Tiapridal - instructions for use, dose, side effects, contraindications

Active substanceTiaprideTiapride

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Tiapride

pills inwards

ORGANICS, JSC Russia

Tiapride

solution w / m in / in

ORGANICS, JSC Russia

Tiapridal®

pills inwards

Sanofi-Aventis France France

Tiapridal®

solution w / m in / in

Sanofi-Aventis France France

Dosage form: & nbsppills

Composition:

1 tablet contains:

active substance: thiapride

hydrochloride - 111.1 mg (in terms of tiapride - 100 mg).

auxiliary substances:

mannitol - 30.0 mg, cellulose

microcrystalline - 14.0 mg,

povidone - 11.0 mg, silicon dioxide colloidal water - 10.5 mg, magnesium stearate - 3.4 mg.

Description:

White or kremovato-white round flat tablets with beveled edges on both sides, with a cross-shaped risk on one side and engraving "T 100" on the other, odorless or with a faint smell.

Pharmacotherapeutic group:antipsychotic (neuroleptic) remedy

ATX: & nbsp

N.05.A.L.03 Tiapride

Pharmacodynamics:

An antipsychotic agent is an atypical neuroleptic that selectively blocks subtypes D2 and D3 of dopamine receptors in vitro without any significant affinity for the receptors of the major central neurotransmitters (including serotonin, noradrenaline, histamine). Studies of neurochemical and behavioral responses, conducted in vivo, confirmed these properties of thiaprid, showing the presence of antidopaminergic effects in the absence of significant sedation, catalepsy and decreased cognitive abilities.

Tiapride is able to act on dopamine receptors previously sensitized to dopamine with any other antipsychotics, and its antidiskinetic effects are associated with this.

In some experimental models of animal stress, including alcohol abstinence in mice and primates, the anxiolytic activity of thiaprid was confirmed.

Tiaprid did not show the formation of physical or psychological dependence.

This atypical pharmacodynamic profile explains the clinical efficacy of thiapride in many disorders, including hyperdophaminergic conditions such as dyskinesia and psycho-behavioral disorders observed in patients with dementia or in alcohol abusers, with fewer neurological side effects than typical neuroleptics.

Tiapride has pronounced analgesic (both with interoceptive and exteroceptive pain), antiemetics due to blockade of dopamine receptors in the trigger zone of the vomiting center, hypothermic action due to blockade of hypothalamus dopamine receptors.

Pharmacokinetics:

Absorption of thiaprid is fast. After ingestion of 200 mg of thiaprid, the maximum plasma concentration in the plasma is reached in 1 hour and is 1.3 μg / ml.

Bioavailability is 75%. When taking tablets immediately before meals, bioavailability increases by 20%, and the maximum concentration in plasma - by 40%. Absorption in the elderly is slowing down.

Distribution in the body occurs quickly (less than 1 hour). Penetrates through the blood-brain barrier and through the placenta without accumulation. The volume of distribution is 1.43 l / kg. The animals were noted for penetration of the drug into breast milk, with a concentration ratio of 1.2: 1 in milk and in blood.

It does not bind to plasma proteins, it binds very weakly to erythrocytes. Tiapride Metabolized slightly (up to 15%), metabolites are mostly inactive. No conjugated metabolites were detected. 70% of the administered dose is found in the urine unchanged. The plasma elimination half-life is 2.9 hours for women and 3.6 hours for men. Excretion occurs mainly by the kidneys by glomerular filtration and tubular secretion, renal clearance is 330 ml / minute.

In patients with impaired renal function, excretion depends on the creatinine clearance, with a decrease in which the excretion of thiaprid slows (see "Method of administration and dose").

Indications:

Have of adults

- Cupping of the psychomotor exciting and aggressive states, especially when chronic alcoholism or elderly patients.

Have adults and children over 6 years

- Different types of chorea, syndrome Gilles de la Tourette.

