Tofisopam (Tablets) Instructions for Use

ATC Code

N05BA23 (Tofisopam)

Active Substance

Tofisopam (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Anxiolytic (tranquilizer)

Pharmacotherapeutic Group

Anxiolytic agent (tranquilizer)

Pharmacological Action

Anxiolytic agent (tranquilizer) from the group of benzodiazepine derivatives. Along with a pronounced anxiolytic effect, other effects characteristic of benzodiazepine tranquilizers – sedative, hypnotic, muscle relaxant, anticonvulsant – are relatively weak. In this regard, Tofisopam is classified as a “daytime” tranquilizer.

The occurrence of the main effects is due to the stimulation of benzodiazepine receptors in the brain, the excitation of which increases the sensitivity of GABA receptors to the mediator. As a result, GABAergic transmission is enhanced: chloride channels work more intensively, hyperpolarization of neuronal membranes is enhanced, and neuronal activity decreases.

Pharmacokinetics

After oral administration, Tofisopam is rapidly and almost completely absorbed from the gastrointestinal tract. C_max is reached within 2 hours, after which the plasma concentration decreases monoexponentially. Tofisopam does not accumulate in the body. Its metabolites do not have pharmacological activity. It is excreted mainly in the urine (60-80%) in the form of conjugates with glucuronic acid and, to a lesser extent (about 30%), in the feces. T_1/2 is 6-8 hours.

Indications

Neuroses, psychopathies, other conditions accompanied by a feeling of emotional tension, restlessness, anxiety, fear; reactive depression with moderately pronounced psychopathic symptoms; premenstrual syndrome, climacteric syndrome; cardialgia (as monotherapy or in combination with other drugs); myasthenia, myopathies, neurogenic muscular atrophies and other pathological conditions with secondary neurotic symptoms when anxiolytics with a pronounced muscle relaxant effect are contraindicated; alcohol withdrawal syndrome.

ICD codes

Dosage Regimen

Administer orally. Initiate treatment at a starting dose of 50 mg, taken two to three times daily.

For moderate anxiety disorders, the typical maintenance dose is 100-150 mg per day, divided into two or three doses.

In cases of severe anxiety or during exacerbations, the daily dose may be increased to a maximum of 300 mg.

Adjust the dosage regimen individually, based on the patient’s clinical condition, disease severity, and individual response.

For geriatric patients or those with hepatic or renal impairment, initiate therapy at the lower end of the dosage range.

Perform dose titration gradually to minimize potential adverse effects.

Limit the treatment course to a maximum of 4-12 weeks, including the tapering period.

Discontinue therapy by gradually reducing the dose to prevent withdrawal symptoms.

Avoid abrupt cessation after prolonged use.

Adverse Reactions

From the digestive system: decreased appetite, constipation, flatulence, nausea, dry mouth are possible; in some cases – cholestatic jaundice.

From the nervous system: headache, insomnia, increased irritability, psychomotor agitation, confusion, convulsive seizures in patients with epilepsy are possible.

Allergic reactions: exanthema, scarlatiniform exanthema, itching.

From the musculoskeletal system: muscle tension, muscle pain.

From the respiratory system: respiratory depression.

Contraindications

Hypersensitivity to tofisopam, other derivatives of the benzodiazepine group; conditions accompanied by severe psychomotor agitation, aggression or severe depression; decompensated respiratory failure; obstructive sleep apnea syndrome; coma; simultaneous use with tacrolimus, sirolimus, cyclosporine; pregnancy, lactation (breastfeeding); children and adolescents under 18 years of age.

With caution

Decompensated chronic respiratory distress, history of acute respiratory failure, closed-angle glaucoma, epilepsy, organic brain lesions (for example, atherosclerosis).

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and lactation (breastfeeding).

Use in Hepatic Impairment

Should be used with caution in patients with impaired liver function. This category of patients has an increased risk of side effects. Dose adjustment is necessary.

Use in Renal Impairment

Should be used with caution in patients with impaired renal function. This category of patients has an increased risk of side effects. Dose adjustment is necessary.

Pediatric Use

Contraindicated for use in children and adolescents under 18 years of age.

Geriatric Use

Should be used with caution in elderly patients. This category of patients has an increased risk of side effects. Dose adjustment is necessary.

Special Precautions

With prolonged use, especially in high doses, the development of drug dependence is possible. Course treatment is recommended for no more than 4-12 weeks, including the period of gradual withdrawal of tofisopam.

It is not recommended to use Tofisopam for chronic psychosis, phobia or obsessive states. In these cases, the risk of suicide attempts and aggressive behavior increases.

In patients with epilepsy, Tofisopam may increase the seizure threshold.

Do not consume alcohol during treatment.

Effect on the ability to drive vehicles and mechanisms

During treatment, patients are prohibited from driving any vehicles and engaging in other activities that require high concentration and speed of psychomotor reactions.

Drug Interactions

With simultaneous use with tofisopam of drugs that are metabolized by CYP3A4, an increase in their plasma concentration is possible.

With simultaneous use of tofisopam with drugs that have a depressant effect on the central nervous system (analgesics, general anesthetics, antidepressants, histamine H₁-receptor blockers, sedative-hypnotics, antipsychotics), their effects are enhanced (for example, sedative effect or respiratory depression).

With simultaneous use, inducers of liver enzymes (alcohol, nicotine, barbiturates, antiepileptic drugs) may enhance the metabolism of tofisopam, which may lead to a decrease in its plasma concentration and a weakening of the therapeutic effect.

With simultaneous use, some antifungal drugs (ketoconazole, itraconazole) may slow down the hepatic metabolism of tofisopam, leading to an increase in its plasma concentration.

With simultaneous use, Tofisopam may increase the plasma level of digoxin.

With simultaneous use, benzodiazepines may affect the anticoagulant effect of warfarin.

Long-term use of disulfiram may inhibit the metabolism of tofisopam.

With simultaneous use, antacids may affect the absorption of tofisopam. Cimetidine and omeprazole inhibit the metabolism of tofisopam.

With simultaneous use, oral contraceptive drugs may reduce the intensity of tofisopam metabolism.

Tofisopam weakens the depressant effect of alcohol on the central nervous system.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.