Tizanidine-Teva

active substances:

tizanidine hydrochloride (tizanidine) 4.58 mg (4.0 mg);

Excipients:

lactose (anhydrous lactose) 115.82 mg;

ProSolv SMCC 501 (microcrystalline cellulose 98%, colloidal silicon dioxide 2%) 45.15 mg;

ProSolv SMCC 901 (microcrystalline cellulose 98%, colloidal silicon dioxide 2%) 45.15 mg;

stearic acid 4.30 mg.

Tizanidine is an agonist of alpha2-adrenergic receptors located in the central nervous system at supraspinal and spinal levels.

By stimulating presynaptic alpha2-adrenergic receptors, tizanidine inhibits the release of excitatory amino acids, stimulating receptors sensitive to N-methyl-D-aspartate (NMDA receptors). As a result, the polysynaptic transmission of excitation is suppressed at the level of intermediate neurons of the spinal cord. Tizanidine does not directly affect skeletal muscle, neuromuscular synapses, or monosynaptic reflexes.

Tizanidine reduces spasticity and clonic convulsions, as a result of which the muscle resistance to passive movements in the joints decreases and the volume of active movements increases.

Pharmacokinetics

Absorption
Absorption of tizanidine is high, the time to reach maximum plasma concentration (TCmax) is 1-2 hours. Bioavailability is 34%. Eating does not affect pharmacokinetics.

Distribution and metabolism Distribution
volume - 2.6 l / kg. Communication with plasma proteins - 30%.
In the dose range from 4 to 20 mg, the pharmacokinetics is linear. Tizanidine is rapidly metabolized to a large extent in the liver (95%) to form inactive metabolites.

Withdrawal
The half-life (T1 / 2) is 3-5 hours. It is excreted mainly by the kidneys (70% - unchanged, 2.7% - in the form of metabolites) and excreted in feces (20%).

In patients with renal failure (creatinine clearance (CC) less than 25 ml / min), the maximum plasma concentration (Cmax) increases by 2 times, T1 / 2 - 14 hours, the area under the concentration-time curve (AUC) increases by 6 time.

Spasticity of skeletal muscles in multiple sclerosis, spinal cord injuries.

• Hypersensitivity to tizanidine or other components of the drug;
• pregnancy;
• period of breastfeeding;
• age up to 18 years (effectiveness and safety have not been established);
• severe impaired liver function;
• simultaneous use with powerful inhibitors of the CYP1A2 isoenzyme (fluvoxamine, ciprofloxacin), alpha2-adrenergic agonists, lactose intolerance, lactase deficiency, glucose-galactose malabsorption.

Carefully

• Patients older than 65 years; renal failure (CC less than 25 ml / min);
• simultaneous use with oral contraceptives, antiarrhythmic drugs, cimetidine, norfloxacin, rofecoxib, ticlopidine, digoxin, beta-adrenoblock

The frequency of side effects is classified in accordance with the recommendations of the World Health Organization: very often - at least 10%; often - at least 1%, but less than 10%; infrequently - not less than 0.1%, but less than 1%; rarely - not less than 0.01%, but less than 0.1%; very rarely - 0.01%, including single messages.

From the nervous system: often - drowsiness, dizziness; rarely - insomnia, hallucinations, sleep disorder.

From the cardiovascular system: often - lowering blood pressure, bradycardia.

From the digestive system: often - dryness of the oral mucosa; rarely - nausea, impaired gastrointestinal function.

On the part of the liver and biliary tract: very rarely - a transient increase in the activity of “liver” transaminases, hepatitis, and liver failure.

From the musculoskeletal system: rarely - muscle weakness.

Other: very often - increased fatigue; often - "cancellation" syndrome *.

* With a sharp cancellation after prolonged treatment and / or taking high doses of the drug (as well as after use together with antihypertensive drugs), the risk of developing tachycardia, increased blood pressure increases, in some cases, acute cerebrovascular accident.

The simultaneous use with powerful inhibitors of the CYP1A2 isoenzyme (fluvoxamine, ciprofloxacin) significantly increases the concentration of tizanidine in the blood plasma and increases the likelihood of adverse reactions.

Antihypertensive drugs, including diuretics, with simultaneous use with tizanidine increase the risk of developing a pronounced decrease in blood pressure and bradycardia.

With simultaneous use with oral contraceptives, antiarrhythmic drugs, cimetidine, norfloxacin, rofecoxib, ticlopidine, tizanidine clearance is significantly reduced.

With the simultaneous use of sedatives and ethanol with tizanidine, the risk of inhibition of the central nervous system increases.

Paracetamol increases TCmax by 16 min (has no clinical significance).

Inside. The initial dose is 2 mg, followed by a dose increase of 2 mg at intervals of at least 3-4 days.
The maximum daily dose is 36 mg.

The dosage regimen should be set individually, the daily dose is divided into several doses (up to 3-4), depending on the needs of the patient. Usually, more than 24 mg / day is not required.

Treatment of patients with renal failure (CC less than 25 ml / min) is recommended to start with a dose of 2 mg once a day. Increasing the dose should be carried out gradually, taking into account tolerance and effectiveness: first increase the dose, and then increase the frequency of use.

In patients over 65 years of age, Tizanidine should be used under close monitoring of renal function due to a possible decrease in glomerular filtration rate.

Symptoms: nausea, vomiting, marked decrease in blood pressure, lengthening of the QT interval (s), dizziness, drowsiness, miosis, anxiety, respiratory failure, coma.

Treatment: gastric lavage, repeated use of activated carbon, conducting forced diuresis, symptomatic therapy, taking a large amount of fluid.

Caution should be exercised when using the drug tizanidine in patients with renal failure. When using the drug Tizanidine in patients with renal failure (CC less than 25 ml / min), a dose reduction may be required.
It is recommended to monitor the functional parameters of the liver 1 time per month in the first 4 months of treatment in those patients taking Tizanidine in a daily dose of 12 mg or higher, as well as in cases where clinical signs are observed suggesting impaired liver function, such as an unexplained nausea, anorexia, feeling tired. In the case when the activity of “liver” transaminases is 3 times or more higher than the upper limit of the norm, the use of the drug Tizanidine should be discontinued.

With the simultaneous use of the drug Tizanidine with inhibitors of the isoenzyme CYP1A2, an increase in the concentration of tizanidine in the blood plasma is possible, which in turn can cause the development of symptoms of overdose, in particular, prolongation of the QT interval (c). The simultaneous use of the drug Tizanidine with inhibitors of the CYP1A2 isoenzyme and other drugs that can lead to a prolongation of the QT interval (c) is not recommended.

In the treatment of tizanidine with patients with cardiovascular disease, coronary heart disease, care should be taken. It is necessary to regularly monitor laboratory indicators of the functional state of the heart and monitor ECG indicators.

Tizanidine should be discontinued gradually due to the risk of developing “withdrawal” syndrome (see section “Side effects”).
Rare cases of muscle weakness have been reported with tizanidine (see section "Side effects"). In clinical studies, it was shown that tizanidine does not adversely affect the strength of muscle contraction.

Influence on the ability to drive vehicles and work with equipment

Caution should be exercised during the use of the drug Tizanidin-Teva due to the possible development of adverse reactions that can adversely affect the ability to drive vehicles and perform potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Pills.