Tiaprizal 12 mg/ml oral solution drops

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Tiaprizal 12 mg/ml oral drops solution

Tiapride

Package leaflet contents:

1. What Tiaprizal is and what it is used for
2. What you need to know before taking Tiaprizal
3. How to take Tiaprizal
4. Possible side effects
5. How to store Tiaprizal
6. Contents of the pack and other information

1. What Tiaprizal is and what it is used for

Tiaprizal belongs to a group of medicines called antipsychotics.

It is indicated for the treatment of severe cases of Huntington's chorea.

2. What you need to know before starting Tiaprizal

Do not take Tiaprizal

• if you are allergic to tiapride or to 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 mammary glands), for example, pituitary prolactinomas or breast cancer,
• if you have phaeochromocytoma (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 taking Tiaprizal:

• if you have bradycardia (slowing of the heart rate), low blood potassium levels, QT interval prolongation (which may lead to ventricular arrhythmias/heart rhythm disturbances), or are being treated with any medicine that may promote any of these conditions (see "Use of Tiaprizal with other medicines"),
• if you develop fever of unknown origin, treatment with Tiaprizal should be discontinued, as this may indicate neuroleptic malignant syndrome, a potentially life-threatening condition characterized by high body temperature, muscle rigidity, and nervous system disturbances (see "Possible side effects"). Cases with atypical features such as absence of muscle rigidity or hypertonia and lower fever have been observed,
• if you develop fever and/or muscle rigidity during treatment with Tiaprizal, particularly if you are already taking any other medicine for mental health disorders,
• if you have or have had alcohol-related problems (see Taking Tiaprizal with food, drinks and alcohol),
• if you have Parkinson's disease, you should not use this medicine except in exceptional cases,
• if you have risk factors for stroke (vascular disease affecting arteries in or leading to the brain),
• in elderly patients with psychosis associated with dementia who are being treated with antipsychotics (as they have an increased risk of death),
• in patients with risk factors for venous thromboembolism (blockage of a blood vessel by a blood clot) (see "Possible side effects"),
• if you have or have had epilepsy, since the group of drugs to which Tiaprizal belongs may increase the risk of epileptic seizures,
• if you have renal impairment (kidney function disorder), as the dose of Tiaprizal should be reduced,
• if the medicine is to be administered to elderly patients, as tiapride may pose 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 thoroughly studied in this patient group,
• if you have personal or family history of breast cancer, you should be monitored by your doctor during treatment with tiapride. Tiapride may increase levels of prolactin (hormone that stimulates milk production in mammary glands),
• if you have leukopenia (reduced number of white blood cells), neutropenia (reduced number of a type of white blood cells, neutrophils), or agranulocytosis (reduced number of a type of white blood cells, granulocytes), as well as infections or fever of unknown origin, inform your doctor, as this may indicate a blood dyscrasia (blood disorder) (see "Possible side effects").

Consult your doctor or pharmacist if any of these symptoms occur.

Use of Tiaprizal with other medicines

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

Specifically, inform your doctor if you are taking any of the following medicines:

Combinations that are contraindicated:

Except in patients with Parkinson's disease, concomitant administration of dopaminergic agonists (cabergoline, quinagolide) with neuroleptics should be avoided.

Combinations not recommended:

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

• Levodopa (a medicine used to treat 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 (a medicine used to relieve pain).

• Medicines that may cause disturbances 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, cyamemazine, sulpiride, haloperol, droperidol, flufenazine, pipamperone, flupentixol, zuclopenthixol (medicines used to treat psychiatric disorders such as psychosis, schizophrenia, anxiety, etc.).

• Some antiparasitic medicines such as halofantrine, lumefantrine, and pentamidine.

  • Other medicines:
  • bepridil (a medicine for angina pectoris),
  • cisapride (a medicine for gastrointestinal motility disorders),
  • intravenous erythromycin, intravenous spiramycin, moxifloxacin (antibiotics),
  • intravenous vincamine (a medicine that improves cerebral blood circulation),
  • mizolastine (a medicine used to treat allergy),
  • difemethilane (a medicine used to treat digestive tract spasms).

