Nerlynx and Food

Grapefruit juice can increase the blood levels of neratinib. This may increase the risk and/or severity of side effects such as diarrhea, nausea, vomiting, abdominal pain, mouth sores, loss of appetite, and liver problems. You should avoid the consumption of grapefruit and grapefruit juice during treatment with neratinib. Be sure to take the medication with food at the same time everyday to maintain consistent blood levels and effects. Talk to your doctor or pharmacist if you have questions on how to take this or other medications you are prescribed. 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.

GENERALLY AVOID: Grapefruit, grapefruit juice, grapefruit hybrids, pomelos, star-fruit, and Seville oranges may increase the plasma concentrations of neratinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in these fruits. Inhibition of hepatic CYP450 3A4 may also contribute. In a study consisting of 24 healthy subjects, neratinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 3.2- and 4.8-fold, respectively, when a single 240 mg oral dose of neratinib was administered with the potent CYP450 3A4 inhibitor ketoconazole (400 mg once daily for 5 days). Also, mean apparent oral clearance of neratinib decreased by approximately 75% and mean elimination half-life increased by 54%. The interaction has not been studied with these fruits. In general, for example, 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 neratinib may increase adverse effects such as diarrhea, nausea, vomiting, abdominal pain, stomatitis, anorexia, and hepatotoxicity.

Food with a high fat content enhances the oral bioavailability of neratinib. In healthy volunteers, administration of neratinib 240 mg with a high-fat meal (approximately 55% fat; 31% carbohydrate; 14% protein) increased neratinib peak plasma concentration (Cmax) and systemic exposure (AUC) by 1.7- and 2.2-fold, respectively, compared to administration under fasting conditions. By contrast, a standard breakfast (approximately 50% carbohydrate; 35% fat; 15% protein) increased the Cmax and AUC of neratinib by 1.2- and 1.1-fold, respectively.

MANAGEMENT: The manufacturer recommends administering neratinib with food at approximately the same time every day. Patients should avoid consumption of grapefruit, grapefruit juice, grapefruit hybrids, pomelos, star-fruit, and Seville oranges during treatment with neratinib.