Indications

Camzny is indicated for the treatment of adults with symptomatic Now York Hoart Association (NYHA] dlass II-III obstructive hypertrophic cardiomyopathy (HCM) to improve functional capacity and symptoms.

Pharmacology
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 tha
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 LVDT obstruction and improves cardiac
tlling pressures.

Dosage & Administration

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.

Pationts may develop hoart failure while taking Mavacamten. Regular LVEF and Valsalva lett ventricular outflow tract (LVDT) gradient assessment is required for caretul titration to achieve an appropriate target
Valsalva LVOT gradient, while maintaining LVEF 250% and avoiding heart failure symptoms.

Daily dosing takes weeks to roach 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, irst 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, oither restart at
2.5 mg or discontinue permanently.

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

Interaction

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 cortain combinations of negatiwe
inotropes.

Contraindications

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

Pregnancy & Lactation

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

Precautions & Warnings

. Heart Failure: Consider interruption of CAMZYOS (Camzoy) in patients with intercurrent illness.
. Drug Interactions Leading to Heart Failure or Loss of Effeetiveness: 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.

Storage Conditions
Koop below 30"C tomperature, away from light & moisture. Keep out of the reach of children.