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concomitant use is required, clinical and laboratory monitoring may be appropriate whenever trofinetide is added to or withdrawn from therapy.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

GENERALLY AVOID: Coadministration of temsirolimus with grapefruit juice may increase the plasma concentrations of sirolimus, a major active metabolite of temsirolimus and known substrate of CYP450 3A4. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism by certain compounds present in grapefruits.

MANAGEMENT: Patients treated with temsirolimus should preferably avoid the consumption of grapefruit or grapefruit juice.