Thiapride, tablets 100 mg 20 pcs

Pharmacotherapeutic group

Antipsychotic medicine (neuroleptic)

ATX code

N05AL03

Pharmacodynamics: Antipsychotic drug (neuroleptic); has sedative sedative analgesic effect. It eliminates dyskinesia of central origin. It has a pronounced analgesic effect both for interoceptive and exteroceptive pain. Antipsychotic effect is caused by blockade of dopamine 02-receptors of mesolimbic and mesocortical system. Sedative action is caused by blockade of adrenoreceptors of reticular formation of brain stem; antiemetic action – by blockade of dopamine 02-receptors of trigger zone of vomiting center; hypothermic action – by blockade of dopamine receptors of hypothalamus.
Pharmacokinetics: After oral administration of 200 mg tiapride, the maximum concentration of the drug in plasma !3 mcg/ml is reached in 1 hour.

The bioavailability of the tablets is 75%. When taken immediately before meals the bioavailability is increased by 20% and the maximum concentration in plasma by 40%. Absorption in the elderly slows down.

Distribution in the body is fast (less than 1 hour). It penetrates through the blood-brain barrier and there is no cumulation through the placenta. The drug penetration into milk was noted in animals with the ratio of concentrations in milk to blood 1:2.

Binding with plasma proteins and erythrocytes is weak. Thiapride metabolism is very low: 70% of the dose is found unchanged in urine. The plasma elimination half-life is 29 hours in women and 36 hours in men. Excretion occurs mainly with urine and renal clearance reaches 330 ml/minute.

Indications

In adults
Short-term course of treatment (no more than 4 weeks) of agitation and aggressive conditions:
– in elderly patients;
– in patients with alcohol dependence with insufficient effectiveness or intolerance to benzodiazepines.
In adults and children over 6 years of age
Severe form of chorea, severe form of Gilles de la Tourette syndrome.
In children over 6 years of age
Behavioral disorders with agitation and aggressiveness.

Pharmacological effect

Pharmacotherapeutic group: antipsychotic (neuroleptic) agent.
ATX code: N05AL03

Pharmacological properties
Pharmacodynamics
An antipsychotic drug is an atypical neuroleptic that in vitro selectively blocks the D2 and D3 subtypes of dopamine receptors without any significant affinity for the receptors of the main central neurotransmitters (including serotonin, norepinephrine, histamine). Neurochemical and behavioral studies conducted in vivo confirmed these properties of tiapride, showing the presence of antidopaminergic effects in the absence of significant sedation, catalepsy and cognitive decline.
Tiapride is able to act on dopamine receptors that have previously been sensitized to dopamine when using any other antipsychotic drugs, and its antidyskinetic effects are associated with this.
Several experimental animal models of stress, including alcohol withdrawal in mice and primates, have confirmed the anxiolytic activity of tiapride.
Tiapride has not shown the formation of physical or mental dependence.
This atypical pharmacodynamic profile explains the clinical effectiveness of tiapride in many disorders, including hyperdopaminergic conditions such as dyskinesias and psychobehavioral disturbances observed in patients with dementia or alcohol abusers, with fewer neurological side effects compared with typical antipsychotics.
Tiapride has a pronounced analgesic (both for interoceptive and exteroceptive pain), antiemetic (due to blockade of dopamine D2 receptors of the trigger zone of the vomiting center), hypothermic effect (due to blockade of dopamine receptors of the hypothalamus).

Pharmacokinetics
Absorption of tiapride is rapid. After oral administration of the drug at a dose of 200 mg, the maximum plasma concentration of tiapride is reached within 1 hour and is 1.3 mcg/ml.
Bioavailability is 75%. When taking tablets immediately before meals, bioavailability increases by 20% and maximum plasma concentration by 40%. Absorption slows down in old age.
Distribution in the body occurs quickly (less than 1 hour). Penetrates the blood-brain barrier and the placenta without accumulation. The volume of distribution is 1.43 l/kg. In animals, penetration of the drug into breast milk was noted; the ratio of concentrations in milk and blood was 1.2.
Does not bind to plasma proteins, weakly binds to erythrocytes. Tiapride is slightly metabolized (up to 15%), the metabolites are mostly inactive. No conjugated metabolites were detected. 70% of the administered dose is found unchanged in the urine.
The plasma half-life is 2.9 hours in women and 3.6 hours in men. Excretion occurs predominantly by the kidneys by glomerular filtration and tubular secretion, renal clearance is 330 ml/min.
In patients with impaired renal function, excretion depends on creatinine clearance, a decrease in which the excretion of tiapride slows down (see section “Dosage and Administration”).

