Package leaflet: Information for the patient

Symcloza, 25 mg, tablets
Symcloza, 100 mg, tablets
Symcloza, 200 mg, tablets
Clozapinum
Please read all of this leaflet carefully before taking this medicine, because it contains
important information for the patient.

Keep this leaflet, as you may need to read it again.
If you have any further questions, please ask your doctor or pharmacist.
This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm other people, even if their symptoms are the same.
If you experience any adverse reactions, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the leaflet

What Symcloza is and what it is used for
Important information before taking Symcloza
How to take Symcloza
Possible side effects
How to store Symcloza
Contents of the pack and other information

1. What Symcloza is and what it is used for

The active substance in 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 causing disturbances in thinking, emotions, and behavior.
Treatment with Symcloza is recommended only for patients who have already used 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 medicines or who experienced severe adverse reactions that could not be managed.
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 using Symcloza

When not to use Symcloza

if the patient is allergic to clozapine or any of the other ingredients of this medicine (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 if it was caused by taking medicines, except for cases of low white blood cell count related to previous chemotherapy;
if the patient previously discontinued treatment with Symcloza due to severe adverse reactions (e.g. agranulocytosis or heart disorders);
if the patient has previously been treated with long-acting (depot) antipsychotic medicines given by injection;
if the patient has impaired bone marrow function currently or in the past;
if the patient has uncontrolled epilepsy (seizures or other types of epileptic fits);
if the patient has acute psychiatric disorders caused by alcohol or drugs (e.g. narcotics);
if the patient has reduced consciousness and severe drowsiness;
if the patient has circulatory collapse, which may result from severe shock;
if the patient has severe kidney function disorders;
if the patient has myocarditis (inflammation of the heart muscle);
if the patient has other severe heart diseases;
if the patient has signs 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 patient's bowel 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, tell the doctor
and do not use Symcloza.
Symcloza 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 particular attention to them in order to minimize the risk of serious,
life-threatening adverse reactions.
Before the patient starts treatment with Symcloza, the patient should tell the doctor if
they have or have ever had:

(or if someone in their family has) blood clots, because medicines such as this have been associated with blood clot formation;
glaucoma (increased pressure in the eye);
diabetes; increased - sometimes significantly - blood glucose levels, occurring in patients with or without a history of diabetes (see section 4);
prostate gland problems or difficulty passing urine;
heart, kidney or liver diseases;
chronic constipation or use of medicines causing constipation (such as anticholinergic medicines);
galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome;
controlled epilepsy;
diseases of the large intestine;
previous abdominal surgeries;
if the patient or in their family history, heart disorders or abnormal heart conduction, called "QT 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.

Tell the doctor immediately before taking the next tablet of Symcloza:

if the patient develops symptoms of a cold, fever, flu-like symptoms, sore throat or any infection. The doctor may recommend urgent blood count testing to check whether these symptoms are related to the medicine;
if the patient experiences sudden increase in body temperature, muscle stiffness, which may lead to loss of consciousness (symptoms of neuroleptic malignant syndrome), which may be a serious adverse reaction requiring immediate treatment;
if the patient has rapid and irregular heartbeat, even at rest, palpitations, difficulty breathing, chest pain or unexplained fatigue. The doctor will check heart function and, if necessary, refer the patient immediately to a cardiologist;
if the patient has nausea, vomiting and (or) loss of appetite. The doctor will check liver function;
if the patient has severe constipation. The doctor will initiate treatment to prevent further complications.

Regular medical check-ups and blood tests
Before starting treatment with Symcloza, 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 infection.
Regular blood tests are essential before starting treatment, during treatment and after
stopping treatment with Symcloza.

The doctor will inform exactly when and where blood tests should be performed. Symcloza may be used only 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 whether the patient is at risk of developing agranulocytosis.
Blood tests should be performed once a week during the first 18 weeks of treatment. Afterwards, tests should be performed at least once a month.
If a decrease in white blood cell count occurs, treatment with Symcloza must be stopped immediately. The white blood cell count should return to normal values.
Blood tests should continue for 4 weeks after stopping treatment with Symcloza.

