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concomitant use is required, clinical and laboratory monitoring may be appropriate whenever trofinetide is added to or withdrawn from therapy.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.

Food enhances the oral absorption and bioavailability of tenofovir, the active entity of tenofovir disoproxil fumarate. According to the product labeling, administration of the drug following a high-fat meal increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of tenofovir by approximately 14% and 40%, respectively, compared to administration in the fasting state. However, administration with a light meal did not significantly affect the pharmacokinetics of tenofovir compared to administration in the fasting state. Food delays the time to reach tenofovir Cmax by approximately 1 hour. Tenofovir disoproxil fumarate may be administered without regard to meals.