Tizanidine (Zanaflex) is an imidazole derivative and is a centrally acting alpha-adrenergic agonist that inhibits the release of excitatory amino acids in spinal interneurons. It may also act by facilitating the action of glycine.
Tizanidine also enhances vibratory inhibition of the H-reflex in humans and reduces abnormal co-contraction, which may partly contribute to its antispasticity effects.45
In placebo-controlled trials, tizanidine reduces muscle tone and frequency of muscle spasms in patients with multiple sclerosis (MS) and spinal cord injury.46–48 Similar efficacy was found in open-label trials for stroke patients.49
In MS, tizanidine reduced spasticity without altering muscle strength, but no consistent positive effect was noted on functional measures (e.g., timed ambulation, upper-extremity function, or movements necessary in activities of daily living).46
When compared to baclofen or diazepam in early trials, tizanidine demonstrated similar efficacy and better tolerability.44,47,50–57 No controlled trials have investigated tizanidine in combination with baclofen or tizanidine therapy in patients with cerebral palsy or developmental delay.
Tizanidine undergoes first-pass hepatic metabolism and subsequently is eliminated by the kidney. Its half-life is approximately 2.5 hours, and peak effect is seen 1 to 2 hours after dosage.
Doses are initiated at 2–4 mg daily and are increased every 3 days by 2–4 mg. Total dose should not exceed 36 mg per day in three divided doses. Little experience has been reported with single doses greater than 8 mg.
Side effects—including dry mouth (45%), drowsiness (54%), and dizziness—are seen primarily when doses exceed 24 mg per day. Visual hallucinations (3%) and elevated liver function tests (5%) are reversible with dose reduction.46 Liver function tests should be performed at baseline; months 1, 3, and 6 of treatment; and periodically thereafter.
Insomnia and weakness have been found to be more frequent with tizanidine than with baclofen.50
Tizanidine does not affect blood pressure but, because central alpha-adrenergic agonists may cause hypotension, concomitant use of antihypertensive agents should be monitored closely, and clonidine should be avoided.23
Reviewed and revised May 2004 by Steven C. Schachter, MD, epilepsy.com Editorial Board.
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