The doctor will also perform a medical examination before starting treatment with Symcloza. The
doctor may order an electrocardiogram (ECG) to check 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 glucose levels (diabetes), the doctor may
order regular blood glucose monitoring.
Symcloza may alter blood lipid levels. Symcloza may cause weight gain. The doctor may monitor
the patient's body weight and blood lipid levels.
If Symcloza causes the patient to feel light-headed, dizzy or faint, caution should be exercised when
rising from a sitting or lying position.
If the patient needs to undergo surgery or is immobilized for a prolonged period for other reasons,
discuss the use of Symcloza 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 Symcloza, as there is limited data on the use of this
medicine in this age group.
Elderly patients (aged 60 years and over)
In elderly patients (aged 60 years and over), the following adverse reactions may occur more
frequently during treatment with Symcloza: fainting or feeling light-headed upon changing position,
dizziness, rapid heartbeat, difficulty passing urine and constipation.
Tell the doctor if the patient has a condition called dementia.
Symcloza with other medicines
Tell the doctor or pharmacist about all medicines the patient is currently taking or has recently taken,
as well as any medicines the patient plans to take, including over-the-counter medicines and herbal
products. Dose adjustments or changes in medicines may be necessary.
Do not use Symcloza together 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 derivative painkillers such as phenylbutazone;
penicillamine, a medicine used, among others, in the treatment of rheumatoid arthritis;
cytotoxic agents, medicines used in chemotherapy;
depot antipsychotic medicines given by injection. These medicines increase the risk of developing agranulocytosis (lack of white blood cells).

Taking Symcloza together with other medicines may affect the action of Symcloza and (or)
other medicines. Tell the doctor if the patient plans to take, is taking (even if treatment is ending)
or has 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 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 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 which may be an ingredient in certain eye drops, cold remedies or 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 cautiously with Symcloza or avoided during treatment with Symcloza, and knows whether a medicine being taken belongs to the groups mentioned. Ask them.

Symcloza with food, drink and alcohol
Do not drink alcohol while taking Symcloza.
Tell the doctor if the patient smokes cigarettes 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 Symcloza.
Pregnancy, breastfeeding and effects on fertility
If the patient is pregnant or 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. Inform the doctor immediately if the patient
becomes pregnant during treatment with Symcloza.
Newborns of mothers who took antipsychotic medicines during the last trimester of pregnancy (last
three months of pregnancy) may experience the following symptoms: tremors, muscle stiffness and (or) weakness, drowsiness, restlessness, breathing problems and feeding difficulties. If the baby develops these symptoms, contact the doctor.
Some women taking medicines used to treat mental illnesses have irregular or absent menstrual periods. As a result of switching treatment to Symcloza from another medicine, normal menstruation may return. Therefore, women of childbearing age should use effective contraceptive methods.
Do not breastfeed during treatment with Symcloza. Clozapine, the active substance in Symcloza, may pass into human milk and affect the baby.
Driving and operating machinery
Symcloza may cause fatigue, drowsiness and seizures, especially during the initial period of treatment. Do not drive or operate machinery if the above symptoms occur.
Symcloza contains monohydrate lactose
If the patient has been previously diagnosed with intolerance to certain sugars, the patient should
consult the doctor before taking the medicine.

3. How to use Symcloza

To minimise the risk of low blood pressure, seizures and drowsiness, it is essential that
the doctor increases the dose of the medicine gradually. Symcloza should always be used as
recommended by the doctor. If in doubt, consult the doctor or pharmacist.
It is very important not to change the dose or stop taking Symcloza without
consulting the doctor first. Treatment should be continued for as long as the doctor advises.
For patients aged 60 years or older, the doctor may start treatment with a lower dose and increase it gradually, as they are more likely to experience certain
adverse reactions (see section 2. Important information before taking Symcloza).
If tablets of this strength do not allow the patient to take the prescribed dose, tablets of other strengths are available.

Treatment of schizophrenia
The usual starting dose is 12.5 mg (half a 25 mg tablet) once or twice daily on the first day, followed by 25 mg once or twice daily on the second day. The tablet should be swallowed with water. If the treatment is well tolerated, the daily dose may then be gradually increased by 25 mg to 50 mg over 2–3 weeks, aiming for 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.
An effective daily dose is usually 200 mg or 450 mg, divided into several single doses.
Some patients may require higher doses. The maximum recommended daily dose is 900 mg. At daily doses exceeding 450 mg, certain adverse reactions (particularly seizures) may become more severe. 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 dose is 200 mg, the patient may take it as a single dose in the evening. If the patient has been taking Symcloza for some time with good effect, the doctor may attempt to reduce the dose. The patient should continue taking Symcloza for at least 6 months.

