Drug Interactions between brimonidine / dorzolamide / latanoprost / timolol ophthalmic and tizanidine

MONITOR: Topically administered alpha-2 adrenergic receptor agonists such as apraclonidine and brimonidine are systemically absorbed, with the potential for producing rare but clinically significant systemic effects such as hypotension and bradycardia. The possibility for an additive or potentiating effect on blood pressure and heart rate should be considered when used with other medications that affect these parameters, such as ophthalmic and systemic beta blockers, vasodilators, cardiac glycosides, and antihypertensive agents.

MANAGEMENT: Blood pressure and pulse rate should be monitored regularly when topical alpha-2 adrenergic receptor agonists are prescribed in combination with cardiovascular drugs. Patients should be advised to notify their physician if they experience slow pulse, irregular heartbeat, dizziness, lightheadedness, or syncope.

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.