Ibrutinib and Alcohol/Food Interactions

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.

ibrutinib - arrhythmias

Fatal and serious cardiac arrhythmias and cardiac failure have occurred with ibrutinib. These adverse reactions occurred in patients with and without preexisting hypertension or cardiac comorbidities; patients with cardiac comorbidities may be at greater risk of these events. Ventricular tachyarrhythmias, atrial fibrillation, and atrial flutter have occurred in patients treated with ibrutinib, especially in patients with acute infections or cardiac risk factors (including hypertension, diabetes mellitus, history of cardiac arrhythmia). Cardiac history and function should be evaluated at baseline, and patients should be monitored for cardiac arrhythmias and cardiac function. Further evaluation (e.g., ECG, echocardiogram) should be obtained as indicated for patients who develop symptoms of arrhythmia (e.g., palpitations, lightheadedness, syncope, chest pain), new onset dyspnea, or other cardiovascular concerns. Cardiac arrhythmias and cardiac failure should be managed appropriately, dosage modification guidelines should be followed, and the risks and benefits of continued ibrutinib treatment should be considered.

ibrutinib - hypertension

The use of ibrutinib may cause hypertension. Blood pressure should be monitored in patients treated with this drug. Antihypertensive medication should be started or adjusted throughout ibrutinib treatment as appropriate, and the dosage modification guidelines should be followed for grade 3 or higher hypertension.