Drug Interactions between anagrelide and pazopanib

GENERALLY AVOID: Anagrelide can cause dose-dependent prolongation of the QT interval. 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 60 healthy adult volunteers given single doses of anagrelide, the maximum mean change in QTcI (individual subject correction) from placebo after baseline correction was 7.0 msec after a 0.5 mg dose and 13.0 msec after a 2.5 mg dose. Torsade de pointes and ventricular tachycardia have been reported with anagrelide treatment. In general, the risk of an individual agent or a combination of 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: Coadministration of anagrelide with other drugs that can prolong the QT interval should generally be avoided. Patients receiving anagrelide should have a cardiovascular examination, including an ECG, prior to initiation of treatment and monitored for cardiovascular effects during treatment. Hypokalemia or hypomagnesemia must be corrected prior to therapy and electrolytes monitored periodically during therapy. Anagrelide should not be used in the presence of known risk factors for QT interval prolongation such as congenital long QT syndrome or a history of acquired QTc prolongation. Periodic electrocardiograms are recommended in patients with heart failure, bradyarrhythmias, or electrolyte abnormalities. 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.