Tizanidine + Miscellaneous - Drug Interactions

It is unclear whether tizanidine prolongs QT interval inhumans

Clinical evidence,mechanism, importance and management

One of most common adverse effects of tizanidine is somnolence or drowsiness (occurring in up to 50 % of patients(See reference number 1)) for which reason manufacturers warn about possibility of increased sedation with other sedative drugs, and alcohol (See reference number 2,3). In addition to additive sedative effects, alcohol increased AUC of tizanidine by about 20 % and its maximum level by 15%, which was associated with an increase in adverse effects of tizanidine (See reference number 3). Patients should be warned.

The UK manufacturers say that concurrent use of digoxin may potentiate bradycardia (See reference number 2)

(c) Drugs that prolong QT interval

The US manufacturer information states that prolongation of QT interval and bradycardia were noted in chronic toxicity studies in dogs at doses equal to maximum dose (See reference number 3). The UK information states that caution should be exercised when tizanidine is prescribed with drugs known to increase QT interval (See reference number 2). In one pharmacological interaction study in healthy subjects,there was no evidence of QT prolongation either with tizanidine 4 mg, or almost 14-fold increased tizanidine levels caused by rofecoxib, , despite increased bradycardia and hypotension (See reference number 4). This suggests that a clinically significant interaction resulting in QT-prolongation is unlikely.

In 20 healthy subjects,no clinically significant interaction occurred between 325mg of paracetamol (acetaminophen) and 4mg of tizanidine (See reference number 1).

Wagstaff AJ,Bryson HM. Tizanidine. A review of its pharmacology, clinical efficacy and tolerability in the management of spasticity associated with cerebral and spinal disorders. Drugs (1997) 53, 435–52.

Zanaflex (Tizanidine hydrochloride). Cephalon Ltd. UK Summary of product characteristics,December 2006.

Zanaflex (Tizanidine hydrochloride). Acorda Therapeutics,Inc. US Prescribing information,July 2006.

Backman JT,Karjalainen MJ, Neuvonen M, Laitila J, Neuvonen PJ. Rofecoxib is a potent inhibitor of cytochrome P450 1A2: studies with tizanidine and caffeine in healthy subjects. Br J Clin Pharmacol (2006) 62, 345–57.