According to consultants for The Medical Letter on Drugs and Therapeutics, tizanidine was recently approved by the U.S. Food and Drug Administration for oral treatment of increased muscle tone associated with spasticity. It has been available in other countries for 12 years as a short-term muscle relaxant.

Tizanidine is a short-acting, centrally active alpha-adrenergic receptor agonist similar to clonidine. However, it lacks the antihypertensive efficacy of clonidine. Therefore, during initial titration of tizanidine, the patient's blood pressure must be monitored. Another agent, baclofen, has been available for many years to reduce the painful muscle spasms associated with multiple sclerosis and other disorders affecting the spinal cord, but it has been ineffective as extended therapy in some patients. Diazepam and dantrolene sodium have also been used to treat spasticity, but these agents are less effective than baclofen.

In its oral form, tizanidine is rapidly and completely absorbed, especially when taken with food. It is excreted in the urine and feces. Since absorption is increased when it is taken with food, taking the drug regularly with meals can increase the consistency of both therapeutic and adverse effects.

The typical initial dosage is one 4-mg tablet taken at night, which can be increased by one-half tablet (2 mg) every three days until a dosing schedule of three times daily can be achieved. Most patients eventually take about 24 mg daily. However, even when given three times a day, tizanidine does not remain effective for a full 24 hours. Peak clinical effects occur one to two hours after each dose and disappear after six hours.

Randomized double-blind studies in patients with multiple sclerosis or spinal cord injuries showed that tizanidine was more effective than placebo in decreasing overall spasticity, and the frequency of daytime muscle spasms and night awakenings caused by spasm. When used together, carefully titrated doses of tizanidine and baclofen may have additive effects.

Dry mouth, dizziness, sedation, hypotension and bradycardia are common side effects but are usually mild to moderate in severity and can be minimized by increasing the dosage gradually. Visual hallucinations or delusions are rare. Increased aminotransferase activity occurred in 5 percent of the patients in the study group, and three patients died as a result of hepatic failure. The safety of tizanidine in children or in pregnant and lactating women has not been determined. In addition, this drug should be used with caution in elderly patients, those with renal or hepatic impairment, and those taking antihypertensives, especially clonidine.

Concurrent use of diazepam or alcohol may potentiate the sedative effects of tizanidine. Because oral contraceptives decrease the clearance of tizanidine by 50 percent, the starting dosage of tizanidine should be reduced in women taking these agents. Tizanidine also increases serum concentrations of phenytoin.

According to the 1997 edition of Redbook, the wholesale cost to pharmacies is $135 for 150 tablets of tizanidine (4 mg). Medical Letter consultants suggest that oral tizanidine can decrease spasticity caused by multiple sclerosis or spinal cord injury.