TIAPRIZAL 100 mg TABLETS

2. What you need to know before you take Tiaprizal

Do not take Tiaprizal

• if you are allergic to tiaprida or any of the other ingredients of this medicine (listed in section 6),
• if you have concomitant prolactin-dependent tumors (hormone that stimulates milk production in the mammary glands), such as pituitary prolactinomas and breast cancer,
• if you have pheochromocytoma (tumor of the adrenal gland),
• if you are being treated with levodopa or other dopaminergic medications (see "Use of Tiaprizal with other medications").

Warnings and precautions

Consult your doctor or pharmacist before starting to take Tiaprizal:

• if you have bradycardia (slow heart rate), low potassium levels in the blood, prolonged QT interval (can induce ventricular arrhythmias/alteration of heart frequency) or are being treated with any medication that favors any of these circumstances (see "Use of Tiaprizal with other medications"),
• if you experience fever of unknown origin, treatment with Tiaprizal should be discontinued as it could be a sign of malignant neuroleptic syndrome, a potentially fatal complication characterized by elevated body temperature, muscle rigidity, and alteration of the nervous system (see "Possible side effects"). Cases with atypical characteristics, such as lack of muscle rigidity or hypertonia and lower fever, have been observed,
• if you experience fever and/or muscle rigidity during treatment with Tiaprizal, particularly if you are already taking any other medication for mental health treatment,
• if you have or have had problems with alcohol (see "Taking Tiaprizal with food, drinks, and alcohol"),
• if you have Parkinson's disease, you should not use this medication unless in exceptional cases,
• if you have risk factors for suffering a stroke (vascular disease that affects the arteries of the brain or those that reach the brain),
• in elderly patients with psychosis related to dementia who are being treated with antipsychotics (as they have a higher risk of death),
• in patients with risk factors for venous thromboembolism (obstruction of a blood vessel by a thrombus) (see "Possible side effects"),
• if you have or have had epilepsy, as the group of medications to which Tiaprizal belongs may favor the appearance of epileptic seizures,
• if you have renal insufficiency (alteration of kidney function), as the dose of Tiaprizal should be decreased,
• if the medication is administered to elderly patients, as tiaprida may present a risk of decreased level of consciousness and coma in these patients, so it should be used with caution,
• if the medication is to be administered to children, as tiaprida has not been extensively investigated in this group of patients,
• if you have a history or family history of breast cancer, you should be monitored by your doctor during treatment with tiaprida. Tiaprida may increase prolactin levels (hormone that stimulates milk production in the mammary glands),
• if you have leukopenia (decrease in the number of white blood cells), neutropenia (decrease in the number of a type of white blood cells, neutrophils), and agranulocytosis (decrease in a type of white blood cells, granulocytes), as well as infections or fever of unknown origin, inform your doctor, as it could be a sign of blood dyscrasia (blood alteration) (see "Possible side effects").

Consult your doctor or pharmacist if you experience such symptoms.

Use of Tiaprizal with other medications

Inform your doctor or pharmacist if you are using, have recently used, or may need to use any other medication.

In particular, inform your doctor if you are using any of the following medications:

Combinations that are contraindicated:

Except in the case of patients with Parkinson's disease, simultaneous administration of dopaminergic agonist medications (cabergoline, quinagolide) with neuroleptics should be avoided.

Combinations that are not recommended:

• Alcohol(see "Taking Tiaprizal with food, drinks, and alcohol").

• Levodopa(medication for the treatment of Parkinson's disease).

• Dopaminergic agonists other than levodopa(amantadine, apomorphine, bromocriptine, entacapone, lisuride, pergolide, piribedil, pramipexole, ropinirole, selegiline) in patients with Parkinson's disease.

• Methadone(medication that calms pain).