In children older than 6 years:

Disorders of behavior with agitation and aggression.

Contraindications:

Hypersensitivity to tiapridu or other components of the drug.
Diagnosed or suspects prolactin-dependent tumors, for example, pituitary prolactinoma and breast cancer.
Pheochromocytoma, suspicion of pheochromocytoma.
Children under 6 years of age (risk of suffocation if the pill enters the respiratory tract).
The period of breastfeeding (see the section on "Application during pregnancy and during the breast
Simultaneous administration of levodopa (see "Interaction with other medicinal products ").
Simultaneous reception cabergoline, quinagolide (see "Interaction with other drugs").
Simultaneous reception cabergoline, quinagolide (see section "Interaction with other drugs").
It is not recommended to use the drug in Parkinson's disease (except in cases of urgent need for tiaprid, see the sections "With caution", "Interaction with other medicines", "Special instructions").

Carefully:Have patients with predisposing factors for the development of arrhythmias (with bradycardia less than 55 beats per minute, with electrolyte disorders, in particular, hypokalemia, hypomagnesemia, congenital lengthening of the interval QT; with concomitant therapy with drugs capable of producing a pronounced bradycardia (less than 55 beats per minute), electrolyte disturbances, slow intracardiac conduction or lengthen the interval QT), as tiapride can extend the interval QT and increase the risk of developing severe ventricular arrhythmias, including the development of ventricular pirouette tachycardia (see "Interactions with other drugs", "Special instructions").

In patients with Parkinson's disease receiving dopamine agonists receptors (amantadine, apomorphine, bromocriptine, entacapone, lisuride, pergolide, piribedil, ropinirole, selegiline), if there is an urgent need for tiapride (see "Interactions with other drugs", "Special instructions").

In patients with severe cardiovascular diseases (due to the possibility of increasing ischemic disorders with a decrease in blood pressure).

In elderly patients (increased risk of sedation, orthostatic

hypotension).

In elderly patients with dementia (see section "Special instructions").

In patients with risk factors for stroke (see section "Special instructions").

In patients with renal disease insufficiency (required correction of the dosing regimen, section "Method of application and dose ").

In patients with epilepsy (antipsychotics may lower threshold of convulsive activity, although this effect in tiaprid is not studied).

In patients with risk factors development of thromboembolism (see section "Special instructions"), In patients who have a history (including family history) of breast cancer (see section "Special instructions").

Children (insufficient data on use of the drug in this category of patients).

In adolescents during the period of sexual maturation (because of the possibility development of undesirable effects from the endocrine system, see the "Side effect" section).

- During pregnancy (see section "Application in pregnancy and in the period of breastfeeding ").

- With the simultaneous use of medicines containing ethanol (see section "Interaction with other drugs").

Pregnancy and lactation:Pregnancy.

Studies conducted on animals, did not reveal a direct or indirect negative impact on pregnancy, embryonic / fetal development, childbirth or postnatal development.

There is a limited number of data on the use of thiapride in pregnancy.

Newborns who, during of the third trimester of pregnancy were subjected to intrauterine antipsychotic drugs, including Tiapridal®, have a risk of developing after birth of unwanted reactions, including extrapyramidal syndrome or withdrawal syndrome, which can vary in severity and duration (see section "Side effect"). It was reported development of psychomotor excitation, muscular hypertonia, muscular hypotension, tremor, drowsiness, respiratory distress,syndrome or difficulty with feeding. Therefore, such Newborns should be under regular medical observation.

In addition, in such newborns it is theoretically possible to develop abdominal swelling and delay the divisions of meconium, tachycardia, hyperexcitability, especially when simultaneous reception of the mother during pregnancy m-holinoblokiruyuschih antiparkinsonian drugs.

Breastfeeding period

Studies in animals have shown, what tiapride penetrates into the breast Milk, however, does it penetrate tiapride in human milk, is unknown. Therefore, during admission Thiapridal breast feeding is not recommended.

