Drug Interaction Report

MONITOR: Coadministration with tebentafusp may increase the plasma concentrations of drugs that are metabolized by CYP450 pathways. The formation of hepatic CYP450 enzymes is down-regulated by increased levels of certain proinflammatory cytokines that are transiently released during initiation of tebentafusp treatment. Thus, tebentafusp may suppress CYP450 enzymes resulting in increased exposures of some CYP450 substrates. Clinical data are currently lacking but risk of an interaction is expected to be greatest during the first 24 hours of the first 3 tebentafusp doses.

MANAGEMENT: Caution is advised when tebentafusp is coadministered with drugs that are CYP450 substrates, particularly those with narrow therapeutic ranges (e.g., antiarrhythmics, anticonvulsants, immunosuppressants, theophylline) or sensitive substrates where increases in plasma levels may be significant or undesirable (e.g., statins, benzodiazepines, opioids). Clinical and/or laboratory monitoring should be considered following the initiation or withdrawal of tebentafusp, and the dosage(s) of the CYP450 substrate(s) adjusted accordingly.

GENERALLY AVOID: Grapefruit juice may significantly increase the plasma concentrations of orally administered everolimus. The mechanism is inhibition of CYP450 3A4 and P-glycoprotein activity in the gut wall by certain compounds present in grapefruit.

MANAGEMENT: Patients treated with everolimus should avoid consumption of grapefruit and grapefruit juice.