• Medications that may induce alterations in heart rhythm (torsades de pointes):

• Antiarrhythmic agents such as quinidine, disopyramide, hydroquinidine, amiodarone, sotalol, dofetilide, and ibutilide.
• Some neuroleptics such as pimozide, sultopride, pipotiazine, sertindole, veralipride, chlorpromazine, levomepromazine, trifluoperazine, ciamemazine, sulpiride, haloperidol, droperidol, flufenazine, pipamperone, flupentixol, and zuclopenthixol (medications for the treatment of psychiatric diseases such as psychosis, schizophrenia, anxiety, etc.).
• Some antiparasitic medications such as halofantrine, lumefantrine, and pentamidine.
• Other medications:
• bepridil (medication for angina pectoris),
• cisapride (medication for gastrointestinal motility disorders),
• erythromycin intravenously, espiramycin intravenously, moxifloxacin (antibiotics),
• vincamine intravenously (medication that improves blood circulation at the cerebral level),
• mizolastine (medication for treating allergies),
• difemanil (medication for treating digestive tract spasms).

Combinations that require precautions:

• Medications that induce a decrease in heart frequency (bradycardia)(in particular, antiarrhythmic class Ia, beta-blockers, some antiarrhythmic class II, some calcium antagonists, cardiac glycosides, pilocarpine, cholinesterase inhibitors).

• Beta-blockers used in heart failure (heart problems)(bisoprolol, carvedilol, metoprolol, nebivolol).

• Agents that decrease potassium levels(diuretics that decrease potassium levels, stimulant laxatives, amphotericin B intravenously, glucocorticoids, cosyntropin).

Medications whose simultaneous administration should be taken into account:

• Antihypertensives(medications for treating high blood pressure): all.

• Medications that depress the central nervous system

Narcotics (analgesics, cough medications, opioid substitution therapy); barbiturates (medications used to produce sedation); benzodiazepines (due to their sedative effect, used for treating anxiety, insomnia, epilepsy, etc.); other non-benzodiazepine anxiolytics; hypnotics; neuroleptics; sedating antidepressants (amitriptyline, doxepin, mianserin, mirtazapine, trimipramine); sedating antihistamines H1; central-acting antihypertensives; other medications: baclofen, thalidomide, pizotifen.

• Beta-blockers(except esmolol, sotalol, and beta-blockers used in heart failure).

• Nitrate derivatives and related compounds(substances that contain nitrates in their composition: such as nitrate derivatives used in the treatment of angina pectoris symptoms, heart failure, etc.).

Keep in mind that these instructions may also apply to medications that have been used before or may be used later.

Taking Tiaprizal with food, drinks, and alcohol

Since alcohol can potentiate the sedative effect of tiaprida, it is not recommended to ingest alcoholic beverages or other medications that contain alcohol in their composition while taking this medication. Consuming alcohol while taking Tiaprizal can also cause an electrolyte imbalance (imbalance of minerals in the blood) and may cause a prolongation of the QT interval (alteration of heart frequency/rhythm) (see Warnings and precautions).

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy

Tiaprizal is not recommended during pregnancy or in women of childbearing age who do not use effective contraceptives.

If you use Tiaprizal during the last three months of pregnancy, your baby may experience tremors, increased muscle tone, drowsiness, agitation, breathing problems, and feeding disorders. If your baby develops any of these symptoms, consult your doctor.

Tiaprida used in the final phase of pregnancy may theoretically induce:

• manifestations such as tachycardia, hyperexcitability, abdominal distension, delayed meconium elimination,
• sedation.

Breastfeeding

You should not breastfeed during treatment with Tiaprizal. If you are taking Tiaprizal, consult your doctor about the best way to feed your baby.

Fertility

Tiaprizal may produce absence of menstruation or ovulation and may decrease fertility.

Driving and using machines

Tiaprida may produce symptoms such as drowsiness, dizziness, or alterations in vision, and decrease reaction capacity. These effects, as well as the disease itself, may hinder your ability to drive vehicles or operate machines. Therefore, do not drive, operate machines, or engage in other activities that require special attention until your doctor assesses your response to this medication.

3. How to take Tiaprizal

Follow exactly the administration instructions of this medicine indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

The dose to be administered should be adjusted for each patient.

