Camzyos®Mavacamten Capsules

1. Indications and Usage
Symptomatic Obstructive Hypertrophic Cardiomyopathy (oHCM): Treatment of adults with New York Heart Association (NYHA) class II-III symptomatic oHCM to improve exercise capacity and symptoms .
2. Dosage and Administration
Administration: Oral administration once daily with or without food. Capsules must be swallowed whole .
Starting Dose:
Standard: 5 mg once daily.
CYP2C19 Poor Metabolizers or with Weak CYP2C19/Mod CYP3A4 Inhibitors: 2.5 mg once daily .
Dose Adjustment: Dosing is guided by echocardiographic monitoring of Left Ventricular Ejection Fraction (LVEF) and LVOT gradient.
Increase: Consider increasing by one dose level if LVEF ≥55% and LVOT gradient ≥30 mmHg.
Hold/Decrease: Interrupt therapy if LVEF <50%. Resume at a lower dose once LVEF recovers to ≥50% .
Contraindicated Combinations: Do not co-administer with moderate/strong CYP2C19 inhibitors or strong CYP3A4 inhibitors .
3. Mechanism of Action
Mavacamten is a first-in-class, allosteric, reversible inhibitor of cardiac myosin.
It binds to cardiac myosin and reduces the number of myosin heads available to interact with actin to generate force. This reduces myocardial contractility, decreases the left ventricular outflow tract (LVOT) gradient, and improves ventricular compliance and diastolic filling .
4. Safety and Warnings
Heart Failure: Mavacamten can cause heart failure by reducing contractility. Monitoring of LVEF is mandatory before initiation and periodically during treatment. Do not initiate therapy if baseline LVEF is <55% .
Contraindications: Severe hepatic impairment (Child-Pugh Class C) and pregnancy .
Reproductive Toxicity: May cause fetal harm. Females of reproductive potential must use effective contraception during treatment and for 4 months after the final dose .
5. Adverse Reactions
Common (>2%): Heart failure, fatigue, dyspnea, dizziness, nausea, and syncope .
Serious: Symptomatic heart failure and severe reduction in LVEF .
6. Drug Interactions
Cytochrome P450 Substrate: Mavacamten is primarily metabolized by CYP2C19 (and CYP3A4).
Inhibitors: Moderate/strong CYP2C19 inhibitors (e.g., fluconazole) or strong CYP3A4 inhibitors (e.g., ketoconazole) are prohibited. Weak inhibitors (e.g., fluoxetine) require dose reduction (e.g., start at 2.5 mg) .
Inducers: Moderate/strong inducers of CYP2C19 or CYP3A4 (e.g., rifampin, carbamazepine) are contraindicated as they may reduce efficacy .
7. Pharmaceutical Information
Chemical Name: 6-[[(1S)-1-phenylethyl]amino]-3-propyl-1H-pyrimidine-2,4-dione .
Molecular Formula: C15H19N3O2 .
Molecular Weight: 273.34 .
Storage: Store at controlled room temperature (20°C to 25°C) .