Drug Interactions between amoxicillin / clarithromycin / vonoprazan and modafinil

GENERALLY AVOID: Coadministration with moderate inducers of CYP450 3A4 may significantly decrease the plasma concentrations of vonoprazan, which is metabolized by the isoenzyme. When coadministered with moderate CYP450 3A4 inducers, vonoprazan systemic exposure (AUC) is predicted to decrease by 50%. Reduced efficacy of vonoprazan may occur.

MANAGEMENT: According to the manufacturer, concomitant use of vonoprazan with moderate CYP450 3A4 inducers should be avoided.

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 inhibitors of CYP450 3A4 may increase the plasma concentrations of modafinil (the racemate) and armodafinil (the R-enantiomer), which are both partially metabolized by the isoenzyme. Conversely, the plasma levels of some of these inhibitors may decrease, since many of them are also substrates of CYP450 3A4, and modafinil and armodafinil have been found to be modest inducers of CYP450 3A4. The clinical significance of this potential interaction is unknown. Clinical monitoring for altered effects of modafinil and armodafinil as well as the CYP450 3A4 inhibitor may be appropriate following addition or withdrawal of one or the other drug. Dose adjustments may be required if an interaction is suspected.