The duration of this treatment is limited. Your doctor will indicate the duration of your treatment.

The route of administration of Tiaprizal 100 mg tablets is oral.

The dose to be administered is different depending on the disease you are suffering from:

Short-term treatment of agitation and aggression in alcoholic patients:

The recommended dose is 300 to 400 mg/day, i.e., 3 to 4 tablets/day, for 1 to 2 months.

Treatment in severe cases of Huntington's Chorea:

Initial dose: up to 1,200 mg/day, i.e., 12 tablets/day, divided into at least three doses, with a progressive reduction to the usual maintenance dose according to individual response.

Children:

The usual dose is 100 to 150 mg/day, i.e., 1 tablet to 1 and a half tablets per day, with a maximum of 300 mg/day (i.e., 3 tablets/day).

Elderly:The initial dose is 100 mg per day. The dose can be progressively increased up to a maximum of 300 mg per day if necessary.

Renal insufficiency:

In patients with altered kidney function, the dose should be reduced according to the doctor's instructions.

Hepatic insufficiency:

In patients with altered liver function, it is not necessary to reduce the dose.

If you think the effect of Tiaprizal is too strong or too weak, inform your doctor or pharmacist.

If you take more Tiaprizal than you should

If you have taken more Tiaprizal than you should, consult your doctor or pharmacist immediately.

Overdose can produce drowsiness, sedation, coma, decreased blood pressure, and extrapyramidal symptoms (tremors, increased muscle tone, decreased movement, hypersalivation, etc.). Cases of death have been reported, mainly when Tiaprizal is combined with other psychotropic agents (medications used to treat central nervous system diseases).

There is no specific antidote for tiaprida. Since tiaprida is moderately dialyzed, hemodialysis should not be used to eliminate the medication.

In case of overdose, appropriate support measures should be established, recommending close monitoring of vital functions and cardiac function control (due to the risk of QT interval prolongation and ventricular arrhythmias) until the patient recovers.

In case of severe extrapyramidal symptoms, anticholinergic agents should be administered.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone: 91.562.04.20, indicating the medication and the amount ingested.

If you forget to take Tiaprizal

Do not take a double dose to make up for forgotten doses.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Adverse effects have been grouped according to their frequency in accordance with the following classification:

• Very frequent: may affect more than 1 in 10 patients,
• Frequent: may affect up to 1 in 10 patients,
• Uncommon: may affect up to 1 in 100 patients,
• Rare: may affect up to 1 in 1,000 patients,
• Very rare: may affect up to 1 in 10,000 patients,
• Frequency not known: cannot be estimated from the available data.

Frequent (may affect up to 1 in 10 patients)

• Increased levels of prolactin in the blood, which can cause other disorders such as chest pain, breast growth and milk secretion, and increased glands (galactorrhea and gynecomastia), menstrual cycle disorders in women (dysmenorrhea, amenorrhea), and can rarely cause abnormal orgasm/impotence in men
• Dizziness/vertigo, headache
• Parkinsonism and related symptoms: tremor, increased muscle tone, slowing of movement, and increased salivation. Generally, these symptoms are reversible with the administration of an anticholinergic (e.g., biperiden)
• Somnolence/drowsiness, insomnia, agitation, indifference
• Asthenia (feeling of weakness)/fatigue.

Uncommon (may affect up to 1 in 100 patients)

• Early dyskinesia, uncontrolled movements (muscle spasm, torticollis, alteration of eye movement, inability to open the mouth) and inability to remain seated, calm. Generally, these symptoms are reversible with the administration of an anticholinergic (e.g., biperiden)
• Confusion, hallucinations
• Seizure, syncope
• Decreased blood pressure (hypotension), normally when standing up (orthostatic hypotension)
• Deep vein thrombosis
• Constipation
• Rash (including erythematous or nodular/irregular rash)
• Milk secretion from the breasts
• Absence of menstruation (amenorrhea)
• Abnormal orgasm
• Weight gain.

