Tizanidin-Tev

General characteristics. Structure:

Active agent: tizanidina hydrochloride (тизанидин) 2,29 mg (2,0 mg) of/4,58 mg (4,0 mg);
excipients: lactose (lactose anhydrous) 57,91 mg / 115,82 mg; проСолв SMCC 501 (cellulose of microcrystallic 98%, silicon dioxide of colloid 2%) 22,575 mg / 45,15 mg; проСолв SMCC 901 (cellulose of microcrystallic 98%, silicon dioxide of colloid 2%) 22,575 mg / 45,15 mg; stearic acid of 2,150 mg / 4,30 mg.

Description
Tablets of 2 mg. Round biconvex tablets of white or almost white color with risky on one party and an engraving of "T2" - on another.
Tablets of 4 mg. Round biconvex tablets of white or almost white color with crosswise risky on one party and an engraving of "T4" - on another.

Pharmacological properties:

Pharmacodynamics. Tizanidin is an agonist of the alfa2-adrenergic receptors located in the central nervous system at the supraspinal and spinal levels.
Stimulating presynaptic alfa2-adrenoceptors, тизанидин suppresses release of the exciting amino acids stimulating the receptors sensitive to N-methyl-D-aspartate (NMDA receptors). Thereof at the level of interneuronels of a spinal cord there is a suppression of polisinaptichesky transfer of excitement. Tizanidin has no direct effect on skeletal muscles, neuromuscular synapses or monosinaptichesky reflexes.
Tizanidin reduces spasticity and clonic spasms owing to what resistance of muscles to the passive movements in joints decreases and the volume of active movements increases.

Pharmacokinetics. Absorption
Absorption of a tizanidin high, time of achievement of the maximum concentration in plasma (TCmax) - 1-2 h. Bioavailability - 34%. Meal does not influence pharmacokinetics.
Distribution and metabolism
Distribution volume - 2,6 l/kg. Communication with proteins of plasma - 30%.
In the range of doses from 4 to 20 mg the pharmacokinetics has linear character. Tizanidin is quickly metabolized substantially in a liver (95%) with formation of inactive metabolites.
Removal
Elimination half-life (T1/2) - 3-5 h. It is removed preferential by kidneys (70% - in not changed look, 2,7% - in the form of metabolites) and allocated with a stake (20%).
At patients with a renal failure (the clearance of creatinine (CC) less than 25 ml/min.) the maximum concentration increases in plasma (Cmax) twice, T1/2 - 14 h, the area under a curve "concentration time" (AUC) increases by 6 times.

Indications to use:

Spasticity of skeletal muscles at multiple sclerosis, injuries of a spinal cord.

Route of administration and doses:

Inside. The initial dose makes 2 mg, with the subsequent increase in a dose on 2 bucketed mg not less than 3-4 days.
The maximum daily dose - 36 mg.
The mode of dosing should be set individually, the daily dose is divided into several receptions (to 3-4) depending on need of the patient. Usually use more than 24 mg/days is not required.
Treatment of patients with a renal failure (KK less than 25 ml/min.) is recommended to begin with a dose 2 mg of 1 times a day. Increase in a dose should be carried out gradually, taking into account portability and efficiency: at first increase a dose then increase frequency rate of use.
At patients 65 years are more senior drug Tizanidin-Tev should be used under careful control of function of kidneys in connection with possible reduction in the rate of glomerular filtering.

Features of use:

It is necessary to be careful at drug use Tizanidin-Tev at patients with a renal failure. At drug use Tizanidin-Tev at patients with a renal failure (KK less than 25 ml/min.) can be required a dose decline.
It is recommended to control functional indicators of a liver in the first 4 months of treatment once a month at those patients who accept drug Tizanidin-Tev in a daily dose of 12 mg and above and also when the clinical signs allowing to assume an abnormal liver function, such as inexplicable nausea, anorexia, feeling of fatigue are observed. In case activity of "hepatic" transaminases is higher than the upper bound of norm by 3 times and more, drug use Tizanidin-Tev should be stopped.
At simultaneous use of drug Tizanidin-Tev with inhibitors of an isoenzyme CYP1A2 increase in concentration of a tizanidin in a blood plasma is possible that in turn can be the cause of development of symptoms of overdose, in particular lengthenings of an interval of QT (c). Simultaneous use of drug Tizanidin-Tev with inhibitors of an isoenzyme CYP1A2 and other drugs which can lead to lengthening of an interval of QT (c) is not recommended.
At treatment tizanidiny patients it is necessary to be careful with cardiovascular diseases, coronary heart disease. It is regularly necessary to control laboratory indicators of a functional condition of heart and to monitorirovat ECG indicators.
Drug withdrawal Tizanidin-Tev should be made gradually because of risk of development of a syndrome of "cancellation" (see the section "Side effect").
It was reported about exceptional cases of emergence of muscular weakness at use of a tizanidin (see the section "Side effect"). During clinical trials it was shown what тизанидин does not exert negative impact on force of muscular contraction.

