Drug Interactions between Bystolic and Marblen

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.

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Concurrent administration with aluminum and magnesium antacids has been shown to decrease the oral bioavailability of certain beta-blockers, although data are conflicting. The exact mechanism of interaction is unknown but may involve cation binding of beta-blockers or a reduction in the dissolution rate due to increased gastric pH. In six healthy volunteers, concomitant administration of a single dose of antacid (magnesium hydroxide-aluminum oxide 1200 mg-1800 mg) reduced the peak plasma concentration (Cmax), area under the concentration-time curve (AUC) and 24-hour urinary excretion of sotalol (160 mg) by 27%, 21% and 9%, respectively, while administration of the antacid 2 hours after the sotalol dose produced no change. Pharmacodynamic data suggest that the negative chronotropic effect of sotalol was also reduced up to 4 hours after administration of the combination, although the lack of a placebo control might have confounded the results. In another study, concomitant administration of an aluminum hydroxide antacid in six healthy volunteers decreased atenolol (100 mg) Cmax and AUC by 37% and 33%, respectively. However, the Cmax and AUC of metoprolol (100 mg) in the same group was increased 25% and 11%, respectively, by administration of the antacid. Two other studies with aluminum hydroxide failed to find a significant effect on pharmacokinetics or pharmacodynamics of atenolol and propranolol. Based on available data, the clinical significance of this potential interaction is difficult to determine. As a precaution, patients may want to consider separating the administration times of beta-blockers and antacids or other aluminum- or magnesium-containing products by at least 2 hours.

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