Active ingredient: Tizanidine - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

• Muscle Relaxants
• Anticonvulsants
• Analgesics
• Skeletal Muscle Relaxants

Dosage Forms

• Tablet

Brands / Synonyms

Pramiracetam; Sirdalud; Ternelin; Tizanidina [Inn-Spanish]; Tizanidine; Tizanidine Hcl; Tizanidinum [Inn-Latin]; Zanaflex; Zanaflex

Indications

For the management of increased muscle tone associated with spasticity

Pharmacology

Tizanidine is a short-acting drug for the management of spasticity. Tizanidine is an agonist at a2-adrenergic receptor sites and presumably reduces spasticity by increasing presynaptic inhibition of motor neurons. In animal models, tizanidine has no direct effect on skeletal muscle fibers or the neuromuscular junction, and no major effect on monosynaptic spinal reflexes. The effects of tizanidine are greatest on polysynaptic pathways. The overall effect of these actions is thought to reduce facilitation of spinal motor neurons.

Mechanism of Action

Tizanidine reduces spasticity by increasing presynaptic inhibition of motor neurons through agonist action at a2-adrenergic receptor sites.

Absorption

Not Available

Toxicity

Not Available

Biotrnasformation / Drug Metabolism

Not Available

Contraindications

Zanaflex is contraindicated in patients with known hypersensitivity to Zanaflex or its ingredients.

Concomitant use of Zanaflex with fluvoxamine, a potent inhibitor of cytochrome P-450 (CYP) 1A2, is contraindicated. Significant alterations of pharmacokinetic parameters of tizanidine including AUC, t½ , and C_max, increased oral bioavailability and decreased plasma clearance have been observed with concomitant fluvoxamine administration.

Drug Interactions

In vitro studies of cytochrome P450 isoenzymes using human liver microsomes indicate that neither tizanidine nor the major metabolites are likely to affect the metabolism of other drugs metabolized by cytochrome P450 isoenzymes.

Acetaminophen: Tizanidine delayed the T_max of acetaminophen by 16 minutes. Acetaminophen did not affect the pharmacokinetics of tizanidine.

Alcohol: Alcohol increased the AUC of tizanidine by approximately 20% while also increasing its C_max by approximately 15%. This was associated with an increase in side effects of tizanidine. The CNS depressant effects of tizanidine and alcohol are additive.

Fluvoxamine: Clinically significant hypotension (decreases in both systolic and diastolic pressure) has been reported with concomitant administration of fluvoxamine following single doses of 4 mg.

Caution is recommended when considering concomitant use of tizanidine with other inhibitors of CYP1A2, such as, antiarrhythmics (amiodarone, mexiletine, propafenone), cimetidine, fluoroquinolones (ciprofloxacin, norfloxacin), rofecoxib, oral contraceptives, and ticlopidine.

Oral Contraceptives: No specific pharmacokinetic study was conducted to investigate interaction between oral contraceptives and tizanidine, but retrospective analysis of population pharmacokinetic data following single and multiple dose administration of 4 mg tizanidine showed that women concurrently taking oral contraceptives had 50% lower clearance of tizanidine than women not on oral contraceptives.