Drug Interactions between bosutinib and desipramine

MONITOR: Bosutinib may cause QTc prolongation without associated arrhythmia. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. In combined data from 870 patients, 0.3% experienced QTcF interval prolongation greater than 500 msec. In addition, 0.9% of patients (including two of the patients with QTcF interval prolongation greater than 500 msec) experienced QTcF increase from baseline greater than 60 msec. In a study with 60 healthy adults, therapeutic and supratherapeutic doses of bosutinib plus moxifloxacin were not associated with QTc prolongation. Torsade de pointes has not been reported with bosutinib; however, its proarrhythmic potential cannot be excluded. In general, the risk of an individual agent or a combination of these agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: Caution is recommended if bosutinib is used in combination with other drugs that can prolong the QT interval. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.