Mavacamten is a selective, allosteric, and reversible cardiac myosin inhibitor, representing the first disease-specific treatment for obstructive hypertrophic cardiomyopathy (HCM) that targets the core pathophysiological mechanism of this condition. Clinical evidence supports its efficacy in improving symptoms, cardiac function, and remodeling, thereby supplementing established treatment regimens. However, mavacamten is extensively metabolized by hepatic cytochromes, and its half-life is contingent upon CYP2C19 phenotype. Consequently, coadministered medications that inhibit or induce these enzymes may significantly alter mavacamten pharmacokinetics, potentially leading to reversible systolic dysfunction or diminished therapeutic efficacy. This paper provides a comprehensive analysis of mavacamten pharmacokinetics and its potential interactions with antithrombotic and antiarrhythmic agents, which are the cornerstones of atrial fibrillation management in HCM population. Our aim is to offer clinicians practical guidance on safely administering mavacamten in conjunction with these medications, discuss the role of pharmacogenomics, and outline rigorous patient safety monitoring strategies to ensure effective and individualized treatment.
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http://dx.doi.org/10.1016/j.hrthm.2024.11.041 | DOI Listing |
J Clin Pharmacol
December 2024
Bristol Myers Squibb, Princeton, NJ, USA.
Mavacamten is a potential inducer of cytochrome P450 (CYP) 3A4 and could reduce the effectiveness of concomitant drugs that are metabolized by CYP3A4, such as midazolam. This study aimed to determine if repeat doses of mavacamten achieving clinically relevant exposures affected midazolam exposure. This was a single-center, open-label study in healthy participants.
View Article and Find Full Text PDFHeart Rhythm
November 2024
Barts Heart Centre, Barts Health NHS Trust, London, UK; Center for Inherited Cardiovascular Diseases, WellSpan Health, Lancaster, Pennsylvania, USA; Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, USA; Center for Inherited Cardiovascular Disease, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. Electronic address:
Clin Pharmacol Ther
November 2024
Laboratoire de Pharmacologie et Toxicologie NeuroCardiovasculaire, UR7296, Hopitaux Universitaires de Strasbourg, Université de Strasbourg, Strasbourg, France.
Mavacamten, the first drug in the class of β-cardiac myosin modulator, is used for the treatment of patients with hypertrophic cardiomyopathy. This orally administered drug demonstrates wide interpatient variability in pharmacokinetics parameters, due in part to variant CYP2C19 alleles. Individuals who are CYP2C19 poor metabolizers have increased exposure and are at increased risk of reduced cardiac hypercontractility.
View Article and Find Full Text PDFCPT Pharmacometrics Syst Pharmacol
September 2024
Bristol Myers Squibb, Princeton, New Jersey, USA.
Mavacamten is a selective, allosteric, reversible cardiac myosin inhibitor that has been developed for the treatment of adults with symptomatic obstructive hypertrophic cardiomyopathy (HCM). A population pharmacokinetic (PopPK) model was developed to characterize mavacamten pharmacokinetics (PK) and the variation in mavacamten exposure associated with intrinsic and extrinsic factors. Data from 12 clinical studies (phases 1, 2, and 3) were used.
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