Tizanidine

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 spaticity caused by multiple sclerosis

or spinal cord injury.

Tizanidine for spasticity. Med Lett Drugs Ther 1997;39

(1004)62-3.

COPYRIGHT 1998 American Academy of Family Physicians
COPYRIGHT 2000 Gale Group