Treatment of severe thought disorders in patients with Parkinson's disease
The usual starting dose is 12.5 mg (half a 25 mg tablet) taken in the evening. The tablet should be swallowed with water. 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 stopped. To avoid such symptoms, the patient's blood pressure should be monitored during the first weeks of treatment. An effective daily dose is usually 25 mg to 37.5 mg, taken as a single evening dose. Doses higher than 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 Symcloza than prescribed
If the patient or someone else takes too many tablets, contact a doctor immediately or call an ambulance.
Symptoms of overdose:
Drowsiness, fatigue, lack of energy, loss of consciousness, coma, confusion (disorientation), hallucinations, agitation, disorganised speech, limb rigidity, tremor, epileptic seizures (convulsions), excessive salivation, dilated pupils, blurred vision, hypotension, circulatory collapse, rapid or irregular heartbeat, shallow breathing or breathing difficulties.

Missing a dose of Symcloza
If a dose is missed, it should be taken as soon as possible. However, do not take the medicine if the next dose is due soon. 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 Symcloza for 48 hours or longer, they should contact the doctor immediately.

Stopping Symcloza
Do not stop taking Symcloza without consulting the doctor, as withdrawal reactions may occur. These include: sweating, headache, nausea, vomiting and diarrhoea.
If the patient experiences any of these symptoms, inform the doctor immediately.
After these symptoms, more severe adverse reactions may occur if the patient does not
receive immediate treatment. Symptoms of the underlying illness may return. 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 taper the daily dose. If immediate discontinuation of Symcloza is necessary, consult the doctor.
If the doctor decides to restart treatment with Symcloza and the patient last took Symcloza more than two days earlier, the starting dose will be 12.5 mg.

If there are any further doubts about the use of this medicine, consult the doctor or pharmacist.

4. Possible adverse effects

Like any medicine, this medicine can cause adverse effects, although not everyone will experience them.
Some adverse effects may be serious and require medical attention. You must
immediately inform your doctor before taking the next dose of Symcloza:
Very common (affects more than 1 in 10 people):

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

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

if the patient experiences symptoms of cold, fever, flu-like symptoms, sore throat or other infections. Blood tests should be urgently performed to determine whether symptoms are related to the medicine;
if the patient experiences seizures.

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

if the patient develops: sudden increase in body temperature, muscle rigidity, which may lead to loss of consciousness (neuroleptic malignant syndrome), as this may indicate serious adverse effects requiring immediate treatment.

Rare (may occur in 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 liver function.

Rare (may occur in 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 unexplained fatigue. The doctor will check heart function and, if necessary, refer the patient immediately to a cardiologist.

Very rare (may occur in up to 1 in 10,000 people):

if the patient is male and develops prolonged, painful erection, called priapism. If erection persists for more than 4 hours, immediate treatment may be required to avoid further complications.

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

if the patient experiences crushing chest pain, tightness in the chest, pressure or squeezing (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 heart attack). In such cases, seek medical attention immediately;
if the patient experiences chest pressure, heaviness, pressure, squeezing, burning or choking sensation (symptoms of inadequate blood and oxygen supply to the heart muscle). The doctor will check the patient's heart function;
if the patient develops symptoms indicating blood clots in the veins, particularly in the legs (symptoms include swelling, pain and redness of the leg), which may travel through blood vessels to the lungs, causing chest pain and difficulty breathing;
if the patient experiences excessive sweating, headache, nausea, vomiting and diarrhoea (symptoms of cholinergic syndrome);
if the patient experiences significantly reduced urine output (a sign of kidney failure);
if the patient develops hypersensitivity reaction (swelling, mainly of the face, lips and throat, as well as the tongue, which may cause itching and be painful).

