Lebreton Louis, Boyer Jean-Christophe, Lafay-Chebassier Claire, Hennart Benjamin, Baklouti Sarah, Cunat Séverine, Vilquin Paul, Medard Yves, Gautier-Veyret Elodie, Laffitte-Redondo Clara, Verstuyft Céline, Ait Tayeb Abd El Kader, Haufroid Vincent, Wils Julien, Lamoureux Fabien, Evrard Alexandre, Davaze-Schneider Julie, Ben-Sassi Mouna, Picard Nicolas, Quaranta Sylvie, Ayme-Dietrich Estelle
Département de Biochimie, Hôpital Pellegrin, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.
Laboratoire de Biochimie et Biologie Moléculaire, Carémeau University Hospital, Nîmes, France.
Clin Pharmacol Ther. 2025 Feb;117(2):387-397. doi: 10.1002/cpt.3502. Epub 2024 Nov 25.
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.
玛伐卡坦是β-心肌肌球蛋白调节剂类的首个药物，用于治疗肥厚型心肌病患者。这种口服药物在药代动力学参数方面表现出较大的患者间变异性，部分原因是CYP2C19等位基因变异。CYP2C19代谢不良的个体药物暴露增加，心脏过度收缩性降低的风险也增加。为确保所有患者的安全，欧洲药品管理局建议进行CYP2C19预防性基因分型，并根据CYP2C19表型，相应地调整玛伐卡坦的维持剂量和初始剂量，并管理药物相互作用。在本文中，我们总结了文献中的证据，支持CYP2C19表型与玛伐卡坦药理特性之间的关联，并基于CYP2C19和CYP3A4/CYP3A5基因型，除生物学指南外，还提供了玛伐卡坦使用的治疗建议。