Dosing and Administration:

Only for adults and children older than

6 years

Always choose minimally effective dose. If allows the patient's condition, treatment should begin with low doses with subsequent titration

(gradual increase).The daily dose of the drug is divided into 2-3 doses.

Cessation of psychomotor

exciting and aggressive

states, especially when

chronic alcoholism or in elderly patients

Only in adults: not more than 200 - 300 mg per day for 1-2 months.

In elderly patients The dose of 200-300 mg per day should be achieved gradually. Treatment should begin with a dose of 50 mg 2 times a day. Then the dose can gradually increase by 50-100 mg every 2-3 days. The average dose used in elderly patients is 200 mg per day, and the maximum dose is 300 mg per day.

Chorea, Gilles de la Tourette syndrome

In adults: 300 - 800 mg per day.

Treatment should begin with a very low dose - 25 mg per day, with its gradual increase until minimum effective dose.

Have children older than 6 years: 3-6 mg / kg in day. The maximum dose is 300 mg per day.

In adults and children duration of treatment is determined in each specific case by a doctor and depends on clinical course of the disease.

Behavioral disorders with agitation and aggressiveness children over the age of 6 years

The dose is 100 - 150 mg per day.

Patients with impaired function kidneys

In patients with renal disease insufficiency of excretion of thiaprid correlates with creatinine clearance.

Therefore, with the clearance of creatinine 30-60 ml / min dose should be reduced by 25 %, when creatinine clearance is 10 / 30ml / min, the dose should be reduced in 2 times, with creatinine clearance less than 10 ml / min, the dose should be reduced 4 times, compared with the doses with normal kidney function.

Patients with impaired hepatic function

The drug is metabolized slightly, so no dose reduction is required.

Side effects:

Frequency of occurrence of undesirable reactions (HP) was presented in accordance with the following grades recommended by the World Health Organization: very often (> 10%); often (> 1%, <10%); infrequently (> 0.1%, <1%); rarely (> 0.01%, <0.1%); very rarely, including individual reports (<0.01%); the frequency is unknown (according to the available data, the frequency can not be determined).

HP, observed during controlled clinical research

It should be noted that in some cases, there were difficulties in differentiating HP and symptoms underlying disease.

Violations from the central and peripheral nervous system

Often - Vertigo / vertigo, headache pain.

- Parkinsonism and related symptoms: tremor, muscular

hypertonicity, hypokinesia, and hypersalivation. These symptoms are usually reversed development with simultaneous reception m-holinoblokiruyuschih antiparkinsonian means.

Infrequently

- Akathisia, muscular dystonia (spasm, torticollis, oculogy crisis, trism). These symptoms are usually are subject to reverse development with simultaneous admission antiparkinsonian means.

Rarely

Acute dyskinesia, usually undergoing reverse development with simultaneous administration of m-cholinoblocking antiparkinsonian agents.

Disorders of the psyche

Often

Drowsiness / drowsiness / lethargy, insomnia, agitation, a state of apathy (indifference).

Disorders from the endocrine systems

InfrequentlyTiaprid causes an increase in the concentration of prolactin in the blood plasma, which is reversible after the drug is discontinued.

Hyperprolactinemia can lead to the development of galactorrhea, amenorrhoea, gynecomastia, an increase in breast (breast) glands, the appearance of pain in dairy (thoracic) glands, orgasmic dysfunction (violation of orgasm) and impotence.

General disorders

Often

- Asthenia / increased fatigue.

Infrequently

- Weight gain.

Post-marketing data

In addition to the above HP very rarely, and only from spontaneous messages were received information on the following HP.

Violations from the blood and lymphatic system

Frequency unknown

- Leukopenia, neutropenia, agranulocytosis (see section "Special instructions ").

Disorders of the psyche

Frequency unknown

Confusion.

