Drug Interaction Report

ADJUST DOSING INTERVAL: The concomitant use of bone marrow depressants or cytotoxic agents with strontium-89 chloride may result in additive myelosuppression. Bone marrow toxicity is expected following the administration of strontium-89 chloride alone, especially with regards to white blood cells (WBCs) and platelets. The nadir of platelet depression for most patients is about 4 to 16 weeks after a strontium-89 chloride injection. Recovery can be slow and may not be complete.

MANAGEMENT: Concomitant use of strontium-89 chloride and a bone marrow suppressant or cytotoxic agent is not generally recommended. Some authorities advise separating strontium-89 chloride administration from that of a cytotoxic agent by an interval of at least 12 weeks, provided that the patient's hematological parameters are stable and within the normal range. The product labeling for the concomitant myelosuppressive/cytotoxic medication should be consulted for more specific recommendations. Patients should be advised to contact their physician if they develop signs and symptoms of myelosuppression such as pallor, dizziness, fatigue, lethargy, fainting, easy bruising or bleeding, or signs of infection such as fever, chills, sore throat, body aches, and other influenza-like symptoms.

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.