Drug Interactions between amoxicillin / clarithromycin / vonoprazan and tofacitinib

ADJUST DOSE: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of tofacitinib, which is metabolized by the isoenzyme. In study subjects, administration with the potent CYP450 3A4 inhibitor ketoconazole increased tofacitinib systemic exposure (AUC) by greater than 2-fold compared to administration of tofacitinib alone. Side effects including lymphopenia, neutropenia, anemia, serious infections, and hyperlipidemia may be increased.

MANAGEMENT: The dosage of tofacitinib should be reduced by 50% when used with potent CYP450 3A4 inhibitors. For example, the dose for patients receiving 10 mg twice daily should be reduced to 5 mg twice daily and the dose for patients receiving 5 mg twice daily should be reduced to 5 mg once daily. For patients receiving 11 mg once daily of the extended-release formulation, the dose should be reduced to 5 mg once daily of the immediate-release formulation. The dose for patients receiving 3.2 mg twice daily should be reduced to 3.2 mg once daily and the dose for patients receiving 4 mg twice daily should be reduced to 4 mg once daily.

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.