Violations from the central and peripheral nervous system

Frequency unknown

Late dyskinesia, characterized by stereotyped involuntary movements,
- mainly language and / or facial muscles (as when using all other neuroleptics, particularly after administration for more than 3 months).
Antiparkinsonian drugs in this condition are ineffective or may lead to increased symptoms.
- Neuroleptic malignant syndrome (see. The "Special instructions") which is a potentially fatal complication, and the occurrence of which is possible when using any of neuroleptics.
Heart Disease

Frequency unknown

Interval lengthening QT, ventricular arrhythmias,such as ventricular pirouette tachycardia, ventricular ventricular tachycardia, capable of passing into ventricular fibrillation and leading to cardiac arrest and the development of sudden death (see "Special instructions")

Vascular disorders

Frequency unknown

Venous thromboembolic complications, including pulmonary embolism, sometimes fatal, and deep vein thrombosis (see section "Special instructions").
Reduction of blood pressure, usually in the form of orthostatic hypotension.

Disorders from the immune system systems

Frequency unknown

Skin allergic reactions.

Pregnancy, postpartum and postnatal conditions

Frequency unknown

The syndrome of "cancellation" in newborns (see the section "Application during pregnancy and during breast-feeding").

Overdose:

Overdose

Symptoms: excessive sedation, drowsiness, depression of consciousness down to coma, arterial hypotension, extrapyramidal symptoms.

Treatment: withdrawal of the drug, symptomatic and detoxication therapy, monitoring of vital body functions (especially cardiac activity (risk of prolongation of the QT interval and development of ventricular rhythm disturbances) until the symptoms of intoxication disappear completely.When severe extrapyramidal symptoms appear, use of anticholinergics. Because the tiapride weakly subjected to dialysis, for its removal from the body it is not recommended to use hemodialysis (see the section "Pharmacokinetics"). There is no specific antidote for tiapride.

There were reports of fatalities in overdose, mainly with the combination of thiapride with other psychotropic drugs.

Interaction:

Contraindicated combinations

Slevodopa

Mutual antagonism of levodopa and antipsychotics

With cabergoline, quinagolide

Mutual antagonism between these dopaminergic drugs and neuroleptics.

Unsupported combinations

With drugs that can cause ventricular tachycardia such as "pirouette" or lengthen the interval QT:

Bradycardia-inducing drugs, such as beta-adrenergic blockers; blocking the number of heartbeats blockers "slow" calcium channels (verapamil, diltiazem); clonidine, guanfacine; cardiac glycosides; Hypokalemia-causing drugs, such as potassium-withdrawing diuretics; laxatives,stimulating peristalsis of the intestine; Amphotericin B for intravenous administration, glucocorticosteroids, tetracosactide (before taking thiaprid, hypokalemia should be adjusted);

antiarrhythmics IA class, such as quinidine, disopyramide;
antiarrhythmic drugs of the III class, such as amiodarone, sotalol, dofetilide, ibutilide;
other drugs, such as pimozide, sultopride, sulpiride, haloperidol, thioridazine, methadone, amisulpride, droperidol, chlorpromazine, levomepromazine, cyamemazine, pipotiazine, sertindole, verialpyride; antidepressants, imipramine derivatives; lithium preparations; beprideil; cisapride, diphemethyl methyl sulphate administered intravenously erythromycin, administered intravenously spiramycin, misolastine, intravenously administered wincamine, halofantrine, lumefantrine, pentamidine, sparfloxacin, moxifloxacin;

selective inhibitors re-uptake of serotonin (citalopram, escitalopram).

If patients can not be avoided simultaneous appointment of these drugs with tiaprid, it follows that conduct a thorough clinical, laboratory (control electrolyte blood composition) and electrocardiographic observation.

With dopaminergic antiparkinsonian drugs (amantadine, apomorphine, bromocriptine, entacapone, lisuride, pergolide, pyribedil, pramipexole, ropinirole, selegiline)

Mutual antagonism dopaminergic antiparkinsonian drugs and neuroleptics. Agonists dopamine receptors can cause or strengthen a psychotic symptoms (see section "Special instructions ").

