Drug Interactions between capivasertib and Venclexta

Food helps to increase the absorption of venetoclax. You should take each dose of venetoclax with a meal and water at approximately the same time each day. Do not consume grapefruit, grapefruit juice, Seville oranges, or starfruit during treatment with venetoclax. Doing so can significantly increase blood levels and effects of the medication. This may increase your risk of developing tumor lysis syndrome, a serious condition that is caused by the rapid breakdown of cancer cells and that can lead to kidney failure and even death. In addition, you may be more likely to experience other side effects such as nausea; vomiting; diarrhea; fatigue; and impaired bone marrow function resulting in low numbers of different types of blood cells, which can increase the risk of anemia, bleeding problems, and infections. Talk to your doctor if you have any questions or concerns. 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.

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GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of capivasertib, which is primarily metabolized by CYP450 3A4. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice but has been studied with other CYP450 3A4 inhibitors. Based on clinical studies and model-informed approaches, concomitant use with the potent CYP450 3A4 inhibitor itraconazole is predicted to increase capivasertib systemic exposure (AUC) by up to 1.7-fold and peak plasma concentration (Cmax) by up to 1.4-fold. Coadministration with the moderate CYP450 3A4 inhibitors erythromycin and verapamil is predicted to increase the AUC and Cmax of capivasertib by up to 1.5-fold 1.3-fold, respectively. 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 capivasertib may increase the risk of adverse effects such as diarrhea, cutaneous adverse reactions, decreased lymphocytes, decreased hemoglobin, hyperglycemia, nausea, and fatigue.

MANAGEMENT: It may be advisable for patients to avoid the consumption of grapefruit, grapefruit juice, or supplements that contain grapefruit during treatment with capivasertib.