mavacamten (Camzyos)
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Indications
- hypertrophic obstructive cardiomyopathy (FDA-approved)
- improves symptomatic hypertrophic obstructive cardiomyopathy reducing need for septal reduction therapy[3]
* effective in Chinese population[4]
Contraindications
- HFrEF
- LV ejection fraction < 50%
- do not initiate therapy if LV ejection fraction < 55%
- LV ejection fraction < 50%
- moderate to strong CYP2C19 inhibitors or strong CYP3A4 inhibitors
- moderate to strong CYP2C19 inducers or moderate to strong CYP3A4 inducers
Dosage
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]
More general terms
References
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/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: https://www.ncbi.nlm.nih.gov/pubmed/32871101 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31793-1/fulltext - ↑ 2.0 2.1 2.2 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: https://www.ncbi.nlm.nih.gov/pubmed/36652223 PMCID: PMC9857843 Free PMC article https://jamanetwork.com/journals/jamacardiology/fullarticle/2800305
- ↑ 3.0 3.1 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: https://www.ncbi.nlm.nih.gov/pubmed/37639243 https://jamanetwork.com/journals/jamacardiology/fullarticle/2809050
- ↑ 4.0 4.1 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: https://www.ncbi.nlm.nih.gov/pubmed/37639259 https://jamanetwork.com/journals/jamacardiology/fullarticle/2809051
- ↑ HIGHLIGHTS OF PRESCRIBING INFORMATION CAMZYOS<TM> mavacamten) capsules for oral use https://packageinserts.bms.com/pi/pi_camzyos.pdf