TIZANIDINE

Posology The effect of tizanidine on spasticity is maximal within 2-3 hours of dosing and it has a relatively short duration of action. The timing and frequency of dosing should therefore be tailored to the individual, and tizanidine should be given in divided doses, up to 3-4 times daily, depending on the patient’s needs.

There is considerable variation in response between patients so careful titration is necessary. Care should be taken not to exceed the dose producing the desired therapeutic effect. It is usual to start with a single dose of 2 mg increasing by 2 mg increments at no less than half-weekly intervals.

The optimum therapeutic response is generally achieved with a daily dose of between 12 and 24 mg, administered in 3 or 4 equally spaced doses. Single doses should not exceed 12 mg. The total daily dose should not exceed 36 mg. 8) may occur at therapeutic doses but these can be minimised by slow titration so that in the large majority of patients they are not a limiting factor.

4). Elderly Experience in the elderly is limited and use of tizanidine is not recommended unless the benefit of treatment clearly outweighs the risk. Pharmacokinetic data suggest that renal clearance in the elderly may be decreased by up to three fold.

Children and adolescents Experience with tizanidine in patients under the age of 18 years is limited. Tizanidine is not recommended for use in this population. Renal impairment In patients with renal insufficiency (creatinine clearance < 25 ml/min) treatment should be started with 2 mg once daily with slow titration to achieve the effective dose.

Dosage increases should be in increments of no more than 2 mg according to tolerability and effectiveness. It is advisable to slowly increase the once-daily dose before increasing the frequency of administration. 4). 4). Method of administration For oral use.

Tabulated list of adverse reactions The adverse effects are classified below by system organ class according to the following convention: Very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1,000 to <1/100) , Rare (≥1/10,000 to < 1/1,000), Very rare, including isolated reports (<1/10,000), Not known (cannot be estimated from the available data) Within each frequency grouping, adverse reactions are ranked in order of decreasing seriousness.

g. g. anti-depressants. ** With slow upward titration of the dose of tizanidine these effects are usually not severe enough to require discontinuation of treatment. With the higher doses recommended for the treatment of spasticity, the adverse reactions reported with low doses are more frequent and more pronounced, but seldom severe enough to require discontinuation of treatment.

In addition the following adverse reactions may occur: confusional state. had been used chronically, and/or in high daily dosages, and/or concomitantly with antihypertensive drugs. 5). Reporting of suspected adverse reactions Reporting of adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard.

Cytochrome P450 (CYP) inhibitors Concomitant use of tizanidine with CYP1A2 inhibitors is not recommended. 5). 5). Severe manifestations of hypotension such a loss of consciousness and circulatory collapse have been observed. Withdrawal syndrome Rebound hypertension and tachycardia have been observed after sudden withdrawal of tizanidine, when it had been used chronically, and/or in high daily dosages, and/or concomitantly with antihypertensive drugs.

In extreme cases, rebound hypertension might lead to cerebrovascular accident. 8). Renal impairment In patients with renal impairment/insufficiency (creatine clearance < 25 mL/min), it is recommended to start treatment at 2 mg once daily.

Dosage increases should be done in small steps according to tolerability and efficacy. If efficacy is to be improved, it is advisable to increase first the once daily dose before increasing the frequency of administration. Cardiovascular, hepatic or renal disorders Caution is required in patients with cardiovascular disorders, coronary artery disease or renal or hepatic disorders.

Regular clinical laboratory and ECG monitoring is recommended during treatment with tizanidine. Hepatic dysfunction Hepatic dysfunction has been reported in association with tizanidine but rarely at daily doses up to 12 mg. It is recommended in all patients that before beginning therapy, liver function tests should be performed in order to establish a baseline and to exclude pre-existing liver disease or significantly impaired hepatic function.

Liver function tests should then be monitored monthly for the first four months of treatment in all patients receiving doses of 12 mg and higher and in those who develop symptoms suggestive of liver/hepatic dysfunction such as unexplained nausea, anorexia or tiredness.

Treatment with tizanidine should be discontinued if serum levels of SGPT (serum glutamic-pyruvic transaminase) and/or SGOT (serum glutamic-oxaloacetic transaminase) are persistently above three times the upper limit of normal range.

The use of tizanidine in patients with significantly impaired hepatic function is contraindicated, because tizanidine is extensively metabolised by the liver. 5). 1.