Combinations requiring precautions in use:

• Medicines that cause a decrease in heart rate (bradycardia) (particularly 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 reduce potassium levels (potassium-depleting diuretics, stimulant laxatives, intravenous amphotericin B, glucocorticoids, cosyntropin).

Medicines whose concomitant administration should be taken into account:

• Antihypertensives (medicines used to treat high blood pressure): all.

• Central nervous system depressants

Narcotics (analgesics, cough medicines, opioid replacement therapy); barbiturates (medicines used to induce sedation); benzodiazepines (due to their sedative effect, used to treat anxiety, insomnia, epilepsy, etc.); other non-benzodiazepine anxiolytics; hypnotics; neuroleptics; sedative antidepressants (amitriptyline, doxepine, mianserin, mirtazapine, trimipramine); sedative H1 antihistamines; centrally acting antihypertensives; 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: for example, nitrate derivatives used to treat symptoms of angina pectoris, heart failure, etc.).

Please note that these instructions may also apply to medicines that have been used previously or may be used in the future.

Taking Tiaprizal with food, drinks and alcohol

Since alcohol may enhance the sedative effect of tiapride, consumption of alcoholic beverages or other medicines containing alcohol is not recommended while taking this medicine. Alcohol consumption while taking Tiaprizal may also cause electrolyte imbalance (imbalance of minerals in the blood) and may lead to QT interval prolongation (disturbance in heart rhythm) (see Warnings and precautions).

Pregnancy, breastfeeding and fertility

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

Pregnancy

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

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

Tiapride used in the late phase of pregnancy may theoretically, particularly at high doses, cause:

• symptoms such as tachycardia, hyperexcitability, abdominal distension, delayed meconium passage,
• 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 absence of ovulation and may reduce fertility.

Driving and use of machines

Tiapride may cause symptoms such as drowsiness, dizziness, or visual disturbances, and may reduce reaction ability. These effects, as well as the underlying illness itself, may impair your ability to drive or operate machinery. Therefore, do not drive or operate machinery or engage in other activities requiring special attention until your doctor has assessed your response to this medicine.

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

It may cause allergic reactions (possibly delayed) because it contains as excipients methylparahydroxybenzoate (E-218) and propylparahydroxybenzoate (E-216).

This medicine contains less than 1 mmol of sodium (23 mg) per 1 ml of solution; i.e., essentially "sodium-free".

3. How to take Tiaprizal

Follow exactly the instructions for use of this medicine as given by your doctor. If in doubt, consult your doctor or pharmacist again.

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

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

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

Treatment in severe cases of Huntington's chorea:

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 administration of this dosing regimen in adults, other more appropriate presentations of this medicine are available.)

Children:

The normal dose is 100 to 150 mg/day (8.33 to 12.5 ml/day), with a maximum of 300 mg/day (25 ml/day), divided into 3–4 doses.

1 ml = 24 drops = 12 mg of tiapride
1 drop = 0.5 mg of tiapride

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

Renal impairment:

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

Hepatic impairment:

In patients with impaired liver function, dose reduction is not necessary.

If you think that 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, contact your doctor or pharmacist immediately.

Overdose may cause somnolence, sedation, coma, decreased blood pressure, and extrapyramidal symptoms (tremor, increased muscle tone, reduced movement, hypersalivation, etc.). Cases of death have been reported, mainly when Tiaprizal is combined with other psychotropic agents (medicines used to treat diseases of the central nervous system).

There is no specific antidote for tiapride. Since tiapride is moderately dialyzable, hemodialysis should not be used to remove the drug.

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

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

In case of overdose or accidental ingestion, contact your doctor or pharmacist immediately or call the Toxicology Information Service at telephone: 91.562.04.20, indicating the medicine 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 may produce adverse effects, although not everyone will experience them.

