Drug Interactions between Isovex and Zanaflex

ADJUST DOSE: Tizanidine may potentiate the hypotensive effect of some medications secondary to its alpha-2 adrenergic activity. 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. The hypotensive effect of tizanidine is dose-related and has been measured following single doses of 2 mg or more. 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 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. In clinical trials, the addition of tizanidine to antihypertensive therapy was associated with a 20% to 30% increase in the incidence of clinically significant decreases in systolic or diastolic blood pressure compared with placebo plus antihypertensive therapy or tizanidine alone. The incidence of orthostatic hypotension was also increased.

MANAGEMENT: A lower initial dosage and cautious dosage titration should be considered when tizanidine is initiated in patients receiving hypotensive medications. Although single doses of less than 8 mg of tizanidine have not been shown to be effective for spasticity in controlled clinical studies, some authorities recommend initiating treatment with single oral doses of 2 mg. The dose can then be gradually increased by 2 to 4 mg, with 1 to 4 days between dosage increases, until the optimum effect is achieved. The dose can be repeated at 6- to 8-hour intervals as needed, up to a maximum of three doses in 24 hours and a total daily dosage of 36 mg. Single doses greater than 16 mg have not been studied. Close monitoring for development of hypotension is recommended. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.

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