Tizanidine-ZZ pills 4mg, 30pcs

Composition

1 tablet contains:

Active ingredient:

tizanidine hydrochloride-4,576 mg in terms of tizanidine-4 mg;

excipients:

lactose monohydrate-140.0 mg;

microcrystalline cellulose

102-129.824 mg; colloidal silicon dioxide (aerosil) – 2.8 mg;

magnesium stearate-2.8 mg

Pharmacological action

Pharmacotherapy group: muscle relaxant of central action

ATX code: M 03 BX 02

Pharmacological properties

Pharmacodynamics

Tizanidine is a central muscle relaxant, the main point of application of its action is located in the spinal cord. By stimulating presynaptic alpha_-2receptors, it inhibits the release of excitatory amino acids that stimulate N-methyl-D-aspartate receptors (NMDA receptors). As a result, polysynaptic transmission of arousal is suppressed at the level of intermediate neurons in the spinal cord. Since this mechanism is responsible for excessive muscle tone, when it is suppressed, muscle tone decreases. In addition to its muscle-relaxing properties, tizanidine also has a central moderate analgesic effect.

The drug Tizanidin-SZ is effective both in acute painful muscle spasm and in chronic spinal and cerebral spasticity. Reduces spasticity and clonic seizures, which reduces resistance to passive movements and increases the volume of active movements.

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

Pharmacokinetics

Suction

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

Distribution

The average volume of distribution at steady state with intravenous use is 2.6 l / kg. Binding to plasma proteins is 30%.

Metabolism

Tnzanidine is rapidly and significantly (about 95%) metabolized in the liver. In vitro, tizanidine is mainly metabolized by the cytochrome P450 isoenzyme CYP1A2. Metabolites are inactive.

Deduction

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

Influence of food

Concomitant food intake does not affect the pharmacokinetics of tizanidine (when used 4 mg in tablet form or 12 mg in modified-release capsules). Despite the fact that the value of C_max increases by 1/3 when taken after a meal, this is not clinically significant. No significant effect on absorption (AUC, area under the concentration-time pharmacokinetic curve) was observed.

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) of ≤25 ml/min) With_mAh tizanidine in plasma in 2 times higher than in healthy volunteers, the ultimate half-life is about 14 hours, which leads to increased (about 6 times) systemic bioavailability of tizanidine (measured by AUC).

Patients with impaired liver function

No special studies have been conducted in this category of patients. Since tizanidine is primarily metabolized in the liver by the cytochrome CYP1A2 isoenzyme, impaired liver function can lead to increased systemic exposure to the drug.

Patients over 65 years of age

Data on pharmacokinetics in patients of this group are limited.

Dependence on gender and race

Gender does not affect the pharmacokinetic properties of tizanidine.

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

Indications

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 hip osteoarthritis.

Skeletal muscle spasticity in neurological diseases, such as multiple sclerosis, chronic myelopathy, degenerative diseases of the spinal cord, consequences of cerebral circulation disorders and cerebral palsy (patients over 18 years of age).

Use during pregnancy and lactation

Pregnancy

Since no controlled studies have been conducted on the use of tizanidine in pregnant women, it should not be used during pregnancy, unless the potential benefit outweighs the possible risk.

No teratogenicity events were detected in animal studies. When used at doses of 10 and 30 mg/kg per day, an increase in gestational age was observed in animals, cases of prenatal and postnatal fetal loss, as well as fetal development delay were recorded. When using the above doses, females showed marked signs of muscle relaxation and sedation. Based on the body surface area, these doses exceeded the maximum recommended dose for humans(0.72 mg/kg per day) by 2.2 and 6.7 times.

Breast-feeding

In animal studies, tizanidine was excreted in small amounts in the milk of lactating females. Do not use the drug during breastfeeding, as there are no data on the penetration of tizanidine into human breast milk.

Pregnancy Test

Before starting the use of Tizanidin-SZ in patients with preserved reproductive potential, it is recommended to obtain the result of a pregnancy test.

Impact on fertility

In animal studies, there was no adverse effect on male and female fertility when using tizanidine at a dose of 10 mg / kg per day and 3 mg/kg/ day, respectively. There was a decrease in fertility in males treated with tizanidine at a dose exceeding 30 mg/kg per day, and in females-at a dose exceeding 10 mg / kg per day. Based on the body surface area, these doses exceeded the maximum recommended dose for humans (0.72 mg/kg per day) by 2.2 and 6.7 times. When using these doses from the mother, behavioral effects and clinical signs were observed, including severe sedation, weight loss and ataxia.

