Tizanidine-Teva tablets 4mg, No. 30

Painful muscle spasm:

• associated with static and functional diseases of the spine (cervical and lumbar syndromes);

• after surgical interventions, for example, for a herniated disc or osteoarthritis of the hip joint.

• Spasticity of skeletal muscles in neurological diseases, for example, in multiple sclerosis, chronic myelopathy, degenerative diseases of the spinal cord, the consequences of cerebrovascular accidents and cerebral palsy (patients over 18 years of age).

The drug Tizanidine-Teva has a narrow therapeutic index and high variability in the concentration of tizanidine in blood plasma, therefore, a careful selection of the dose is required.

The dose and dosage regimen should be selected individually, depending on the needs of the patient. The use of the drug at an initial dose of 2 mg 3 times a day reduces the risk of side effects. The drug is taken orally.

The 2 mg and 4 mg tablets can be divided into portions at risk to facilitate swallowing.

For painful muscle spasm, Tizanidine-Teva is usually used in a dose of 2 mg or 4 mg 3 times a day. In severe cases, an additional use of 2 mg or 4 mg is possible (preferably at bedtime due to the possible increase in drowsiness).

For skeletal muscle spasticity due to neurological diseases, the initial daily dose should not exceed 6 mg, divided into 3 doses. The dose can be increased gradually, by 2-4 mg, at intervals of 3-4 to 7 days. As a rule, the optimal therapeutic effect is achieved with a daily dose of 12 to 24 mg, divided into 3 or 4 doses at regular intervals. Do not exceed a dose of 36 mg per day.

Use in patients over 65 years of age

The experience of using the drug Tizanidine-Teva in patients over the age of 65 is limited. It is recommended to start therapy with a minimum dose with a gradual increase until the optimal balance of tolerance and effectiveness of therapy is achieved.

Use in patients with impaired renal function

Treatment of patients with renal insufficiency (CC less than 25 ml / min) is recommended to start with a dose of 2 mg once a day. Increasing the dose is carried out in small 'steps' taking into account the tolerance and effectiveness. If it is necessary to achieve a more pronounced effect, it is recommended to first increase the dose applied once a day, after which the frequency of application is increased.

Use in patients with impaired liver function

The use of the drug Tizanidine-Teva in patients with severe liver dysfunction is contraindicated.

In patients with moderate liver dysfunction, the drug should be used with caution; it is recommended to start therapy with a minimum dose, with a gradual increase until the optimal balance of tolerance and effectiveness of therapy is achieved.

Recommendations for monitoring liver function indicators are indicated in the 'Special instructions' section.

Interruption of treatment

When discontinuing therapy with Tizanidine-Teva, in order to reduce the risk of developing rebound hypertension and tachycardia, the dose should be slowly reduced until the drug is completely discontinued, especially in patients receiving high doses of the drug for a long time.

1 tablet contains:

active ingredient tizanidine hydrochloride (in terms of tizanidine) 4.58 mg (4.00 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.

• Hypersensitivity to tizanidine or to any other component of the drug.

• Severe liver dysfunction.

• Concomitant use with potent inhibitors of the CYP1A2 isoenzyme, such as fluvoxamine or ciprofloxacin.

• Not recommended for patients with rare hereditary diseases such as lactase deficiency, lactose intolerance, glucose-galactose malabsorption, since the dosage form contains lactose.

• Experience with the drug in patients under 18 years of age is limited. The use of the drug Tizanidin-Teva in patients of this population is not recommended.

  Carefully

• It is recommended to be careful when using the drug in patients over 65 years of age, patients with impaired renal function, patients with moderate liver dysfunction. Caution must be exercised while using Tizanidine-Teva with drugs that prolong the QT interval (for example, cisapride, amitriptyline, azithromycin).

Pharmacodynamics

Tizanidine is a centrally acting muscle relaxant. The main point of application of its action is in the spinal cord. By stimulating presynaptic alpha2 receptors, it inhibits the release of excitatory amino acids that stimulate N-methyl-D-aspartate receptors (NMDA receptors). As a result, polysynaptic transmission of excitation is suppressed at the level of intermediate neurons of the spinal cord. Since it is this mechanism that is responsible for excess muscle tone, then when it is suppressed, muscle tone decreases. In addition to muscle relaxant properties, tizanidine also has a central, moderate analgesic effect.

The drug Tizanidine-Teva is effective both in acute painful muscle spasm and in chronic spasticity of spinal and cerebral origin. Reduces spasticity and clonic convulsions, as a result of which resistance to passive movements decreases and the range of active movements increases.

