Drug Interaction Report

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.

ADJUST DOSING INTERVAL: The bioavailability of metoprolol may be enhanced by food.

MANAGEMENT: Patients may be instructed to take metoprolol at the same time each day, preferably with or immediately following meals.

ADJUST DOSING INTERVAL: Concurrent administration with calcium salts may decrease the oral bioavailability of atenolol and possibly other beta-blockers. The exact mechanism of interaction is unknown. In six healthy subjects, calcium 500 mg (as lactate, carbonate, and gluconate) reduced the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of atenolol (100 mg) by 51% and 32%, respectively. The elimination half-life increased by 44%. Twelve hours after the combination, beta-blocking activity (as indicated by inhibition of exercise tachycardia) was reduced compared to that with atenolol alone. However, during a 4-week treatment in six hypertensive patients, there was no difference in blood pressure values between treatments. The investigators suggest that prolongation of the elimination half-life induced by calcium coadministration may have led to atenolol cumulation during long-term dosing, which compensated for the reduced bioavailability.

MANAGEMENT: It may help to separate the administration times of beta-blockers and calcium products by at least 2 hours. Patients should be monitored for potentially diminished beta-blocking effects following the addition of calcium therapy.