Drug Interactions between glasdegib and inotuzumab ozogamicin

GENERALLY AVOID: Inotuzumab ozogamicin may cause 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 a randomized clinical study in patients with relapsed or refractory acute lymphoblastic leukemia, increases in Fridericia-corrected QT interval (QTcF) of >=60 msec from baseline occurred in 4 of 162 (3%) patients receiving inotuzumab ozogamicin; however, no patients had QTcF values greater than 500 msec. Two patients (1%) had Grade 2 QT prolongation, while no patient had Grade 3 or higher QT prolongation or torsade de pointes. 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 inotuzumab ozogamicin with other drugs that can prolong the QT interval should generally be avoided. Caution and clinical monitoring are recommended if concomitant use cannot be avoided or if inotuzumab ozogamicin is used in patients with other risk factors for QT prolongation. The manufacturer suggests obtaining electrocardiograms and serum electrolytes at baseline and regularly during treatment. 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.