Why the study?
Mavacamten exhibits wide pharmacokinetic variability partly due to CYP2C19 alleles, creating a need for therapeutic recommendations based on CYP2C19 and CYP3A4/CYP3A5 genotype.
How should mavacamten dosing be adapted based on CYP2C19 and CYP3A4/CYP3A5 genotype in patients with hypertrophic cardiomyopathy?
How should mavacamten dosing be adapted based on CYP2C19 and CYP3A4/CYP3A5 genotype in patients with hypertrophic cardiomyopathy?
Provides pharmacogenetic recommendations for mavacamten dosing based on CYP2C19 and CYP3A4/CYP3A5 genotypes to ensure safety in patients with hypertrophic cardiomyopathy.
Clinicians should integrate CYP2C19/CYP3A genotyping into mavacamten dosing for HCM; extends pharmacogenetic guidance into cardiovascular guidelines.
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. To ensure the safety of all patients, European Medicines Agency recommends CYP2C19 preemptive genotyping, and consecutively, to adapt maintenance and initial mavacamten doses, and to manage drug-drug interactions, according to CYP2C19 phenotype. In this article, we summarize evidence from the literature supporting the association between CYP2C19 phenotype and pharmacological features of mavacamten and provide, beyond biologic guidelines, therapeutic recommendations for the use of mavacamten based on CYP2C19 and CYP3A4/CYP3A5 genotype.
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Lebreton et al. (2024) studied this question.
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