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.

ADJUST DOSING INTERVAL: Consumption of food has led to a 27% decrease in the bioavailability of orally administered tacrolimus.

MANAGEMENT: Tacrolimus should be administered at least one hour before or two hours after meals.

GENERALLY AVOID: Grapefruit juice has been reported to increase tacrolimus trough concentrations. Data are limited, but inhibition of the CYP450 enzyme system appears to be involved.

MANAGEMENT: The clinician may want to recommend that the patient avoid ingesting large amounts of grapefruit juice while taking tacrolimus.