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

Heart Rhythm

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:

Published: November 2024

AI Article Synopsis

  • * Its effectiveness can be influenced by the individual's CYP2C19 genetic profile and interactions with other medications that affect liver enzymes, which could lead to adverse effects or reduced effectiveness.
  • * The paper aims to provide healthcare professionals with guidance on safely prescribing mavacamten alongside commonly used drugs for managing atrial fibrillation in HCM patients, emphasizing the importance of genetic factors and patient safety monitoring.

Article 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 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.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.hrthm.2024.11.041DOI Listing

Publication Analysis

Top Keywords

mavacamten pharmacokinetics
8
mavacamten
6
managing drug-drug
4
drug-drug interactions
4
interactions mavacamten
4
mavacamten focus
4
focus combined
4
combined antiarrhythmic
4
antiarrhythmic drugs
4
drugs anticoagulants
4

Similar Publications

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 PDF

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

Heart 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:

Article Synopsis
  • * Its effectiveness can be influenced by the individual's CYP2C19 genetic profile and interactions with other medications that affect liver enzymes, which could lead to adverse effects or reduced effectiveness.
  • * The paper aims to provide healthcare professionals with guidance on safely prescribing mavacamten alongside commonly used drugs for managing atrial fibrillation in HCM patients, emphasizing the importance of genetic factors and patient safety monitoring.
View Article and Find Full Text PDF

French-Speaking Network of Pharmacogenetics (RNPGx) Recommendations for Clinical Use of Mavacamten.

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 PDF

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.

View Article and Find Full Text PDF
Article Synopsis
  • Aficamten is a new drug that helps reduce heart issues in patients with obstructive hypertrophic cardiomyopathy by targeting heart muscle contractility and maintaining safe blood flow levels.
  • * In a clinical trial involving 282 patients, those receiving aficamten were able to maintain effective heart function with minimal side effects, including a stable reduction in heart muscle contraction without significant adverse events.
  • * The findings suggest that using a tailored dosing strategy for aficamten is effective and safe, improving cardiovascular health without worsening conditions like heart failure.
View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!