Simcloza

Leaflet accompanying the packaging: patient information

Symcloza, 25 mg, tablets

Symcloza, 100 mg, tablets

Symcloza, 200 mg, 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 them, even if their symptoms are the same as yours.
• If the patient experiences any side effects, including any not listed in this leaflet, they should tell their doctor or pharmacist. See section 4.

Table of contents of the leaflet

• 1. What Symcloza is and what it is 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 packaging and other information

1. What Symcloza is and what it is used for

The active substance of Symcloza is clozapine, which belongs to a group of medicines called neuroleptics (medicines used to treat specific 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 illness that causes disturbances in thinking, emotions, and behavior. The use of 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 who have not responded to these medicines or have experienced severe side effects that could not be controlled. Symcloza is also used to treat severe thought disorders, emotional disturbances, and behavioral disturbances 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 the patient is allergic to clozapine or any of the other ingredients of this medicine (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 for cases of low white blood cell count in the blood related to previously administered chemotherapy;
• if the patient has previously stopped taking Symcloza due to severe side effects (e.g., agranulocytosis or heart disorders);

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• if the patient is or has been treated with long-acting antipsychotic medicines (depot) in the form of 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 severe drowsiness;
• if the patient has circulatory collapse, which may be a consequence of severe shock;
• if the patient has severe kidney function disorders;
• 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, and loss of appetite);
• if the patient has other severe liver function disorders;
• if the patient has paralytic ileus (the intestine does not work properly and the patient has severe constipation);
• if the patient is taking any medicines that suppress the proper functioning of the bone marrow;
• 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 Symcloza. Symcloza should not be taken by patients who are unconscious or in a coma.

Warnings and precautions

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

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

• (or a family member) 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);
• galactose intolerance, lactase deficiency, or glucose-galactose malabsorption syndrome;
• controlled epilepsy;
• colon disease;
• previous abdominal surgery;
• if the patient has experienced or has a family history of heart disorders or abnormal heart conduction, known as "QT interval prolongation";
• if the patient is at risk of stroke, e.g., if they have: high blood pressure, cardiovascular problems, or problems with blood vessels in the brain.

The patient should tell their doctor immediately before taking the next Symcloza tablet:

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

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

Medical check-ups and blood tests

Before starting treatment with Symcloza, the doctor will conduct an interview 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 infection.

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

• The doctor will inform the patient exactly when and where to have the tests done. Symcloza can only be taken if the patient has a normal white blood cell count.
• Symcloza may cause a significant decrease in the number of white blood cells in the blood (agranulocytosis). Only regular blood tests can confirm that the patient is 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 the white blood cell count decreases, treatment with Symcloza 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 Symcloza.

The doctor will also perform a physical examination before starting treatment with Symcloza. The doctor may order an electrocardiogram (ECG) to check the 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 treatment with Symcloza. If the patient has high blood sugar (diabetes), the doctor may order regular blood sugar tests. Symcloza may cause changes in lipid levels in the blood. Symcloza may cause weight gain. The doctor may monitor the patient's weight and lipid levels in the blood. If Symcloza causes the patient to feel dizzy, lightheaded, or faint, they should be careful when standing up from a sitting or lying position. If the patient needs to undergo surgery or is immobilized for a longer period, they should discuss taking Symcloza with their doctor. There is a risk of developing 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.

Older adults (65 years of age and older)

In older adults (65 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. The patient should tell their doctor if they have a condition called dementia.

Symcloza 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.

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.

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 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 anti-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 Symcloza or should be avoided during treatment with Symcloza, and they know whether the medicine belongs to the mentioned groups. The patient should ask them about it.

  Symcloza with food and drink and alcohol

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

  Pregnancy, breastfeeding, and fertility

  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. The patient should tell their doctor immediately if they become pregnant while taking Symcloza. In newborns of mothers who took 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 medicines for mental illnesses have irregular periods or do not have them at all. As a result of switching treatment to Symcloza, normal menstruation may return. Therefore, women of childbearing age should use effective contraception. The patient should not breastfeed while taking Symcloza. Clozapine, the active substance of Symcloza, may pass into breast milk and affect the baby.

  Driving and using machines

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

  Symcloza contains lactose monohydrate

  If the patient has previously been diagnosed with intolerance to some sugars, they should contact their doctor before taking the medicine.

