Drug Interactions between sebetralstat and Zonacort

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Coadministration with grapefruit juice may increase the plasma concentrations of sebetralstat. The mechanism is decreased clearance of sebetralstat due to inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. The interaction has not been studied with grapefruit juice but has been reported for the potent CYP450 3A4 inhibitor, itraconazole. In a clinical study, sebetralstat peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 2.4-fold and 5.2-fold, respectively, following concomitant administration of the potent CYP450 3A4 inhibitor, itraconazole (200 mg once daily for 6 days). In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Increased exposure to sebetralstat may increase the risk and/or severity of adverse effects such as headache and QT prolongation. The use of sebetralstat alone at doses 2.5 times the maximum recommended dose has been associated with a mean increase in corrected QT (QTc) interval of 10.4 msec. Although clinical data are lacking for sebetralstat, in general, prolongation of the QT interval may increase the risk of ventricular arrhythmias such as ventricular tachycardia and torsade de pointes.

MANAGEMENT: Consumption of food or drinks containing grapefruit should generally be avoided during treatment with sebetralstat.