MAVACAMTEN CAP,ORAL
Clinical Criteria Summary
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Exclusion Criteria
- Left ventricular ejection fraction (e.g., per echocardiogram) < 55%
- Concomitant strong CYP2C19 inhibitors
- Concomitant moderate to strong CYP2C19 inducers or moderate to strong CYP3A4 inducers
- Concomitant use with disopyramide or ranolazine
Inclusion Criteria
- Care provided by a VA/VA Community Care cardiologist or locally designated expert in managing obstructive hypertrophic cardiomyopathy
- Diagnosis of obstructive hypertrophic cardiomyopathy with New York Heart Association (NYHA) class II-III symptoms
- Peak left ventricular outflow tract gradient at least 50 mm Hg at rest, after Valsalva maneuver, or post-exercise
- Inadequate benefit from or unable to use a non-vasodilating beta-blocker
- Inadequate benefit from or unable to use a non-dihydropyridine calcium channel blocker
- Patient and provider enrolled in the CAMZYOS REMS program
Additional Inclusion Criteria
- For patients who can become pregnant: Pregnancy excluded prior to receiving mavacamten
- For patients who can become pregnant: Counseling provided on potential risks vs. benefits of treatment and use of effective contraception during therapy and for 4 months after stopping treatment
- For patients on weak-to-moderate CYP2C19 inhibitor or moderate-to-strong CYP3A4 inhibitor: Additional monitoring planned and/or mavacamten dose modified as appropriate per prescribing information
Clinical Notes & Management Considerations
- Clinical trial inclusion criteria note unexplained left ventricular hypertrophy with maximal left ventricular wall thickness of ≥15 mm (or ≥13 mm if familial hypertrophic cardiomyopathy)
- If current treatment includes both a non-dihydropyridine calcium channel blocker and a beta-blocker, discontinue one agent before initiating mavacamten
- Mavacamten may reduce the effectiveness of combined hormonal contraceptives; advise patients to use an alternative contraceptive method not affected by CYP450 enzyme induction or add nonhormonal contraception
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Indication & Patient Population
- • Adults with symptomatic New York Heart Association (NYHA) class II-III obstructive hypertrophic cardiomyopathy (HCM) to improve functional capacity and symptoms.
Clinical & Diagnostic Criteria
- • Diagnosis of obstructive HCM defined as unexplained left ventricular hypertrophy with maximal left ventricular wall thickness ≥15 mm (or ≥13 mm if familial HCM).
- • Peak left ventricular outflow tract (LVOT) gradient ≥50 mm Hg at rest, after Valsalva maneuver, or post-exercise.
- • Left ventricular ejection fraction (LVEF) ≥55%.
Dosing & Titration Requirements
- • Recommended starting dose is 5 mg once daily without regard to food.
- • Initiation or up-titration is not recommended if LVEF <55%.
- • Subsequent titration doses are 2.5 mg, 5 mg, 10 mg, or 15 mg once daily.
- • Dosing should be individualized to achieve a target reduction in LVOT to less than 30 mm Hg and a mavacamten plasma concentration between 350 to 700 ng/mL.
Monitoring & Assessment Requirements
- • Echocardiogram assessments of LVEF are required prior to and during treatment.
- • Monitor LVEF and Valsalva LVOT gradient at week 4, week 8, and week 12 to appropriately adjust dose.
- • During maintenance therapy, adjust treatment dose every 12 weeks based on patient’s LVEF and Valsalva LVOT gradient.
- • Assess patient’s clinical status prior to and regularly during treatment; adjust dose accordingly.
- • Evaluate cardiac function if signs/symptoms of heart failure occur (e.g., new or worsening arrhythmia, dyspnea, chest pain, fatigue, palpitations, leg edema, or elevations in NT-proBNP).
Treatment Interruption & Discontinuation Criteria
- • Treatment must be interrupted if LVEF is <50% at any visit.
- • Treatment should be interrupted if the patient experiences heart failure symptoms or worsening clinical status.
Contraindications & Drug Interactions
- • Contraindicated with moderate to strong CYP2C19 inhibitors or strong CYP3A4 inhibitors.
- • Contraindicated with moderate to strong CYP2C19 inducers or moderate to strong CYP3A4 inducers.
- • Avoid concomitant use with disopyramide, ranolazine, verapamil with beta-blockers, or diltiazem with beta-blockers.
REMS & Programmatic Requirements
- • Use is restricted to the CAMZYOS REMS Program.
- • Prescribers must be certified by enrolling in the program.
- • Patients must enroll and comply with ongoing monitoring requirements.
- • Pharmacies must be certified and only dispense to authorized patients.
Place in Therapy / Sequential Use
- • Considered for symptomatic obstructive HCM when a non-vasodilating beta-blocker is ineffective or not tolerated, or after failure of a non-DHP CCB.
- • For patients with persistent severe symptoms despite beta-blocker or non-DHP CCB therapy, addition of disopyramide or septal reduction therapy may be considered.