Package leaflet: Information for the user

Tiaprid PMCS 100 mg tablets hydrochloride

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you. - Keep this leaflet. You may need to read it again. - If you have any further questions, ask your doctor or pharmacist. - This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours. - If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet 1. What Tiaprid PMCS 100 mg is and what it is used for 2. What you need to know before you take Tiaprid PMCS 100 mg 3. How to take Tiaprid PMCS 100 mg 4. Possible side effects 5. How to store Tiaprid PMCS 100 mg 6. Contents of the pack and other information

1. What Tiaprid PMCS 100 mg is and what it is used for

Tiaprid PMCS 100 mg contains the active ingredient tiapride hydrochloride, which belongs to a group of medicines called , atypical neuroleptic agents.

Tiaprid PMCS 100 mg is a medicinal product which acts on the mental functions and has a positive effect on severe forms of involuntary and abnormal movements of the patient.

Tiaprid PMCS 100 mg is used for behaviour disorders in the elderly or chronic including withdrawal symptoms if the digestion of alcohol is stopped abruptly. It can also be used for severe forms of abnormal movements (Huntington’s ). Tiaprid PMCS 100 mg tablets can be used by adults and children from the age of 6.

2. What you need to know before you take Tiaprid PMCS 100 mg

Do not take Tiaprid PMCS 100 mg - if you are allergic to tiapride or any of the other ingredients of this medicine (listed in section 6). - if you suffer from a rare disease of the adrenal gland, so-called pheochromocytoma accompanied by headaches, hot flushes and periodic rise in blood pressure. - if you are concomitantly taking a levodopa-containing medicine or other medicines (see section ’Other medicines and Tiaprid PMCS 100 mg’) if you are administered levodopa for the treatment of Parkinson’s disease (a disease displayed by a strong trembling and muscle rigidity). - if you suffer concomitantly from brain cancer producing the hormone prolactin and/or breast cancer.

Warnings and precautions Talk to your doctor before taking Tiaprid PMCS 100 mg: Like with other neuroleptic agents, neuroleptic malignant syndrome (a complication with possible deadly consequences), characterised by hyperthermia (increased internal body heat above the normal range), muscle rigidity and autonomic dysfunction (failure of the part of the nervous system

1/8 responsible for controlling internal bodily functions that are not affected by will) may occur. Cases with unusual symptoms such as lack of muscle rigidity or increased muscle tension and lower fever reduction have been reported. In the event of elevated body temperature of unknown origin, use of tiapride should be discontinued. If the internal body temperature rises above the normal range for unknown origin, administration of tiapride should be discontinued.

Other than in exceptional cases, tiapride should not be taken by patients with Parkinson’s disease.

Neuroleptic agents may reduce the threshold for epileptic seizures., although this has not been evaluated in tiapride. If you have epilepsy, you will be thoroughly monitored while being treated with tiapride.

If you have kidney problems, your physiciandoctor will adjust your dose of tiapride because of a possible risk of unconsciousnesscoma due to overdoseage (see section 3).

If you are an older patient, the physician will assess your treatment with tiapride individually with respect to the potential risks (decreased level of consciousness and coma, increased risk of death due to concomitant use of antipsychoticssedative effect, with concurrent use with antipsychotics, and increased risk of death).

QT prolongation (in cardiology, the time measured between the beginning of the Q wave and the end of the T wave in the electric cycle of the heart): Tiapride may cause QT prolongation, which increases the risk of cardiac arrhythmia. For this reason before administering the medicine to you, your doctor will monitor factors that may support the occurrence of arrhythmia, such as: - Slowed heart rate (bradycardia), less than 55 beats per minute - Electrolytic imbalance, especially hypokalaemia (low level of potassium in the blood) - Congenital QT prolongation - Concomitant use of medicines that likely cause a clear reduction in heart rate (<55 heart beats/min), electrolytic imbalance, reduced intracardiac conduction or QT prolongation.

If you are a patient with stroke risk factors, your doctor will thoroughly monitor your treatment with Tiaprid PMCS 100 mg, because increased caution is necessary in this case.

Venous thromboembolism (a condition characterised by the formation of a blood clot at a specific site in the blood circulation and its subsequent “travelling” to the lungs): Cases of venous thromboembolism have been reported in connection with the use of antipsychotics, sometimes deadly. If you have or had blood clots in your veins in the past, your doctor will thoroughly monitor your treatment with Tiaprid PMCS 100 mg, because increased caution is necessary in this case.

