Drug Interactions between sebetralstat and Sprycel

Do not consume grapefruit or grapefruit juice during treatment with dasatinib. Grapefruit juice can significantly increase the blood levels and effects of dasatinib, which may result in excessive slowing of heart rate or other conduction disturbances and it may affect your bone marrow function, resulting in low numbers of different types of blood cells. You may be more likely to develop anemia, bleeding problems, or infections due to low blood cell counts. Talk to your doctor if you have any questions or concerns. You should seek immediate medical attention if you develop sudden dizziness, lightheadedness, fainting, shortness of breath, heart palpitations, paleness, fatigue, unusual bruising or bleeding, fever, chills, diarrhea, sore throat, muscle aches, blood in phlegm, weight loss, pain or burning during urination, red or inflamed skin, or body sores during treatment with dasatinib. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

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.