Mavacamten

Mavacamten 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.

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.

The recommended starting dose is 5 mg orally once daily without regard to food; allowable subsequent doses with titration are 2.5 mg, 5 mg, 10 mg, or 15 mg orally once daily. The maximum recommended dose is 15 mg orally once daily.

Patients may develop heart failure while taking Mavacamten. Regular LVEF and Valsalva left ventricular outflow tract (LVOT) gradient assessment is required for careful titration to achieve an appropriate target Valsalva LVOT gradient, while maintaining LVEF ≥50% and avoiding heart failure symptoms.

Daily dosing takes weeks to reach steady-state drug levels and therapeutic effects, and genetic variation in metabolism and drug interactions can cause large differences in exposure.

When initiating or titrating Mavacamten, first consider LVEF then consider the Valsalva LVOT gradient and patient clinical status to guide appropriate Mavacamten dosing. Follow the algorithms for Initiation and Maintenance for appropriate Mavacamten dosing and monitoring schedules.

If LVEF <50% while taking Mavacamten, interrupt treatment. Follow the algorithm for Interruption for guidance on interrupting, restarting, or discontinuing Mavacamten. If interrupted at 2.5 mg, either restart at 2.5 mg or discontinue permanently.

Pediatric Use: The safety and effectiveness of Mavacamten have not been established in pediatric patients.

Weak CYP2C19 inhibitors and moderate CYP3A4 inhibitors: May increase risk of heart failure. If initiating an inhibitor, CAMZYOS dose reduction and additional monitoring are required.

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.

Mavacamten is contraindicated with concomitant use of:

• Moderate to strong CYP2C19 inhibitors or strong CYP3A4 inhibitors
• Moderate to strong CYP2C19 inducers or moderate to strong CYP3A4 inducers

The presence of Mavacamten in human or animal milk, the drug’s effects on the breastfed infant, and the effects on milk production are unknown. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Mavacamten and any potential adverse effects on the breastfed child from Mavacamten or from the underlying maternal condition.

• Heart Failure: Consider interruption of CAMZYOS (mavacamten) in patients with intercurrent illness. 
• Drug Interactions Leading to Heart Failure or Loss of Effectiveness: Advise patients of the potential for drug interactions including with over-the-counter medications.
• Embryo-Fetal Toxicity: May cause fetal harm. Advise females of reproductive potential to use effective contraception until 4 months after the last dose. Use a contraceptive not affected by CYP450 enzyme induction or add nonhormonal contraception.

Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.