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.

ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of bosutinib. When given with a high-fat meal, bosutinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 1.8- and 1.7-fold, respectively.

GENERALLY AVOID: Coadministration with grapefruit juice is likely to increase the plasma concentrations of bosutinib, which is primarily metabolized by CYP450 3A4. However, the interaction has not been studied. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.

MANAGEMENT: Bosutinib should be administered with a meal. The consumption of grapefruit, grapefruit juice, and supplements that contain grapefruit extract should be avoided.