Introduction
Camzyos (mavacamten) is a first-in-class cardiac myosin inhibitor developed by Bristol Myers Squibb for the treatment of symptomatic obstructive hypertrophic cardiomyopathy (HCM). Approved by the FDA in April 2022, it represents a novel therapeutic approach targeting the underlying pathophysiology of HCM rather than merely managing symptoms.
Mechanism of Action
Mavacamten is a selective allosteric inhibitor of cardiac myosin that reduces excessive actin-myosin cross-bridge formation. It modulates the number of myosin heads that can enter "on-state" (actin-binding competent state), thereby decreasing hypercontractility and improving diastolic function. This mechanism directly addresses the fundamental biomechanical abnormality in HCM by reducing left ventricular outflow tract (LVOT) obstruction and improving myocardial energetics.
Indications
Camzyos is indicated for the treatment of adults with symptomatic New York Heart Association (NYHA) class II-III obstructive hypertrophic cardiomyopathy to improve functional capacity and symptoms.
Dosage and Administration
Initial dose: 5 mg orally once daily Titration: Dose adjustments are based on echocardiographic LVOT gradient and ejection fraction measurements at 4-week intervals Maintenance dose: 2.5 mg, 5 mg, 10 mg, or 15 mg once daily Special populations:- Renal impairment: No dosage adjustment necessary
- Hepatic impairment: Not recommended in patients with moderate to severe hepatic impairment
- Elderly: No specific dosage adjustment required
Pharmacokinetics
Absorption: Rapidly absorbed with median Tmax of approximately 1 hour Distribution: Extensive tissue distribution, volume of distribution ~100 L Metabolism: Primarily via CYP2C19 (74%) and CYP3A4 (18%) with minor contributions from other enzymes Elimination: Terminal half-life ~6-9 days; primarily excreted in feces (88%) with minimal renal excretion (6%) Protein binding: >97%Contraindications
- Concomitant use with moderate to strong CYP2C19 inhibitors or strong CYP3A4 inhibitors
- Concomitant use with disopyramide, ranolazine, verapamil, diltiazem, or other drugs that significantly reduce systolic function
- Ejection fraction <50%
Warnings and Precautions
Black Box Warning: Risk of heart failure due to systolic dysfunction. Camzyos reduces systolic contraction and can cause heart failure or totally block ventricular function. Requires experienced clinicians with expertise in HCM management.- Echocardiographic monitoring of LVEF and LVOT gradient required before and during treatment
- Risk of heart failure exacerbation
- Potential for arrhythmias
- Requires Risk Evaluation and Mitigation Strategy (REMS) program
Drug Interactions
Major interactions:- CYP2C19 inhibitors (e.g., fluconazole, fluvoxamine): Increase mavacamten exposure
- CYP3A4 inhibitors (e.g., clarithromycin, itraconazole): Increase mavacamten exposure
- CYP2C19 inducers (e.g., rifampin): Decrease mavacamten exposure
- CYP3A4 inducers (e.g., carbamazepine, phenytoin): Decrease mavacamten exposure
- Negative inotropes: Additive effects on cardiac contractility
Adverse Effects
Common (≥10%):- Dizziness (27%)
- Syncope (6%)
- Fatigue (5%)
- Heart failure (2%)
- Atrial fibrillation (3%)
- Decreased ejection fraction
- Ventricular arrhythmias
Monitoring Parameters
- Echocardiogram: LVEF and LVOT gradient at baseline and every 4 weeks during dose initiation and titration
- ECG monitoring for arrhythmias
- Symptoms of heart failure
- CYP2C19 genotyping recommended before initiation
- Pregnancy testing in women of reproductive potential
Patient Education
- Take exactly as prescribed; do not adjust dose without medical supervision
- Report any symptoms of heart failure (shortness of breath, swelling, weight gain)
- Inform all healthcare providers about Camzyos use
- Use effective contraception during treatment and for 4 months after discontinuation
- Do not breastfeed during treatment
- Understand the REMS program requirements
- Be aware of potential dizziness and avoid driving if affected
References
1. FDA Prescribing Information: Camzyos (mavacamten). April 2022 2. Olivotto I, Oreziak A, Barriales-Villa R, et al. Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2020;396(10253):759-769 3. Ho CY, Mealiffe ME, Bach RG, et al. Evaluation of mavacamten in symptomatic patients with nonobstructive hypertrophic cardiomyopathy. J Am Coll Cardiol. 2020;75(21):2649-2660 4. Spertus JA, Fine JT, Elliott P, et al. Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): health status results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2021;397(10293):2467-2475 5. ClinicalTrials.gov: EXPLORER-HCM (NCT03470545) and MAVA-LTE (NCT03723655)