Drug Interaction Report

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.

ADJUST DOSING INTERVAL: Food may reduce the oral absorption and bioavailability of zafirlukast. In two separate studies, one using a high-fat and the other a high-protein meal, administration of zafirlukast with food reduced the mean bioavailability by approximately 40%.

MANAGEMENT: To ensure maximal oral absorption, zafirlukast should be administered at least 1 hour before or 2 hours after meals.

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.