With ethanol

Ethanol increases sedation antipsychotics. Therefore, during treatment with thiapride drink alcohol and medications, containing ethanol.

Combinations that require care

With cholinesterase inhibitors (donepezil, rivastigmine, galantamine, pyridostigmine bromide, neostigmine bromide)

Because of the ability of these drugs cause bradycardia to increase risk of ventricular rhythm disturbances.

Combinations that follow taking into account

With antihypertensive drugs (all)

Additive hypotensive effect, increased orthostatic risk hypotension.
With nitrates
Increased risk of decline blood pressure and, in in particular, the development of orthostatic hypotension.
With drugs that depress function of the central nervous system: morphine derivatives (analgesics, anticalculus preparations); barbiturates; benzodiazepines and others anxiolytics; sleeping pills preparations; antidepressants with sedative action (amitriptyline, doxepin, mianserin, mirtazapine, trimipramine); blockers H2-gistaminovyh receptors with sedative effect; antihypertensives central action (for clonidine and guanfacin, see also "Unsupported combinations"); baclofen; thalidomide and pisotifen

Perhaps cumulative oppression central nervous system and decreased reaction.

Special instructions:

Malignant neuroleptic syndrome

Malignant neuroleptic syndrome is characterized by pallor, hyperthermia, rigidity of muscles, dysfunction of the autonomic nervous system, impaired consciousness. Signs of autonomic nervous system dysfunction, such as increased sweating and lability of blood pressure and pulse, may precede the onset of hyperthermia and, therefore, be early warning signs.In the case of an unexplained increase in body temperature, treatment with thiapride should be discontinued. Cause malignant Neuroleptic Syndrome remains unclear. It is assumed that its mechanism is played by the blockade of dopamine receptors in the striatum and the hypothalamus, and congenital predisposition (idiosyncrasy) is not ruled out. The development of the syndrome can be facilitated by intercurrent infection, disturbance of the water-electrolyte balance (in particularly, dehydration, hyponatremia), simultaneous administration of lithium, organic brain damage.

The elongation of the OT interval Tiapride may cause lengthening of the interval QT. It is known that this effect increases the risk of developing serious ventricular arrhythmias, such as ventricular pirouette tachycardia (see section "Side effect").

Before the appointment of therapy with neuroleptics, if the patient's condition allows, it is necessary to exclude the presence of factors, predisposing to the development of these severe rhythm disturbances (bradycardia less than 55 beats per minute, hypokalemia, hypomagnesemia, inhibition of intraventricular conduction and congenital elongated interval QT or lengthening the interval QT when using other drugs that extend the interval QT) (see the sections "Contraindications", "With caution", "Side effect").

Patients with the above risk factors,

predisposing to lengthen the interval QT, If tiaprid is needed, special care must be taken.

Hypokalemia and hypomagnesemia should be corrected before the drug is started, in addition, medical supervision, monitoring of blood electrolytes and ECG should be provided.

Extrapyramidthe syndrome With extrapyramidal syndrome, caused by antipsychotics, should be prescribed anticholinergic preparations (and not dopamine receptor agonists) (see section "Interaction with other drugs").

Stroke

In randomized clinical trials, compared with some atypical antipsychotics with placebo performed in elderly patients with dementia, there was a triple increase in the risk of developing cerebrovascular complications. The mechanism of this risk is unknown. It can not be ruled out that such a risk increases with other neuroleptics or in other populationspatients, therefore tiapride should be used with caution in patients with risk factors for stroke.

Older patients with dementia

In elderly patients with psychoses associated with dementia, in the treatment with antipsychotic drugs, there was an increase risk of death. An analysis of 17 placebo-controlled trials (mean duration over 10 weeks) showed that the majority of patients who received atypical antipsychotics had a 1.6-1.7 times greater risk of death than patients receiving placebo. In a 10-week placebo-controlled study, the incidence of fatal outcomes with atypical neuroleptics was 4.5% for these patients, and 2.6% for placebo.

