Zavesca Mavacamten Capsules

1. Indications and Usage
Obstructive Hypertrophic Cardiomyopathy (oHCM):
Indicated for the treatment of adult patients with symptomatic NYHA class II-III obstructive HCM to improve exercise capacity and symptoms.
2. Dosage and Administration
Patient Selection and Monitoring:
Baseline Assessment: Assess LVEF by echocardiogram prior to initiation. Do not initiate in patients with LVEF < 55%.
Monitoring: Perform echocardiograms at Weeks 4, 8, and 12 after initiation or dose modification, then every 12 weeks thereafter.
LVEF Hold: Interrupt treatment if LVEF < 50%. Resume at a lower dose once LVEF recovers to ≥ 50%.
Recommended Dosage:
Initial Dose: 5 mg orally once daily. (Note: 2.5 mg is recommended for patients on weak CYP2C19 inhibitors or moderate CYP3A4 inhibitors).
Titration: Dose adjustments are based on echocardiographic assessment of LVEF and LVOT gradient. Maximum dose is 15 mg once daily.
3. Mechanism of Action
Myosin Inhibition:
Mavacamten is a selective, allosteric, reversible inhibitor of cardiac myosin.
Physiological Effect:
It reduces the number of myosin heads available to interact with actin, thereby decreasing hypercontractility. This reduces the left ventricular outflow tract (LVOT) gradient and improves ventricular filling pressures without compromising heart rate or systolic function excessively.
4. Safety and Warnings
New or Worsening Heart Failure:
Mavacamten can reduce myocardial contractility, which may lead to heart failure. Monitor for signs and symptoms of heart failure.
Decreased LVEF:
Mavacamten can decrease LVEF. Monitor LVEF by echocardiogram regularly.
Concomitant Medications:
Avoid concomitant use with moderate to strong CYP2C19 or CYP3A4 inhibitors and inducers.
5. Adverse Reactions
Most Common:
Fatigue, dyspnea, diarrhea, and heart failure.
Serious Adverse Events:
Decreased LVEF (< 50%) and heart failure requiring hospitalization.
6. Drug Interactions
CYP2C19 Inhibitors (e.g., fluconazole):
Increase mavacamten exposure. Reduce mavacamten dose by one level (e.g., 15 mg → 10 mg).
CYP3A4 Inhibitors (e.g., clarithromycin):
Increase mavacamten exposure. Reduce mavacamten dose by one level.
Metabolic Enzymes:
Mavacamten is metabolized primarily by CYP2C19, and secondarily by CYP3A4 and CYP2C9.
7. Pharmaceutical Information
Chemical Composition:
Active Ingredient: Mavacamten.
Storage:
Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15-30°C (59-86°F).