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.

ADJUST DOSING INTERVAL: Food does not appear to substantially alter the pharmacokinetics of tipranavir. When tipranavir capsules or oral solution was coadministered with ritonavir capsules at steady-state, no clinically significant changes in tipranavir peak plasma concentration (Cmax) and systemic exposure (AUC) were observed under fed conditions (500 to 682 kcal, 23% to 25% calories from fat) relative to fasted conditions. The effect of food on tipranavir exposure during coadministration with ritonavir tablets has not been evaluated. High-fat foods may enhance the gastrointestinal absorption of tipranavir. In a multiple-dose study, administration of tipranavir capsules with a high-fat meal (868 kcal, 53% from fat, 31% from carbohydrates) increased the oral bioavailability of tipranavir by 31% compared to administration with toast and skimmed milk, but did not significantly affect tipranavir Cmax. Thus, tipranavir may be safely taken with standard or high-fat meals.

MANAGEMENT: Tipranavir coadministered with low-dose ritonavir should be taken with food to improve the gastrointestinal tolerability of ritonavir. According to the product labeling, tipranavir coadministered with ritonavir capsules or solution can be taken with or without meals, whereas tipranavir coadministered with ritonavir tablets must be taken with meals.