MYK-224 + itraconazole

MYK-224 + itraconazole is an investigational **combination** involving **MYK-224**, an oral small molecule cardiac myosin inhibitor, and **itraconazole**, a broadly used antifungal agent often included in clinical studies to evaluate potential pharmacokinetic drug–drug interactions. MYK-224 is designed to selectively inhibit cardiac myosin ATPase, reducing actin-myosin cross-bridge formation and contractility, making it a next-generation therapy similar in class to mavacamten but with a shorter half-life for flexible dosing. Its main indications under clinical investigation include hypertrophic cardiomyopathy (especially obstructive forms) and heart failure with preserved ejection fraction (HFpEF)[1][2][3][5]. The combination with itraconazole is not for therapeutic effect but to assess whether itraconazole (a strong CYP3A4 and moderate CYP2C9 inhibitor) alters the pharmacokinetics of MYK-224 due to shared metabolic pathways[3][5]. MYK-224 was originally developed by MyoKardia and subsequently by Bristol Myers Squibb following acquisition[5], while itraconazole is a long-established antifungal drug developed and manufactured by several companies. MYK-224 acts as a **cardiac myosin modulator**, offering a novel targeted therapy for patients with hypertrophic cardiomyopathy and potentially HFpEF, while itraconazole does not have direct cardiac effects relevant to this combination.