Drug Interaction Report

MONITOR: Coadministration with epcoritamab may increase the plasma concentrations of drugs that are substrates of CYP450 isoenzymes. Initiation of epcoritamab treatment causes transient release of cytokines that may suppress CYP450 isoenzymes, although the potential for an interaction has not been studied. According to the manufacturer, the highest drug-drug interaction risk would be from the first dose on the first day of cycle 1, up to 14 days after the first 48 mg dose on day 15 of cycle 1, as well as during and after cytokine release syndrome.

MANAGEMENT: Caution is advised when epcoritamab is administered 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 at the initial phase of treatment with epcoritamab as well as during and after cytokine release syndrome, and the dosage(s) of the CYP450 substrate(s) adjusted accordingly.

GENERALLY AVOID: Some beverages such as tonic water contain varying amounts of quinine. Coadministration of a single 430 mg dose of quinine has been shown to increase plasma concentrations of astemizole and its metabolite, desmethylastemizole. Elevated levels of these agents may cause a prolongation of the electrocardiographic QT interval and potentially fatal ventricular arrhythmias. Although pharmacokinetic data have indicated that the amounts of quinine in beverages (up to 80 mg quinine in 32 oz of tonic water) are not sufficient to produce a significant effect, the potential for an interaction exists if large amounts of tonic water are ingested. Also, grapefruit juice has been shown to inhibit CYP450 enzymes, which may lead to increased serum astemizole concentrations. The risk of life-threatening ventricular arrhythmias may be increased.

MANAGEMENT: Patients should be counseled to limit consumption of quinine-containing beverages and avoid grapefruit juice while they are taking astemizole.