Tizanidine-SZ, tablets 2 mg 30 pcs

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Indications

Painful muscle spasm:

related to static and functional diseases of the spine (cervical and lumbar syndromes);

after surgical interventions, such as for a herniated disc or osteoarthritis of the hip joint.

Spasticity of the skeletal muscles in neurological diseases, e.g., multiple sclerosis, chronic myelopathy, degenerative diseases of the spinal cord, sequelae of cerebral palsy and infantile cerebral palsy (patients over 18 years).

Active ingredient

Composition

1 tablet contains:

the active substance:

tizanidine hydrochloride – 2.288 mg in terms of tizanidine – 2 mg;

excipients:

Lactose monohydrate – 70.0 mg;

Microcrystalline cellulose 102 – 64.912 mg;

Colloidal silica (aerosil) – 1.4 mg;

Magnesium stearate – 1.4 mg.

How to take, the dosage

The drug Tizanidine-SZ has a narrow therapeutic index and a high variability of tizanidine plasma concentrations; therefore, careful dosage selection is necessary.

The dose and dosing regimen should be adjusted individually according to the patient’s needs. The use of the drug in the 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 two equal parts.

In painful muscle spasm, Tizanidine-SZ is usually used in a dose of 2 mg or 4 mg 3 times daily.

In severe cases, an additional 2 mg or 4 mg may be used (preferably before bedtime because of possible increased drowsiness).

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

The use in patients over 65 years of age

The experience of using Tizanidine-SZ in patients aged 65 years and older is limited. It is recommended to start therapy with minimum dose with gradual increase until optimal balance of tolerability and efficacy is achieved.

The use in patients with renal impairment Treatment of patients with renal impairment (CKD less than 25 ml/min) is recommended to start with a dose of 2 mg once daily. Increase the dose in small “steps” with regard to tolerability and efficacy. If a more pronounced effect is needed, it is recommended to first increase the dose administered once daily, followed by increasing the frequency of administration.

Patient use in patients with hepatic impairment

The use of Tizanidine-SZ in patients with severe hepatic impairment is contraindicated.

In patients with mild hepatic impairment, use with caution; it is recommended that therapy start at the lowest dose with gradual increasing until an optimal balance of tolerability and efficacy is achieved. For recommendations on control of liver function, see section “Cautions”.

If therapy is discontinued to reduce the risk of ricochet hypertension and tachycardia, the dose should be slowly reduced until complete withdrawal, especially in patients who have been treated with high doses for a prolonged period of time.

Interaction

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

The concomitant use of Tizanidine-Z with inducers of CYP1A2 isoenzyme may decrease the plasma concentration of Tizanidine and this may decrease the therapeutic effect of the drug.

Controlled combinations with tizanidine

The simultaneous use of tizanidine with fluvoxamine or ciprofloxacin, CYP1A2 inhibitors, is contraindicated. When using tizanidine with fluvoxamine or ciprofloxacin a 33-fold and 10-fold increases in AUC of tizanidine are observed, respectively. Concomitant use may result in significant and prolonged hypotension accompanied by somnolence, dizziness, decreased rate of psychomotor reactions (in some cases up to circulatory collapse and loss of consciousness).

Not recommended combinations with tizanidine

Combinations with tizanidine requiring caution

Hypotensive drugs

The concomitant use of the drug Tizanidine-SZ with hypotensive drugs, including diuretics, may sometimes cause a marked decrease in BP (in some cases up to and including circulatory collapse and loss of consciousness) and bradycardia.

In abrupt withdrawal of the drug Tizanidine-SZ after concomitant use with hypotensive drugs, tachycardia and increased BP have been noted, which in some cases can lead to acute cerebral circulation disorder.

Rifampicin

The simultaneous use of tizanidine and rifampicin leads to 50% decrease of tizanidine concentration in plasma. As a consequence, the therapeutic effect of the drug may decrease, which may be of clinical significance in some patients. Prolonged concomitant use of rifampicin and tizanidin should be avoided if careful selection of the tizanidine dose (increase) is not possible.

Tobacco smoking

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

Alcohol

Other drugs

Special Instructions

Hypotension may occur against the background of using the drug Tizanidine-SZ, as well as a result of drug interaction with CYP1A2 isoenzyme inhibitors and/or hypotensive drugs. Significant decrease in BP may lead to loss of consciousness and circulatory collapse.

Contraception

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

Patients who have drowsiness, dizziness or any signs of arterial hypotension while taking the drug should be advised to refrain from activities which require high concentration and quick reaction time, such as driving vehicles and operating machinery.

Contraindications

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

– Serious hepatic dysfunction.

– Not recommended for patients with rare hereditary diseases such as lactase deficiency, lactose intolerance, glucose-galactose malabsorption because the drug form contains lactose.

– Experience of using the drug in patients under 18 years of age is limited. The use of Tizanidine-SZ in patients in this population is not recommended.

Side effects

Drowsiness, increased fatigue, dizziness, dry mouth, decreased blood pressure, nausea, gastrointestinal disturbances, and increased liver transaminase activity have been reported with low doses recommended to relieve painful muscle spasm. Usually the adverse reactions described above are moderate and transient.

When taking higher doses recommended for the treatment of spasticity, the above HP occur more frequently and are more severe, 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 disturbances, hallucinations, and hepatitis.

The adverse reactions (HP) are grouped according to the MedDRA classification of organs and organ systems, within each group listed in decreasing order of frequency of occurrence. The following criteria were used to assess the incidence of HP: very common (≥1/10); frequent (≥1/100, <1/10); infrequent (≥1/1000, <1/100); rare (≥1/10000, <1/1000); very rare (<1/10000), including individual reports.

Nervous system disorders: very common – drowsiness, dizziness.

Psychiatric disorders: often – insomnia, sleep disturbances.

Cardiac disorders: infrequent – bradycardia.

Vascular disorders: often – decreased BP (in some cases pronounced, up to and including circulatory collapse and loss of consciousness).

Digestive system disorders: very common – gastrointestinal disorders, dry mouth; frequent – nausea.

Muscular and connective tissue disorders: very common – muscle weakness.

General disorders and disorders at the site of administration: very often – increased fatigue.

Laboratory and instrumental data: often – increased liver transaminase activity. When abrupt withdrawal of Tizanidine-SZ after long-term treatment and/or taking high doses of the drug (as well as after concomitant use with hypotensive drugs) tachycardia and high BP have been reported, which may in some cases lead to acute cerebral circulation disorders, therefore the dose of Tizanidine-SZ should be reduced gradually until complete withdrawal of the drug.

Anecdotal reports of HP according to clinical practice use

Since post-registration reports of HP come voluntarily from a population of uncertain size, it is not possible to reliably estimate the frequency of occurrence (frequency is unknown).

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

Psychiatric disorders: hallucinations, confusion.

Nervous system disorders: dizziness.

Visual disorders: blurred vision.

Liver and biliary tract disorders: hepatitis, liver failure.

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

General disorders and disorders together with the administration: asthenia, withdrawal syndrome.

If any of the side effects listed in the instructions worsen, or if you notice any other side effects not listed in the instructions, tell your doctor.

Overdose

To date, there have been several reports of Tizanidine-SZ overdose, including a case in which the dose taken was 400 mg. In all cases, recovery has been uneventful.

Symptoms: nausea, vomiting, decreased BP, prolonged QT interval (c), dizziness, somnolence, miosis, anxiety, respiratory depression, coma.

Treatment. Multiple applications of activated charcoal are recommended to eliminate the drug from the body. Forced diuresis may also accelerate excretion of tizanidine. Thereafter, symptomatic treatment is carried out.

Pregnancy use

Pregnancy

There have been no controlled studies of tizanidine in pregnant women; it should not be used during pregnancy unless the potential benefit exceeds the possible risk.

There have been no studies in animals showing teratogenicity. When administered in doses of 10 and 30 mg/kg per day in animals, an increase in gestational age and cases of prenatal and postnatal fetal loss as well as fetal retardation have been reported. When the above doses were used in females, pronounced signs of myorelaxation and sedation were observed. Based on body surface area, the indicated doses exceeded the maximum recommended dose for humans (0.72 mg/kg per day) by a factor of 2.2 and 6.7.

Breastfeeding

Pregnancy test

Pregnancy test results are recommended before starting Tizanidine-SZ in patients with preserved reproductive potential.

In animal studies, there have been no adverse effects on fertility in male and female animals when using Tizanidine at a dose of 10 mg/kg/day and 3 mg/kg/day, respectively. There was a decrease in fertility in males receiving tizanidine at a dose greater than 30 mg/kg/day and in females at a dose greater than 10 mg/kg/day. Based on body surface area, the indicated doses exceeded the maximum recommended dose for humans (0.72 mg/kg per day) by a factor of 2.2 and 6.7. Behavioral effects and clinical signs including marked sedation, weight loss, and ataxia were noted on the maternal side when the indicated doses were administered.

Similarities