The muscle relaxant effect (measured on the Ashworth scale and using the 'pendulum' test) and side effects (decreased heart rate (HR) and decreased blood pressure (BP)) of the drug depend on the concentration of tizanidine in the blood plasma.

Pharmokinetics

Suction

Tizanidine is absorbed quickly and almost completely. The maximum concentration in blood plasma (Cmax) is reached approximately 1 hour after taking the drug. Due to the pronounced metabolism during the 'first pass' through the liver, the average bioavailability is about 34%. Cmax of tizanidine is 12.3 ng / ml and 15.6 ng / ml after single and multiple doses of tizanidine at a dose of 4 mg, respectively.

Distribution

The average volume of distribution at steady state when administered intravenously is 2.6 l / kg. Plasma protein binding is 30%.

Metabolism

Tizanidine is rapidly and largely (about 95%) metabolized in the liver. In vitro, tizanidine is metabolized mainly by the CYP1A2 isoenzyme of the cytochrome P450 system. The metabolites are inactive.

Withdrawal

The average half-life of tizanidine from the systemic circulation is 2-4 hours, excretion is carried out mainly by the kidneys (approximately 70% of the dose) in the form of metabolites; the share of unchanged substance is about 4.5%.

Influence of food

Simultaneous food intake does not affect the pharmacokinetics of tizanidine (when using 4 mg in the form of tablets or 12 mg in the form of modified-release capsules).

Despite the fact that the Cmax value increases by 1/3 when taken after meals, this is not clinically significant. There is no significant effect on absorption (AUC, area under the concentration-time pharmacokinetic curve).

Tizanidine in the dose range from 1 mg to 20 mg has linear pharmacokinetics.

Features of pharmacokinetics in certain groups of patients

Patients with impaired renal function

In patients with impaired renal function (creatinine clearance (CC)? 25 ml / min), the Cmax of tizanidine in blood plasma is 2 times higher than in healthy volunteers, the final half-life reaches 14 hours, which leads to an increased (approximately 6 times) systemic bioavailability of tizanidine (measured by AUC).

Patients with impaired liver function

Special studies have not been conducted in patients of this category. Since tizanidine is predominantly metabolized in the liver by the cytochrome CYP1A2 isoenzyme, abnormal liver function may lead to an increase in systemic exposure to the drug.

Patients over 65

Pharmacokinetic data in this group of patients are limited.

Dependence on gender and race

Gender has no effect on the pharmacokinetic properties of tizanidine.

The effect of ethnicity and race on the pharmacokinetics of tizanidine has not been studied.

Side effects

Nervous system disorders: very often - drowsiness, dizziness; frequency unknown - headache, ataxia, dysarthria.

Mental disorders: often - insomnia, sleep disturbances; rarely - hallucinations *; frequency unknown - confusion.

Heart disorders Painful muscle spasm:

- associated with static and functional diseases of the spine (cervical and lumbar syndromes);

- after surgical interventions, for example, for a herniated disc or osteoarthritis of the hip joint.

Spasticity of skeletal muscles in neurological diseases, for example, in multiple sclerosis, chronic myelopathy, degenerative diseases of the spinal cord, the consequences of cerebrovascular accidents and cerebral palsy (patients over 18 years of age).

a: often - bradycardia.

Vascular disorders: often - a decrease in blood pressure (in some cases, pronounced, up to circulatory collapse and loss of consciousness).

Digestive system disorders: very often - gastrointestinal disorders, dry mouth; often - nausea; frequency unknown - abdominal pain, vomiting.

Musculoskeletal and connective tissue disorders: very common - muscle weakness.

Immune system disorders: frequency unknown - hypersensitivity reactions, including anaphylactic reactions, angioedema and urticaria.

Violations of the organ of vision: frequency unknown - blurred vision.

Violations of the skin and subcutaneous tissues: rarely - skin rash; frequency unknown - erythema, pruritus, dermatitis.

Liver and biliary tract disorders: very rarely - hepatitis, liver failure.

General disorders and disorders at the injection site: very often - increased fatigue; often - withdrawal syndrome **; frequency unknown - asthenia, loss of appetite.

Laboratory and instrumental data: often - an increase in the activity of hepatic transaminases.

* Hallucinations are usually possible in patients using potentially hallucinogenic drugs, such as antidepressants.

** With a sharp withdrawal of the drug Tizanidine-Teva after prolonged treatment and / or taking high doses of the drug (as well as after using it together with antihypertensive drugs), the risk of developing tachycardia, an increase in blood pressure, in some cases - an acute violation of cerebral circulation increases, and therefore the dose of Tizanidine-Teva should be reduced gradually until the drug is completely discontinued.

If any of the side effects indicated in the instructions are aggravated, or you notice any other side effects that are not indicated in the instructions, inform your doctor.

