Tizanidine, tablets 4 mg 30 pcs

Pharmacotherapeutic group: Myorelaxant of central action

ATC code: M03BX

Pharmacodynamics:

Indications

Painful muscle spasm:

• related to static and functional disorders of the spine (cervical and lumbar syndrome)
• After surgical interventions such as disc herniations or osteoarthritis of the hip joint.

Spasticity of the skeletal muscles in neurological diseases – in multiple sclerosis chronic myelopathy in degenerative diseases of the spinal cord, the consequences of circulatory disorders cerebral palsy (in patients over 18 years).

Active ingredient

Tizanidine

Composition

In one tablet:

The active ingredient:

tizanidine hydrochloride – 4.576 mg, in terms of tizanidine – 4.000 mg.

Auxiliary substances:

Lactose monohydrate (milk sugar) – 100,000 mg,

Microcrystalline cellulose – 90.624 mg,

stearic acid – 3,800 mg,

silicon dioxide colloid – 1,000 mg.

How to take, the dosage

Tizanidine has a narrow therapeutic index and high variability in plasma tizanidine concentrations, so careful dosage selection is necessary.

The initial dose of 2 mg 3 times daily can minimize the risk of adverse reactions. The drug is prescribed orally. The dose should be carefully adjusted to the individual needs of the patient.

In painful muscle spasm, a dose of 2 mg or 4 mg 3 times a day is prescribed. In severe cases, an additional 2 mg or 4 mg may be taken before bedtime (preferably before bedtime because of possible increased drowsiness).

In cases of skeletal muscle spasticity due to neurological diseases, the dose should be adjusted individually.

The initial daily dose should not exceed 6 mg divided into three doses – 2 mg 3 times a day. The dose can be gradually increased by 2-4 mg at intervals of 3 to 4 to 7 days. Usually the 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 the drug in patients aged 65 years and older is limited.

It is recommended to start therapy with the lowest dose with gradual increase until an optimal balance of tolerability and efficacy is achieved.

In patients with renal insufficiency (with creatinine clearance less than 25 ml/min), the recommended starting dose is 2 mg once daily. Increase the dose slowly, taking into account tolerability and efficacy. If a more pronounced effect is needed, it is recommended to first increase the dose prescribed once daily and then increase the number of times prescribed.

The use in patients with impaired renal function

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. Increase the dose in small “steps” with regard to tolerability and efficacy. If it is necessary to achieve a more pronounced effect, it is recommended to increase the dose 1 time per day first, then the frequency of use.

The use of the drug in patients with hepatic impairment

The use of the drug in patients with severe hepatic impairment is contraindicated. The use of the drug in patients with moderate hepatic impairment should be used with caution. It is recommended to start with low doses with gradual increase until optimal balance of tolerability and effectiveness of therapy is achieved (see “Cautionary Note”).

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

Interaction

Concomitant use of tizanidine and:

CYP1A2 isoenzyme inhibitors may increase tizanidine plasma concentrations. In turn, increase in plasma concentration of tizanidine may lead to symptoms of drug overdose, including prolongation of QT(c) interval.

The inducers of CYP1A2 isoenzyme may lead to decreased tizanidine plasma levels. Reduced plasma levels of tizanidine may lead to a decrease in the therapeutic effect of the drug.

Controlled combinations of tizanidine

The simultaneous use of tizanidine with fluvoxamine or ciprofloxacin, which are CYP1A2 inhibitors, is contraindicated.

When using tizanidine with fluvoxamine or ciprofloxacin a 33-fold and 10-fold increase in AUC of tizanidine is observed, respectively. The result of combined use can be clinically significant and prolonged decrease in blood pressure accompanied by drowsiness, dizziness, decrease in speed of psychomotor reactions (in some cases up to collapse and loss of consciousness).

Unrecommended combinations of tizanidine

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

Combinations with tizanidine requiring caution

Caution should be exercised when using tizanidine with drugs that prolong the QT interval (e.g., cisapride amitriptyline azithromycin).

