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concomitant use is required, clinical and laboratory monitoring may be appropriate whenever trofinetide is added to or withdrawn from therapy.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

ADJUST DOSING INTERVAL: Food may delay the gastrointestinal absorption of tamsulosin. The time to maximum plasma concentration (Tmax) is reached by 4 to 5 hours under fasted conditions and by 6 to 7 hours when tamsulosin is administered with food. The delay in Tmax has the desirable effect of smoothing the tamsulosin plasma concentration profile, thereby reducing fluctuation of the plasma peak and trough concentrations with multiple dosing. Food may also affect the extent of absorption of tamsulosin. It has been reported that taking tamsulosin under fasted conditions results in a 30% increase in bioavailability (AUC) and 40% to 70% increase in peak plasma concentration (Cmax) compared to fed conditions. The effects of food on the pharmacokinetics of tamsulosin are consistent regardless of whether tamsulosin is taken with a light meal or a high-fat meal.

MANAGEMENT: To ensure uniformity of absorption, tamsulosin should be administered approximately one-half hour following the same meal each day.