Use at pregnancy and during breastfeeding
Use during pregnancy and during breastfeeding is contraindicated.

Influence on ability to management of transport and work with the equipment
It is necessary to be careful during drug use Tizanidin-Tev owing to possible development of side reactions which can negatively influence ability to control of motor transport and performance of potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

Frequency of side effects is classified according to recommendations of World Health Organization: very often - not less than 10%; often - not less than 1%, but less than 10%; infrequently - not less than 0,1%, but less than 1%; seldom - not less than 0,01%, but less than 0,1%; very seldom - 0,01%, including single messages.
From a nervous system: often - drowsiness, dizziness; seldom - sleeplessness, hallucinations, frustration of a dream.
From cardiovascular system: often - a lowering of arterial pressure, bradycardia.
From the alimentary system: often - dryness of a mucous membrane of an oral cavity; seldom - nausea, dysfunction of a GIT.
From a liver and biliary tract: very seldom - passing increase in activity of "hepatic" transaminases, hepatitis, a liver failure.
From a musculoskeletal system: seldom - muscular weakness.
Others: very often - increased fatigue; often - a syndrome of "cancellation" *.

* At sharp cancellation after long treatment and/or reception of high doses of drug (and also after use together with hypotensive drugs) the risk of development of tachycardia, increase in the ABP, in some cases - an acute disorder of cerebral circulation increases.

Interaction with other medicines:

Simultaneous use with powerful inhibitors of an isoenzyme CYP1A2 (флувоксамин, ciprofloxacin) considerably increases concentration of a tizanidin in a blood plasma and increases probability of development of side reactions.
Hypotensive drugs, including diuretics, at simultaneous use with tizanidiny increase risk of development of the expressed decrease in the ABP and bradycardia.
At simultaneous use with peroral contraceptive drugs, antiarrhytmic drugs, Cimetidinum, norfloxacin, rofekoksiby, tiklopidiny the clearance of a tizanidin considerably decreases.
At simultaneous use with tizanidiny sedative drugs and ethanol the risk of oppression of the central nervous system increases.
Paracetamol increases TCmax for 16 min. (clinical value has no).

Contraindications:

• Hypersensitivity to a tizanidin or other components of drug;
• pregnancy;
• breastfeeding period;
• age up to 18 years (efficiency and safety are not established);
• the expressed abnormal liver functions;
• simultaneous use with powerful inhibitors of an isoenzyme CYP1A2 (флувоксамин, ciprofloxacin), alfa2-adrenomimetikam, a lactose intolerance, deficit of lactase, glyukozo-galaktozny malabsorption.
With care

• Patients are more senior than 65 years; renal failure (KK less than 25 ml/min.);
• simultaneous use with peroral contraceptive drugs, antiarrhytmic drugs, Cimetidinum, norfloxacin, rofekoksiby, tiklopidiny, digoxin, beta adrenoblockers, sedative drugs, ethanol, diuretics, hypotensive drugs.

Overdose:

Symptoms: nausea, vomiting, the expressed decrease in the ABP, lengthening of an interval of QT (c), dizziness, drowsiness, a miosis, alarm, disturbance of breath, a lump.
Treatment: gastric lavage, repeated use of absorbent carbon, carrying out an artificial diuresis, symptomatic therapy, reception of a large amount of liquid.

Storage conditions:

Period of validity 3 years. Not to use after a period of validity. To store at a temperature not above 25 °C. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Tablets of 2 mg, 4 mg.
On 10 tablets in the blister from polyvinylchloride and aluminum foil.
On 2, 3, 5 or 10 blisters together with the application instruction in a cardboard pack.