Overview
11 DESCRIPTION CAMZYOS capsules for oral use contain mavacamten, a cardiac myosin inhibitor. The chemical name of mavacamten is 3-(1-methylethyl)-6-[[(1S)-1-phenylethyl]amino]-2,4(1 H ,3 H )-pyrimidinedione. The molecular formula is C 15 H 19 N 3 O 2 , and the molecular weight is 273.33 g/mol.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 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. 12.
Indications
- 1 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. CAMZYOS is a cardiac myosin inhibitor 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. ( 1 )
Common Doses
- 5 mg
- 2.5 mg
- 10 mg
- 15 mg
Dosage
2 DOSAGE AND ADMINISTRATION Dosage must be individualized based on clinical status and echocardiographic assessment of patient response. Refer to the Full Prescribing Information for instructions. ( 2.1 ) 2.1 Initiation, Maintenance, and Interruption of Treatment Confirm absence of pregnancy and usage of effective contraception in females of reproductive potential [see Warnings and Precautions (5.4) ] . Initiation or up-titration of CAMZYOS in patients with LVEF
Black Box Warning
WARNING: RISK OF HEART FAILURE 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
Contraindications
- 4 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) ] • Strong CYP2C19 inhibitors. ( 4 , 5.2 ) • Moderate to strong CYP2C19 inducers or moderate to strong CYP3A4 inducers. ( 4 , 5.2 )
Side Effects
- 6 ADVERSE REACTIONS The following adverse reaction is discussed in other sections of the labeling: • Heart failure [see Warnings and Precautions (5.1) ] Adverse reactions occurring in >5% of patients and more commonly on CAMZYOS than on placebo were dizziness (27%) and syncope (6%). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Bristol-Myers Squibb at 1-800-721-5072 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.
Interactions
- 7 DRUG INTERACTIONS • Weak to moderate CYP2C19 inhibitors and moderate to strong CYP3A4 inhibitors : May increase risk of heart failure. If initiating an inhibitor, CAMZYOS dose reduction and additional monitoring are required. ( 2.2 , 7.1 ) • Negative inotropes : Close medical supervision and LVEF monitoring is recommended if a negative inotrope is initiated, or the dose of a negative inotrope is increased. Avoid certain combinations of negative inotropes. ( 7.3 ) 7.