Package Leaflet: Information for the User

Tiaprizal 12 mg/ml Oral Solution

Tiaprida

Tiaprizal belongs to a group of medications known as antipsychotics.

It is indicated for thetreatment of severe cases of Huntington's Disease.

Do not take 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 (a hormone that stimulates milk production in the mammary glands), for example, pituitary prolactinomas and breast cancer,
• if you have pheochromocytoma (a tumor of the adrenal gland),
• if you are being treated with levodopa or other dopaminergic medicines (see “Use of Tiaprizal with other medicines”).

Warnings and precautions

Consult your doctor or pharmacist before starting to take Tiaprizal:

• if you have bradycardia (slowing of the heart rate), low levels of potassium in the blood, prolongation of the QT interval (may induce ventricular arrhythmias/alteration of heart rate) or are being treated with any medicine that favors any of these circumstances (see “Use of Tiaprizal with other medicines”),
• if a fever of unknown origin appears, discontinue treatment with Tiaprizal as it could be the 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 hypertension and lower fever have been observed.
• if a fever and/or muscle rigidity appear during treatment with Tiaprizal and particularly if you are already taking any other medicine 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, do not use this medicine except in exceptional cases,
• if you have risk factors for suffering a stroke (vascular disease that affects the arteries of the brain or that reach the brain),
• in elderly patients with dementia-related psychosis, who are being treated with antipsychotics (since they have a higher risk of death),
• in patients with risk factors for venous thromboembolism (obstruction of a blood vessel by a clot) (see “Possible side effects”),
• if you have or have had epilepsy, since the group of medicines to which Tiaprizal belongs may favor the appearance of seizures,
• if you have renal insufficiency (alteration of kidney function), since the dose of Tiaprizal must be reduced,
• if the medicine is administered to elderly patients, since tiapride may present a risk of decreased level of consciousness and coma in these patients, so it must be used with caution,
• if the medicine is to be administered to children, since tiapride has not been thoroughly 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 (a 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 cell, neutrophils) and agranulocytosis (decrease in a type of white blood cell, granulocytes), as well as unknown origin infections or fever, inform your doctor, as it could be a hematological disorder (blood disorder) (see “Possible side effects”).

Consult your doctor or pharmacist if such symptoms appear.

Use of Tiaprizal with other medicines

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

Specifically, inform 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, simultaneous administration of dopamine agonist medicines (cabergoline, quinagolide) with neuroleptics should be avoided.

Combinations that are not recommended:

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

• Levodopa(medicine for Parkinson's disease treatment).

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

• Metadona(medicine for pain relief).

• Medicines 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, sulpiride, 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 medicines such as halofantrine, lumefantrine, and pentamidine.

• Other medicines:
• bepridil (medicine for angina pectoris),
• cisapride (medicine for gastrointestinal motility disorders),
• intravenous erythromycin, spiramycin, moxifloxacin (antibiotics),
• intravenous vincamine (medicine that improves cerebral blood circulation),
• mizolastine (medicine for allergy treatment),
• difemanil (medicine for treating spasms of the digestive apparatus).

Combinations that require caution:

• Medicines that induce bradycardia (slowing of the heart rate)(particularly class Ia antiarrhythmic agents, beta-blockers, some class II antiarrhythmic agents, 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, laxatives, amphotericin B intravenously, glucocorticoids, cosyntropin).

Medicines whose simultaneous administration should be taken into account:

• Anti-hypertensive medicines(medicines for treating high blood pressure): all.

• Medicines that depress the central nervous system

Narcotics (analgesics, cough medicines, opioid replacement therapy); barbiturates (used to produce sedation); benzodiazepines (used for anxiety, insomnia, epilepsy, etc.); other non-benzodiazepine anxiolytics; hypnotics; neuroleptics; sedative antidepressants (amitriptyline, doxepin, mianserin, mirtazapine, trimipramine); H1 antihistamines; anti-hypertensive medicines with central action; other medicines: baclofen, thalidomide, pizotifen.

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

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

Be aware that these instructions may also apply to medicines that have been used before or may be used afterwards.

Taking Tiaprizal with food, drinks, and alcohol

Since alcohol may potentiate the sedative effect of tiapride, it is not recommended to consume alcoholic beverages or other medicines containing alcohol while taking this medicine. The consumption of alcohol while taking Tiaprizal may also cause electrolyte imbalance (imbalance of minerals in the blood) and may cause prolongation of the QT interval (alteration of heart rate/frequency) (see Warnings and precautions).

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or intend to become pregnant, consult your doctor or pharmacist before using this medicine.

Pregnancy

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

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

Tiapride used in the final stages of pregnancy may theoretically, and particularly at high doses:

- manifest 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 amenorrhea (absence of menstruation) or anovulation (absence of ovulation) and may decrease fertility.

Driving and operating machinery

Tiapride may cause symptoms such as drowsiness, dizziness, or visual disturbances, and may decrease your reaction time. These effects, as well as the underlying disease, may make it difficult for you to drive vehicles or operate machinery. Therefore, do not drive, operate machinery, or engage in other activities that require special attention until your doctor evaluates your response to this medicine.

Important information about some of the components of Tiaprizal 12 mg/ml oral drops in solution

It may cause allergic reactions (possibly delayed) because it contains parahydroxybenzoic acid methyl ester (E-218) and parahydroxybenzoic acid propyl ester (E-216) as excipients.

