Drug Interaction Report

MONITOR: Coadministration with trofinetide may increase the plasma concentrations of drugs that are substrates of CYP450 3A4 via inhibition of the isoenzyme. Based on pharmacokinetic modeling, concomitant use of trofinetide and oral midazolam, a sensitive CYP450 3A4 substrate, is predicted to increase midazolam systemic exposure (AUC) by approximately 1.33-fold. Clinical data are currently lacking.

MANAGEMENT: Caution is advised if trofinetide is coadministered with CYP450 3A4 substrates, particularly sensitive substrates or those with a narrow therapeutic range. If concomitant use is required, clinical and laboratory monitoring may be appropriate whenever trofinetide is added to or withdrawn from therapy. The prescribing information for concomitant medications should be consulted to assess the benefits versus risks of coadministration and for any dosage adjustments that may be required.

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.