Drug Interaction Report

MONITOR CLOSELY: Coadministration of radiolabeled ibritumomab tiuxetan and drugs that interfere with platelet function or coagulation may potentiate the risk of bleeding complications. Radiolabeled ibritumomab tiuxetan commonly causes severe and prolonged thrombocytopenia, and the risk is increased further in patients with mild thrombocytopenia at the initiation of therapy. Haemorrhage, including fatal cerebral hemorrhage, has occurred in a minority of patients in clinical studies. The median time to thrombocyte nadir was 7 to 9 weeks, and the median duration of thrombocytopenia was 22 to 35 days. However, in less than 5% of the cases, patients experienced severe cytopenia that extended beyond 12 weeks following administration of the radiolabeled ibritumomab tiuxetan therapeutic regimen. Platelet transfusions were given to 22% of patients in clinical trials.

MANAGEMENT: Caution is advised if radiolabeled ibritumomab tiuxetan is used in combination with drugs that interfere with platelet function or coagulation. Close clinical and laboratory observation for bleeding complications is recommended during and after treatment.

GENERALLY AVOID: Grapefruit and grapefruit juice may significantly increase the plasma concentrations of dasatinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruit. Because grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4, the magnitude of interaction is greatest for those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability). In general, 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. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict. Because dasatinib prolongs the QT interval, high plasma levels of dasatinib may increase the risk of ventricular arrhythmias such as torsade de pointes and sudden death.

MANAGEMENT: Patients treated with dasatinib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Some authorities recommend close monitoring for toxicity (e.g., myelosuppression, bleeding complications, fluid retention, bradycardia or other conduction disturbances) and a reduction of dasatinib dosage to a range of 20 to 40 mg daily should be considered if there are no alternatives and concomitant use with a potent CYP450 3A4 inhibitor is necessary.