Precautions of Mavacamten

1. Heart Failure

Mavacamten reduces myocardial contractility and may induce heart failure or significant ventricular dysfunction. Patients experiencing severe intercurrent illnesses (e.g., severe infections) or arrhythmias (e.g., atrial fibrillation or other uncontrolled tachyarrhythmias) are at an increased risk of developing systolic dysfunction and heart failure.

Assess patients’ clinical status and left ventricular ejection fraction (LVEF) regularly before and during treatment, and adjust the dosage of mavacamten accordingly. New-onset or worsening arrhythmias, dyspnea, chest pain, fatigue, palpitations, leg edema, or elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) may be signs and symptoms of heart failure, and cardiac function should be evaluated promptly.

Asymptomatic reduction in LVEF, intercurrent illnesses, and arrhythmias require additional considerations for dosage adjustment.

Initiation of mavacamten is not recommended for patients with LVEF below 55%. Concomitant use of mavacamten with disopyramide, ranolazine, verapamil combined with beta-blockers, or diltiazem combined with beta-blockers should be avoided. These drugs and drug combinations increase the risk of left ventricular systolic dysfunction and heart failure symptoms, and clinical experience with such combinations is limited.

2. Heart Failure or Loss of Efficacy Due to CYP450-mediated Drug Interactions

Mavacamten is primarily metabolized by the CYP2C19 and CYP3A4 enzymes. Concomitant use of mavacamten with drugs that interact with these enzymes may result in life-threatening drug interactions, such as heart failure or loss of therapeutic efficacy.

Inform patients of the potential for drug interactions, including interactions with over-the-counter drugs (e.g., omeprazole, esomeprazole, or cimetidine). Advise patients to inform their healthcare providers of all concomitant products used before and during mavacamten treatment.

3. Mavacamten REMS Program

Due to the risk of heart failure associated with systolic dysfunction, mavacamten is available only through a restricted program called the Mavacamten REMS Program.

Key requirements of the Mavacamten REMS Program include the following:

Prescribers must be certified by enrolling in the Mavacamten REMS Program.

Patients must enroll in the Mavacamten REMS Program and comply with ongoing monitoring requirements.

Pharmacies must be certified by enrolling in the Mavacamten REMS Program and may dispense mavacamten only to authorized patients.

Wholesalers and distributors may distribute mavacamten only to certified pharmacies.

4. Embryo-fetal Toxicity

Based on findings from animal studies, mavacamten may cause fetal harm when administered to pregnant women. Confirm that females of reproductive potential are not pregnant before initiating treatment, and advise patients to use effective contraception during mavacamten treatment and for 4 months after the last dose.

Combination hormonal contraceptives containing ethinyl estradiol and norethindrone may be used concomitantly with mavacamten. However, mavacamten may reduce the effectiveness of some other combination hormonal contraceptives. If such combination hormonal contraceptives are used, advise patients to add a non-hormonal contraceptive method (e.g., condoms) during the concomitant use period and for 4 months after the last dose of mavacamten.

FDA，2025.04