Special instructions

Neuroleptic malignant syndrome

Neuroleptic malignant syndrome is characterized by pallor, hyperthermia, muscle rigidity, dysfunction of the autonomic nervous system, and 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 represent early warning symptoms. If there is an unexplained increase in body temperature, treatment with tiapride should be discontinued. The cause of the development of neuroleptic malignant syndrome remains unclear. It is assumed that blockade of dopamine receptors in the striatum and hypothalamus plays a role in its mechanism; congenital predisposition (idiosyncrasy) cannot be ruled out. The development of the syndrome can be facilitated by intercurrent infection, disturbances in water and electrolyte balance (in particular, dehydration, hyponatremia), simultaneous administration of lithium, and organic brain damage.

Cases with atypical manifestations of neuroleptic malignant syndrome, for example, without muscle rigidity or hypertension and with less severe hyperthermia, have been observed.

QT prolongation

Tiapride may cause QT prolongation. This effect is known to increase the risk of developing serious ventricular arrhythmias, such as torsade de pointes (see section 4.4).

Before prescribing antipsychotic therapy, if the patient’s condition allows, it is necessary to monitor factors predisposing to the development of these severe rhythm disturbances (bradycardia less than 55 beats per minute, hypokalemia, hypomagnesemia, congenital long QT interval, concomitant use of other drugs causing bradycardia less than 55 beats per minute, hypokalemia, hypomagnesemia, slowing of intracardiac conduction or prolongation of the QT interval) (see sections “Contraindications”, “With caution”, “Side effects”).

Patients with the above risk factors predisposing to prolongation of the QT interval should be especially careful when prescribing tiapride. Hypokalemia and hypomagnesemia should be corrected before starting the drug, in addition, medical supervision, monitoring of blood electrolytes and ECG should be provided.

Extrapyramidal syndrome

For extrapyramidal syndrome caused by antipsychotics, anticholinergic drugs (rather than dopamine receptor agonists) should be prescribed (see section “Interaction with other drugs”).

Stroke

In randomized clinical trials comparing some atypical antipsychotics with placebo in elderly patients with dementia, a threefold increase in the risk of cerebrovascular events was observed. The mechanism of this risk is unknown. An increase in this risk cannot be ruled out with other antipsychotics or in other patient populations, so tiapride should be used with caution in patients with risk factors for stroke.

Elderly patients with dementia

In elderly patients with psychosis associated with dementia, an increased risk of death was observed when treated with antipsychotic drugs. An analysis of 17 placebo-controlled studies (mean duration greater than 10 weeks) found that most patients taking atypical antipsychotics had a 1.6 to 1.7 times greater risk of death than patients taking placebo. During a 10-week placebo-controlled clinical trial, the death rate was 4.5% in the atypical antipsychotic group and 2.6% in the placebo group. Although causes of death varied in clinical trials with atypical antipsychotics, most causes of death were either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia).

Observational studies have confirmed that, like treatment with atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may also increase mortality. The extent to which the increase in mortality may be due to the antipsychotic drug rather than certain patient characteristics is unclear.

Venous thromboembolic complications

When using antipsychotic drugs, cases of venous thromboembolic complications (VTE), sometimes fatal, have been observed (see section “Side effects”). Therefore, tiapride should be used with caution in patients with risk factors for developing HTO. Since patients taking antipsychotics often have acquired risk factors for developing HTO, any potential risk factors for developing HTO should be identified before and during treatment with Tiapride, and measures aimed at preventing thromboembolic complications should be implemented while taking it.

Breast cancer

Tiapride may increase plasma prolactin concentrations. Therefore, when using tiapride in patients with a history (including family history) of breast cancer, caution should be exercised (see section “With caution”). Such patients should be closely monitored.

Patients with epilepsy

Due to the fact that tiapride may lower the threshold for seizure activity, when tiapride is used in patients with epilepsy, the latter should be under strict medical supervision.

Patients with Parkinson’s disease taking dopamine receptor agonists

Except in exceptional cases, Tiapride should not be used in patients with Parkinson’s disease. If there is an urgent need to treat patients with Parkinson’s disease who are taking dopamine receptor agonists with antipsychotics, a gradual reduction in the doses of the latter should be carried out until complete withdrawal (abrupt withdrawal of dopamine receptor agonists may increase the patient’s risk of developing neuroleptic malignant syndrome) (see sections “With caution”, “Interaction with other drugs”).

