Drug Interaction Report

MONITOR: The sedative effect of tizanidine may be potentiated by concomitant use of other agents with central nervous system (CNS) depressant effects. In addition, tizanidine and many of these agents (e.g., alcohol, anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, muscle relaxants) also can exhibit hypotensive effects, which may be additive during coadministration and may increase the risk of symptomatic hypotension and orthostasis, particularly during initiation of therapy or dose escalation. Tizanidine itself is a central alpha-2 adrenergic agonist. Pharmacologic studies have found tizanidine to possess between 1/10 to 1/50 of the potency of clonidine, a structurally similar agent, in lowering blood pressure. In a single-dose study where blood pressure was monitored closely after dosing, two-thirds of patients treated with an 8 mg dose had a 20% reduction in either the diastolic or systolic blood pressure. The reduction was seen within 1 hour after dosing, peaked 2 to 3 hours after dosing, and was associated at times with bradycardia, orthostatic hypotension, lightheadedness, dizziness, and rarely, syncope. The hypotensive effect of tizanidine is dose-related and has been measured following single doses of 2 mg or more.

MANAGEMENT: Caution is advised and more gradual dose titration may be appropriate when tizanidine is used with other substances that can cause CNS depression and/or hypotension, particularly in elderly or debilitated patients. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to avoid rising abruptly from a sitting or recumbent position. Patients should contact their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or excessive CNS effects that interfere with their normal activities.

GENERALLY AVOID: Concurrent use of ethanol and phenothiazines may result in additive CNS depression and psychomotor impairment. Also, ethanol may precipitate dystonic reactions in patients who are taking phenothiazines. The two drugs probably act on different sites in the brain, although the exact mechanism of the interaction is not known.

MANAGEMENT: Patients should be advised to avoid alcohol during phenothiazine therapy.

MONITOR: Coadministration of two or more sympathomimetic agents may increase the risk of adverse effects such as nervousness, irritability, and increased heart rate. Central nervous system (CNS) stimulants, particularly amphetamines, can potentiate the adrenergic response to vasopressors and other sympathomimetic agents. Additive increases in blood pressure and heart rate may occur due to enhanced peripheral sympathetic activity.

MANAGEMENT: Caution is advised if two or more sympathomimetic agents are coadministered. Pulse and blood pressure should be closely monitored.