Zanaflex Capsules® (tizanidine hydrochloride) is a short-acting drug indicated for the management of spasticity. Because of the short duration of effect, treatment with Zanaflex Capsules® (tizanidine hydrochloride) should be reserved for those daily activities and times when relief of spasticity is most important.

Important Safety Information:

• Use with fluvoxamine or ciprofloxacin is contraindicated and results in significant increases in tizanidine plasma levels.
• There is a limited data base for chronic use of single doses above 8 mg and multiple doses above 24 mg per day.
• Tizanidine is an alpha2-adrenergic agonist and can produce hypotension. In a single-dose study where patients were not titrated, two-thirds of patients given 8 mg of Zanaflex experienced hypotension, which may be minimized by titration of dose. The hypotensive effect is dose related and has been measured following single doses of 2 mg or more.
• Tizanidine occasionally causes liver injury, most often of the hepatocellular type.
• Patients should be advised that sedation may interfere with daily activities. These effects appear to be dose related.
• Visual hallucinations or delusions occurred in 3% (5/170) of study patients in two North American clinical trials.
• Use with caution in hepatic or renally impaired patients.
• Use with oral contraceptives results in 50% decrease in tizanidine clearance.
• To discontinue therapy, taper the dose in patients receiving high doses over long time periods to reduce the risk of hypertension, tachycardia and hypertonia.
• In vitro studies indicate that neither tizanidine nor the major metabolites are likely to affect the metabolism of other drugs metabolized by cytochrome P450 isoenzymes.
• Most common adverse events with tizanidine include dry mouth (49%), somnolence (48%), asthenia [weakness, fatigue and/or tiredness] (41%), dizziness (16%) and increased ALT (5%). Other adverse events include UTI, infection and constipation.
• Food has complex effects on tizanidine pharmacokinetics, which differ for the different formulations. These pharmacokinetic differences may result in clinically significant differences when switching formulations, or changing administration during a fed or fasted state. These changes may result in increased adverse events or a delayed/more rapid onset of activity, depending on the nature of the switch.