Grapefruit-Mavacamten Interaction Leading to Reduced Ejection Fraction

BACKGROUND: Mavacamten reduces left ventricular outflow tract obstruction in obstructive hypertrophic cardiomyopathy but carries a risk of exposure-dependent systolic dysfunction due to its narrow therapeutic window. CASE SUMMARY: A 57-year-old male with obstructive hypertrophic cardiomyopathy was started on mavacamten resulting in progressive reduction in left ventricular outflow tract gradient with preserved left ventricular ejection fraction (LVEF) over the first several months. Around month 5, he began consuming grapefruit-containing energy drinks daily. After approximately 2 months of exposure, LVEF declined to 45% to 50%. Mavacamten and grapefruit exposure were discontinued, resulting in normalization of LVEF. Rechallenge with mavacamten in the absence of grapefruit did not reproduce systolic dysfunction. DISCUSSION: Clinical trials report reversible LVEF reduction with mavacamten; however, real-world pharmacokinetic interactions are less well described. This case demonstrates a probable grapefruit-mediated interaction leading to transient systolic dysfunction. TAKE-HOME MESSAGE: Unrecognized dietary cytochrome P450 enzyme inhibition may increase mavacamten exposure and cause reversible systolic dysfunction.