Tiapride may increase levels of the prolactin hormone. For this reason, caution is necessary. If you or a member of your family has had breast cancer, you will be thoroughly monitored during treatment with tiapride.

Lowered white blood cell count (leukopenia, neutropenia, agranulocytosis) has been reported in connection with the use of antipsychotics, including tiapride. In case of Uunexplained infections andor fever, contact your doctor immediately as they may be a symptom of blood composition problems. and require immediate blood tests.

Use of tiapride in children and adolescents has not been studied in detail (see section 3).

Other medicines and Tiaprid PMCS 100 mg The effects of Tiaprid PMCS 100 mg and effect of other concomitant medicines may influence each other. Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

2/8

Dopaminergic agonists (medicines with effects similar to , natural substance with important function in the nervous system) and Tiaprid PMCS 100 mg cancel out each others’ effects and should not be used together. Patients with Parkinson’s disease take the lowest effective dose of levodopa and tiapride.

Medications that act on the central nervous system, such as pain , cough suppressants, sleeping medications, medications that calm you down, treat depression or , prevent vomiting, antihistamines, centrally-acting medications against high blood pressure and other medications (baclofen, thalidomide, pizotifen, clonidine) may increase the effect of tiapride and cause reduced attention and greater sleepiness. Alcohol also increases the effect of tiapride, primarily through an increase in general sedation and significant sleepiness. For this reason, avoid using alcohol while taking the medicinal product.

Not recommended combinations: Combinations with the following medicines, which may induce serious heart rate disorders (torsades de pointes) or QT prolongation (interval on an electrocardiogram report): - Medicines causing a reduced heart rate (bradycardia), such as beta blockers, calcium channel blockers that cause bradycardia such as diltiazem and verapamil, clonidine, guanfacine; cardiac glycozides (digoxin), pilocarpine, cholinesterase inhibitors, certain class II anti-arrhythmics. - Medicines that cause electrolyte imbalance, especially hypokalaemia (low level of potassium in the blood): hypokalaemic diuretics (medicines that increase the formation and excretion of urine, reduce the potassium content in the blood, which must be subsequently supplied by other medicines or food), stimulating laxatives (stool loosener), i.v. (intravenous) amphotericin B, glucocorticoids, tetracosactides, cosyntropin. Your doctor will correct hypokalaemia (low level of potassium in the blood). - Class IA anti-arrhythmics (medicines that treat heart rhythm disorders), such as quinidine, hydroquinidine, disopyramide. - Class III anti-arrhythmics, such as amiodarone, sotalol, dofetilide, ibutilide. - Certain antiparasitics, such as halofantrine, lumefantrine, pentamidine. - Certain neuroleptics (medications for treating psychosis), such as , , , , , , , , , , , , , , , , . - Other medications, such as methadone, antidepressants, lithium, bepridil, cisapride, i.v. erythromycin, i.v. vincamine, sparfloxacin, diphemanil, mizolastine, i.v. spiramycin, moxifloxacin.

The efficacy of high blood pressure medications and medications that treat coronary heart disease may be increased while taking Tiaprid PMCS 100 mg and may therefore lead to a large decrease in blood pressure, which manifests as dizziness with loss of consciousness after quickly standing up.

Tiaprid PMCS 100 mg with food, drink and alcohol Tiaprid PMCS 100 mg may be taken with or without food. Alcoholic drinks may not be consumed with the treatment of Tiaprid PMCS 100 mg.

Pregnancy, and breast-feeding and fertility If you are pregnant or breast-feeding, think you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before taking this medicine. Caution should be exercised when using the product during pregnancy.

Pregnancy Tiaprid PMCS 100 mg is not recommended during pregnancy and in women who may become pregnant and who are not using effective contraception. If you are taking Tiaprid PMCS 100 mg during the last three months of your pregnancy, your baby may have restlessness, muscle tension, tremors, drowsiness, breathing and feeding problems. If your baby develops any of these symptoms, contact your physician.

3/8

Breastfeeding You should not breast-feed during treatment with Tiaprid PMCS 100 mg. If you are taking TIaprid PMCS 100 mg, consult your physician about the best way to feed your baby.

Fertility Tiaprid PMCS 100 mg may cause amenorrhea (absence of menstruation) or anovulation (absence of ovulation) and reduce fertility. If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. Driving and using machines Tiaprid PMCS 100 mg may worsen the ability to drive and use machines because it may cause sedation, even when used correctly (see section 4).

