Drug Interaction Report

Ventricular pauses and bradycardia, mostly asymptomatic, have been observed in clinical studies with ticagrelor. Theoretically, the risk of symptomatic bradycardia may be increased during concomitant use of other agents known to induce bradycardia. However, in PLATO, a large, randomized, double-blind efficacy and safety comparison study with clopidogrel in patients with acute coronary syndromes, no evidence of clinically significant adverse interactions was observed during concomitant administration with one or more drugs known to induce bradycardia including beta-blockers (96%), the calcium channel blockers diltiazem and verapamil (33%), and digoxin (4%).

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.