Drug Interaction Report

MONITOR: Coadministration with telithromycin may increase the plasma concentrations of metoprolol. The proposed mechanism is telithromycin inhibition of CYP450 2D6, the isoenzyme responsible for the metabolic clearance of metoprolol. Coadministration of telithromycin and metoprolol has resulted in an increase of approximately 38% in the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of metoprolol, with no change in the elimination half-life. Single-dose metoprolol had no significant effect on the AUC of telithromycin.

MANAGEMENT: In patients treated with metoprolol for heart failure, the increased exposure to metoprolol may be of clinical importance, thus coadministration with telithromycin should be considered with caution. Excessive beta blockade may worsen heart failure in patients who have dependency to sympathetic stimulation in maintaining hemodynamic function.

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.