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concomitant use is required, clinical and laboratory monitoring may be appropriate whenever trofinetide is added to or withdrawn from therapy.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: Alcohol may potentiate some of the pharmacologic effects of carbamazepine. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

In a small, randomized, crossover study, the administration of carbamazepine with grapefruit juice (compared to water) increased plasma drug concentrations by approximately 40%. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

MANAGEMENT: Patients receiving carbamazepine should be advised to avoid or limit consumption of alcohol. Given the drug's narrow therapeutic index, patients receiving carbamazepine therapy should preferably avoid the regular consumption of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels. Patients should be advised to report signs of carbamazepine toxicity (nausea, visual disturbances, dizziness, or ataxia) to their physicians.