Drug Interaction Report

MONITOR: Coadministration with moderate inhibitors of CYP450 3A4 may increase the plasma concentrations of ticagrelor, which is primarily metabolized by the isoenzyme. In healthy volunteers, administration of ticagrelor in combination with the moderate CYP450 3A4 inhibitor diltiazem resulted in increased ticagrelor peak plasma concentration (Cmax) and systemic exposure (AUC) by 69% and 174%, respectively. For the active metabolite, the Cmax was decreased by 38% and the AUC was unchanged. Ticagrelor had no effect on the plasma levels of diltiazem.

MANAGEMENT: Although administration with moderate CYP450 3A4 inhibitors is thought to be generally safe, it may be advisable to monitor pharmacologic response to ticagrelor more closely following the addition and withdrawal of these agents. Discontinuation of the concomitant medication may be required if an interaction is suspected.

ADJUST DOSING INTERVAL: Food may variably affect the bioavailability of different oral formulations and salt forms of erythromycin. The individual product package labeling should be consulted regarding the appropriate time of administration in relation to food ingestion. Grapefruit juice may increase the plasma concentrations of orally administered erythromycin. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. In an open-label, crossover study consisting of six healthy subjects, the coadministration with double-strength grapefruit juice increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of a single dose of erythromycin (400 mg) by 52% and 49%, respectively, compared to water. The half-life was not affected. The clinical significance of this potential interaction is unknown.

MANAGEMENT: In general, optimal serum levels are achieved when erythromycin is taken in the fasting state, one-half to two hours before meals. However, some erythromycin products may be taken without regard to meals.

Ethanol, when combined with erythromycin, may delay absorption and therefore the clinical effects of the antibiotic. The mechanism appears to be due to slowed gastric emptying by ethanol. Data is available only for erythromycin ethylsuccinate. Patients should be advised to avoid ethanol while taking erythromycin salts.