Drug-Drug Interaction

Fluvoxamine (Luvox)
The effect of fluvoxamine on the pharmacokinetics of tizanidine was studied in 10 healthy subjects. The Cmax, AUC, and half-life of tizanidine increased by 12-fold, 33-fold, and 3-fold, respectively. These changes resulted in significant decreases in blood pressure, increased drowsiness and psychomotor impairment.

Ciprofloxacin (Cipro)
The effect of ciprofloxacin on the pharmacokinetics of tizanidine was studied in 10 healthy subjects. The Cmax and AUC of tizanidine increased by 7-fold and 10-fold, respectively. These changes resulted in significant decreases in blood pressure, increased drowsiness and psychomotor impairment.

CYP1A2 Inhibitors
The interaction between tizanidine and either fluvoxamine or ciprofloxacin is most likely due to inhibition of CYP1A2 by fluvoxamine or ciprofloxacin. Although there have been no clinical studies evaluating the effects of other CYP1A2 inhibitors on tizanidine, other CYP1A2 inhibitors, such as zileuton, other fluoroquinolones, antiarrythmics (amiodarone, mexiletine, propafenone and verapamil), cimetidine, famotidine oral contraceptives, acyclovir and ticlopidine, may also lead to substantial increases in tizanidine blood concentrations.

Please see below for Important Safety Information.

Be sure your patient received what you prescribed

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.

For Full Prescribing Information - Click Here Information For Patients Guide - Click Here