tract infection or pneumonia, such as fever, cough, difficulty breathing, wheezing;
• if you experience nausea, vomiting, and (or) loss of appetite. Your doctor will check your liver function.

Rare(may affect up to 1 in 1,000 people)or very rare(may affect less than 1 in 10,000 people):

• if you experience rapid and irregular heartbeat, even at rest, palpitations, difficulty breathing, chest pain, or severe fatigue. Your doctor will check your heart function and, if necessary, refer you to a cardiologist immediately.

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

• if you are a man and experience prolonged, painful erection of the penis, known as priapism. If the erection lasts more than 4 hours, immediate treatment may be necessary to prevent further complications.

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

• if you experience chest pain, feeling of tightness in the chest, pressure or squeezing (chest pain that 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 these cases, contact your doctor immediately;
• if you experience pressure in the chest, feeling of heaviness, pressure, squeezing, burning, or feeling of suffocation (symptoms of insufficient blood flow and oxygen to the heart muscle). Your doctor will check your heart function;
• if you experience symptoms of blood clots in the veins, especially in the legs (symptoms include swelling, pain, and redness of the leg), which can travel through the blood vessels to the lungs, causing chest pain and difficulty breathing;
• if you experience excessive sweating, headache, nausea, vomiting, and diarrhea (symptoms of cholinergic syndrome);

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• if you experience significantly reduced urine output (a sign of kidney failure);
• if you experience an allergic reaction (swelling, mainly of the face, lips, and throat, as well as the tongue, which can cause itching and be painful).

If any of the above points apply to you, tell your doctor before taking the next Symcloza tablet.

Other side effects:

Very common(affects more than 1 in 10 people):
Drowsiness, dizziness, rapid heartbeat, excessive salivation.
Common(may affect up to 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, tremors, stiffness, restlessness, seizures, muscle spasms, involuntary movements, inability to move, inability to remain still, changes in ECG, high blood pressure, fainting or feeling lightheaded when changing positions, sudden loss of consciousness, nausea, vomiting, loss of appetite, dry mouth, minor liver function test abnormalities, urinary incontinence, difficulty urinating, fatigue, fever, increased sweating, increased body temperature, speech disorders (e.g., slurred speech).
Uncommon(may affect up to 1 in 100 people):
Lack of white blood cells in the blood (agranulocytosis), speech disorders (e.g., stuttering).
Rare(may affect up to 1 in 1,000 people):
Low red blood cell count in the blood (anemia), restlessness, agitation, confusion, delirium, circulatory collapse, arrhythmia, myocarditis or pericarditis, pericardial effusion, difficulty swallowing (e.g., choking), high blood sugar (glucose) levels, diabetes, pulmonary embolism (venous thromboembolism), liver inflammation, jaundice (liver disease causing yellowing of the skin/ dark urine/itching), pancreatitis leading to severe abdominal pain, increased levels of an enzyme called creatine phosphokinase in the blood.
Very rare(may affect less than 1 in 10,000 people):
Increased platelet count in the blood with possible blood clotting in the blood vessels, decreased platelet count in the blood, uncontrolled movements of the mouth, tongue, and limbs, obsessive and compulsive thoughts and actions, skin reactions, swelling of the parotid gland (enlargement of the salivary glands), breathing difficulties, complications caused by uncontrolled blood sugar (glucose) levels (e.g., coma or ketoacidosis), very high levels of triglycerides or cholesterol in the blood, heart muscle disease (cardiomyopathy), cardiac arrest, liver damage (fulminant liver necrosis), kidney inflammation, sudden unexplained death.
Frequency not known(frequency cannot be estimated from the available data):
Liver disorders, including fatty liver, liver necrosis, hepatotoxicity/liver damage, liver disorder causing scarring of the liver, leading to loss of liver function, including life-threatening liver diseases, such as liver failure (which can lead to death), liver damage (damage to liver cells or bile ducts or both), and liver transplantation, changes in brain wave tests (electroencephalogram/EEG), diarrhea, discomfort in the stomach, heartburn, discomfort in the stomach after eating, feeling of weakness, muscle cramps, muscle pain, nasal congestion, bedwetting, sudden, uncontrolled increase in blood pressure (a syndrome of symptoms resembling a pheochromocytoma), uncontrolled twisting of the body to one side (pleurothotonus), disorders of ejaculation in men (semen does not come out of the body but goes into the bladder - dry orgasm or retrograde ejaculation), rash, purple spots on the skin, fever or itching due to blood vessel inflammation, colon inflammation with diarrhea, abdominal pain, fever, and change in skin color, butterfly-shaped rash on the face, joint pain, muscle pain, fever, and fatigue (lupus erythematosus).
In elderly patients with dementia, treatment with antipsychotic medicines is associated with a slightly increased risk of death compared to patients not taking antipsychotic medicines.

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety, 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, website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
Reporting side effects will help to gather more information on the safety of the medicine.

5. How to store Symcloza

Keep the medicine out of the sight and reach of children. Do not take Symcloza after the expiry date stated on the carton and blister after EXP. The expiry date refers to the last day of the month stated. There are no special precautions for storing the medicine. Medicines should not be disposed of via wastewater or household waste. Ask your 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 Symcloza contains

• The active substance of Symcloza is clozapine. One tablet contains 25 mg, 100 mg, or 200 mg of clozapine.
• The other ingredients are: lactose monohydrate, magnesium stearate, cornstarch, povidone K30, colloidal silicon dioxide, talc.

What Symcloza looks like and contents of the pack

Symcloza, 25 mg, tablets are light yellow to yellow, round, approximately 6.0 mm in diameter, uncoated tablets, with "FC" embossed on one side and "1" on either side of the break line and smooth on the other side.
The tablet can be divided into equal doses.
Symcloza, 100 mg, tablets are light yellow to yellow, round, approximately 10.0 mm in diameter, uncoated tablets, with "FC" embossed on one side and "3" on either side of the break line and smooth on the other side.
The tablet can be divided into equal doses.
Symcloza, 200 mg, tablets are light yellow to yellow, capsule-shaped, approximately 17.0 mm long and 8.0 mm wide, uncoated tablets, with "F" and "C" embossed on one side with three break lines and "7" embossed on the other side with three break lines.
The break line on the tablet is only to facilitate breaking the tablet and not to divide it into equal doses.
Symcloza tablets are available in PVC/PVDC/Aluminum blisters containing 50 or 90 tablets.
Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder

Symphar Sp. z o.o.
ul. Koszykowa 65
00-667 Warsaw
tel.: +48 22 822 93 06
e-mail: symphar@symphar.com

Manufacturer/Importer

Symphar Sp. z o.o.
ul. Chełmżyńska 249
04-458 Warsaw

This medicine is authorized in the Member States of the European Economic Area under the following names:

Poland: Symcloza

Date of last revision of the leaflet:

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