Tiaprid PMCS 100 mg contains sodium Tiaprid PMCS 100 mg contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially “sodium-free”.

3. How to take Tiaprid PMCS 100 mg

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure. The dose is individual and must always be determined by the doctor. Tiaprid PMCS 100 mg is used in adults and children from the age of 6 usually as follows: Adults - For the treatment of behaviour disorders in elderly patients with dementia: the usual dose is 200 mg to 400 mg (2-4 tablets) daily divided into two or three partial doses. Starting dose of 50 mg (i.e., ½ tablet) twice daily, gradually increasing over 2–3 days to 100 mg (i.e., 1 tablet) 3 times daily. The average dose is 300 mg/day (i.e., 3 tablets daily); the maximum recommended dose is 400 mg/day (i.e., 4 tablets daily).

400 mg (3-4 tablets) daily divided into three partial doses, over 1-2 months. - Severe chorea in Huntington’s disease: In severe forms of abnormal movements, the dosage is strictly individual with large dose range from 300 mg to 1200 mg (3-12 tablets).

Elderly patients As elderly people are very sensitive to the effect of tiapride, the dosage determined by the doctor must be followed very carefully.

Use in children and adolescents from the age of 6 The normal dose is 100 – 150 mg/day to a maximum 300 mg/day.

The doctor will always determine the exact dose, the number taken during the day and length of treatment.

The doctor will reduce the dose in renal insufficiency.Renal insufficiencyimpairment The dose should be reduced to 75% of the normal dose in patients with creatinine clearance 30-60 ml / min, to 50% of the normal dose in patients with creatinine clearance 10-30 ml / min, and to 25% of the normal dose in patients with creatinine clearance less than 10 ml / min.

Hepatic impairment As the medicinal product is minimally metabolised in the liver, it is not necessary to reduce the dose.

If you take more Tiaprid PMCS 100 mg than you should

4/8 After taking a larger number of tablets, the following symptoms can appear: drowsiness and sedation, coma, decreased blood pressure, muscle contractions in the face and neck, uncontrolled protrusion of the tongue and long-term contraction of the masseter muscles, stiff limb muscles. Muscle spasms in the face and neck, uncontrolled sticking out of the tongue, long-term spasm of chewing muscles, somnolence, sedation or loss of consciousness, decrease of blood pressure may appear if taking a greater number of tablets. The trembling and rigidity of limb muscles may also appear. Deadly consequences have been reported especially in combination with other substances that act on the central nervous system. Contact your doctor or the nearest emergency service immediately if you overdose of this medicine or if it has been taken accidently by a child.

If you forget to take Tiaprid PMCS 100 mg Take the tablets immediately as soon as you remember. Do not take a double dose to make up for a forgotten dose. Tell your doctor if you forget to take more than one dose.

If you stop taking Tiaprid PMCS 100 mg Do not stop treatment without informing the doctor. Symptoms of your disease may reappear or get worse.

Information for the physician Suitable supportive measures are recommended while strictly monitoring vital functions. Monitoring of the heart rate is recommended until the patient recovers (risk of QT prolongation and subsequent ventricular heart rhythm disorders).

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

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

Common (may affect up to 1 in 10 people): - Tiapride causes an elevation of prolactin (hormone) levels in plasma, which may, in some cases, induce other disorders. Breast pain, breast enlargement (gynecomastia), galactorrhea (creation and excretion of milk from the mammary gland outside of breastfeeding), menstrual problems (missed periods, pain during menstruation, menstrual cramps) in females and orgasm disorder and impotence in males may be less common. - Drowsiness/sleepiness, insomnia, agitation (an emotional state of excitement or restlessness), impassivity. - Tiapride causes an elevation of prolactin (hormone) levels in plasma. This may lead to galactorrhea (creation and excretion of milk from the mammary gland outside of breastfeeding), missed periods, enlarged breasts in males, menstrual problems and/or erectile dysfunction. - Parkinsonism’s related symptoms (tremor, increased muscle tension, reduced mobility and an inability to produce movement, increased salivation). These symptoms are generally reversible upon administration of anticholinergics (e.g. Biperiden). - disease and associated symptoms: tremor, increased muscle tension, reduced mobility and increased salivation. These signs are generally reversible after administering antiparkinson agents (medications used to treat Parkinson’s disease- dampen the effect of acetylcholine in the brain and increase the effect of dopamine).

