Drug Interaction Report

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of vemurafenib, which has been shown in vitro to be a substrate of the isoenzyme. According to the product labeling, administration of a single 960 mg dose of vemurafenib with the potent CYP450 3A4 inducer rifampin at a dosage of 600 mg once daily resulted in a 40% decrease in vemurafenib systemic exposure (AUC) relative to vemurafenib administered alone, with no effect on peak plasma concentration (Cmax). The extent to which other, less potent CYP450 3A4 inducers may affect vemurafenib is unknown.

MANAGEMENT: The potential for diminished pharmacologic effects of vemurafenib should be considered during coadministration with CYP450 3A4 inducers. Alternative treatments or a dose adjustment of vemurafenib may be required if an interaction is suspected.

Administration with food may delay the absorption of modafinil (the racemate) and armodafinil (the R-enantiomer) without significantly affecting their overall bioavailability. According to the product labeling, modafinil's absorption may be delayed by approximately one hour if taken with food. Similarly, the time to reach peak plasma concentration (Tmax) of armodafinil may be delayed by approximately 2 to 4 hours in the fed state.