Drug Interactions between apraclonidine ophthalmic and tizanidine

MONITOR: Topically administered alpha-2 adrenergic agonists such as apraclonidine and brimonidine may potentiate the hypotensive and sedative effects of tizanidine, which is a muscle relaxant with centrally-acting 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. 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. Topically applied alpha-2 adrenergic receptor agonists are systemically absorbed. Although commercially available agents are hydrophilic and do not readily distribute across the ocular-blood barrier into the central nervous system, prolonged use may increase the risk of systemic effects. There have been occasional reports of bradycardia, chest heaviness or burning, palpitation, reduced blood pressure, and orthostatic hypotension when apraclonidine 1% eyedrop was administered once or twice a day for 4 weeks to individuals not undergoing laser surgery.

MANAGEMENT: Caution is advised if tizanidine is used in combination with topical alpha-2 adrenergic agonists. 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. Patients should also avoid activities requiring mental alertness until they know how these agents affect them.