This medicine contains less than 1 mmol of sodium (23 mg) per 1 ml of solution; it is essentially “sodium-free”.

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

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

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

The administration route of Tiaprizal 12 mg/ml oral drops in solution is oral.

Treatment in severe cases of Huntington's disease:

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

(For the administration of this dosing regimen in adults, other more suitable presentations of this medication are available).

Children:

The usual dose is 100 to 150 mg/day (8.33 to 12.5 ml/day), with a maximum of 300 mg/day (25 ml/day) distributed in 3-4 doses.

1 ml = 24 drops = 12 mg of tiapride

1 drop = 0.5 mg of tiapride

Older adults:The initial dose is 100 mg/day. The dose can be increased progressively to a maximum of 300 mg/day if necessary.

Renal insufficiency:

In patients with kidney function impairment, the dose must be reduced according to your doctor's instructions.

Liver insufficiency:

In patients with liver function impairment, the dose does not need to be reduced.

If you estimate that the action 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 may cause drowsiness, sedation, coma, decreased blood pressure, and extrapyramidal symptoms (tremor, 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 tiapride. Since tiapride is dialyzed moderately, hemodialysis should not be used to eliminate the medication.

In case of overdose, appropriate supportive measures should be initiated, 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 Toxicological Information Service, phone: 91.562.04.20, indicating the medication and the amount ingested.

If you forgot to take Tiaprizal:

Do not take a double dose to compensate for the missed doses.

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

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

• Very common: may affect more than 1 in 10 patients,
• Common: 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 available data.

Common (may affect up to 1 in 10 patients)

• Increased levels of prolactin in the blood, which may cause other disorders such as chest pain, milk production and secretion by the breasts and increased gland size (galactorrhea and ginecomastia), menstrual cycle disorders in women (dysmenorrhea, amenorrhea), and may produce abnormal orgasm/impotence in men on rare occasions
• Dizziness/dizziness, headache
• Parkinsonism and related symptoms: tremor, increased muscle tone, slowed movement, and increased salivation. These symptoms are generally reversible with the administration of an anticholinergic (e.g. biperideno)
• Drowsiness/drowsiness, insomnia, agitation, indifference
• Weakness/asthenia (sensation of weakness)/fatigue.

Uncommon (may affect up to 1 in 100 patients))

• Early discinesia, 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. biperideno)
• Confusion, hallucinations
• Convulsion, syncope
• Decreased blood pressure (hypotension), usually when standing (orthostatic hypotension)
• Deep vein thrombosis
• Constipation
• Rash (including erythematous or nodular/irregular rash)
• Milk production by the breasts
• Absence of menstruation (amenorrhea)
• Abnormal orgasm
• Weight gain.

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

• Loss of consciousness
• Leucopenia (decreased white blood cell count), neutropenia (decreased neutrophil count) and agranulocytosis (decreased granulocyte count) (see "Warnings and precautions")
• Decreased sodium levels in the blood (hyponatremia), a condition known as "inappropriate antidiuretic hormone secretion syndrome (SIHAD")
• Acute discinesia (alteration of movement). These symptoms are generally reversible with the administration of antiparkinsonian medication (for the treatment of Parkinson's disease)
• After prolonged periods of treatment (over 3 months), tardive discinesia has been reported, as 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. 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, tiaprida can cause neuroleptic malignant syndrome, a potentially fatal complication, characterized by fever of unknown origin and muscle rigidity (see section 2 "What you need to know before starting to take Tiaprizal")
• Prolongation of the QT interval, ventricular arrhythmias such as torsades de pointes, ventricular tachycardia (accelerated 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")
• Thrombi 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 starting to take Tiaprizal") in some cases, pulmonary embolism can cause death
• Pneumonia caused by aspiration of food or liquid particles into 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 production by the breasts (galactorrhea)
• Enlargement of breast tissue in men (ginecomastia)
• Impotence (erectile dysfunction).

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

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

Reporting of side effects

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

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

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

Store below 25 °C.

Medicines should not be disposed of through drains or in the trash. Dispose of packaging and medications you no longer need at the SIGRE collection point of the pharmacy. If in doubt, ask your pharmacist how to dispose of packaging and medications you no longer need. In this way, you will help protect the environment.

Composition of Tiaprizal 12 mg/ml oral drops in solution

* The active ingredient is tiapride. Each 1 ml of oral solution contains 12 mg of tiapride base which isequivalent to 13.33 mg of tiapride hydrochloride.

* The other components are sodium saccharin (E-954), methyl parahydroxybenzoate (E-218), propyl parahydroxybenzoate (E-216), purified water.

1 ml of oral solution = 24 drops = 12 mg of tiapride base (13.33 mg of tiapride hydrochloride)

1 drop = 0.5 mg of tiapride

Appearance of the product and contents of the packaging

It is presented in the form of a colorless and transparent liquid.

Each package contains 60 ml of solution and a dosing syringe.

Other presentations:

• Tiaprizal 100 mg injectable solution. Package with 12 ampoules of 2 ml.
• Tiaprizal 100 mg tablets. Package with 20 or 24 tablets.

Holder of the marketing authorization and responsible for manufacturing

Responsible for manufacturing:

Sofarimex - Indústria Química e Farmacêutica, S.A.

Av. das Indústrias -Alto do Colaride

Agualva

2735-213 - Cacém

Portugal

Last review date of this prospectus:September 2023

The detailed information of this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/