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.

GENERALLY AVOID: Theoretically, the coadministration with grapefruit juice may increase the plasma concentrations of pimozide. The mechanism is decreased clearance of pimozide due to inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. The use of pimozide alone has been associated with dose-dependent prolongation of the QT interval. Although clinical data are lacking, this interaction may result in potentiation of the proarrhythmic effect of pimozide and consequently an increased risk of ventricular arrhythmias such as ventricular tachycardia and torsade de pointes. In addition, alcohol may potentiate some of the pharmacologic effects of pimozide. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: The manufacturer recommends avoiding grapefruit juice (and probably grapefruits) during therapy with pimozide. Patients should also be advised to avoid or limit consumption of alcohol.