  3. How to take Symcloza

  In order to minimize the risk of low blood pressure, seizures, and drowsiness, it is necessary for the doctor to gradually increase the dose of Symcloza. Symcloza should always be taken as directed by the doctor. 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 Symcloza without consulting the doctor first. The patient should continue treatment for as long as the doctor recommends. In the case of patients 60 years of age or older, 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 usual 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. The patient should 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, 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 exactly how to divide the daily dose. If the patient has been taking Symcloza for some time with good results, the doctor may try to reduce the dose. The patient should take Symcloza for at least 6 months.

  Treatment of severe thought disorders in patients with Parkinson's disease

  The usual initial dose is 12.5 mg (half a 25 mg tablet) in the evening. The patient should swallow the tablet with water. 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, dizziness, or confusion, the dose increase should be delayed or stopped. To avoid these symptoms, the patient's blood pressure should be checked 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. The patient should always take the smallest effective dose of the medicine.

  Taking a higher dose of Symcloza than recommended

  If the patient has taken too many tablets, they should contact their 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, 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 the patient misses a dose, 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 Symcloza for 48 hours or longer, they should contact their doctor immediately.

  Stopping treatment with Symcloza

  The patient should not stop taking Symcloza without consulting their doctor, as withdrawal reactions may occur. These include: sweating, headache, nausea, vomiting, and diarrhea. If the patient experiences any of these symptoms, they should tell their doctor immediately. After these symptoms, more severe side effects may occur if the patient does not receive immediate treatment. The symptoms of the disease may return. It is recommended to gradually reduce the dose by 12.5 mg over one to two weeks. The doctor will inform the patient how to reduce the daily dose. If it is necessary to stop taking Symcloza immediately, the patient should consult their doctor. If the doctor decides to restart treatment with Symcloza, and the patient has taken the last dose of Symcloza more than two days ago, the initial 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, Symcloza can cause side effects, although not everybody gets them.

  Some side effects can be serious and require medical attention. The patient should tell their doctor immediately before taking the next Symcloza tablet:

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

  • if the patient experiences severe constipation. The doctor will provide treatment to prevent further complications.

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

  • if the patient experiences symptoms of cold, fever, flu-like symptoms, sore throat, or other infections. The doctor may recommend urgent blood tests to check if these symptoms are related to the medicine;
  • if the patient experiences seizures.

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

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

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

  • if the patient has symptoms of respiratory tract infection or pneumonia, such as fever, cough, difficulty breathing, wheezing;
  • if the patient experiences nausea, vomiting, and (or) loss of appetite. The doctor will check the 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 the patient experiences rapid and irregular heartbeat, even at rest, palpitations, difficulty breathing, chest pain, or severe fatigue. The doctor will check the heart function and, if necessary, immediately refer the patient to a cardiologist.

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

  • if the patient is a man and experiences prolonged, painful erection, 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 the patient experiences 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, the patient should see a doctor immediately;
  • if the patient experiences pressure in the chest, feeling of heaviness, pressure, squeezing, burning, or feeling of choking (symptoms of insufficient blood flow and oxygen to the heart muscle). The doctor will check the patient's heart function;
  • if the patient experiences 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 the patient experiences excessive sweating, headache, nausea, vomiting, and diarrhea (symptoms of cholinergic syndrome);

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  • if the patient experiences significantly reduced urine output (a sign of kidney failure);
  • if the patient experiences 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 the patient, they should tell their 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, high levels of a certain type of white blood cell, 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):
  Low white blood cell count, speech disorders (e.g., stuttering).
  Rare(may affect up to 1 in 1,000 people):
  Low red blood cell count, restlessness, agitation, confusion, delirium, circulatory collapse, arrhythmia, myocarditis or pericarditis, pericardial effusion, difficulty swallowing (e.g., choking), high blood sugar, 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 with possible blood clotting in blood vessels, decreased platelet count, uncontrolled movements of the lips, tongue, and limbs, obsessive and compulsive thoughts and behaviors, skin reactions, swelling of the parotid gland, breathing difficulties, complications due to uncontrolled blood sugar levels (e.g., coma or ketoacidosis), very high levels of triglycerides or cholesterol in the blood, heart muscle disease (cardiomyopathy), cardiac arrest, severe constipation with abdominal pain and stomach cramps caused by intestinal obstruction (paralytic ileus), abdominal distension, abdominal pain, severe 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 (pseudo-pheochromocytoma syndrome), 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 disease with diarrhea, abdominal pain, fever, change in skin color, rash on the face in the shape of a butterfly, joint pain, muscle pain, fever, and fatigue (lupus erythematosus).
  In older adults 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 not listed in this 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, 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

  The medicine should be stored out of sight and reach of children.
  Symcloza should not be taken after the expiry date stated on the carton and blister after EXP. 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 packaging 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 silica, and 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 and not to divide the tablet 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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