Mavacamten (1 brand name, 1 dosage form, 1 route)
Available dosage forms: CAPSULE.
Routes of administration: ORAL.
Brand Names
- CAMZYOS
Boxed Warning
CAMZYOS reduces left ventricular ejection fraction (LVEF) and can cause heart failure due to systolic dysfunction [see Warnings and Precautions (5.1)]. Echocardiogram assessments of LVEF are required prior to and during treatment with CAMZYOS. Initiation of CAMZYOS in patients with LVEF <55% is not recommended. Interrupt CAMZYOS if LVEF is <50% at any visit or if the patient experiences heart failure symptoms or worsening clinical status [see Dosage and Administration (2.1) and Warnings and Precautions (5.1)]. Concomitant use of CAMZYOS with certain cytochrome P450 inhibitors or discontinuation of certain cytochrome P450 inducers may increase the risk of heart failure due to systolic dysfunction; therefore, the use of CAMZYOS is contraindicated with the following [see Contraindications (4) and Warnings and Precautions (5.2)]: • Strong CYP2C19 inhibitors • Moderate to strong CYP2C19 inducers or moderate to strong CYP3A4 inducers Because of the risk of heart failure due to systolic dysfunction, CAMZYOS is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called CAMZYOS REMS PROGRAM [see Warnings and Precautions (5.3)].
Indications and Usage
CAMZYOS® is indicated for the treatment of adults with symptomatic New York Heart Association (NYHA) class II-III obstructive hypertrophic cardiomyopathy (HCM) to improve functional capacity and symptoms.
Contraindications
CAMZYOS is contraindicated with concomitant use of: • Strong CYP2C19 inhibitors [see Warnings and Precautions (5.2) , Drug Interactions (7.1) ] •Moderate to strong CYP2C19 inducers or moderate to strong CYP3A4 inducers [see Warnings and Precautions (5.2), Drug Interactions (7.1)]
Adverse Reactions
The following adverse reaction is discussed in other sections of the labeling: •Heart failure [see Warnings and Precautions (5.1)]
Mechanism of Action
Mavacamten is an allosteric and reversible inhibitor selective for cardiac myosin. Mavacamten modulates the number of myosin heads that can enter “on actin” (power-generating) states, thus reducing the probability of force-producing (systolic) and residual (diastolic) cross-bridge formation. Excess myosin actin cross-bridge formation and dysregulation of the super-relaxed state are mechanistic hallmarks of HCM. Mavacamten shifts the overall myosin population towards an energy-sparing, recruitable, super-relaxed state. In HCM patients, myosin inhibition with mavacamten reduces dynamic LVOT obstruction and improves cardiac filling pressures.
Overdosage
Clinical Experience and Effects •Cardiovascular effects may include reduced LVEF (left ventricular ejection fraction), heart failure, hypotension, and asystole refractory to medical intervention. •Neurological effects may include dizziness and syncope. •An infant death was reported after accidental ingestion of three 15 mg capsules (45 mg). •An adult administered a single dose of 144 mg developed a vasovagal reaction, hypotension, and asystole, but the subject recovered. Management •Discontinue CAMZYOS treatment. •Provide medically supportive measures to maintain hemodynamic stability and monitor left ventricular function. •Consider administering activated charcoal (pediatric dose is 1 g/kg; adult dose is 50 g) within 2 hours of ingestion in addition to other supportive measures. The benefit of activated charcoal is negligible after 6 hours [see Clinical Pharmacology (12.3)]. •Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations.