Tizanidin-SZ, tablets 4 mg 30 pcs

Indications

Painful muscle spasm:

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

Active ingredient

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 silica (aerosil) – 2.8 mg;

Magnesium stearate – 2.8 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. As a rule, the optimal therapeutic effect is achieved at 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.

Application in patients over 65 years

The experience with 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.

Application in patients with renal impairment

The treatment of patients with renal impairment (CKR less than 25 ml/min) is recommended to start with a dose of 2 mg once daily. The dose is increased in small “steps” taking into account tolerability and efficacy. If a more pronounced effect is needed, it is recommended to first increase the dose administered once daily, after which the frequency of use is increased.

Application in patients with hepatic impairment

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

In patients with moderate hepatic impairment, use with caution; it is recommended that therapy begin with the lowest dose and gradually increase until an optimal balance of tolerability and efficacy is achieved. For recommendations on monitoring of liver function, see section “Cautions”.

Cessation of treatment

If therapy with Tizanidine-SZ is discontinued to decrease 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 long 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 isoenzyme inhibitors, is contraindicated.

In concomitant use of tizanidine with fluvoxamine or ciprofloxacin a 33-fold and 10-fold increase in AUC of tizanidine is noted, 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

It is not recommended to use tizanidine concomitantly with other CYP1A2 isoenzyme inhibitors – antiarrhythmic drugs (amiodarone, mexiletine, propafenone), cimetidine, some fluoroquinolones (enoxacin, pefloxacin, norfloxacin), rofecoxib, oral contraceptives, ticlopidine.

Combinations with tizanidine that require caution Care should be taken when using Tizanidine-SZ concomitantly with drugs that prolong the QT interval (e.g., cisapride, amitriptyline, azithromycin).

Hypotensive drugs

The simultaneous use of the drug Tizanidine-SZ with hypotensive drugs, including diuretics, can 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, and careful selection of the tizanidine dose (increase) is recommended when this is not possible.

Smoking tobacco

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

Alcohol should be avoided during therapy with the drug because it may increase the likelihood of adverse events (e.g., decreased BP and lethargy). Tizanidine may increase the depressant effect of alcohol on the central nervous system.

Other drugs

Sedatives, sleeping pills (benzodiazepine, baclofen) and other drugs such as antihistamines may also increase the sedative effect of Tizanidine. The drug should be avoided with other alpha2 adrenoreceptor agonists (e.g., clonidine) due to the potential increase in the hypotensive effect.

Special Instructions

Hypotension may occur during the use of 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.

Liver function abnormalities associated with tizanidine have been reported, but these cases have been rare with daily doses up to 12 mg. In this regard, it is recommended to monitor functional “liver function tests” once a month during 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 clinical signs suggestive of liver dysfunction are observed, such as unexplained nausea, anorexia and fatigue. If serum alanine aminotransferase (ALT) and aspartate aminotransferase (ACT) activity persistently exceeds the upper limit of normal by 3 times or more, the use of Tizanidine-SZ should be stopped.

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 and for 1 day after discontinuation of the drug, patients of preserved reproductive potential should use reliable methods of contraception (with correct and continuous use, the rate of pregnancy is < 1%).

Influence on driving and operating ability

. Patients who experience drowsiness, dizziness or any signs of arterial hypotension while using the drug should be advised to refrain from activities requiring high concentration and quick reactions, such as driving vehicles and operating machinery.

Synopsis

Contraindications

Cautions

Cautions are advised for use in patients over 65 years of age, patients with impaired renal function, patients with moderate hepatic function.

Cautions are advised for concomitant use of Tizanidine-SZ with agents that prolong the QT interval (e.g., cisapride, amitriptyline, azithromycin).

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 undesirable reactions (HPs) 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.

Mental disorders: often – insomnia, sleep disturbances.

Cardiac disorders: infrequent – bradycardia.

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

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

Muscle and connective tissue disorders very often- muscular weakness.

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

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

Anecdotal reports of HP according to clinical practice use Because HP is reported voluntarily from a population of uncertain size in the post-registration period, 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, hepatic failure.

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

General disorders and disorders Injection: asthenia, withdrawal syndrome.

If any of the indicated instructions side effects worsen, or you notice anyany other side effects not

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

As controlled studies of tizanidine use in pregnant women have not been conducted, 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 registered. 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

In animal studies, tizanidine was excreted in small amounts with milk of lactating females. The drug should not be used during breastfeeding, as there are no data on the penetration of tizanidine into human milk.

Pregnancy test

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

In animal studies, there were no adverse effects on fertility in male and female animals when Tizanidine was used at doses 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/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