ZANAFLEX

Absorption and

DistributionFollowing oral administration, tizanidine is essentially completely absorbed. The absolute oral bioavailability of tizanidine is approximately 40% (CV = 24%), due to extensive first-pass hepatic metabolism. Tizanidine is extensively distributed throughout the body with a mean steady state volume of distribution of 2.4 L/kg (CV = 21%) following intravenous administration in healthy adult volunteers. Tizanidine is approximately 30% bound to plasma proteins. Differences ...

Tizanidine’s capacity to reduce increased muscle tone associated with spasticity was demonstrated in two adequate and well controlled studies in patients with multiple sclerosis or spinal cord injury (Studies 1 and 2). Single-Dose Study in Patients with Multiple Sclerosis with Spasticity In Study 1, patients with multiple sclerosis were randomized to receive single oral doses of drug or placebo. Patients and assessors were blind to treatment assignment and efforts were made to reduce the likelihood that assessors would become aware indirectly of treatment assignment (e.g., they did not provide...

The following adverse reactions are described elsewhere in other sections of the prescribing information: Hypotension [see Warnings and Precautions ( 5.1 )] Liver Injury [see Warnings and Precautions ( 5.2 )] Sedation [see Warnings and Precautions ( 5.3 )] Hallucinosis/Psychotic-Like Symptoms [see Warnings and Precautions ( 5.4 )] Hypersensitivity Reactions [see Warnings and Precautions ( 5.6 )] The most common adverse reactions (greater than 2% of 264 patients taking tizanidine and greater than...

Zanaflex is contraindicated in patients taking potent inhibitors of CYP1A2, such as fluvoxamine or ciprofloxacin [see Drug Interactions ( 7.1 , 7.2 )] . Concomitant use with potent inhibitors of CYP1A2, such as fluvoxamine or ciprofloxacin ( 4 , 5.5 , 7.1 , 7.2 )

Hypotension: monitor for signs and symptoms of hypotension, in particular in patients receiving concurrent antihypertensives; Zanaflex should not be used with other α 2 -adrenergic agonists ( 5.1 , 7.7 ) Risk of liver injury: monitor ALTs; discontinue Zanaflex if liver injury occurs ( 5.2 ) Sedation: Zanaflex may interfere with everyday activities; sedative effects of Zanaflex, alcohol, and other CNS depressants are additive ( 5.3 , 7.5 , 7.6 ) Hallucinations: consider discontinuation of Zanafle...

7 DRUG INTERACTIONS 7.1 Fluvoxamine Concomitant use of fluvoxamine and Zanaflex is contraindicated. Changes in pharmacokinetics of tizanidine when administered with fluvoxamine resulted in significantly decreased blood pressure, increased drowsiness, and increased psychomotor impairment [see Contraindications ( 4 ) and Clinical Pharmacology ( 12.3 )] . 7.2 Ciprofloxacin Concomitant use of ciproflo...