Lost Rate Control and Tachycardia-Induced Cardiomyopathy as a Result of an Interaction Between Enzalutamide and Diltiazem

BACKGROUND: There is a theoretical drug interaction between enzalutamide, a potent cytochrome P 3A4 (CYP 3A4) inducer, and diltiazem, a CYP3A4 substrate. Resources recommend avoiding the combination. CASE SUMMARY: The patient was taking diltiazem for rate control of permanent atrial fibrillation. After initiating enzalutamide for prostate cancer, he became persistently tachycardic, developed heart failure, and was admitted. On admission, enzalutamide was held, and diltiazem was stopped. His left ventricular ejection fraction was reduced from a baseline of 52% to <15%. The patient regained rate control with metoprolol and was asymptomatic at discharge. DISCUSSION: This case describes the interaction between enzalutamide and diltiazem that resulted in a loss of rate control and subsequent heart failure. It provides a cautionary example of the complications that may arise with gaps in drug interaction management and timely monitoring and follow-up. TAKE-HOME MESSAGE: Streamlined, multidisciplinary approaches to monitoring and managing drug interactions of uncertain clinical significance, particularly in the field of cardio-oncology, are needed.