Hypotensive drugs

The concomitant use of tizanidine with hypotensive drugs, including diuretics, can sometimes cause significant decreases in blood pressure (in some cases up to and including collapse and unconsciousness) and bradycardia.

In abrupt withdrawal of tizanidine after use with hypotensive drugs the development of tachycardia and increase in blood pressure in some cases may lead to acute cerebral circulation disorder were noted.

Rifampicin

The simultaneous use of tizanidine and rifampicin leads to 50% decrease of tizanidine concentration in plasma. Consequently, the therapeutic effect of tizanidine may decrease, which may be of clinical significance in some patients. Prolonged co-administration of rifampicin and tizanidin should be avoided and careful selection of the tizanidine dose (increase) is recommended when this is not possible.

Smoking

The systemic bioavailability of tizanidine in male smokers (more than 10 cigarettes per day) is reduced by about 30%. Long-term therapy with tizanidine in male smokers may require higher than average therapeutic doses.

Ethanol

Alcohol should be avoided during therapy with tizanidine because it may increase the likelihood of adverse events (e.g., decreased blood pressure and lethargy). Tizanidine may increase the suppressive effect of ethanol on the central nervous system.

Sedative hypnotics (benzodiazepine baclofen) and other drugs such as antihistamines may also increase the sedative effect of tizanidine. Tizanidine should be avoided with other alpha2-adrenomimetics (e.g., clonidine) due to the potential increase in hypotensive effect.

Interaction with food: see section “Pharmacokinetics”.

Special Instructions

Hypotension may occur against the background of using tizanidine and also as a result of drug interaction with CYP1A2 isoenzyme inhibitors and/or hypotensive drugs. Significant decrease in blood pressure may lead to loss of consciousness and circulatory collapse.

There have been reported cases of liver function abnormalities associated with tizanidine; however, when using daily doses up to 12 mg, these cases have been rare. Therefore it is recommended that liver function tests be monitored monthly during the first 4 months of treatment in patients receiving tizanidine at a daily dose of 12 mg or more, and also in cases where clinical signs suggestive of hepatic impairment, such as unexplained nausea, anorexia and fatigue, have been observed. In cases when serum ALT and ACT levels consistently exceed the upper limit of normal by a factor of 3 or more, the drug should be discontinued.

Alcohol should be abstained during treatment.

Because of the risk of withdrawal, the dose of the drug should be reduced gradually.

Patients with preserved reproductive potential should be advised of the adverse effects of the drug on the developing fetus identified in an animal study. During treatment and for 1 day after discontinuation of tizanidine, patients of preserved reproductive potential should use reliable methods of contraception.

Influence on ability to operate vehicles and machinery:

In view of the adverse reaction profile, it is recommended to refrain from activities requiring high concentration and rapid reaction such as driving vehicles or operating machines and mechanisms.

Synopsis

Round, flat cylindrical tablets, white or white with a yellowish tint, with a cross-shaped ridge and bevel.

Contraindications

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

– severe hepatic impairment;

– simultaneous use with potent CYP1A2 isoenzyme inhibitors (fluvoxamine and ciprofloxacin);

– pregnancy;

– period of breastfeeding;

– childhood under 18 years of age (efficacy and safety not established).

– it is not recommended to use the drug in patients with rare hereditary galactose intolerance with glucose-galactose malabsorption lactase deficiency because the drug contains lactose.

Cautions:

Cautious use of tizanidine is recommended in patients with moderate hepatic impairment Congenital Q-T Interval Syndrome and concomitant use with Q-T interval prolonging agents and in patients aged >65 years. It is necessary to monitor regularly the laboratory indexes of cardiac function and ECG indexes.

Side effects

When using low doses recommended to relieve painful muscle spasm drowsiness increased fatigue dizziness dry mouth decreased blood pressure nausea gastrointestinal disorders increased liver transaminases activity was noted. Usually the above mentioned adverse reactions are moderate and transient.