Adverse effects have been grouped according to their frequency using the following classification:

• very common: may affect more than 1 in 10 people,
• common: may affect up to 1 in 10 people,
• uncommon: may affect up to 1 in 100 people,
• rare: may affect up to 1 in 1,000 people,
• very rare: may affect up to 1 in 10,000 people,
• 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 may cause other disorders such as breast pain, breast enlargement and milk secretion, and enlargement of the glands (galactorrhea and ginecomastia), menstrual cycle disorders in women (dysmenorrhea, amenorrhea), and may rarely cause abnormal orgasm/impotence in men
• Dizziness/vertigo, headache
• Parkinsonism and related symptoms: tremor, increased muscle tone, slowed movement, and increased salivation. These symptoms are generally reversible with 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, eye movement disorders, inability to open the mouth), and inability to remain seated and calm. These symptoms are generally reversible with administration of an anticholinergic (e.g., biperiden)
• Confusion, hallucinations
• Seizure, syncope
• Decreased blood pressure (hypotension), usually upon standing (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 (reduced number of white blood cells), neutropenia (reduced number of a type of white blood cells, neutrophils), and agranulocytosis (reduction in a type of white blood cells, granulocytes) (see “Warnings and precautions”)
• Decreased sodium levels in the blood (hyponatremia), a condition known as “syndrome of inappropriate antidiuretic hormone secretion (SIADH)”
• Acute dyskinesia (movement disorders). These symptoms are generally reversible with administration of anti-Parkinson medication
• After prolonged periods of treatment (longer than 3 months), tardive dyskinesia has been reported, as with all medications used to treat psychiatric disorders (neuroleptics). This is characterized by involuntary, rhythmic movements, mainly of the tongue and/or face. If these movements occur, consult your doctor, who will decide on the necessary measures. Anti-Parkinson medication should not be used as an antidote, as it is ineffective and may even worsen symptoms
• As with all neuroleptics, tiapride may cause neuroleptic malignant syndrome, a potentially life-threatening condition characterized by fever of unknown origin and muscle rigidity (see section 2 “What you need to know before starting Tiaprizal”)
• QT interval prolongation, ventricular arrhythmias such as torsades de pointes, ventricular tachycardia (accelerated heart rate), which could lead to ventricular fibrillation or cardiac arrest and sudden death (see also section 2 “Warnings and precautions” and “Use of Tiaprizal with other medicines”)
• Blood clots in the veins, mainly in the legs (with swelling, pain, and redness in the legs), which may travel through blood vessels to the lungs causing chest pain and difficulty breathing. If you experience these symptoms, consult your doctor immediately (see section 2 “What you need to know before starting Tiaprizal”). Sometimes, pulmonary embolism can be fatal
• Inflammation of 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)
• Elevated levels of creatine phosphokinase in the blood, muscle weakness and/or muscle pain (rhabdomyolysis)
• Breast enlargement and pain
• Milk secretion from the breasts (galactorrhea)
• Enlargement of the mammary glands in men (gynecomastia)
• Impotence (erectile dysfunction)

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

• Withdrawal syndrome in newborns (see “Pregnancy, breastfeeding and fertility”)
• Falls, especially in elderly patients

Reporting of adverse reactions

If you experience any type of adverse reaction, consult your doctor or pharmacist, even if it is a possible adverse reaction not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Medicinal Products: https://www.notificaram.es. By reporting adverse reactions, you can help provide 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 expiry date stated on the packaging after EXP. The expiry date is the last day of the month indicated.

Store below 25 ºC.

Medicines should not be disposed of via wastewater or household waste. Dispose of unused medicines and their containers at the SIGRE collection point at your pharmacy. If you are in doubt, ask your pharmacist how to dispose of medicines and containers you no longer need. This will help protect the environment.

6. Contents of the package and other information

Composition of Tiaprizal 12 mg/ml oral drops solution

• The active substance is tiapride. Each 1 ml of oral solution contains 12 mg of tiapride base, equivalent to 13.33 mg of tiapride hydrochloride.
• The other components are sodium saccharin (E-954), methyl p-hydroxybenzoate (E-218), propyl p-hydroxybenzoate (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 pack

Presented as a colorless and transparent liquid.

Each container holds 60 ml of solution and includes a dosing syringe.

Other presentations:

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

Marketing Authorization Holder and Manufacturer

Manufacturer responsible:

Sofarimex - Indústria Química e Farmacêutica, S.A.

Av. das Indústrias - Alto do Colaride

Agualva

2735-213 - Cacém

Portugal

Date of the most recent review of this leaflet: September 2023

Detailed information on this medicinal product is available on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS): http://www.aemps.gob.es/