If any of the above points apply to the patient, inform the doctor
before taking the next dose of Symcloza.
Other adverse effects:
Very common (affects more than 1 in 10 people):
Somnolence, dizziness, tachycardia, excessive salivation.
Common (may occur in up to 1 in 10 people):
High white blood cell count (leukocytosis), high count of a certain type of white blood cells in the blood (eosinophilia), weight gain, blurred vision, headache, tremor, stiffness, motor restlessness, convulsions, muscle twitching, involuntary movements, inability to perform movement, inability to remain still, changes in ECG recording, hypertension, fainting or feeling of emptiness in the head upon changing position, sudden loss of consciousness, nausea, vomiting, loss of appetite, dryness of the oral mucosa, minor abnormalities in liver function test results, urinary incontinence, difficulty urinating, fatigue, fever, increased sweating, increased body temperature, speech disorders (e.g. slurred speech).
Uncommon (may occur in up to 1 in 100 people):
Absence of white blood cells in the blood (agranulocytosis), speech disorders (e.g. stuttering).
Rare (may occur in up to 1 in 1,000 people):
Low red blood cell count (anaemia), motor restlessness, agitation, confusion, delirium, circulatory collapse, arrhythmia, myocarditis or pericarditis, pericardial effusion, difficulty swallowing (e.g. choking), high blood glucose concentration, diabetes, pulmonary embolism (venous thromboembolic disease), hepatitis, jaundice (liver disease causing yellowing of the skin/dark urine/itching), pancreatitis leading to severe upper abdominal pain, increased blood activity of an enzyme called creatine kinase.
Very rare (may occur in up to 1 in 10,000 patients):
Increased platelet count with possible blood clotting in blood vessels, decreased platelet count, uncontrolled movements of the mouth, tongue and limbs, intrusive thoughts and compulsive behaviours (obsessive-compulsive symptoms), skin reactions, swelling of the parotid gland (salivary gland enlargement), breathing difficulties, complications caused by uncontrolled blood glucose concentration (e.g. coma or ketoacidosis), very high triglyceride or cholesterol levels in the blood, heart muscle disease (cardiomyopathy), cardiac arrest, severe constipation with abdominal pain and stomach cramps due to intestinal obstruction (paralytic ileus), abdominal distension, abdominal pain, severe liver damage (fulminant hepatic necrosis), kidney inflammation, sudden unexplained death.
Frequency not known (frequency cannot be estimated from available data):
Liver disorders, including fatty liver, hepatic necrosis, hepatotoxicity/liver damage, liver disorder causing replacement of normal tissue with scar tissue, leading to loss of liver function, including liver diseases causing life-threatening complications such as liver failure (which may lead to death), liver damage (damage to liver cells or bile ducts or both), and liver transplantation, changes in brain wave test (electroencephalogram/EEG), diarrhoea, feeling of discomfort in the stomach, heartburn, feeling of discomfort in the stomach after a meal, feeling of muscle weakness, muscle cramps, muscle pain, nasal congestion, nocturnal enuresis, sudden, uncontrolled increase in blood pressure (pseudo-phaeochromocytoma syndrome), uncontrolled tilting of the body to one side (pleurototonus), ejaculation disorders in men (semen does not exit the body but enters the bladder - dry orgasm or retrograde ejaculation), rash, purple-red spots on the skin, fever or itching due to vasculitis, inflammation of the large intestine with diarrhoea, abdominal pain, fever, skin colour changes, butterfly-shaped facial rash, 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 of adverse effects
If any adverse effects occur, including any adverse effects not listed in this leaflet, inform your doctor or pharmacist. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions, 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
Adverse effects can also be reported to the marketing authorization holder.
Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store the medicine Symcloza

Keep this medicine out of sight and reach of children.
Do not use the Symcloza medicine after the expiry date stated on the cardboard box and
blister pack following: EXP. 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. Such measures will help
protect the environment.

6. Contents of the pack and other information

What Symcloza contains

The active substance is clozapine. Each tablet contains 25 mg, 100 mg or 200 mg of clozapine.
The other ingredients are: lactose monohydrate, magnesium stearate, maize starch, povidone K30, colloidal anhydrous silica, 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, embossed on one side with "FC" and "1" on both sides 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, embossed on one side with "FC" and "3" on both sides 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 in length and 8.0 mm in width, uncoated tablets, embossed on one side with "F" and "C" with three break lines, and on the other side with an embossed "7" and three break lines.
The break line on the tablet is intended only to facilitate breaking for easier swallowing and does not ensure division into equal doses.

Symcloza tablets are available in PVC/PVDC/Aluminium blisters containing 50 or 90 tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Symphar Sp. z o.o.
ul. Koszykowa 65
00-667 Warsaw
tel.: +48 22 822 93 06
e-mail: [email protected]

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

This medicinal product is authorised in the European Economic Area under the following names:
Poland: Symcloza