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: Acute ethanol ingestion may potentiate the CNS effects of many benzodiazepines. Tolerance may develop with chronic ethanol use. The mechanism may be decreased clearance of the benzodiazepines because of CYP450 hepatic enzyme inhibition. Also, it has been suggested that the cognitive deficits induced by benzodiazepines may be increased in patients who chronically consume large amounts of alcohol.

MANAGEMENT: Patients should be advised to avoid alcohol during benzodiazepine therapy.