TIAPRIZAL 100 mg INJECTABLE SOLUTION

2. What you need to know before you use Tiaprizal

Do not use Tiaprizal

• if you are allergic to tiapride 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 "Using Tiaprizal with other medicines").

Warnings and precautions

Talk to your doctor or pharmacist before you start taking Tiaprizal:

• if you have bradycardia (slow heart rate), low potassium levels in the blood, prolonged QT interval (can induce ventricular arrhythmias/heart rate alteration) or are being treated with any medication that favors any of these circumstances (see "Using Tiaprizal with other medicines"),
• if you develop a fever of unknown origin, you should discontinue treatment with Tiaprizal 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"). Atypical cases have been observed, such as the absence of muscle rigidity or hypertonia and lower fever,
• if you develop fever and/or muscle rigidity during treatment with Tiaprizal, especially if you are already taking any other medication for mental health treatment,
• if you have or have had problems with alcohol (see "Using Tiaprizal with food, drinks, and alcohol"),
• if you have Parkinson's disease, you should not use this medicine unless in exceptional cases,
• if you have risk factors for stroke (vascular disease affecting 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 that Tiaprizal belongs to may favor the appearance of epileptic seizures,
• if you have kidney failure (alteration of kidney function), as the dose of Tiaprizal should be decreased,
• if the medicine is administered to elderly patients, as tiapride may present a risk of decreased level of consciousness and coma in these patients, so it should be used with caution,
• if the medicine is to be administered to children, as tiapride 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 tiapride. Tiapride 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 disorder (blood alteration) (see "Possible side effects").

Talk to your doctor or pharmacist if you experience such symptoms.

Using Tiaprizal with other medicines

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

In particular, tell your doctor if you are using any of the following medicines:

Combinations that are contraindicated:

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

Combinations that are not recommended:

• Alcohol(see "Using 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).

• Medicines that may induce heart rhythm alterations (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, zuclopenthixol (medicines 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),
• intravenous erythromycin, intravenous spiramycin, moxifloxacin (antibiotics),
• intravenous vincamine (medication that improves blood circulation to the brain),
• mizolastine (medication for treating allergies),
• difemanil (medication for treating digestive system spasms).

Combinations that require precautions:

• Medicines that induce a decrease in heart rate (bradycardia)(in particular, class Ia antiarrhythmics, beta-blockers, some class II antiarrhythmics, 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(potassium-decreasing diuretics, stimulant laxatives, intravenous amphotericin B, glucocorticoids, cosyntropin).

Medicines whose simultaneous administration should be taken into account:

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

• Medicines that depress the central nervous system

Narcotics (analgesics, cough medicines, opioid substitution therapy); barbiturates (medicines used to produce sedation); benzodiazepines (for 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 after.

Using Tiaprizal with food, drinks, and alcohol

Since alcohol can enhance the sedative effect of tiapride, it is not recommended to consume alcoholic beverages or other medications that contain alcohol in their composition while using this medicine. Consuming alcohol while taking Tiaprizal can also cause an electrolyte imbalance (mineral imbalance in the blood) and may cause a prolongation of the QT interval (heart rate/frequency alteration) (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 using this medicine.

Pregnancy

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

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

Tiapride used in the final phase of pregnancy may theoretically induce, especially at high doses:

• 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 cause absence of menstruation or ovulation and may decrease fertility.

Driving and using machines

Tiapride may cause symptoms such as drowsiness, dizziness, or vision changes, and may decrease your reaction ability. These effects, as well as the disease itself, may impair 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 medicine.

Important information about some of the ingredients of Tiaprizal 100 mg Solution for Injection

This medicine contains less than 1 mmol of sodium (23 mg) per 2 ml ampoule of solution for injection; it is essentially "sodium-free".

3. How to use 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 Solution for Injection is intramuscular (IM) or intravenous (IV).

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 per day (three to four ampoules per day) for 1 to 2 months.

Treatment of severe cases of Huntington's Chorea:

Initial dose: up to 1,200 mg/day (12 ampoules per day) with progressive reduction to the usual maintenance dose according to individual response.

In the case of higher doses, daily doses should be administered in injections spaced 4 or 6 hours apart.

Children:

The recommended dose is 1 to 1.5 ampoules per day, i.e., 100 to 150 mg per day, with a maximum of 3 ampoules per day, i.e., 300 mg per 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.

Kidney failure:

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

Liver failure:

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, tell your doctor or pharmacist.

If you use more Tiaprizal than you should

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

Overdose can cause 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 (medicines used to treat central nervous system diseases).

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

In case of overdose, appropriate supportive measures should be initiated, with 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 medicine and the amount administered or ingested.

If you forget to use Tiaprizal

Do not use 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. These symptoms are generally 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. These symptoms are generally 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")
• Decreased sodium level in the blood (hyponatremia), a disease called "inadequate secretion of antidiuretic hormone syndrome (SIHAD)"
• Acute dyskinesia (movement disorder). These symptoms are generally reversible with the administration of antiparkinsonian medication (for the treatment of Parkinson's disease)
• After prolonged treatment periods (over 3 months), late 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
• Lung inflammation (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)
• Chest 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 is not listed 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. Conservation 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.

No special storage conditions are required.

Medicines should not be thrown away through the sewers or in the trash. Deposit the packaging and unused medicines in the SIGRE Point of the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and unused medicines. This way, you will help protect the environment.

6. Packaging Contents and Additional Information

Composition of Tiaprizal 100 mg injectable solution

• The active ingredient is tiapride. Each 2 ml ampoule contains 100 mg of tiapride base, equivalent to 111.10 mg of tiapride hydrochloride.
• The other components are sodium chloride and water for injectable preparations.

Appearance of the Product and Packaging Contents

It is presented as a colorless or practically colorless and transparent liquid.

Each packaging contains 12 ampoules of 2 ml.

Other Presentations:

• Tiaprizal 100 mg tablets, packaging with 20 or 24 tablets.
• Tiaprizal 12 mg/ml oral drops in solution, packaging with a 60 ml bottle and a dosing syringe.

Marketing Authorization Holder and Manufacturer

Manufacturer:

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/