Tizanidine (Zanaflex) is supplied as 2 and 4 mg tablets for oral administration. Zanaflex tablets are composed of the active ingredient, tizanidine hydrochloride (2.288 mg equivalent to 2 mg tizanidine base and 4.576 mg equivalent to 4 mg tizanidine base), and the inactive ingredients, silicon dioxide colloidal, stearic acid, microcrystalline cellulose and anhydrous lactose.

Side Effects
Forty-five of 264 (17%) patients receiving tizanidine and 13 of 261 (5%) patients receiving placebo in three multiple dose, placebo-controlled clinical studies discontinued treatment for adverse events. When patients withdrew from the study, they frequently had more than one reason for discontinuing. The adverse events most frequently leading to withdrawal of tizanidine treated patients in the controlled clinical studies were asthenia (weakness, fatigue and/or tiredness) (3%), somnolence (3%), dry mouth (3%), increased spasm or tone (2%) and dizziness (2%).

Drug Interactions
In vitro studies of cytochrome P450 isoenzymes using human liver microsomes indicate that neither tizanidine nor the major metabolites are likely to affect the metabolism of other drugs metabolized by cytochrome P450 isoenzymes.

Acetaminophen: Tizanidine delayed the Tmax of acetaminophen by 16 minutes. Acetaminophen did not affect the pharmacokinetics of tizanidine.

Alcohol: Alcohol increased the AUC of tizanidine by approximately 20% while also increasing its Cmax by approximately 15%. This was associated with an increase in side effects of tizanidine. The CNS depressant effects of tizanidine and alcohol are additive.

Fluvoxamine: Clinically significant hypotension (decreases in both systolic and diastolic pressure) has been reported with concomitant administration of fluvoxamine following single doses of 4 mg (see DRUG INTERACTIONS, CONTRAINDICATIONS).

Caution is recommended when considering concomitant use of tizanidine with other inhibitors of CYP1A2, such as, antiarrhythmics (amiodarone, mexiletine, propafenone), cimetidine, fluoroquinolones (ciprofloxacin, norfloxacin), rofecoxib, oral contraceptives, and ticlopidine.

Oral Contraceptives: No specific pharmacokinetic study was conducted to investigate interaction between oral contraceptives and tizanidine, but retrospective analysis of population pharmacokinetic data following single and multiple dose administration of 4 mg tizanidine showed that women concurrently taking oral contraceptives had 50% lower clearance of tizanidine than women not on oral contraceptives.

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Page last modified: May 2007