When taking higher doses recommended for the treatment of spasticity, the above-described PUIs occur more frequently and are more severe but do not require withdrawal of the drug. In addition, the following phenomena have been reported with tizanidine: bradycardia muscle weakness insomnia sleep disturbance hallucinations hepatitis.

The frequency of side effects listed below was determined according to the following (World Health Organization classification): very common (more than 10%); common (more than 1% and less than 10%); infrequent (more than 01% and less than 1%); rare (more than 001% and less than 01%); very rare (less than 001%) including individual reports; frequency is unknown (cannot be estimated using available data).

Nervous system disorders: very common – drowsiness dizziness.

Psychiatric disorders: often – insomnia sleep disorders.

Cardiovascular system: often – decrease of blood pressure (in some cases expressed up to collapse and loss of consciousness); rarely – bradycardia.

In the digestive system: very often – dry mouth gastrointestinal disorders; frequently – nausea.

Laboratory findings: often – increased activity of microsomal liver enzymes.

Muscular system disorders: very common – muscle weakness.

General disorders: very common – increased fatigue “withdrawal” syndrome.

In case of abrupt withdrawal of tizanidine after long-term treatment and/or administration of high doses of the drug (as well as after concomitant use together with hypotensive agents) development of tachycardia and increased arterial pressure which may cause acute impairment of cerebral circulation in individual cases have been noted; therefore the drug dose should be reduced gradually until complete withdrawal of the drug.

Manual reports of adverse events based on clinical use:

The following adverse events have been reported with tizanidine without any indication of a causal relationship to the drug in clinical practice (frequency of adverse events has not been established).

Psychiatric disorders: frequency unknown – hallucinations confusion.

Nervous system disorders: frequency unknown – vertigo.

An organ of vision: frequency unknown – blurred vision.

Hepatic and biliary tract disorders: frequency unknown – hepatitis liver failure.

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

Skin and subcutaneous tissue: frequency unknown – skin rash erythema skin itching dermatitis.

General disorders: frequency unknown – asthenia withdrawal syndrome.

In abrupt withdrawal of tizanidine, cases of ricochet hypertension and tachycardia have been reported in individual cases of ricochet increase in blood pressure leading to acute cerebral circulatory disturbances.

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 known cases of tizanidine overdose, including one in which the dose taken was 400 mg. In all cases, recovery was uneventful.

Symptoms:

Nausea vomiting marked decrease in blood pressure QT(c) interval prolongation dizziness drowsiness miosis restlessness respiratory impairment coma.

Treatment:

In order to eliminate tizanidine from the body, gastric lavage, multiple administration of activated charcoal, taking plenty of fluids is recommended. Carrying out forced diuresis may also accelerate tizanidine excretion. Subsequent symptomatic treatment is carried out.

Pregnancy use

Pregnancy

There have been no controlled studies of tizanidine in pregnant women and it should not be used during pregnancy unless the potential benefit to the mother outweighs the possible risk to the fetus.

There have been no studies in animals showing teratogenicity. When administered in doses of 10 and 30 mg/kg/day in animals an increase in gestational age has been noted in cases of prenatal and postnatal fetal loss as well as delayed fetal development. When using the above doses in females there were marked signs of myorelaxation and sedation.

Pregnancy testing is recommended before starting Tizanidine 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 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 exceeding 30 mg/kg/day and in females at a dose exceeding 10 mg/kg/day. Based on body surface area, these doses exceeded the maximum recommended dose for humans (072 mg/kg per day) by a factor of 22 and 67.

Breastfeeding

Breastfeeding should be stopped during treatment with tizanidine because there are no data on penetration of the drug into breast milk. In animal studies tizanidine was excreted in small amounts with milk of lactating females.

Similarities

Sirdalud, Tizalud, Tizanil, Tizanidin-Teva, Tizanidin, Sirdalud MR