Drug Interaction Report

MONITOR: Coadministration with elranatamab may increase the plasma concentrations of drugs that are substrates of CYP450 isoenzymes. Initiation of elranatamab 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 after the first dose of elranatamab on day 1 and up to 14 days after the 32 mg dose on day 4, as well as during and after cytokine release syndrome.

MANAGEMENT: Caution is advised when elranatamab is administered with drugs that are metabolized by CYP450 isoenzymes, particularly those with a narrow therapeutic index such as carbamazepine, colchicine, cyclosporine, disopyramide, phenytoin, quinidine, theophylline, warfarin, macrolide immunosuppressants, vinca alkaloids, and some narcotic analgesics. Clinical and/or laboratory monitoring is recommended following the initiation of elranatamab, and the dosage(s) of the CYP450 substrate(s) may be adjusted accordingly.

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.