Drug Interaction Report

MONITOR: Coadministration with tarlatamab may increase the plasma concentrations of drugs that are substrates of CYP450 3A4 isoenzymes. Initiation of tarlatamab treatment causes transient release of cytokines that may suppress CYP450 isoenzymes, although the potential for interaction has not been studied. According to the manufacturer, the highest drug-drug interaction risk would be during and for up to 14 days after the occurrence of cytokine release syndrome.

MANAGEMENT: Caution is advised when tarlatamab is coadministered with drugs that are metabolized by CYP450 isoenzymes, particularly those with a narrow therapeutic range, where minimal changes to concentration may lead to significant adverse reactions, such as carbamazepine, colchicine, cyclosporine, disopyramide, phenytoin, quinidine, theophylline, warfarin, macrolide immunosuppressants, vinca alkaloids, and some narcotic analgesics. Clinical and/or laboratory monitoring are recommended, particularly during and after cytokine release syndrome, and individual product labeling for the CYP450 substrate(s) should be consulted for specific dosage adjustment recommendations.

ADJUST DOSING INTERVAL: Consumption of food can decrease the rate and extent of gastrointestinal absorption of sirolimus. Also, the consumption of grapefruit juice may result in increased sirolimus trough concentrations.

MANAGEMENT: Experts recommend that this drug be taken either at least one hour prior to eating or consistently with or without food to avoid variations in sirolimus blood levels. The manufacturer recommends against using grapefruit juice for dilution of sirolimus doses. Patients should be monitored for clinical and laboratory evidence of altered immunosuppressant effects.