Camzyos for symptomatic obstructive hypertrophic cardiomyopathy in adults and pediatrics

Camzyos is an oral medication used to treat symptomatic obstructive hypertrophic cardiomyopathy (HCM) in adults and pediatric patients weighing 30 kg or more. It works by helping to improve heart function and reduce symptoms associated with this heart condition. Treatment requires careful monitoring and dose adjustment to balance benefits and risks.

Camzyos is approved for the treatment of symptomatic obstructive hypertrophic cardiomyopathy (HCM) in:

• Adults
• Pediatric patients weighing 30 kg or more

The treatment aims to improve functional capacity and alleviate symptoms associated with obstructive HCM.

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Camzyos is a cardiac myosin inhibitor that reduces the excessive contractility of the heart muscle characteristic of obstructive hypertrophic cardiomyopathy. By modulating the heart's contractile proteins, it helps to decrease obstruction and improve heart function.

General dosing guidance

Doses must be individualized based on clinical status and echocardiographic monitoring, particularly left ventricular ejection fraction (LVEF) and left ventricular outflow tract (LVOT) gradient.

Adults

• Starting dose: 5 mg orally once daily, without regard to food.
• Dose titration options: 2.5 mg, 5 mg, 10 mg, or 15 mg once daily.
• Maximum dose: 15 mg once daily.
• Do not initiate therapy if LVEF is less than 55%.
• Interrupt treatment if LVEF falls below 50% or if the patient develops heart failure symptoms.

Pediatric patients (≥30 kg)

• Patients ≥45 kg: start at 5 mg orally once daily.
• Patients 30 kg to
• Allowable dose titrations include 1 mg, 2.5 mg, 5 mg, 10 mg, or 15 mg.
• Maximum dose: 15 mg once daily.
• Not studied in patients weighing less than 30 kg.

Dosing considerations

• Swallow capsules whole; do not break, open, or chew.
• If a dose is missed, take it as soon as possible; do not take two doses in one day.
• Dose increases should be delayed during intercurrent illness or arrhythmias that may impair systolic function.
• Dose adjustments required with concomitant CYP2C19 and CYP3A4 inhibitors or inducers:
  • With weak CYP2C19 or moderate CYP3A4 inhibitors: start at recommended dose.
  • With moderate CYP2C19 or strong CYP3A4 inhibitors: start at one dose level below.
  • Interrupt treatment if LVOT gradient falls below 20 mm Hg on the lowest dose.

• Concomitant use with strong CYP2C19 inhibitors.
• Concomitant use with moderate to strong CYP2C19 inducers.
• Concomitant use with moderate to strong CYP3A4 inducers.

Heart failure risk

Camzyos can reduce heart muscle's pumping ability (systolic function), leading to heart failure. Patients must have LVEF ≥55% before starting treatment. LVEF should be regularly monitored during treatment, with interruption of Camzyos if LVEF drops below 50% or if heart failure symptoms occur.

Drug interactions

Concomitant use with strong CYP2C19 inhibitors or moderate to strong CYP2C19 or CYP3A4 inducers is contraindicated due to risk of heart failure or loss of effectiveness. Careful dose adjustments are required when using moderate inhibitors.

Restricted distribution

Camzyos is available only through the CAMZYOS REMS Program, which requires prescriber certification, patient enrollment, and monitoring to manage the risk of heart failure.

Embryo-fetal toxicity

Camzyos may cause fetal harm. Females of reproductive potential must confirm non-pregnancy before treatment and use effective contraception during treatment and for 4 months after the last dose.

Common adverse reactions

• Dizziness (27%)
• Syncope (6%)

Serious reactions

• Heart failure due to reduced systolic function
• Reduction in LVEF below 50%, usually reversible upon treatment interruption

Syncope was the only adverse reaction leading to discontinuation in clinical trials.

Camzyos is metabolized primarily by CYP2C19 and CYP3A4 enzymes. Co-administration with strong CYP2C19 inhibitors or moderate to strong CYP2C19 or CYP3A4 inducers is contraindicated due to increased risk of heart failure or loss of efficacy.

Dose adjustments and monitoring are necessary when given with moderate CYP2C19 or CYP3A4 inhibitors. Patients and providers should be aware of interactions with common medications, including some over-the-counter drugs like omeprazole, esomeprazole, and cimetidine.

Pregnancy

Camzyos may cause fetal harm based on animal studies. Pregnancy must be excluded before starting treatment. Females of reproductive potential must use effective contraception during treatment and for 4 months after the last dose.

Contraception

Combined hormonal contraceptives containing ethinyl estradiol and norethindrone are acceptable, but Camzyos may reduce effectiveness of some contraceptives. Additional nonhormonal contraception is recommended during and for 4 months after treatment.

Lactation

No data provided.