TIZANIDINE

Posology For oral administration 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 total daily dose should not exceed 36 mg, although it is usually not necessary to exceed 24 mg daily. 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.

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 in some cases significantly decreased by up to three fold.

Caution is therefore indicated when using tizanidine in elderly patients. Children Experience with tizanidine in patients under the age of 18 years is limited. Tizanidine is not recommended for use in children. 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. Renal function should be monitored as appropriate in these patients.

Hepatic Impairment Tizanidine is contraindicated in patients with significantly impaired hepatic function.

5 Interaction with other medicinal products and other forms of interaction). Severe manifestations of hypotension such as loss of consciousness and circulatory collapse have also 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 Undesirable effects). Hepatic dysfunction Since hepatic dysfunction has been reported in association with tizanidine, but rarely at daily doses up to 12 mg, it is recommended that liver function tests should be monitored monthly for the first four months in patients receiving doses of 12 mg and higher and in patients who develop clinical symptoms suggestive of hepatic dysfunction, such as unexplained nausea, anorexia or tiredness.

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

Renal insufficiency In patients with renal insufficiency (creatinine 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 has to be improved, it is advisable to increase first the once daily dose before increasing the frequency of administration. Tizanidine should be kept out of the reach of children. This medicinal product contains lactose.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine. 5 Interaction with other medicinal products and other forms of interaction CYP inhibitors Concomitant administration of drugs known to inhibit the activity of CYP1A2 may increase the plasma levels of tizanidine.

3 Contraindications and section

The use of tizanidine in patients with significantly impaired hepatic function is contraindicated, because tizanidine is extensively metabolised by the liver. Concomitant use of tizanidine with strong inhibitors of CYP1A2 such as fluvoxamine or ciprofloxacin is contra-indicated (see section