Drug Interactions between capivasertib and Orap

You should avoid the consumption of large amounts of grapefruits and grapefruit juice while taking pimozide. Grapefruit can raise the levels of pimozide in your body. This can affect the rhythm of your heart and cause other side effects. Call your doctor if you have symptoms of blurred vision or nausea. You should seek immediate medical attention if you develop sudden dizziness, lightheadedness, fainting, shortness of breath, or fast or pounding heartbeats during treatment with pimozide. Do not increase or decrease the amount of grapefruit products in your diet without first talking to your doctor. You should avoid or limit the use of alcohol while being treated with pimozide. Alcohol can increase the nervous system side effects of pimozide such as dizziness, drowsiness, and difficulty concentrating. Some people may also experience impairment in thinking and judgment. Talk to your doctor or pharmacist if you have any questions or concerns.

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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.