Drug Interactions between aspirin / caffeine / dihydrocodeine and tebentafusp

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.

One study has reported that coadministration of caffeine and aspirin lead to a 25% increase in the rate of appearance and 17% increase in maximum concentration of salicylate in the plasma. A significantly higher area under the plasma concentration time curve of salicylate was also reported when both drugs were administered together. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that coadministration of aspirin and caffeine may lead to higher salicylate levels faster.