Rare (may affect up to 1 in 1,000 patients)

• Loss of consciousness
• Leukopenia (decrease in the number of white blood cells), neutropenia (decrease in the number of a type of white blood cells, neutrophils) and agranulocytosis (decrease in a type of white blood cells, granulocytes) (see "Warnings and Precautions")
• Decrease in sodium levels in the blood (hyponatremia), a disease called "inadequate secretion of antidiuretic hormone syndrome (SIHAD)"
• Acute dyskinesia (alteration of movements). Generally, these symptoms are reversible with the administration of antiparkinsonian medication (for the treatment of Parkinson's disease)
• After prolonged treatment periods (over 3 months), tardive dyskinesia has been reported, as is the case with all medications for the treatment of psychological disorders (neuroleptics), characterized by involuntary, rhythmic movements, mainly of the tongue and/or face. If these movements occur, consult a doctor and they will decide what measures to take. The administration of antiparkinsonian medication (for the treatment of Parkinson's disease) should not be used as an antidote, as it is ineffective or may even worsen the symptoms
• Like all neuroleptics, tiapride can cause malignant neuroleptic syndrome, a potentially fatal complication, characterized by fever of unknown origin and muscle rigidity (see section 2 "What you need to know before taking Tiaprizal")
• Prolongation of the QT interval, ventricular arrhythmias such as torsades de pointes, ventricular tachycardia (acceleration of heart rate), which could result in ventricular fibrillation or cardiac arrest and sudden death (see also section 2 "Warnings and Precautions" and "Use of Tiaprizal with other medications")
• Blood clots in the veins, mainly in the legs (with inflammation, pain, and redness in the legs) that can travel through the blood vessels to the lungs, causing chest pain and difficulty breathing; if you notice these symptoms, consult a doctor immediately (see section 2 "What you need to know before taking Tiaprizal"); sometimes pulmonary embolism can cause death
• Inflammation in the lungs (pneumonia) due to aspiration caused by food or liquid particles entering the lungs, altered breathing (respiratory depression)
• Intestinal obstruction (including a type of obstruction called ileus)
• Increased liver enzymes
• Rash (urticaria)
• Elevation of creatine phosphokinase levels in the blood, muscle weakness, and/or muscle pain (rhabdomyolysis)
• Breast growth and pain
• Milk secretion from the breasts (galactorrhea)
• Increased breast tissue in men (gynecomastia)
• Impotence (erectile dysfunction).

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

• Withdrawal syndrome in newborns (see "Pregnancy, Breastfeeding, and Fertility")
• Falls, especially in elderly patients.

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that does not appear in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Tiaprizal

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

Do not use this medicine after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

Store below 30°C.

Medicines should not be disposed of through wastewater or household waste. Deposit the packaging and any unused medicines in the SIGRE Point at the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and any unused medicines. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Tiaprizal 100 mg Tablets

• The active ingredient is tiapride. Each tablet contains 100 mg of tiapride base, which is equivalent to 111.10 mg of tiapride hydrochloride.
• The other ingredients are mannitol (E-421), microcrystalline cellulose, povidone, colloidal silica, and magnesium stearate.

Appearance of the Product and Package Contents

White, round, flat tablets with a cross on one side and the engraving "T100" on the other side.

The tablet can be divided into equal doses.

Each package contains 20 or 24 tablets.

Other Presentations:

• Tiaprizal 100 mg injectable solution, packaging with 12 ampoules of 2 ml.
• Tiaprizal 12 mg/ml oral drops in solution, packaging with a 60 ml bottle and a dosing syringe.

Marketing Authorization Holder and Manufacturer

Manufacturer:

Famar Health Care Services Madrid, S.A.U.

Avda. de Leganés, 62

28923 Alcorcón (Madrid)

Spain

or

Delpharm Dijon

6 Boulevard de l’Europe

21800 Quetigny

France

Date of the Last Revision of this Prospectus:September 2023

Detailed information about this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/