Tiapride

Pharmacological properties

Tiapride refers to substituted o-methoxybenzamides (orthopramides), a group of substances with a central effect.

Thiapride is characterized by a high affinity for central dopaminergic receptors, especially if they are pre-sensitized with dopamine. Thiapride acts in an antidopaminergic way, mainly on donamine D₂-receptors, due to which the antidiscinetic effect of the drug is achieved.

Unlike traditional antipsychotics, Tiapride has a slight cataleptic effect. Due to these properties, Tiapride is used to treat disorders of coordination of movement of central origin.

Pharmacological and clinical studies have shown that Tiapride has antiemetic properties.

Pharmacokinetics Following oral administration of 200 mg of Tiapride C_max in blood plasma, 1.3 μg / ml is achieved over 1 hour. The absolute bioavailability of Tiapride is 75%. After Concomitant Eating C_max in blood plasma increases by 40%. In the elderly, the absorption of the drug slows down. Thiapride is rapidly distributed throughout the body. It crosses the BBB and the placental barrier, without accumulating. Thiapride does not bind to plasma proteins, but to a small extent binds to red blood cells. T_½ from blood plasma - 5.3 hours. The metabolism of Tiapride is poorly expressed. 70% of the dose taken is excreted unchanged in the urine, and renal clearance is 330 ml / min. Excretion correlates with creatinine clearance. In patients with impaired renal function, the dose of the drug should be selected according to the degree of damage.

Indications

Tiaprilan is used for dyskinesia and movement disorders such as Huntingtons disease. early and late dyskinesia.

Psychomotor disorders in the elderly. Psychomotor disturbances in chronic alcoholism.

Application

Thiaprilan tablets should be taken whole, not chewed, washed down with a sufficient amount of liquid, preferably during meals.

The dose of the drug is set individually. The daily dose is divided into 3 doses.

Dyskinesia and movement disorders

Early dyskinesia: 150-400 mg / day; tardive dyskinesia: 300-800 mg / day.

Huntingtons disease: 300–1200 mg / day.

Psychomotor disorders in the elderly: 200-400 mg / day.

Psychomotor disorders in chronic alcoholism: 300-400 mg / day.

Impaired liver or kidney function. For patients with severe renal failure, the dose should be reduced. A dose reduction is recommended, as well as a temporary cessation of treatment. For patients with creatinine clearance of 11–20 ml / min, the daily dose should be reduced by 2 times, and with creatinine clearance of 10 ml / min, it is recommended ¹/₄ standard dose (the tablet can be divided).

Patients with impaired liver function dose adjustment is not required.

The duration of treatment depends on the clinical symptoms.

Contraindications

Hypersensitivity to the active substance or any components of the drug; prolactin-dependent tumor, epithelial breast cancer; pheochromocytoma; simultaneous use of levodopa.

Side effects

Side effects are classified by severity and frequency: very often (1/10); often (1/100, 1/10); sometimes (1/1000, 1/100): rarely (1/10 000, 1/1000): very rarely (1/10 000), including isolated cases.

In each group, adverse reactions are presented in decreasing order of severity.

It must be borne in mind that in some cases, adverse reactions are difficult to distinguish from the symptoms of the underlying disease.

From the side of the central nervous system: often - dizziness, headache, parkinsonism and parkinson-like symptoms, such as tremors, hypokinesia, increased salivation; rarely - akathisia, dystonia (spasms, torticollis, oculogyric crisis, trismus); very rarely - acute dyskinesia.As with all other antipsychotic drugs, after prolonged treatment with Tiapride, tardive dyskinesia may develop (characterized by rhythmic involuntary movements, especially of the tongue and / or face), therefore strict monitoring of the patient is necessary. This was reported after treatment with a drug lasting more than 3 months. In such cases, treatment with anticholinergic antiparkinsonian drugs is not indicated, since they either have no effect or can worsen the patients condition.

The development of malignant antipsychotic syndrome is a potentially life-threatening complication that may arise as a result of treatment with antipsychotic drugs.

All these symptoms can be completely eliminated using antiparkinsonian drugs.

