Drug Interactions between albendazole and Metoprolol Succinate ER

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: Food enhances the oral bioavailability of albendazole, which is rapidly converted by hepatocytes and intestinal mucosal cells into the active metabolite, albendazole sulfoxide (ABZSX), following absorption. The proposed mechanism is stimulation of gastric acid secretion, as the absorption of albendazole is thought to be pH-dependent. According to the product labeling, plasma concentrations of ABZSX are up to 5-fold higher on average when albendazole is administered with a fatty meal (fat content approximately 40 g) compared to administration in the fasted state. In one study of six healthy male volunteers, administration of a single 10 mg/kg oral dose of albendazole in combination with a high-fat meal (57 g fat, 1399 kcal) increased the mean ABZSX peak plasma concentration (Cmax) and systemic exposure (AUC) by 6.5- and 9.4-fold, respectively, and delayed the time to reach Cmax (Tmax) from 2.5 to 5.3 hours compared to administration in the fasted state with water. The elimination half-life was not affected.

MONITOR: Grapefruit juice may increase the oral bioavailability of albendazole, which is rapidly converted by hepatocytes and intestinal mucosal cells into the active metabolite, albendazole sulfoxide (ABZSX), following absorption. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. In six healthy male volunteers, administration of a single 10 mg/kg oral dose of albendazole in combination with 250 mL of double-strength grapefruit juice increased the mean ABZSX peak plasma concentration (Cmax) and systemic exposure (AUC) by 3.2- and 3.1-fold, respectively, compared to administration with water. However, because pharmacokinetic interactions involving grapefruit juice are often subject to a high degree of interpatient variability, the extent to which a given patient may be affected is difficult to predict.

MANAGEMENT: To ensure maximal oral absorption, albendazole should be taken with food. Grapefruit juice may also enhance the oral bioavailability of albendazole.

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.