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: Zanaflex 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
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.