Children

The use of tiapride in children has not been studied enough. Therefore, caution should be used when prescribing tiapride to children. Due to the lack of clinical data, caution is recommended when prescribing this drug to children. Moreover, it is recommended to have children’s learning abilities tested annually, as the drug may affect cognitive function. It is necessary to regularly adjust the dose depending on the clinical condition of the child.

Hematological disorders

Leukopenia, neutropenia and agranulocytosis have been observed with the use of antipsychotic drugs, including Tiapride. Unexplained infections or fever may be signs of hematological disorders (see section “Side effects”) and require immediate hematological evaluation.

Kidney failure

In case of renal failure, the dose of Tiapride should be reduced (due to the possible risk of coma due to impaired excretion of tiapride).

Ethanol

During treatment with Tiaprid, you should not take alcoholic beverages or medications containing ethanol (see section “Interaction with other drugs”).

Impact on the ability to drive vehicles and machinery

Even when used in recommended doses, tiapride can have a sedative effect, which leads to impaired ability to drive vehicles and engage in potentially hazardous activities. Therefore, it is necessary to refrain from engaging in these activities while taking Tiapride.

Active ingredient

Tiapride

Composition

Composition per 1 tablet:
Active ingredient: tiapride hydrochloride – 111.10 mg, in terms of tiapride – 100.00 mg.
Excipients: microcrystalline cellulose (MCC-101 Premium) – 37.70 mg, microcrystalline cellulose (MCC-102) – 18.00 mg, croscarmellose sodium – 5.40 mg, magnesium stearate – 2.70 mg, colloidal silicon dioxide – 2.70 mg, povidone-25 – 2.40 mg.

Pregnancy

Pregnancy
There are very limited data on the use of tiapride in pregnant women. Tiapride passes through the placenta. The use of the drug is not recommended during pregnancy and in women of reproductive age who do not use effective methods of contraception.
Neonates exposed in utero to antipsychotic drugs, including tiapride, during the third trimester of pregnancy are at risk of developing adverse reactions after birth, including extrapyramidal or withdrawal syndromes, which may vary in severity and duration (see Adverse Reactions section). Psychomotor agitation, muscle hypertonicity, muscle hypotonia, tremor, somnolence, respiratory distress syndrome or feeding difficulties have been reported. Therefore, such newborns should be under regular medical supervision.
In addition, in such newborns it is theoretically possible to develop abdominal bloating and delayed passage of meconium, tachycardia, hyperexcitability, especially when the mother simultaneously takes m-anticholinergic antiparkinsonian drugs during pregnancy.
Injectable antipsychotic drugs used in emergency situations can cause a decrease in blood pressure in pregnant women.
Breastfeeding period
Animal studies have shown that tiapride passes into breast milk. It is unknown whether tiapride passes into human breast milk, but the risk of exposure to the baby cannot be ruled out. When using the drug, breastfeeding is contraindicated.
Fertility
In animals, decreased fertility has been observed due to the pharmacological effects of tiapride (prolactin-mediated effect).

Data from preclinical studies
In animal studies (rodents), tiapride did not demonstrate direct or indirect teratogenic or embryotoxic effects. Studies in rabbits have demonstrated embryotoxic effects of tiapride at the highest doses (80 and 160 mg/kg body weight/day).

Contraindications

• Hypersensitivity to tiapride or other excipients of the drug.
• Diagnosed or suspected prolactin-dependent tumors, such as pituitary prolactinoma and breast cancer.
• Pheochromocytoma, suspected pheochromocytoma.
• Children under 6 years of age (risk of suffocation if the tablet enters the respiratory tract).
• Breastfeeding period (see section “Use during pregnancy and breastfeeding”).
• Concomitant use of levodopa (see section “Interaction with other drugs”).
• Simultaneous use of cabergoline, quinagolide (see section “Interaction with other drugs”).
The use of the drug in Parkinson’s disease is not recommended (except in cases of urgent need to use tiapride, see sections “With caution”, “Interaction with other drugs”, “Special instructions”).

