Drug Interactions between nirogacestat and sibutramine

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Grapefruit, grapefruit juice, Seville oranges, and starfruit may significantly increase the plasma concentrations and pharmacologic effects of nirogacestat. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in these fruits. Coadministration of multiple doses of nirogacestat (150 mg twice daily) with the moderate CYP450 3A4 inhibitors erythromycin and fluconazole are predicted to increase the AUC of nirogacestat by 2.73-fold and 3.18-fold, respectively. The interaction has not been studied with grapefruit, Seville oranges, or starfruit. 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 systemic exposure to nirogacestat may increase the risk of adverse effects including diarrhea, ovarian toxicity, hepatotoxicity, electrolyte abnormalities, and non-melanoma skin cancers.

MANAGEMENT: Patients treated with nirogacestat should avoid consumption of grapefruit, grapefruit juice, Seville oranges, starfruit, or any supplement containing grapefruit.

Using sibutramine with alcohol can increase the risk of cardiovascular side effects such as increased heart rate, chest pain, or blood pressure changes. In addition, you may also be more likely to experience nervous system side effects such as dizziness, drowsiness, depression, and difficulty concentrating. You should avoid or limit the use of alcohol while being treated with sibutramine. Do not use more than the recommended dose of sibutramine, and avoid activities requiring mental alertness such as driving or operating hazardous machinery until you know how the medication affects you. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medication without first talking to your doctor.

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