Key result
Fluconazole co-administration with mavacamten triggers acute heart failure and transient systolic dysfunction.
Why the study?
The safe use of mavacamten for obstructive hypertrophic cardiomyopathy requires careful monitoring due to potential drug–drug interactions that may cause heart failure.
Does the concomitant use of strong CYP2C19 inhibitors like fluconazole cause acute heart failure in patients taking mavacamten for obstructive hypertrophic cardiomyopathy?
Case Report (n=1)
Does the concomitant use of strong CYP2C19 inhibitors like fluconazole cause acute heart failure in patients taking mavacamten for obstructive hypertrophic cardiomyopathy?
This case highlights the critical importance of monitoring drug-drug interactions, specifically CYP2C19 inhibitors, in patients on mavacamten to prevent acute systolic dysfunction and heart failure.
May warrant caution with CYP2C19 inhibitors during mavacamten therapy; leaves open need for prospective interaction studies in obstructive HCM.
Background Cardiac myosin inhibition is the first disease-specific therapeutic strategy for obstructive hypertrophic cardiomyopathy. Mavacamten, the first-in-class agent, has demonstrated an excellent safety profile and sustained efficacy in both clinical trials and real-world practice. However, its safe use requires careful monitoring and thorough patient education regarding potential drug–drug interactions. Case summary We report a case of acute heart failure occurring after long-term clinical stability on mavacamten following concomitant fluconazole administration. It is reasonable to assume that the pharmacokinetic interaction resulted in excessive mavacamten exposure, leading to transient systolic dysfunction, severe functional mitral regurgitation, and adverse left ventricular remodelling. Discussion This case report highlights the consequences of pharmacological interactions between Mavacamten and a strong CYP2C19 inhibitor. Drug-drug interaction should always be considered and systematically excluded in a patient presenting with unexplained heart failure and left ventricular remodelling during mavacamten therapy.
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Marchionni et al. (2026) conducted a case report in Obstructive hypertrophic cardiomyopathy (n=1). Mavacamten and fluconazole co-administration was evaluated on Acute heart failure and left ventricular remodelling. Concomitant fluconazole administration during mavacamten therapy resulted in excessive mavacamten exposure, leading to acute heart failure and transient systolic dysfunction.
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