Grandaxin, tablets 50 mg, 20 pcs.

Pharmacodynamics

Tophizopam is a mild anxiolytic with short-term action and a broad therapeutic index. The exact mechanism of action is unknown. Tofizopam differs from other 1,4-benzodiazepines both in its chemical structure and in its clinical and pharmacological effects.

The drug is effective in treating anxiety disorders, including those accompanied by vegetative manifestations, fatigue, apathy. Unlike other benzodiazepines, tofizopam has no sedative, hypnotic, muscle relaxant and anticonvulsant activity. The drug does not have adverse effects on memory, psychomotor and cognitive function, but has moderate stimulant activity.

Because of absence of muscle relaxant effect the drug can also be used in patients with myopathy, myasthenia gravis and neurogenic muscle atrophy in which the use of muscle relaxants is contraindicated or undesirable. With long-term use, tofizopam does not cause the development of physical or mental dependence.

Pharmacokinetics

Intake. When administered orally, it is rapidly and almost completely absorbed from the gastrointestinal tract. Cmax is reached within 1-1.5 h.

Distribution. About 50% of tofizopam is bound to blood proteins.

Metabolism. After absorption, tofizopam undergoes significant presystemic metabolism in the liver. The main metabolic pathway is demethylation.

Elimation. It is excreted mainly by the kidneys (about 60%) and in the form of metabolites through the intestine. T1/2 is 6-8 hours.

Indications

alcohol withdrawal syndrome.

Active ingredient

Composition

Active substance:

Tofizopam50 mg;

Supplements:

stearic acid – 1 mg;

magnesium stearate – 1 mg;

gelatin – 3.5 mg;

Talc, 2 mg;

potato starch, 20.5 mg;

lactose monohydrate, 92 mg;

MC, 10 mg

How to take, the dosage

Internal.

Adults. The usually recommended dose is 1 to 2 tablets 1 to 3 times a day (total daily dose 50 to 300 mg). If used irregularly, 1 to 2 tablets may be taken. The maximum dose is 300 mg. Gradual increase in dose is usually not necessary; treatment can be started at the required dose, as the drug is well tolerated and during its administration there is usually no decrease in activity and mental wakefulness.

Children and adolescents under the age of 18 years. Use in children and adolescents under 18 years of age is contraindicated. There is insufficient experience with the drug in children and adolescents under 18 years of age.

Particular patient groups. There is no information about special patient groups. Clinical studies of efficacy and safety of Grandaxin® Tablets 50 mg (tofizopam) in elderly patients with renal and hepatic impairment have not been conducted.

Interaction

Plasma concentrations of drugs that are metabolized by CYP3A4 isoenzyme may increase with tofizopam, therefore concomitant use of tacrolimus, sirolimus, cyclosporine and tofizopam is contraindicated.

The use of tofizopam with drugs that have CNS depressant effect (analgesics, general anesthetics, antidepressants, sedatives, hypnotics), H1-histamine receptor blockers, antipsychotics increases their effects (for example, sedative effect or respiratory depression).

Opioids: Co-administration of sedative drugs such as benzodiazepines or similar drugs such as Grandaxin® with opioids increases the risk of sedation, respiratory depression, coma and death due to the additive CNS depressant effect of these drugs. Doses and duration of co-administration of these drugs should be limited.

Hepatic enzyme inducers (alcohol, nicotine, barbiturates, antiepileptic drugs) may increase the metabolism of tofizopam, which may lead to a decrease in its plasma concentration and weaken therapeutic effect.

Some antifungal drugs (ketoconazole, itraconazole) may slow hepatic metabolism of tofizopam, which leads to an increase in its plasma concentration.

Some hypotensive drugs (clonidine, BMCC) may increase the effects of tofizopam. β-adrenoblockers may slow down the metabolism of the drug, but this effect is of no clinical significance.

Digoxin: Tofizopam may increase plasma concentrations of digoxin.

Warfarin: benzodiazepines may affect the anticoagulant effect of warfarin.

Disulfiram: prolonged use of disulfiram may inhibit the metabolism of tofizopam.

Antacids have different effects on absorption of tofizopam. Cimetidine and omeprazole inhibit the metabolism of tofizopam.

The oral contraceptives may decrease the metabolic rate of tofizopam.

Alcohol: tofizopam attenuates the suppressive effect of alcohol on perception.

Special Instructions

Contraindications

Side effects

Unwanted reactions are listed below by organ system class and frequency: very common (≥1/10); common (≥1/100, < 1/10); infrequent (≥1/1000, < 1/100); rare (≥1/10000, < 1/1000); very rare (≤1/10 000) or observed with unknown frequency (cannot be estimated based on available data).

In each frequency category, adverse reactions are listed in decreasing order of severity.

For most adverse reactions, no data are available to determine their frequency.

Mental disorders: very rare – confusion; frequency unknown – agitation, increased irritability, feeling of mental tension, worsening of appetite.

Nervous system disorders: insomnia; very rare – the drug may provoke seizures in patients with epilepsy.

Respiratory system, thorax and mediastinum: respiratory depression.

Gastrointestinal disorders: nausea, vomiting, constipation, flatulence, dry mouth.

Liver and biliary tract disorders: very rare – cholestatic jaundice.

Skin and subcutaneous tissue disorders: exanthema, scarlet-like exanthema.

Skeletal, muscular and connective tissue disorders: muscle tension, muscle pain.

General disorders and disorders at the site of administration: headache, skin itching.

Overdose

Symptoms: CNS suppression effects occur only after high doses (50-120 mg/kg). Such doses may cause vomiting, confusion, coma, respiratory depression and/or epileptic seizures.

Treatment: If CNS function is severely depressed, it is not recommended to induce vomiting. Flush the stomach. Administration of activated charcoal helps to reduce absorption of the drug. Basic physiological parameters should be constantly monitored and appropriate symptomatic therapy should be used. In case of respiratory depression, ventilatory ventilation may be administered. Administration of CNS stimulants is not recommended. Hypotension is best eliminated by IV fluids and transferring patient to Trendelenburg position. If these measures do not restore BP, dopamine or norepinephrine may be administered. Dialysis and induced diuresis are ineffective.

Flumazenil can be administered as an antagonist, but its use in tofizopam overdose has not been clinically tested.

Pregnancy use

Pregnancy. Tofizopam crosses the placental barrier. The use of this drug is contraindicated in pregnancy.

The period of breastfeeding. The drug is excreted into the breast milk, so it is not recommended to use it during breastfeeding.