What is the recommended dosing schedule and echocardiographic monitoring for mavacamten (Camzyos) in an adult with symptomatic obstructive hypertrophic cardiomyopathy?

Mavacamten Dosing Schedule and Echocardiographic Monitoring

Start mavacamten at 5 mg orally once daily, then titrate every 4 weeks based on echocardiographic assessment of LVEF and Valsalva LVOT gradient, with mandatory LVEF monitoring before each dose adjustment to maintain LVEF ≥50%. 1

Initial Dosing and Patient Selection

• Begin with 5 mg orally once daily without regard to food in adult patients with symptomatic obstructive HCM 1
• Do not initiate mavacamten if baseline LVEF <55%, as this increases risk of systolic dysfunction 1
• Confirm absence of pregnancy and effective contraception in females of reproductive potential before starting therapy 1
• Mavacamten is recommended for patients with persistent symptoms despite beta-blockers or calcium channel blockers (Class 1 recommendation) 2

Echocardiographic Monitoring Schedule

Initiation Phase (First 12 Weeks)

• Obtain echocardiogram at week 4 to assess LVEF and Valsalva LVOT gradient 1
• Obtain echocardiogram at week 8 to reassess LVEF and Valsalva LVOT gradient 1
• Obtain echocardiogram at week 12 before considering any dose adjustment 1
• Real-world data confirms significant gradient reduction occurs rapidly, with mean Valsalva LVOT gradient decreasing from 72 mmHg to 29 mmHg by week 4 3

Maintenance Phase (After Week 12)

• Obtain echocardiogram every 12 weeks once stable dose achieved 1
• Continue monitoring LVEF and Valsalva LVOT gradient at each visit 1
• The 2024 AHA/ACC guidelines emphasize that mavacamten should be titrated to maximum tolerated dose with echocardiographic surveillance of LVEF 2

Dose Titration Algorithm

When to Increase Dose (at 4-week intervals minimum)

• If Valsalva LVOT gradient ≥30 mmHg AND LVEF ≥55%: increase by one dose level 1
• Available dose escalations: 5 mg → 10 mg → 15 mg (maximum dose) 1
• Do not up-titrate if LVEF is 50-54%, even if gradient remains elevated 1

When to Decrease Dose

• If LVEF 50-54%: reduce dose by one level (15 mg → 10 mg; 10 mg → 5 mg; 5 mg → 2.5 mg) 1
• If Valsalva LVOT gradient <20 mmHg AND LVEF ≥55%: consider dose reduction by one level 1

When to Interrupt Treatment

• If LVEF <50% at any time: immediately interrupt mavacamten regardless of dose 1
• Obtain echocardiogram 2 weeks after interruption to reassess LVEF 1
• If LVEF recovers to ≥50%: restart at reduced dose (one level lower than interruption dose) 1
• If LVEF remains <50% at 2 weeks: obtain another echocardiogram at 4 weeks 1
• In clinical trials, 5.7% of patients developed LVEF <50% attributable to the drug, but up to 7-10% when considering intercurrent clinical conditions 2

Critical Monitoring Considerations

Intercurrent Illness or Arrhythmia

• Delay dose increases during serious infection or uncontrolled tachyarrhythmia (e.g., atrial fibrillation) that may impair systolic function 1
• Consider interrupting mavacamten during intercurrent illness, as these patients are at greater risk of developing systolic dysfunction 1
• Obtain echocardiogram to assess LVEF if patient develops new arrhythmia, dyspnea, chest pain, fatigue, palpitations, or leg edema 1

Drug Interaction Adjustments

• If starting weak CYP2C19 inhibitor or moderate CYP3A4 inhibitor: reduce mavacamten dose by one level 1
• Schedule echocardiogram 4 weeks after inhibitor initiation, and do not up-titrate for 12 weeks 1
• Never combine with moderate-to-strong CYP2C19 inhibitors (e.g., omeprazole, esomeprazole) or strong CYP3A4 inhibitors—this is an absolute contraindication 1

Common Pitfalls to Avoid

• Do not skip echocardiographic monitoring intervals, as daily dosing takes weeks to reach steady-state and genetic variation in CYP2C19 metabolism causes large differences in drug exposure 1, 4
• Do not continue mavacamten if LVEF drops below 50%—this requires immediate interruption per FDA REMS program 1
• Avoid concomitant use with disopyramide, ranolazine, or verapamil/diltiazem combined with beta-blockers, as these increase risk of left ventricular systolic dysfunction 1
• In pregnant women, mavacamten is contraindicated due to teratogenic effects 2
• If patient develops systolic dysfunction (LVEF <50%), cardiac myosin inhibitors must be discontinued 2

Clinical Response Expectations

• 64% of patients achieve ≥1 NYHA class improvement by median follow-up of 261 days in real-world experience 3
• Valsalva LVOT gradient reduction is rapid, with 71% of patients achieving gradient <30 mmHg by week 4 3
• Success is determined by symptom response, not measured gradient alone, as gradients vary throughout daily life 2
• The echocardiography-based dose-titration strategy identifies the lowest individualized dose required to provide improvements in LVOT obstruction, functional capacity, and symptoms 4