Drug Interactions between amoxicillin / clarithromycin / vonoprazan and ruxolitinib topical

GENERALLY AVOID: Coadministration with potent inhibitors of CYP450 3A4 may increase plasma concentrations (Cmax) and systemic exposure (AUC) of topical ruxolitinib, which is primarily metabolized by the isoenzyme. Following administration of ketoconazole (200 mg twice daily for four days), a potent CYP450 3A4 inhibitor, healthy subjects then received a single dose of ruxolitinib (10 mg orally). The Cmax and AUC of ruxolitinib increased 33% and 91% respectively, compared to healthy subjects receiving the oral ruxolitinib dose alone. Increased exposure to ruxolitinib may increase the risk of adverse events. However, clinical data for topical ruxolitinib are not available.

MANAGEMENT: Concomitant use of topical ruxolitinib with potent inhibitors of CYP450 3A4 should generally be avoided. It may be advisable to monitor patients for the development of adverse effects. Consultation with individual package labeling, as well as relevant institutional protocols, may be advisable for further guidance.

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.

Coadministration with mild or moderate inhibitors of CYP450 3A4 may modestly increase the plasma concentrations of ruxolitinib, which is primarily metabolized by the isoenzyme. In healthy subjects, administration of a single 10 mg dose of ruxolitinib following pretreatment with the moderate CYP450 3A4 inhibitor erythromycin (500 mg twice daily for four days) resulted in an 8% increase in ruxolitinib peak plasma concentration (Cmax) and a 27% increase in systemic exposure (AUC) compared to administration of ruxolitinib alone. The change in the pharmacodynamic marker, pSTAT3 inhibition, was consistent with the corresponding exposure information. No dosage adjustment is recommended when ruxolitinib is coadministered with mild or moderate CYP450 3A4 inhibitors. However, clinical data for topical ruxolitinib are not available. Consultation with individual package labeling, as well as relevant institutional protocols, may be advisable for further guidance.