Drug Interaction Report

GENERALLY AVOID: Prophylactic use of systemic corticosteroids prior to CD19- or BCMA-directed genetically modified autologous T cell immunotherapy may interfere with the therapeutic effects of such drugs as axicabtagene ciloleucel, brexucabtagene autoleucel, idecabtagene vicleucel, ciltacabtagene autoleucel and lisocabtagene maraleucel. The mechanism for this interaction has not been delineated. Administration of systemic corticosteroids in an effort to manage the toxicities associated with these drugs does not affect the expansion and persistence of CAR T cells.

MANAGEMENT: The prophylactic use of systemic corticosteroids prior to CD19- or BCMA-directed genetically modified autologous T cell immunotherapy with drugs such as axicabtagene ciloleucel, brexucabtagene autoleucel, idecabtagene vicleucel, ciltacabtagene autoleucel and lisocabtagene maraleucel is not recommended. However, systemic corticosteroids may be used for the management of adverse effects associated with these drugs, such as cytokine release syndrome and neurological-related toxicities, without affecting the expansion and persistence of CAR T cells.

Although they are often combined in clinical practice, the concomitant use of beta-2 adrenergic agonists and corticosteroids may result in additive hypokalemic effects. Since beta-2 agonists can sometimes cause QT interval prolongation, the development of hypokalemia may potentiate the risk of ventricular arrhythmias including torsade de pointes. However, clinical data are limited, and the potential significance is unknown. Patients who are receiving systemic or nebulized formulations of beta-2 agonists, high dosages of inhaled beta-2 agonists, or systemic corticosteroid therapy may be at a greater risk of developing hypokalemia.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations and systemic effects of orally administered budesonide. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. According to the manufacturer, the systemic exposure of oral budesonide approximately doubles after extensive intake of grapefruit juice.

MANAGEMENT: Patients receiving budesonide should avoid the regular consumption of grapefruits and grapefruit juice to prevent undue increases in plasma budesonide levels and systemic effects.

GENERALLY AVOID: Use of anticholinergic agents with alcohol may result in sufficient impairment of attention so as to render driving and operating machinery more hazardous. In addition, the potential for abuse may be increased with the combination. The mechanism of interaction is not established but may involve additive depressant effects on the central nervous system. No effect of oral propantheline or atropine on blood alcohol levels was observed in healthy volunteers when administered before ingestion of a standard ethanol load. However, one study found impairment of attention in subjects given atropine 0.5 mg or glycopyrrolate 1 mg in combination with alcohol.

MANAGEMENT: Alcohol should generally be avoided during therapy with anticholinergic agents. Patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them.