Drug Interaction Report

MONITOR: Coadministration with glofitamab may increase the plasma concentrations of drugs that are substrates of CYP450 isoenzymes. Initiation of glofitamab 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 day 8 of cycle 1, up to 14 days after the first 30 mg dose on day 1 of cycle 2, as well as during and after cytokine release syndrome.

MANAGEMENT: Caution is advised when glofitamab is administered with drugs that are metabolized by CYP450 isoenzymes, particularly sensitive CYP450 substrates and/or 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 glofitamab as well as 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: Grapefruit juice may significantly increase the plasma concentrations of ivabradine. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. According to the product labeling, administration with grapefruit juice (quantity unknown) resulted in an approximately twofold increase in ivabradine systemic exposure (AUC). Elevated plasma levels of ivabradine may increase the risk of excessive bradycardia and conduction disturbances.

ADJUST DOSING INTERVAL: Food delays the absorption of ivabradine by approximately 1 hour and increases plasma exposure by 20% to 40% compared to fasting conditions.

MANAGEMENT: Patients treated with ivabradine should avoid or limit consumption of grapefruit or grapefruit juice. The manufacturer recommends taking ivabradine with meals to reduce variability in exposure.