Drug Interactions between capivasertib and Xalkori

Do not consume grapefruit or grapefruit juice during treatment with crizotinib unless directed otherwise by your doctor. Grapefruit juice can increase the blood levels of crizotinib to dangerous levels and cause an irregular heart rhythm that may be serious. You should seek immediate medical attention if you develop sudden dizziness, lightheadedness, fainting, shortness of breath, or fast or pounding heartbeats during treatment with crizotinib. You may take crizotinib with or without food, but take it the same time each day. 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.

The recommended maximum number of medicines in the 'multikinase inhibitors' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'multikinase inhibitors' category:

• capivasertib
• Xalkori (crizotinib)

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.