Special conditions

Hypotension can occur with the use of the drug Tizanidine-Teva, as well as as a result of drug interactions with inhibitors of the CYP1A2 isoenzyme and / or antihypertensive drugs. A pronounced decrease in blood pressure can lead to loss of consciousness and circulatory collapse.

Cases of liver dysfunction associated with tizanidine have been reported, but these cases have been rare with a daily dose of up to 12 mg. In this regard, it is recommended to monitor functional 'liver function tests' once a month in the first 4 months of treatment in patients receiving tizanidine in a daily dose of 12 mg or more, as well as in cases where clinical signs are observed that suggest liver dysfunction such as unexplained nausea, anorexia, feeling tired. In the case when the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the serum persistently exceeds the upper limit of the norm by 3 times or more, the use of the drug Tizanidine-Teva should be discontinued.

Contraception

Patients with preserved reproductive potential should be informed about the adverse effects of the drug on the developing fetus, identified in animal studies. During the use of the drug, as well as within 1 day after discontinuation of the drug, patients with preserved reproductive potential should use reliable methods of contraception (with correct and prolonged use of which, the pregnancy rate is <1%).

Influence on the ability to drive vehicles and work with equipment

Patients who experience drowsiness, dizziness or any signs of arterial hypotension while using the drug should be advised to refrain from activities that require a high concentration of attention and a quick reaction, for example, driving vehicles and mechanisms.

Drug interactions

When using the drug Tizanidine-Teva with inhibitors of the isoenzyme CYP1A2, it is possible to increase the concentration of tizanidine in the blood plasma. In turn, an increase in the concentration of tizanidine in the blood plasma can lead to symptoms of drug overdose, including prolongation of the QT interval (c).

The simultaneous use of the drug Tizanidine-Teva with inducers of the isoenzyme CYP1A2 can lead to a decrease in the concentration of tizanidine in the blood plasma, which can lead to a decrease in the therapeutic effect of the drug.

Contraindicated combinations with tizanidine

Concomitant use of tizanidine with fluvoxamine or ciprofloxacin, inhibitors of the CYP1A2 isoenzyme, is contraindicated.

When tizanidine is used with fluvoxamine or ciprofloxacin, a 33-fold and 10-fold increase in tizanidine AUC is observed, respectively. The result of simultaneous use may be significant and prolonged hypotension, accompanied by drowsiness, dizziness, a decrease in the speed of psychomotor reactions (in some cases, up to circulatory collapse and loss of consciousness).

Combinations with tizanidine not recommended

It is not recommended to use tizanidine simultaneously with other inhibitors of the CYP1A2 isoenzyme - antiarrhythmic drugs (amiodarone, mexiletine, propafenone), cimetidine, some fluoroquinolones (enoxacin, pefloxacin, norfloxacin), rofecoxib, oral contraceptives, ticlopidin.

Combinations with tizanidine requiring caution

Caution must be exercised while using Tizanidine-Teva with drugs that prolong the QT interval (for example, cisapride, amitriptyline, azithromycin).

Antihypertensive drugs

The simultaneous use of the drug Tizanidine-Teva with antihypertensive drugs, including diuretics, can sometimes cause a pronounced decrease in blood pressure (in some cases up to circulatory collapse and loss of consciousness) and bradycardia.

With a sharp withdrawal of the drug Tizanidine-Teva after simultaneous use with antihypertensive drugs, the development of tachycardia and an increase in blood pressure were noted, which in some cases can lead to acute cerebrovascular accident.

Rifampicin

The simultaneous administration of tizanidine and rifampicin leads to a 50% decrease in the concentration of tizanidine in the blood plasma. As a result, the therapeutic effect of the drug may be reduced, which may be of clinical significance for some patients. Long-term simultaneous use of rifampicin and tizanidine should be avoided; if it is impossible, careful selection of the dose of tizanidine (increase) is recommended.

Smoking tobacco

The systemic bioavailability of tizanidine in smoking patients (more than 10 cigarettes per day) is reduced by about 30%. Long-term drug therapy in this category of patients may require higher doses of tizanidine than the average therapeutic dose.

Alcohol

During drug therapy, alcohol should be avoided, as it can increase the likelihood of developing adverse events (for example, a decrease in blood pressure and lethargy). Tizanidine can increase the depressing effect of alcohol on the central nervous system.

Other medicines

Sedatives, sleeping pills (benzodiazepine, baclofen), and other drugs such as antihistamines can also increase the sedative effect of tizanidine.

Avoid taking the drug with other alpha2-adrenergic receptor agonists (for example, clonidine) due to the potential increase in the hypotensive effect.