Tizanil, tablets 4 mg 30 pcs

By stimulating presynaptic a2-receptors, it suppresses the release of excitatory amino acids that stimulate receptors for N-methyl-D-aspartate (NMDA-receptors). As a consequence, polysynaptic transmission of excitation is suppressed at the level of intermediate neurons of the spinal cord.

Since this mechanism is responsible for excessive muscle tone, when it is inhibited, muscle tone decreases. It also has a central moderately pronounced analgesic effect.

Pharmacokinetics:

It is absorbed quickly and almost completely. Maximum concentration in blood plasma is reached about 1 hour after intake. Because of the pronounced metabolism during “first passage” through the liver, the average bioavailability is about 34%. Binding to plasma proteins is 30%.

The pharmacokinetics of tizanidine is linear in dose range from 4 to 20 mg. The inter-individual variability of pharmacokinetic parameters is low. Gender has no effect on the pharmacokinetics of tizanidine. It is metabolized in liver, mainly by cytochrome P450 system isoenzyme 1A2.

The metabolites are inactive. The elimination half-life is 2-4 hours. It is eliminated mainly by the kidneys as metabolites, a small part of it is eliminated unchanged. Average value of maximum concentration in plasma in patients with renal insufficiency (creatinine clearance less than 25 ml/min) was 2 times higher than in healthy volunteers, and excretion half-life was prolonged up to 14 hours.

Contemporaneous intake of food has no clinically significant effect on the pharmacokinetics of tizanidine.

Indications

Active ingredient

Composition

How to take, the dosage

In painful muscle spasm: 2-4 mg three times a day. In severe cases an additional 2-4 mg should be taken before going to bed.

In case of skeletal muscle spasticity: the initial daily dose should not exceed 6 mg divided into 3 doses. The dose may be increased gradually by 2-4 mg at intervals of 3-7 days. The optimal therapeutic effect is achieved with a daily dose of 12-24 mg divided into 3-4 doses at regular intervals.

The maximum daily dose is 36 mg.

In patients with renal insufficiency, it is recommended to start treatment with a dose of 2 mg once daily. The dose should be increased gradually with regard to tolerability and efficacy. If a higher dose is necessary, first the dosage prescribed once daily is increased, after which the frequency of administration is increased.

Interaction

Simultaneous use of tizanidine with fluvoxamine or ciprofloxacin (CYP1A2 isoenzyme inhibitors) leads to a 33-fold increase in the AUC of tizanidine. As a result, clinically significant and prolonged BP decrease may occur, leading to drowsiness, weakness and delayed psychomotor reactions (in some cases, loss of consciousness); prolongation of the QT interval (see “Overdose”).

The concomitant use of tizanidine with other CYP1A2 isoenzyme inhibitors – antiarrhythmic drugs (amiodarone, mexiletine, propafenone), cimetidine, fluoroquinolones (enoxacin, pefloxacin, norfloxacin), rofecoxib, oral contraceptives, ticlopidine is not recommended.

The antihypertensive drugs increase the risk of marked BP decrease and bradycardia.

Ethanol, CNS depressants may increase the sedative effect of tizanidine; therefore, it is not recommended to use tizanidine concomitantly with CNS depressants and/or alcohol.

Special Instructions

Liver function abnormalities associated with tizanidine have been reported, but these cases have been rare with daily doses up to 12 mg. In this regard, it is recommended to monitor liver function tests once a month during the first 4 months of treatment in patients treated with tizanidine at a daily dose of 12 mg or higher, as well as in cases when clinical signs suggestive of liver dysfunction are observed, such as unexplained nausea, anorexia, fatigue. In cases where serum AST and ALT levels persistently exceed VGN by a factor of 3 or more, Tizanil should be discontinued.

Patients with congenital QT interval prolongation syndrome should be prescribed with caution because preclinical studies of chronic toxicity in animals (dogs) have noted prolongation of the QT interval when using the drug at a dose equivalent to the maximum human dose.

In patients with coronary heart disease and/or heart failure, ECG should be monitored regularly.

In patients with myasthenia gravis, use with extreme caution only in cases where the expected benefit significantly exceeds the possible risk.

Impact on the ability to drive or perform work requiring increased speed of physical and mental reactions.

If drowsiness, dizziness, or decreased BP develop during therapy with Tizanil, refrain from activities requiring high concentration and rapid reactions, such as driving or operating machinery.

Contraindications

Side effects

Overdose

Treatment: repeated administration of activated charcoal is recommended for elimination of the drug from the body. Forced diuresis may also accelerate excretion of tizanidine. Further symptomatic therapy is carried out.

Pregnancy use

It is contraindicated in children under 18 years of age (due to insufficient data).

As there have been no controlled studies of tizanidine use in pregnant women, it should not be used during pregnancy unless the expected benefit to the mother outweighs the possible risk to the fetus.

Tizanidine passes slightly into the breast milk, so the drug should be discontinued during breastfeeding.

Similarities