Contraindications

• Hypersensitivity to tizanidine or to any other component of the drug.
• Severe hepatic impairment.
• Concomitant use with potent inhibitors of the CYP1A2 isoenzyme, such as fluvoxamine or ciprofloxacin.
• It is not recommended for patients with rare hereditary diseases such as lactase deficiency, lactose intolerance, glucose-galactose malabsorption, as the dosage form contains lactose.
• Experience with the drug in patients under 18 years of age is limited. The use of Tizanidin-SZ in patients of this population is not recommended.

With caution

Caution is recommended when using the drug in patients over 65 years of age, patients with impaired renal function, patients with moderate hepatic impairment.

Caution should be exercised when using Tizanidin-SZ concomitantly with drugs that prolong the QT interval (for example, cisapride, amitriptyline, azithromycin).

Side effects

Drowsiness, increased fatigue, dizziness, dry mouth, decreased blood pressure, nausea, gastrointestinal disorders, and increased activity of hepatic transaminases were observed when taking small doses recommended for relieving painful muscle spasms. Usually, the above-described adverse reactions are moderate and transient.

When taking higher doses recommended for the treatment of spasticity, the above symptoms are more frequent and more pronounced, but they rarely require discontinuation of the drug due to the severity of PR. In addition, the following phenomena may occur: bradycardia, muscle weakness, insomnia, sleep disorders, hallucinations, hepatitis.

Adverse reactions are grouped according to the MedDRA classification of Organs and organ systems, and within each group they are listed in decreasing order of frequency. The following criteria were used to assess the incidence of HP: very common (≥ 1/10); common (from ≥ 1/100, < 1/10); uncommon (≥ 1/1000, <1/100); rare(≥ 1/10000, < 1/1000); very rare (

Nervous system disorders: very often ‒ drowsiness, dizziness.

Mental disorders: often ‒ insomnia, sleep disorders.

Cardiac disorders: infrequently-bradycardia.

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

Disorders of the digestive system: very often–gastrointestinal disorders, dry mouth; often–nausea.

Musculoskeletal and connective tissue disorders: very often ‒ muscle weakness.

General disorders and disorders at the injection site: very often ‒ increased fatigue.

Laboratory and instrumental data: often–increased activity of hepatic transaminases. If Tizanidin-SZ is abruptly discontinued after prolonged treatment and/or taking high doses of the drug (as well as after simultaneous use with antihypertensive drugs), tachycardia and increased blood pressure were observed, which in some cases can lead to acute cerebrovascular accident, and therefore the dose of Tizanidin-SZ should be reduced gradually until the drug is completely discontinued.

Individual HP reports based on clinical use data Since HP reports are received voluntarily in the post-marketing period from a population of indeterminate size, it is not possible to reliably estimate the frequency of their occurrence (the frequency is unknown).

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

Mental disorders: hallucinations, confusion.

Nervous system disorders: dizziness.

Visual disturbances: blurred vision.

Liver and biliary tract disorders: hepatitis, liver failure.

Skin and subcutaneous tissue disorders: skin rash, erythema, pruritus, dermatitis.

General disorders and disorders of joint use: asthenia, withdrawal syndrome.

If any of the side effects listed in the instructions get worse, or you noticeany other side effects not listed in the instructions, tell your doctor.

Interaction

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

Concomitant use of Tizanidine-SZ with inducers of the CYP1A2 isoenzyme may lead to a decrease in the concentration of tizanidine in blood plasma, which may 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 using tizanidine with fluvoxamine or ciprofloxacin, a 33-fold and 10-fold increase in tizanidine AUC was 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).

Not recommended combinations with tizanidine

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, ticlopidine.

Combinations with tizanidine that require caution Caution should be exercised when using Tizanidine-SZ concomitantly with drugs that prolong the QT interval (for example, cisapride, amitriptyline, azithromycin).

Antihypertensive drugs

Concomitant use of Tizanidine-SZ with antihypertensive drugs, including diuretics, can sometimes cause a marked decrease in blood pressure (in some cases, up to circulatory collapse and loss of consciousness) and bradycardia.

