Drug Interactions between aprepitant and ivabradine

GENERALLY AVOID: Coadministration with moderate inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of ivabradine, which is primarily metabolized by the isoenzyme. According to the product labeling, administration of ivabradine with the moderate CYP450 3A4 inhibitor diltiazem (120 mg twice daily) resulted in approximately 3-fold increases in ivabradine peak plasma concentration (Cmax) and systemic exposure (AUC) compared to administration of ivabradine alone. Likewise, administration with verapamil (120 mg twice daily) increased the Cmax and AUC of ivabradine by approximately 2-fold. Grapefruit juice, another moderate CYP450 3A4 inhibitor, increased ivabradine AUC by a little over 2-fold. Elevated plasma levels of ivabradine may increase the risk of excessive bradycardia and conduction disturbances.

MANAGEMENT: Concomitant use of ivabradine with moderate CYP450 3A4 inhibitors should generally be avoided. If coadministration is required, some authorities recommend initiating ivabradine at a dosage of 2.5 mg twice daily, provided the resting heart rate is at or above 70 beats per minute and heart rate is closely monitored.