Although the causes of death in clinical studies with atypical antipsychotics varied, most of the causes of death were either cardiovascular (eg, heart failure, sudden death), or infectious (eg, pneumonia) by nature. Observational studies have confirmed that, like treatment with atypical antipsychotics, treatment with conventional antipsychotic drugs can also increase mortality. The extent to which an increase in mortality may be due to an antipsychotic drug, rather than to certain features of patients, is unclear.

Venous thromboembolic oslo / ds

When using antipsychotic drugs, there have been cases of venous thromboembolic complications (WTO), sometimes with a fatal outcome (see section "Side effect"). therefore tiapride should be used with caution in patients with risk factors for developing WTO. Since patients taking antipsychotics often have acquired risk factors for developing WTO, any potential risk factors for WTO development should be identified before and during treatment with the drug Tiapridal, and during the reception should be carried out activities aimed at preventing thromboembolic complications.

Mammary cancer Tiaprid can increase the concentration of prolactin in the blood plasma. Therefore, when using tiaprid in patients who have a history of family history (including family history) of breast cancer, you should be careful (see "With caution").Such patients should be carefully monitored.

Patients with epilepsy Because, what tiapride can lower the threshold of convulsive activity, with the appointment of tiaprid to patients with epilepsy, the latter should be under strict medical supervision.

Patients with Parkinson's disease, receptor agonists of dopamine receptors Apart from exceptional cases, the drug Tiapridal should not be used in patients with Parkinson's disease. If there is an urgent need for treatment with neuroleptics patients with the disease Parkinson's, taking dopamine receptor agonists, should gradually reduce the doses of the latter until complete withdrawal (abrupt withdrawal of dopamine receptor agonists may increase the risk of developing a patient's malignant neuroleptic syndrome) (see Sections "FROM caution, "" Interaction with other drugs ").

Children

The use of thiaprid in children is not well understood. Therefore, when prescribing tiaprid, children should be careful. Due to the lack of clinical data, caution should be exercised when prescribing this medication to children.Moreover, it is recommended to check the ability of children to learn annually, since the drug can affect cognitive functions. It is necessary to regularly adjust the dose depending on thethe child's condition. Hematologic disorders When using antipsychotic drugs, including Tiapridal®, leukopenia, neutropenia, and agranulocytosis were observed. Unexplained infections or fever may be signs of hematologic disorders (see the "Side effect" section) and require an immediate hematological examination.

Ethanol

During treatment with Tiapridal Do not drink alcohol or medication containing ethanol (see the section "Interaction with le kardsgve other means and").

Effect on the ability to drive transp. cf. and fur:

Even when used in recommended doses tiapride can have a sedative effect, which leads to a violation ability to manage vehicles and engage in potentially dangerous activities. therefore it is necessary to refrain from studying these activities during the administration of the drug Tiapridal®.

Form release / dosage:

Tablets of 100 mg.

For 10 tablets in a blister of PVC and aluminum foil.

2 blisters together with instructions for use in a cardboard box.

Packaging:

For 10 tablets in a blister of PVC and aluminum foil.

2 blisters together with instructions for use in a cardboard box.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

List B.

Shelf life:

5 years.

Do not use the product after the expiry date printed on the package. Conditions of leave from pharmacies

Terms of leave from pharmacies:On prescription

Registration number:П N015978 / 01

Date of registration:30.09.2009

The owner of the registration certificate:Sanofi-Aventis FranceSanofi-Aventis France France

Manufacturer: & nbsp

SANOFI WINTHROP INDUSTRIE France

Information update date: & nbsp28.08.2015

Illustrated instructions

Instructions

Tiapridal® (Tiapridal®)