Treating Spasticity with Capsules vs Tablets - Healthcare Professionals

Zanaflex Capsules^® (tizanidine hydrochloride) are not interchangeable with tizanidine tablets or Zanaflex^® (tizanidine hydrochloride) tablets.^2,5

Food has complex effects on Zanaflex pharmacokinetics. This may result in clinically significant differences when switching between Zanaflex Capsules^® (tizanidine hydrochloride) and Zanaflex tablets or generic tizanidine tablets when either formulation is taken with or without food. These changes may result in increased adverse events or a delayed/more rapid onset of activity, depending on the nature of the switch.^2,5

Stop! Zanaflex Capsules are not interchangeable with tizanidine tablets or Zanaflex tablets

The figure below shows the mean 8-hour plasma concentration of tizanidine versus time with and without food for each formulation.

Mean Plasma Concentration versus Time Graph - Treating Spasticity with Zanaflex.

Effects and Adverse Events Are Related to Plasma Levels of Tizanidine²

Significant pharmacokinetic changes including plasma level differences occur when administering Zanaflex Capsules^® (tizanidine hydrochloride) or tablets with food.^2,5
These (pharmacokinetic) differences can result in clinically important differences in effectiveness and adverse events.^2,5

In a 4-way crossover, open label, single 6 mg dose study in 96 healthy volunteers, plasma levels of tizanidine, when administered with food:

Rose more slowly and peaked at approximately 3 hours (median) following a dose of Zanaflex Capsules^® (tizanidine hydrochloride) when compared to the tablet formulation. Peak levels (Cmax =4.6ng/mL) decrease slightly compared to the fasted state (Cmax=5.4ng/mL) (p=ns).^2,5
Rise more rapidly and peak at approximately 1.4 hours following a dose of Zanaflex tablets (tmax p=0.0001 compared to Zanaflex Capsules^® (tizanidine hydrochloride) when given with food). Peak levels (Cmax=6.8ng/mL) increase compared to the fasted state (Cmax=5.4 ng/mL) (p=ns).^2,5

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.

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Zanaflex Capsules® (tizanidine hydrochloride) are not interchangeable with tizanidine tablets or Zanaflex® (tizanidine hydrochloride) tablets.2,5

Effects and Adverse Events Are Related to Plasma Levels of Tizanidine2

Zanaflex Capsules^® (tizanidine hydrochloride) are not interchangeable with tizanidine tablets or Zanaflex^® (tizanidine hydrochloride) tablets.^2,5

Effects and Adverse Events Are Related to Plasma Levels of Tizanidine²