When the drug Tizanidin-SZ was abruptly discontinued after simultaneous use with antihypertensive drugs, tachycardia and increased blood pressure were observed, which in some cases can lead to acute cerebrovascular accident.

Rifampicin

Simultaneous use of tizanidine and rifampicin leads to a 50% decrease in the concentration of tizanidine in 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 concomitant use of rifampicin and tizanidine should be avoided if it is not possible, careful selection of the dose of tizanidine (increase) is recommended.

Tobacco smoking

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

Alcohol

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

Other medicinal products

Sedatives, sleeping pills (benzodiazepine, baclofen), and other medications such as antihistamines may also increase the sedative effect of tizanidine. Avoid taking the drug with other alpha_-2-adrenergic agonists (for example, clonidine) due to the potential increase in the hypotensive effect.

How to take, course of use and dosage

The drug Tizanidin-SZ has a narrow therapeutic index and high variability in the concentration of tizanidin in blood plasma, so careful dose selection is necessary.

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

The drug is taken orally. Tablets 2 mg and 4 mg can be divided into two equal parts.

In case of painful muscle spasm, the drug Tizanidin-SZ is usually used at a dose of 2 mg or 4 mg 3 times a day.

In severe cases, additional use of 2 mg or 4 mg is possible (preferably before bedtime due to possible increased drowsiness).

If skeletal muscle spasticity is caused by 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 the dose of 36 mg per day.

Use in patients over 65 years of age

Experience with the use of Tizanidin-SZ in patients over the age of 65 years and older is limited. It is recommended to start therapy with a minimum dose with a gradual increase until the optimal ratio of tolerability and effectiveness of therapy is achieved.

Use in patients with impaired renal function

Treatment of patients with renal insufficiency (creatinine clearance 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 tolerability 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 Tizanidin-SZ in patients with severe hepatic impairment is contraindicated.

In patients with moderate hepatic impairment, the drug should be used with caution; it is recommended to start therapy with a minimum dose, with a gradual increase until the optimal ratio of tolerability and effectiveness of therapy is achieved. Recommendations for monitoring liver function indicators are listed in the section “Special instructions”.

Interruption of treatment

When discontinuing therapy with Tizanidine-SZ 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.

Overdose

To date, several reports of overdose with Tizanidine-SZ have been received, including a case where the dose taken was 400 mg. In all cases, the recovery was uneventful.

Symptoms: nausea, vomiting, decreased blood pressure, prolongation of the QT interval (c), dizziness, drowsiness, miosis, anxiety, respiratory depression, coma.

Treatment. To remove the drug from the body, repeated use of activated carbon is recommended. Forced diuresis may also accelerate the elimination of tizanidine. In the future, symptomatic treatment is carried out.

Description

Tablets are white or almost white in color, round, flat-cylindrical with a chamfer and a risk on one side.

Special instructions

Hypotension may occur during the use of the drug Tizanidin-SZ, as well as as a result of drug interaction with inhibitors of the CYP1A2 isoenzyme and/or antihypertensive drugs. A marked decrease in blood pressure can lead to loss of consciousness and circulatory collapse.

Cases of tizanidine-related hepatic impairment have been reported, but these cases were rare with a daily dose of up to 12 mg.In this regard, it is recommended to monitor functional “liver tests” once a month in the first 4 months of treatment in patients who receive tizanidine at a daily dose of 12 mg or higher, as well as in cases where there are clinical signs that suggest impaired liver function, such as unexplained nausea, anorexia, fatigue. If the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (ACT) in serum persistently exceeds the upper limit of normal by 3 times or more, the use of Tizanidin-SZ 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 proper and prolonged use, the frequency of pregnancy is

Influence on the ability to drive vehicles and mechanisms

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

Form of production

Tablets 2 mg and 4 mg. 10 tablets in a cell contour package made of PVC film and aluminum foil. 30 tablets in polymer cans of the BP type made of low-pressure polyethylene with lids made of high-pressure polyethylene or in polymer bottles made of low-pressure polyethylene with lids made of high-pressure polyethylene. Each jar, bottle,2,3,5 cell contour packages together with the instructions for use are placed in a cardboard pack.

Storage conditions

In a place protected from light, at a temperature not exceeding 25 ° C. Keep out of reach of children.

Shelf

life is 3 years. Do not use after the expiration date indicated on the package.

Active ingredient

Tizanidine

Conditions of release from pharmacies

By prescription

Dosage form

Tablets