Mavacamten approved as  Camzyos for the treatment of adults with symptomatic New York Heart Association class II – III obstructive hypertrophic cardiomyopathy (HCM) to improve functional capacity and symptoms.

It is the first and only FDA-approved cardiac myosin inhibitor that specifically targets the source of obstructive HCM.

It is an allosteric and reversible inhibitor selective for cardiac myosin. 

It  modulates the number of myosin heads that can enter actin power-generating states, thus reducing the probability of systolic and diastolic cross-bridge formation. 

Excess myosin actin cross-bridge formation and dysregulation of the super-relaxed state are mechanistic hallmarks of HCM. 

Camzyos shifts the overall myosin population towards an energy-sparing, recruitable, super-relaxed state. 

In HCM patients, myosin inhibition with Mavacamten reduces dynamic left ventricle outlet tract obstruction and improves cardiac filling pressures.

Phase 3 EXPLORER-HCM trial demonstrated benefit in patients receiving mavacamten versus placebo.

Mavacamten, 2.5 mg, 5 mg, 10 mg, 15 mg capsules for the treatment of adults with symptomatic New York Heart Association (NYHA) class II-III obstructive hypertrophic cardiomyopathy  for improved functional capacity and symptoms. 

It targets the underlying pathophysiology of the disease.

Mavacamten reduces left ventricular ejection fraction (LVEF) and can cause heart failure due to systolic dysfunction. 

Echocardiogram assessments of LVEF are required prior to and during treatment with mavacamten. 

Initiation of the drug  in patients with LVEF <55% is not recommended. 

If LVEF is <50% at any visit or if the patient experiences heart failure symptoms or worsening clinical status, the drug is discontinued.

Concomitant use with certain cytochrome P450 inhibitors or discontinuation of certain cytochrome P450 inducers may increase the risk of heart failure due to systolic dysfunction.

Mavacamten use is contraindicated with moderate to strong CYP2C19 inhibitors or strong CYP3A4 inhibitors, and moderate to strong CYP2C19 inducers or moderate to strong CYP3A4 inducers. 

Available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) PROGRAM. 

Adverse reactions occurring in >5% of patients: dizziness and syncope.

Mavacamten reduces systolic contraction and can cause heart failure or totally block ventricular function. 

Patients who experience a serious intercurrent illness are at greater risk of developing systolic dysfunction and heart failure.

Assessing clinical status and LVEF prior to and regularly during treatment and adjust dose accordingly is required.

New or worsening arrhythmia, dyspnea, chest pain, fatigue, palpitations, leg edema, or elevations in N-terminal (NT)-pro hormone b-type natriuretic peptide (NT-proBNP) may be signs and symptoms of heart failure and should also prompt an evaluation of cardiac function.

Asymptomatic LVEF reduction, intercurrent illnesses, and arrhythmias require additional dosing considerations.

Should be avoided with concomitant use in patients on disopyramide, ranolazine, verapamil with a beta blocker, or diltiazem with a beta blocker

It  is primarily metabolized by CYP2C19 and CYP3A4 enzymes, and concomitant use of Mavacamten and drugs that interact with these enzymes may lead to life-threatening drug interactions such as heart failure or loss of effectiveness.

Mavacamten may cause fetal toxicity when administered to a pregnant female, based on animal studies. 

Confirm absence of pregnancy in females of reproductive potential prior to treatment and advise patients to use effective contraception during treatment.

Adverse reactions occurring in >5% of patients: dizziness (27%) and syncope (6%).

Moderate to strong CYP2C19 Inhibitors or strong CYP3A4 Inhibitors: Concomitant use increases Mavacamten exposure, which may increase the risk of heart failure due to systolic dysfunction, therefore concomitant use is contraindicated.

Moderate to strong CYP2C19 Inducers or moderate to strong CYP3A4 Inducers: use decreases Mavacamten exposure, which may reduce efficacy. 

The risk of heart failure due to systolic dysfunction may increase with discontinuation of these inducers as the levels of induced enzyme normalizes:

Concomitant use is contraindicated.

Mavacamten is an inducer of CYP3A4, CYP2C9, and CYP2C19:Concomitant use with CYP3A4, CYP2C19, or CYP2C9 substrates may reduce plasma concentration of these drugs. 

Progestin and ethinyl estradiol are CYP3A4 substrates, and concomitant use may decrease exposures of ethinyl estradiol and progestin, which may lead to contraceptive failure or an increase in breakthrough bleeding. 

Mavacamten may cause fetal harm when administered to a pregnant female. 

The presence of Mavacamten in human or animal milk, the drug’s effects on the breastfed infant, or the effects on milk production are unknown. 


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