Camzyos (Mavacamten) for Obstructive Hypertrophic Cardiomyopathy
Indication
Camzyos is indicated exclusively for adults with symptomatic NYHA class II-III obstructive hypertrophic cardiomyopathy to improve functional capacity and symptoms. 1 The 2024 AHA/ACC guidelines now give this a Class 1 recommendation for patients with persistent symptoms despite beta blockers or non-dihydropyridine calcium channel blockers 2, 3.
Dosing Regimen
Starting Dose and Titration
Start at 5 mg orally once daily (without regard to food) in patients with LVEF ≥55%. Available doses are 2.5 mg, 5 mg, 10 mg, and 15 mg once daily, with a maximum of 15 mg daily 1.
Critical Monitoring Algorithm
The dosing is not straightforward—it requires weeks to reach steady-state, and genetic variation plus drug interactions cause massive exposure differences 1. Follow this strict sequence:
At each visit, prioritize LVEF first, then consider Valsalva LVOT gradient and clinical status:
Initiation Phase (Weeks 4,8,12):
- If LVEF ≥55% and Valsalva gradient ≥20 mmHg → increase dose by one level
- If LVEF 50-54% → maintain current dose
- If LVEF <50% → interrupt treatment immediately 1
Maintenance Phase (Week 16 onward, every 12 weeks):
- If LVEF ≥60% and Valsalva gradient ≥20 mmHg → increase dose
- If LVEF 50-59% → maintain dose
- If LVEF <50% → interrupt treatment 1
Treatment Interruption:
- If LVEF <50% at any visit, stop mavacamten immediately
- Recheck LVEF in 2 weeks, then every 2 weeks until ≥50%
- Once LVEF recovers to ≥50%, restart at one dose level lower (or discontinue if already at 2.5 mg) 1
Drug Interaction Adjustments
With weak CYP2C19 or moderate CYP3A4 inhibitors: Reduce dose by one level (15→10 mg, 10→5 mg, 5→2.5 mg) 1
Contraindications
Absolute Contraindications
Mavacamten is strictly contraindicated with:
- Moderate to strong CYP2C19 inhibitors (e.g., fluconazole, fluvoxamine)
- Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir)
- Moderate to strong CYP2C19 or CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin)
- Pregnancy due to teratogenic effects 3, 1
These combinations dramatically increase heart failure risk from systolic dysfunction 1.
Clinical Contraindications
Do not initiate or up-titrate if LVEF <55% 1. The 2024 guidelines explicitly state that cardiac myosin inhibitors must be discontinued if LVEF drops below 50% 2, 3.
Common Adverse Effects
Most Significant: Reduced LVEF and Heart Failure
The primary safety concern is dose-dependent, reversible reduction in LVEF that can cause heart failure. This is why Camzyos is only available through a REMS program requiring mandatory LVEF monitoring 1.
In clinical trials:
- Mean LVEF decreased by 6-15% depending on dose 4
- Most reductions were reversible with dose adjustment or interruption 4, 5
- One patient experienced inappropriate ICD shock 6
Other Common Adverse Events
- Atrial fibrillation (most common definitely/possibly related adverse event) 4, 5
- Dizziness and fatigue (particularly with beta-blocker intolerance) 7
- Most adverse events in trials were mild (80%) and unrelated to drug (79%) 4
Critical Safety Considerations
Delay dose increases during intercurrent illness (serious infection) or uncontrolled arrhythmias (atrial fibrillation, tachyarrhythmias) that may impair systolic function. Consider interrupting mavacamten entirely during acute illness 1.
REMS Program Requirements
Because of heart failure risk, Camzyos is only available through the CAMZYOS REMS PROGRAM, which mandates:
- Confirmation of negative pregnancy test and effective contraception in females of reproductive potential
- Regular echocardiographic LVEF assessments per the monitoring algorithm
- Prescriber and pharmacy certification 1
Special Populations
Pregnancy and Women of Childbearing Potential
Mavacamten is absolutely contraindicated in pregnancy (Class 3: Harm recommendation) due to teratogenic effects 3. Confirm negative pregnancy test and effective contraception before initiating 1.
Pediatric Use
Recent data from the SCOUT-HCM trial showed mavacamten significantly reduced LVOT gradients in adolescents (12 to <18 years) with obstructive HCM, with a mean reduction of -48.5 mmHg vs -0.5 mmHg with placebo (p<0.001) 6. However, current FDA approval is limited to adults only 1.
Athletes
Mavacamten may permit safe return to competitive sports in athletes with exercise-induced LVOTO who cannot tolerate beta-blockers, though this requires stress imaging to confirm gradient resolution and shared decision-making 7.