Mental disorders: often - fatigue, drowsiness, insomnia, sedation, anxiety arousal, apathy.

From the endocrine system: rarely - Tiapride causes hyperprolactinemia, which is reversible after discontinuation of treatment. The following adverse reactions can be noted: galactorrhea, amenorrhea, breast enlargement, breast tenderness, frigidity in women, as well as gynecomastia and impotence in men.

General disorders and reactions at the injection site: often - asthenia / fatigue; rarely - weight gain; in some cases - an allergy. In addition, the development of postural hypotension has been reported.

special instructions

Special care should be taken when using the drug in such cases:

• elderly people: like other antipsychotic drugs, Tiapride can increase the incidence of sedation and arterial hypotension due to hypersensitivity;
• in severe cardiovascular diseases (due to possible side effects from hemodynamics, especially arterial hypotension);
• patients with renal failure (in this case, the risk of overdose should be considered);
• patients with Parkinsons disease: in rare cases, Tiapride should not be used in patients with Parkinsons disease;
• history of patients with epilepsy: antipsychotic drugs can lower the epileptogenic threshold. Although this phenomenon has not been sufficiently studied with respect to Tiapride, strict monitoring of patients is required.

Close monitoring of the patients condition is necessary, since Tiapride lowers the seizure threshold.

The drug should not be used in patients with pheochromocytoma, since severe hypertensive crises caused by substances with a similar chemical composition have been reported.

Malignant antipsychotic syndrome. In case of hyperthermia of unknown origin, treatment with Tiapride should be stopped immediately. Hyperthermia can be a manifestation of a malignant antipsychotic syndrome (akathisia, chills, hyperthermia, impaired consciousness, autonomic disorders), which can rarely occur due to the use of antipsychotic drugs. This can especially be manifested during therapy with high doses (for example, use in chronic alcoholism).

Use during pregnancy and lactation. There is no experience with the use of Tiapride for the treatment of pregnant women, therefore, in such cases, the drug is prescribed only according to absolute indications. It is also recommended to reduce the duration of treatment with the drug during pregnancy. If possible, the dose of an antipsychotic drug, as well as an antiparkinsonian drug (if used) at the end of pregnancy should be reduced in connection with the atropine-like properties of the latter.

Neurological control is recommended, and in the case of the simultaneous use of an antiparkinsonian drug, the digestive function of the newborn.

Tiapride is excreted in breast milk, so you should avoid using the drug during lactation.

Children. Since the experience with Tiapride in this age group is insufficient, the drug should not be prescribed to children.

Influence on the ability to drive vehicles and work with other mechanisms. Thiapride affects reactivity, as a result of which during the treatment period it is necessary to refrain from driving vehicles or working with other mechanisms.

Interactions

During the treatment with the drug, it is necessary to avoid the simultaneous use of alcohol, since this can lead to an increase in the sedative effect.

The combined use of Tiapride with levodopa should be avoided, since levodopa and antipsychotic drugs can mutually reduce the severity of the effects of each other. In the case of the use of antipsychotics in patients with Parkinsons disease, a drug that causes less pronounced extrapyramidal side effects (for example, chlorpromazine, levomepromazine) should be chosen.

With the simultaneous use of Tiapride with antihypertensive drugs, there is a risk of enhancing their effects (postural hypotension).

The simultaneous use of other drugs that suppress the central nervous system (for example, analgesics and morphine derivatives that suppress cough, most antihistamines, barbiturates, benzodiazepines and other tranquilizers, clonidine), increases this effect.

Overdose

Symptoms: experience with overdose of Tiapride is negligible. with an overdose, fatigue, sedation, coma, arterial hypotension, severe Parkinsons syndrome may develop.

In case of acute overdose, it is necessary to take into account the possible intake of various drugs by the patient.

Treatment. There is no specific antidote. Therapy is symptomatic and careful monitoring of heart function and respiratory function.

For severe extrapyramidal symptoms, anticholinergics should be prescribed.

Storage conditions

At a temperature not exceeding 25 ° C.