Uncommon (may affect up to 1 in 100 people): - Restlessness, muscle tension disorders (spasms, neck spasm (torticollis), uncontrolled eye movements (nystagmus), jaw spasms (trismus), (restlessness). These symptoms are generally reversible upon administration of anticholinergics (e.g. Biperiden). - Confusion, hallucinations. - Syncope (short loss of consciousness), convulsions.

5/8 - Hypotension, usually orthostatic (is defined as a sudden drop in blood pressure caused by a change in posture, such as when a person stands up quickly), deep vein thrombosis (blood clot in the veins). - Constipation. - Skin rash (including redness or urticaria/spots). - Missed periods, orgasm abnormal. - Restlessness, muscle tension disorders (spasms, contractions of the neck muscles, unintended eye movements, masseter muscle spasms). These signs are generally reversible after the administration of antiparkinson agents.

Rare (may affect up to 1 in 1000 people): - Loss of consciousness. - Low white blood cell count (leucopenia, neutropenia, agranulocytosis). - Low sodium concentration in the blood (hyponatremia), syndrome associated with water excretion disorder and low sodium levels (SIADH). - Early (tongue and esophageal spasms, tics). This symptom is generally reversible upon administration of anticholinergics (e.g. Biperiden). - Similarly to other antipsychotics (neuroleptics), cases of were reported upon prolonged administration (more than three months), characterised by rhythmic involuntary movements, particularly of the tongue and/or facial muscles. Inform your physician immediately upon occurrence of such movements; your physician will decide about necessary steps to be taken. Antiparkinsonian agenty should not be used as antidote, as they are ineffective or may cause worsening of the symptoms. - Similarly to all other neuroleptics, neuroleptic malignant syndrome (NMS) may appear which may be lethal (see the section ”What you need to know before taking Tiaprid PMCS 100 mg “). - Cardiac conduction disorders (prolongation of the QT interval) and serious heart rhythm disorders (such as torsades de pointes, ventricular tachycardia acceleration), as well as ventricular fibrillation, arrest and sudden deaths were also reported (see the section “Warnings and precautions” and “Other medicines and Tiaprid PMCS 100 mg “). - Venous thrombosis (a condition characterised by the formation of a blood clot at a specific site in the blood circulation), particularly in legs (with swelling, pain and redness); the thrombus (blood clot in the veins) may travel through the circulation to lungs causing chest pain and shortness of breath. If you observe any of the above symptoms, immediately seek medical help (see the section ”What you need to know before taking Tiaprid PMCS 100 mg “). In some cases, pulmonary embolism may be lethal. - Certain forms of pneumonia caused by involuntary entry of e.g. food or liquids to lungs (pulmonary aspiration), impaired respiration (respiratory depression). - IConstipation, intestinal blockage (obstruction, ileus). - Elevated liver enzymes. - Skin rash (urticaria). - Creatine phosphokinase (CPK) elevation, breakdown of skeletal muscles (rhabdomyolysis).

Not known (from available datacannot be estimated from the available data): - Drug withdrawal syndrome neonata (see „Pregnancy, lactation and fertility“). - Falls, especially in elderly patients. - Lowered white blood cell count (leukopenia, neutropenia, agranulocytosis).

Reporting of side effects If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Tiaprid PMCS 100 mg

Keep this medicine out of the sight and reach of children.

6/8

Store in the original package below 25 °C.

Do not use this medicine after the expiry date which is stated on the carton and the blister after “EXP”. The expiry date refers to the last day of that month.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Tiaprid PMCS 100 mg contains - The active substance is tiapride hydrochloride. Each tablet contains 111.1 mg of tiapride hydrochloride, corresponding to 100 mg of tiapride. - The other ingredients are mannitol, microcrystalline cellulose granulated, povidone 25, sodium starch glykolate (type A), silica, colloidal anhydrous and magnesium stearate.

What Tiaprid PMCS 100 mg looks like and contents of the pack Tiaprid PMCS 100 mg tablets are almost white, round tablets with a dividing cross on one side and a diameter of 9.5 mm. The tablet can be divided into four equal doses.

They are supplied in a blister pack of 20, 30, 50, 60, 90, 100 or 500 tablets. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer PRO.MED.CS Praha a.s., Telčská 377/1, Michle, 140 00 Prague 4, Czech Republic

This medicinal product is authorised in the Member States of the EEA under the following names: Slovak Republic Tiaprid PMCS 100 mg Lithuania Tiapride PMCS 100 mg tabletės Poland Tiaprid PMCS Romania Tiapridă PMCS 100 mg comprimate

This leaflet was last revised in

7/8