Imbruvica and Food

Ibrutinib should be taken once daily at approximately the same time everyday. Do not consume grapefruit, grapefruit juice, or Seville oranges unless directed otherwise by your doctor. Grapefruit and Seville oranges may significantly increase the blood levels of ibrutinib. This may increase the risk of side effects such as nausea, vomiting, diarrhea, abdominal pain, constipation, hemorrhage, kidney problems, and impaired bone marrow function resulting in low numbers of different types of blood cells. You may also be more likely to develop anemia, bleeding problems, or infections due to low blood cell counts. You should contact your doctor if you develop paleness, fatigue, dizziness, fainting, unusual bruising or bleeding, fever, chills, diarrhea, sore throat, muscle aches, shortness of breath, blood in phlegm, weight loss, red or inflamed skin, body sores, and pain or burning during urination. Also seek immediate medical attention if you experience signs and symptoms that may suggest kidney damage such as nausea, vomiting, loss of appetite, increased or decreased urination, sudden weight gain or weight loss, fluid retention, swelling, shortness of breath, muscle cramps, tiredness, weakness, dizziness, confusion, and irregular heart rhythm. 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: Coadministration with grapefruit, grapefruit juice, or Seville oranges may significantly increase the plasma concentrations of ibrutinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Pharmacokinetic modeling suggests that other moderate CYP450 3A4 inhibitors such as diltiazem and erythromycin may increase ibrutinib systemic exposure (AUC) by 6- to 9-fold under fasting condition. The safety and efficacy of these exposures are unknown. The highest ibrutinib dose evaluated in clinical trials was 12.5 mg/kg (actual doses of 840 to 1400 mg) given for 28 days, which yielded single dose AUC values that were approximately 50% greater than steady-state exposures seen at the highest indicated dose of 560 mg.

ADJUST DOSING INTERVAL: Food increases the oral bioavailability of ibrutinib. The mechanism of interaction is unknown. According to the product labeling, administration with food increases ibrutinib exposure approximately 2-fold compared to administration after overnight fasting.

MANAGEMENT: Patients treated with ibrutinib should avoid consumption of Seville oranges, grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Ibrutinib should be taken once daily at approximately the same time each day.