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mavacamten (Camzyos)

Indications: - hypertrophic obstructive cardiomyopathy (FDA-approved) - improves symptomatic hypertrophic obstructive cardiomyopathy reducing need for septal reduction therapy [3] - may be useful for treatment of HFpEF (investigational) [5] * effective in Chinese population [4] Contraindications: - HFrEF - LV ejection fraction < 50% - do not initiate therapy if LV ejection fraction < 55% - moderate to strong CYP2C19 inhibitors or strong CYP3A4 inhibitors - moderate to strong CYP2C19 inducers or moderate to strong CYP3A4 inducers Dosage: - start 5 mg/day, maximum 15 mg/day Capsules: 2.5 mg, 5 mg, 10 mg, & 15 mg * echocardiogram for LV ejection fraction prior to initiation Pharmacokinetics: - bioavailability of at > 85% with maximum level in 1 hour (4 hours with high fat meal - protein binding 97-98% - extensively metabolized through CYP2C19 (74%), CYP3A4 (18%), & CYP2C9 (8%) - 85% recovered in urine (3% unchanged), 7% recovered in feces (1% unchanged) - 1/2life 6-9 days in normal CYP2C19 metabolizers, prolonged in poor metabolizers to 23 days Drug interactions: - weak CYP2C19 inhibitors & moderate CYP3A4 inhibitors may increase risk of heart failure - negative inotropes Mechanism of action: - cardiac myosin ATPase inhibitor - reduces left-ventricular outflow tract obstruction - improves cardiopulmonary exercise testing beyond peak oxygen uptake (pVO2) [2] - broad benefits on maximal exercise capacity [2]

General

enzyme inhibitor cardiotonic agent

Database Correlations

PUBCHEM cid=117761397

References

  1. 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 Aug 29; [e-pub]. PMID: 32871100 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31792-X/fulltext - Papadakis M, Basu J, Sharma S. Mavacamten: Treatment aspirations in hypertrophic cardiomyopathy. Lancet 2020 Aug 29; [e-pub] PMID: 32871101 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31793-1/fulltext
  2. Wheeler MT, Olivotto I, Elliott PM et al Effects of Mavacamten on Measures of Cardiopulmonary Exercise Testing Beyond Peak Oxygen Consumption. A Secondary Analysis of the EXPLORER-HCM Randomized Trial. JAMA Cardiol. 2023;8(3):240-247 PMID: 36652223 PMCID: PMC9857843 Free PMC article https://jamanetwork.com/journals/jamacardiology/fullarticle/2800305
  3. Desai MY, Owens A, Wolski K et al Mavacamten in Patients With Hypertrophic Cardiomyopathy Referred for Septal Reduction. Week 56 Results From the VALOR-HCM Randomized Clinical Trial. JAMA Cardiol. Published online August 28, 2023. PMID: 37639243 https://jamanetwork.com/journals/jamacardiology/fullarticle/2809050
  4. Tian Z, Li L, Li X et al Effect of Mavacamten on Chinese Patients With Symptomatic Obstructive Hypertrophic Cardiomyopathy. The EXPLORER-CN Randomized Clinical Trial. JAMA Cardiol. Published online August 28, 2023 PMID: 37639259 https://jamanetwork.com/journals/jamacardiology/fullarticle/2809051
  5. Lou N Mavacamten Shows Promise in Heart Failure With Normal to Supranormal EF. Cardiac myosin inhibitor linked to improvements in biomarkers in small study. MedPage Today September 30, 2024 https://www.medpagetoday.com/meetingcoverage/hfsa/112194
  6. HIGHLIGHTS OF PRESCRIBING INFORMATION CAMZYOS mavacamten) capsules for oral use https://packageinserts.bms.com/pi/pi_camzyos.pdf