What is the role of tizanidine in the treatment of spasticity?

Updated: Mar 01, 2018
  • Author: Krupa Pandey, MD; Chief Editor: Stephen A Berman, MD, PhD, MBA  more...
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Answer

Data from approximately 50 clinical trials indicate that tizanidine (Zanaflex) is effective for the management of spasticity due to cerebral or spinal damage. Tizanidine is an imidazoline derivative and a central alpha2-noradrenergic agonist.

The antispasticity effects of tizanidine are the probable result of inhibition of the H-reflex. The drug also may facilitate inhibitory actions of glycine and reduce release of excitatory amino acids and substance P; it may have analgesic effects as well. While spasms and clonus are reduced in patients using tizanidine, the Ashworth Scale does not reveal significant differences from placebo groups. In the long term, however, tizanidine does improve spasms and clonus.

Patients report less muscle weakness from tizanidine than from baclofen or diazepam. In placebo-controlled studies, the efficacy of tizanidine in reducing muscle tone is comparable to that of baclofen and better than that of diazepam. When combined with baclofen, tizanidine presents the opportunity to maximize therapeutic effects and minimize adverse effects by reducing the dosages of both drugs.

If tizanidine is prescribed in conjunction with baclofen or benzodiazepines, the patient should be advised of possible potential additive effects, including sedation. In addition, when tizanidine is prescribed with benzodiazepines, liver enzymes should be monitored closely, since the combination increases the likelihood of liver toxicity.

Tizanidine is a short-acting drug with extensive first-pass hepatic metabolism to inactive compounds following an oral dose. The half-life is 2.5 hours, with peak plasma level at 1-2 hours, and therapeutic and side effects dissipate within 3-6 hours. Therefore, use must be directed to those activities and times when relief of spasticity is most important and titrated to avoid intolerance.

Tizanidine should be started at a low dose, 2-4 mg, preferably at bedtime. It should be titrated carefully to each patient, with the dosage increased slowly and gradually. The average maintenance dosage of tizanidine is 18-24 mg/day, with the maximum recommended dosage being 36 mg/day. Patients with impaired kidney function also require gradual titration, since they show a 2-fold increase in plasma concentration.

Dry mouth, somnolence, asthenia, and dizziness are the most common adverse events associated with tizanidine. Liver function problems (5%), orthostasis, and hallucinations (3%) are rare tizanidine-related adverse events.


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