Drug Interactions between amoxicillin / clarithromycin / vonoprazan and palovarotene

GENERALLY AVOID: Coadministration with potent inhibitors of CYP450 3A4 may increase the plasma concentrations and adverse effects of palovarotene, which is primarily metabolized by the isoenzyme. Concomitant use of ketoconazole, a potent CYP450 3A4 inhibitor, with palovarotene at steady-state plasma levels increased its peak plasma concentration (Cmax) and systemic exposure (AUC) by 121% and 212%, respectively. Increased concentrations of palovarotene may increase the risk of adverse reactions such as dry skin, dry lips, alopecia, pruritus, erythema, paronychia, cellulitis, decubitus ulcer, xerophthalmia, night blindness, depression, mood alterations, and pseudotumour cerebri (benign intracranial hypertension).

MANAGEMENT: According to the manufacturer, concomitant use of palovarotene with potent CYP450 3A4 inhibitors should generally be avoided.

MONITOR: Coadministration with weak inhibitors of CYP450 3A4 may increase the plasma concentrations and adverse effects of palovarotene, which is primarily metabolized by the isoenzyme. Pharmacokinetic modeling simulations suggest that coadministration of palovarotene with cimetidine, a weak CYP450 3A4 inhibitor, resulted in a slight increase in the Cmax and AUC of palovarotene of approximately 10%; however, the clinical significance is unknown. Increased concentrations of palovarotene may increase the risk of adverse effects such as dry skin, dry lips, alopecia, pruritus, erythema, paronychia, cellulitis, decubitus ulcer, xerophthalmia, night blindness, depression, mood alterations, and pseudotumour cerebri (benign intracranial hypertension).

MANAGEMENT: Caution and clinical monitoring are recommended if palovarotene is coadministered with weak CYP450 3A4 inhibitors. The benefits versus risks of coadministration should be assessed. Patients should be advised to notify their health care professional if they experience increased effects of palovarotene such as dry skin, dry lips, alopecia, pruritus, erythema, paronychia, cellulitis, decubitus ulcer, xerophthalmia, night blindness, depression, mood alterations, and pseudotumor cerebri.

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.