Tizanidine is a lipid-soluble drug, which is only slightly soluble in water and methanol. A muscle immobilized by spasticity was given a score of 4. The absolute oral bioavailability of tizanidine is approximately 40% (CV = 24%), due to extensive first-pass hepatic metabolism. Cross-study comparison of pharmacokinetic data following single dose administration of 6 mg Zanaflex showed that younger subjects cleared the drug four times faster than the elderly subjects. Depressed cardiac function is also observed including most often bradycardia and hypotension. These events appeared to be dose related.Table 1 lists signs and symptoms that were reported in greater than 2% of patients in three multiple dose, placebo-controlled studies who received Zanaflex where the frequency in the Zanaflex group was greater than the placebo group. Zanaflex is a central alpha-2-adrenergic agonist indicated for the management of spasticity. Zanaflex should be given to pregnant women only if the benefit outweighs the risk to the unborn fetus. Each study had a 13-week active treatment period which included a 3-week titration phase to the maximum tolerated dose up to 36 mg/day in three divided doses, a 9-week plateau phase where the dose of tizanidine was held constant and a 1-week dose tapering. Approximately 95% of an administered dose is metabolized. There were no differences in the number of spasms occurring in each group.In a 7-week study (Study 2), 118 patients with spasticity secondary to spinal cord injury were randomized to either placebo or Zanaflex. In such a case, use with caution. Patients should be informed of the signs and symptoms of severe allergic reactions and instructed to discontinue Zanaflex and seek immediate medical care should these signs and symptoms occur. Labor & delivery. Therefore, dialysis is not likely to be an efficient method of removing drug from the body. Because many drugs are excreted in human milk, caution should be exercised when Zanaflex is administered to a nursing woman.Safety and effectiveness in pediatric patients have not been established.Zanaflex is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Zanaflex should be used with caution in renally impaired patients [ No specific pharmacokinetic study was conducted to investigate gender effects. A score of 1 indicated a slight spastic catch while a score of 2 indicated more marked muscle resistance. Inform patients that they should not take more Zanaflex than prescribed because of the risk of adverse events at single doses greater than 8 mg or total daily doses greater than 36 mg. Tell patients that they should not suddenly discontinue Zanaflex, because rebound hypertension and tachycardia may occur.Warn patients that they may experience hypotension and to be careful when changing from a lying or sitting to a standing position. The CNS depressant effects of Zanaflex with alcohol and other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants) may be additive. If higher doses are required, individual doses rather than dosing frequency should be increased. Zanaflex is not recommended in this patient population [ Tizanidine clearance is reduced by more than 50% in elderly patients with renal insufficiency (creatinine clearance < 25 mL/min) compared to healthy elderly subjects; this would be expected to lead to a longer duration of clinical effect. Monitoring of aminotransferase levels is recommended for baseline and 1 month after maximum dose is achieved, or if hepatic injury is suspected. In the majority of cases a decrease in sensorium was observed including lethargy, somnolence, confusion and coma. The antispasmodic activity of tizanidine results from agonism at central pre-synaptic alpha2-receptors. Cyclobenzaprine and Zanaflex (tizanidine) are muscle relaxants used to relieve muscle spasms associated with painful muscle and skeletal conditions. 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 direct care to patients and were prohibited from asking questions about side effects).