Drug Interactions between amoxicillin / clarithromycin / vonoprazan and ivabradine

CONTRAINDICATED: Coadministration with potent 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 potent CYP450 3A4 inhibitor ketoconazole (200 mg once daily) resulted in approximately 3.5- and 7-fold increases in ivabradine peak plasma concentration (Cmax) and systemic exposure (AUC), respectively, compared to administration of ivabradine alone. Elevated plasma levels of ivabradine may increase the risk of excessive bradycardia and conduction disturbances.

MANAGEMENT: Concomitant use of ivabradine with potent CYP450 3A4 inhibitors is considered contraindicated. Some authorities consider concomitant administration of ivabradine and itraconazole to be contraindicated during and for 2 weeks after treatment with itraconazole.

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of ivabradine, which is primarily metabolized by the isoenzyme. According to the product labeling, potent CYP450 3A4 inhibitors such as ketoconazole and josamycin have been shown to increase ivabradine systemic exposure (AUC) by approximately 7- to 8-fold, and moderate CYP450 3A4 inhibitors such as diltiazem, verapamil and grapefruit juice have been shown to increase ivabradine systemic AUC by approximately 2- to 3-fold. Elevated plasma levels of ivabradine may increase the risk of excessive bradycardia and conduction disturbances.

MANAGEMENT: Caution is advised when ivabradine is prescribed with CYP450 3A4 inhibitors. Patients should be monitored for adverse effects such as bradycardia and atrial fibrillation, and the dosage of ivabradine adjusted as necessary in accordance with the product labeling.

Although some in vitro data indicate synergism between macrolide antibiotics and penicillins, other in vitro data indicate antagonism. When these drugs are given together, neither has predictable therapeutic efficacy. Data are available for erythromycin, although theoretically this interaction could occur with any macrolide. Except for monitoring of the effectiveness of antibiotic therapy, no special precautions appear to be necessary.