Tizanil pills 4mg №20

Mechanism of action

Pharmacological action - analgesic, muscle relaxant.

Pharmacodynamics

Tizanidine is a centrally acting muscle relaxant. The main point of application of its action is in the spinal cord. Stimulating presynaptic α₂-adrenoreceptors, tizanidine inhibits the release of excitatory amino acids that stimulate receptors for N-methyl-D-aspartate (NMDA-receptors). As a result, at the level of the intermediate neurons of the spinal cord, polysynaptic transmission of excitation is suppressed. Since it is this mechanism that is responsible for excessive muscle tone, when it is suppressed, muscle tone decreases.

Pharmacokinetics

Absorption is high; C_max in blood plasma is achieved 1 h after administration. Bioavailability is about 34%. Food intake does not affect pharmacokinetics.

V_ss - 160 l. Communication with plasma proteins - 30%. In the dose range from 4 to 20 mg, pharmacokinetics is linear.

It is metabolized rapidly and substantially in the liver (95%) by a CYP1A2 isoenzyme with the formation of inactive metabolites. Excreted mainly by the kidneys (70% of the dose in the form of metabolites, 2.7% - unchanged). Output in two phase: T_1/2 in the first phase - 2.5 hours; end T_1/2 - 22 h. Average T_1/2 unchanged substance - 2-4 hours

In patients with renal insufficiency (Cl creatinine <25 ml / min) C_max in plasma increases by 2 times, T_1/2 - 14 h, AUC increases 6 times.

Indications drug tizanil^®

painful muscle spasms;

spasticity in multiple sclerosis;

spasticity in spinal cord injuries;

spasticity due to traumatic brain injury.

Contraindications

hypersensitivity to tizanidine and other components of the drug;

severe liver dysfunction;

simultaneous use with powerful inhibitors of CYP1A2 isoenzymes (including fluvoxamine, ciprofloxacin);

hereditary lactose intolerance, lactase deficiency, glucose-galactose malabsorption;

children's age up to 18 years.

Carefully: renal failure; hypotension; bradycardia; simultaneous intake of oral contraceptives; age over 65 years. Do not abruptly cancel tizanil^®, the dose is reduced gradually.

Use during pregnancy and lactation

Since controlled studies on the use of tizanidine in pregnant women have not been conducted, it should not be used during pregnancy, unless the expected benefit to the mother outweighs the possible risk to the fetus.

Tizanidine slightly penetrates into breast milk, so during the breastfeeding period, the drug should be withdrawn.

Side effects

Nervous system: drowsiness, dizziness, hallucinations, insomnia, sleep disturbance.

From the CCC: bradycardia, a decrease in blood pressure (in some cases pronounced, up to collapse and loss of consciousness).

Gastrointestinal: dry mouth, nausea, dyspepsia, increased activity of hepatic transaminases, hepatitis, liver failure.

Musculoskeletal system: muscle weakness.

Other: fatigue, hypercreatininemia.

With the abrupt cancellation of the drug after prolonged treatment and / or taking high doses of the drug (as well as after simultaneous use with antihypertensive drugs): tachycardia, increased blood pressure, acute cerebrovascular accident.

Interaction

The simultaneous use of tizanidine with fluvoxamine or Ciprofloxacin (CYP1A2 isoenzyme inhibitors) leads to a 33-fold increase in AUC of tizanidine. As a result, a clinically significant and prolonged decrease in blood pressure may occur, leading to drowsiness, weakness, and slowing down of psychomotor reactions (in some cases to loss of consciousness); prolongation of the QT interval (see. "Overdose").

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

Antihypertensive drugs increase the risk of marked reduction in blood pressure and bradycardia.

Ethanol, CNS depressants, can increase the sedative effect of tizanidine, therefore, simultaneous use of tizanidine with CNT depressants and (or) alcohol is not recommended.

Dosage and administration

Inside

Relief of painful muscle spasm: on 2-4 mg 3 times a day, in severe cases - additionally at night 2-4 mg.

Treatment of spasticity of skeletal muscles in neurological diseases: the initial dose is 2 mg 3 times a day, then the dose is gradually increased by 2-4 mg at intervals of 3-7 days. The optimal daily dose is 12-24 mg in 3-4 doses, the maximum daily dose is 36 mg.

In patients with renal insufficiency (with Cl creatinine <25 ml / min), administration starts with 2 mg 1 time per day. If necessary, increase the dose gradually, taking into account tolerability. If it is necessary to obtain a more pronounced effect, it is recommended to first increase the dose prescribed 1 time per day, then the frequency of administration.

Overdosage

Symptoms: nausea, vomiting, decrease in blood pressure, dizziness, drowsiness, agitation, prolongation of the QT interval, miosis, anxiety, respiratory failure, coma.

Treatment: gastric lavage, reception of Activated carbon, conducting forced diuresis, symptomatic therapy.

Special notes

Reported cases of liver dysfunction associated with taking tizanidine, however, when using a daily dose of up to 12 mg, these cases were rarely observed. In this regard, it is recommended to monitor functional liver function tests 1 time per month in the first 4 months of treatment in those patients who are prescribed tizanidine in a daily dose of 12 mg and above, as well as in cases where there are clinical signs suggesting impaired liver function, such as unexplained nausea, anorexia, fatigue. In the case when the activity of AST and ALT in serum stably exceed VGN by 3 times or more, the use of Tizanil^® should stop.

Patients with congenital lengthening of the QT interval tizanidine should be prescribed with caution, because in preclinical studies of chronic toxicity in animals (dogs), the QT interval was lengthened with the use of the drug in a dose equivalent to the maximum dose for humans.

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

Patients with myasthenia should be used with extreme caution only in cases where the expected benefit significantly exceeds the possible risk.

Influence on the ability to drive a car or perform work that requires increased speed of physical and mental reactions. With the development of drowsiness, dizziness or decrease in blood pressure during therapy with Tizanil^® one should refrain from types of work requiring high concentration of attention and quick reaction, for example, driving a car or working with machinery.

Storage conditions of the drug Tizanil

In a dry, dark place at a temperature of no higher than 30 ° C.

Keep out of the reach of children.