With caution
• In patients with predisposing factors for the development of arrhythmias (with bradycardia less than 55 beats per minute; with electrolyte disturbances, in particular with hypokalemia, hypomagnesemia; with congenital prolongation of the QT interval; with concomitant therapy with drugs that can cause severe bradycardia (less than 55 beats per minute), electrolyte disturbances, slow intracardiac conduction or prolong the QT interval), since Tiapride may prolong the QT interval and increase the risk of developing severe ventricular arrhythmias, including the development of torsades de pointes (see sections “Interaction with other drugs”, “Special instructions”).
• In patients with Parkinson’s disease taking dopamine receptor agonists (amantadine, apomorphine, bromocriptine, entacapone, lisuride, pergolide, piribedil, ropinirole, selegiline), if there is an urgent need to use tiapride (see sections “Interaction with other drugs”, “Special instructions”).
• In patients with severe cardiovascular diseases (due to the possibility of increased ischemic disorders with a decrease in blood pressure).
• Elderly patients (increased risk of developing decreased level of consciousness, coma, 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 failure (adjustment of the dosage regimen is required, see sections “Dosage and Administration”, “Special Instructions”).
• In patients with impaired liver function (see section “Dosage and Administration”).
• In patients with epilepsy (neuroleptics may lower the seizure threshold, although this effect has not been studied with tiapride).
• In patients with risk factors for the development of thromboembolism (see section “Special instructions”).
• In patients with a history (including family history) of breast cancer (see section “Special instructions”).
• In children (there is insufficient data on the use of the drug in this category of patients).
• In adolescents during puberty (due to the possibility of developing undesirable effects from the endocrine system, see section “Side effects”).
• During pregnancy (see section “Use during pregnancy and breastfeeding”).
• When using drugs containing ethanol simultaneously (see section “Interaction with other drugs”).

Side Effects

The incidence of adverse reactions (HP) is presented in accordance with the following gradations recommended by the World Health Organization (WHO): very often (≥ 10%); often (≥ 1%, < 10%); uncommon (≥ 0.1%, < 1%); rare (≥0.01%, <0.1%); very rare, including isolated reports (<0.01%), frequency unknown (frequency cannot be determined from available data).

Nervous system disorders: often – dizziness/vertigo, headache.

Parkinsonism and associated symptoms (extrapyramidal symptoms): tremor, muscle hypertonicity, hypokinesia and hypersalivation. These symptoms are usually reversed while taking m-anticholinergic antiparkinsonian drugs.

Uncommon: akathisia, muscular dystonia (spasm, torticollis, oculogyric crisis, trismus). These symptoms are usually reversed while taking m-anticholinergic antiparkinsonian drugs. Convulsions, fainting.

Rarely – acute dyskinesia, which usually reverses while taking m-anticholinergic antiparkinsonian drugs. Tardive dyskinesia, characterized by stereotypical involuntary movements, mainly of the tongue and/or facial muscles (as with the use of all other antipsychotics, especially after their use for more than 3 months). Antiparkinsonian drugs are not effective for this condition or may worsen symptoms. Malignant neuroleptic syndrome, which is a potentially fatal complication, and the occurrence of which is possible with the use of any antipsychotics (see section “Special instructions”). Loss of consciousness.

Endocrine system disorders: often – hyperprolactinemia, which can lead to the development of amenorrhea, galactorrhea, gynecomastia, breast enlargement, pain in the mammary glands, orgasmic dysfunction (orgasm dysfunction) and erectile dysfunction. These symptoms are reversible after discontinuation of the drug. Disorders of the blood and lymphatic system: rarely – leukopenia, neutropenia, agranulocytosis (see section “Special instructions”).

Mental disorders: often – somnolence/drowsiness, drowsiness, insomnia, agitation, indifference (indifference); infrequently – confusion, hallucinations.

Metabolic and nutritional disorders: rarely – hyponatremia, syndrome of inadequate secretion of antidiuretic hormone.

Cardiac disorders: rarely – prolongation of the QT interval, ventricular arrhythmias, such as torsades de pointes, ventricular tachycardia, which can lead to ventricular fibrillation or cardiac arrest and sudden death (see section “Special Instructions”).

Vascular disorders: uncommon – decreased blood pressure, usually in the form of orthostatic hypotension, deep vein thrombosis; rarely – pulmonary embolism, sometimes fatal (see section “Special Instructions”).

Respiratory, thoracic and mediastinal disorders

Rarely – aspiration pneumonia, respiratory depression (when used with other central nervous system [CNS] depressants).

Gastrointestinal disorders: infrequently – constipation; rarely – intestinal obstruction, ileus.

Disorders of the liver and biliary tract: rarely – increased activity of liver enzymes.

Skin and subcutaneous tissue disorders: uncommon – skin rash, including erythematous rash, maculopapular rash; rarely – urticaria.

