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Managing drug–drug interactions with mavacamten : A focus on combined use of antiarrhythmic drugs and anticoagulants

Ricci, Fabrizio LU ; Molinari, Lorenzo V. ; Mansour, Davide ; Galanti, Kristian ; Vagnarelli, Fabio ; Renda, Giulia ; Gallina, Sabina ; Owens, Anjali ; Luzum, Jasmine A. and Olivotto, Iacopo , et al. (2025) In Heart Rhythm 22(2). p.510-525
Abstract

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... (More)

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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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Antiarrhythmic drugs, Anticoagulants, Drug–drug interaction, Hypertrophic cardiomyopathy, Mavacamten, Pharmacogenomics, Pharmacokinetics
in
Heart Rhythm
volume
22
issue
2
pages
16 pages
publisher
Elsevier
external identifiers
  • pmid:39613202
  • scopus:85211075288
ISSN
1547-5271
DOI
10.1016/j.hrthm.2024.11.041
language
English
LU publication?
yes
id
51c3f07f-3874-45e3-a635-9d6499f8d24f
date added to LUP
2025-01-31 15:25:37
date last changed
2025-07-05 04:12:45
@article{51c3f07f-3874-45e3-a635-9d6499f8d24f,
  abstract     = {{<p>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.</p>}},
  author       = {{Ricci, Fabrizio and Molinari, Lorenzo V. and Mansour, Davide and Galanti, Kristian and Vagnarelli, Fabio and Renda, Giulia and Gallina, Sabina and Owens, Anjali and Luzum, Jasmine A. and Olivotto, Iacopo and Khanji, Mohammed Y. and Chahal, Anwar A.}},
  issn         = {{1547-5271}},
  keywords     = {{Antiarrhythmic drugs; Anticoagulants; Drug–drug interaction; Hypertrophic cardiomyopathy; Mavacamten; Pharmacogenomics; Pharmacokinetics}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{510--525}},
  publisher    = {{Elsevier}},
  series       = {{Heart Rhythm}},
  title        = {{Managing drug–drug interactions with mavacamten : A focus on combined use of antiarrhythmic drugs and anticoagulants}},
  url          = {{http://dx.doi.org/10.1016/j.hrthm.2024.11.041}},
  doi          = {{10.1016/j.hrthm.2024.11.041}},
  volume       = {{22}},
  year         = {{2025}},
}