Musculoskeletal and connective tissue disorders: rarely – rhabdomyolysis, increased creatine phosphokinase activity in the blood serum.

Disorders of the reproductive system and mammary gland: infrequently – amenorrhea, orgasmic dysfunction; rarely – enlarged mammary glands, pain in the mammary glands, galactorrhea, gynecomastia, erectile dysfunction.

Pregnancy, postpartum and postnatal conditions: frequency unknown – withdrawal syndrome in newborns (see section “Use during pregnancy and breastfeeding”).

General disorders: often – asthenia, feeling of fatigue; infrequently – weight gain.

Injuries, intoxications and therapeutic manipulations: frequency unknown – falls, especially in elderly patients.

Interaction

Contraindicated combinations

With levodopa

Mutual antagonism of levodopa and antipsychotics.

With cabergoline, quinagolide

Mutual antagonism between these dopaminergic drugs and antipsychotics.

Combinations not recommended

With drugs that can cause torsade de pointes (TdP) or prolong the QT interval:

drugs that cause bradycardia, such as beta blockers; blockers of “slow” calcium channels that reduce the number of heart contractions (verapamil, diltiazem); clonidine, guanfacine; cardiac glycosides;
drugs that cause hypokalemia, such as potassium-sparing diuretics; laxatives that stimulate intestinal motility;
amphotericin B for intravenous use, glucocorticosteroids, tetracosactide (hypokalemia must be corrected before taking tiapride);
class IA antiarrhythmics such as quinidine, disopyramide;
class III antiarrhythmic drugs such as amiodarone, sotalol, dofetilide, ibutilide;
other drugs such as pimozide, sultopride, sulpiride, haloperidol, thioridazine, methadone, amisulpride, droperidol, chlorpromazine, levomepromazine, cyamemazine, pipothiazine, sertindole, veraliprid; antidepressants, imipramine derivatives; lithium preparations; bepridil; cisapride, difemanil methylsulfate, IV erythromycin, IV spiramycin, mizolastine, IV vincamine, halofantrine, lumefantrine, pentamidine, sparfloxacin, moxifloxacin;
selective serotonin reuptake inhibitors (citalopram, escitalopram).

If patients cannot avoid the simultaneous administration of these drugs with tiapride, then careful clinical, laboratory (monitoring of blood electrolyte composition) and electrocardiographic monitoring should be carried out.

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

Mutual antagonism of dopaminergic antiparkinsonian drugs and antipsychotics. Dopamine receptor agonists may cause or intensify psychotic symptoms (see section “Special Instructions”).

With ethanol

Ethanol enhances the sedative effect of neuroleptics. Therefore, during treatment with tiapride, you should not drink alcoholic beverages or medications containing ethanol.

Combinations requiring caution

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

The ability of these drugs to cause bradycardia increases the risk of developing ventricular arrhythmias.

Combinations to Consider

With antihypertensive drugs

Additive hypotensive effect, increased risk of orthostatic hypotension.

With nitrates

The risk of low blood pressure and, in particular, the development of orthostatic hypotension increases.

With drugs that depress the function of the central nervous system: morphine derivatives (analgesics, antitussives); barbiturates; benzodiazepines and other anxiolytics; sleeping pills; antidepressants with sedative effects (amitriptyline, doxepin, mianserin, mirtazapine, trimipramine); H1-histamine receptor blockers with sedative effects; centrally acting antihypertensives (for clonidine and guanfacine, see also “Not recommended combinations”); baclofen; thalidomide and pizotifen

Cumulative CNS depression and decreased response are possible.

Overdose

Data on tiapride overdose are limited.
Symptoms: excessive sedation, drowsiness, depression of consciousness up to coma, arterial hypotension, extrapyramidal symptoms.
Treatment: drug withdrawal, symptomatic and detoxification therapy, monitoring vital functions of the body, especially cardiac activity (risk of prolongation of the QT interval and development of ventricular arrhythmias), until the symptoms of intoxication completely disappear. If severe extrapyramidal symptoms occur, use anticholinergic drugs.
Since tiapride is poorly dialyzable, it is not recommended to use hemodialysis to remove it from the body (see section “Pharmacokinetics”).
There is no specific antidote.
There have been reports of fatal overdoses, mainly when tiapride was combined with other psychotropic drugs.

Storage conditions

At a temperature not exceeding 25 °C.
Keep out of the reach of children.

Shelf life

2 years.
Do not use after expiration date.

Manufacturer

Ozon, Russia