Camzyos (mavacamten)

Camzyos (mavacamten) capsules is a prescription medicine used to improve functional capacity and treat the symptoms of New York Heart Association (NYHA) class II-III obstructive hypertrophic cardiomyopathy (HCM). Camzyos may be used alone or with other medications.

Camzyos belongs to a class of drugs called Cardiac Myosin Inhibitors.

It is not known if Camzyos is safe and effective in children.

Warnings

Camzyos reduces left ventricular ejection fraction (LVEF) and can cause heart failure due to systolic dysfunction.

Concomitant use of Camzyos with certain cytochrome P450 inhibitors or discontinuation of certain cytochrome P450 inducers may increase the risk of heart failure due to systolic dysfunction; therefore, the use of Camzyos is contraindicated with the following:

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

Because of the risk of heart failure due to systolic dysfunction, Camzyos is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called Camzyos REMS Program.

Side Effects

Camzyos may cause serious side effects including:

• hives,
• difficulty breathing,
• swelling of your face, lips, tongue, or throat,
• fainting, and
• reduced left ventricular ejection fraction from the heart

Get medical help right away, if you have any of the symptoms listed above.

The most common side effects of Camzyos include:

Tell the doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Camzyos. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Dosages

Initiation, Maintenance, and Interruption of Treatment

• Confirm absence of pregnancy and usage of effective contraception in females of reproductive potential.
• Initiation or up-titration of Camzyos in patients with LVEF
• The recommended starting dose is 5 mg once daily without regard to food; allowable subsequent doses with titration are 2.5, 5, 10, or 15 mg once daily.
• Patients may develop heart failure while taking Camzyos. 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 Camzyos, first consider LVEF then consider the Valsalva LVOT gradient and patient clinical status to guide appropriate Camzyos dosing.
• Follow the algorithms for Initiation (Figure 1) and Maintenance (Figure 2) for appropriate Camzyos dosing and monitoring schedules.
• If LVEF

Figure 1: Initiation Phase

Initiation Phase – Illustration

Figure 2: Maintenance Phase

Maintenance Phase – Illustration

Figure 3: Treatment Interruption at Any Clinic Visit if LVEF

Maintenance Phase – Illustration

• Delay dose increases when there is intercurrent illness (e.g., serious infection) or arrhythmia (e.g., atrial fibrillation or other uncontrolled tachyarrhythmia) that may impair systolic function. Consider interruption of Camzyos in patients with intercurrent illness.

Missed Or Delayed Doses

• If a dose is missed, it should be taken as soon as possible, and the next scheduled dose should be taken at the usual time the following day. Exact timing of dosing during the day is not essential, but two doses should not be taken on the same day.
• Swallow capsules whole. Do not break, open, or chew the capsules.

Concomitant Administration Of Weak CYP2C19 Or Moderate CYP3A4 Inhibitors

• Initiate Camzyos at the recommended starting dosage of 5 mg orally once daily in patients who are on stable therapy with a weak CYP2C19 inhibitor or a moderate CYP3A4 inhibitor.
• Reduce dosage of Camzyos by one level (i.e., 15 → 10 mg; 10 → 5 mg; or 5 → 2.5 mg) in patients who initiate a weak CYP2C19 inhibitor or a moderate CYP3A4 inhibitor.
• Schedule clinical and echocardiographic assessment 4 weeks after inhibitor initiation, and do not up-titrate Camzyos until 12 weeks after inhibitor initiation.
• Avoid initiation of concomitant weak CYP2C19 and moderate CYP3A4 inhibitors in patients who are on stable treatment with 2.5 mg of Camzyos because a lower once-daily dose is not available.

IMAGES

Drug Interactions

Potential For Other Drugs To Affect Plasma Concentrations Of Camzyos

• Mavacamten is primarily metabolized by CYP2C19 and to a lesser extent by CYP3A4 and CYP2C9. Inducers and inhibitors of CYP2C19 and moderate to strong inhibitors or inducers of CYP3A4 may affect the exposures of mavacamten. (See Table 1)

Table 1: Established and Potentially Significant Pharmacokinetic Drug Interactions with Camzyos

Impact Of Other Drugs On Camzyos

Initiate Camzyos at the recommended starting dosage of 5 mg orally once daily in patients who are on stable therapy with a weak CYP2C19 inhibitor or a moderate CYP3A4 inhibitor.

Reduce dose of Camzyos by one level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients who are on Camzyos treatment and intend to initiate a weak CYP2C19 inhibitor or a moderate CYP3A4 inhibitor. Avoid initiation of concomitant weak CYP2C19 and moderate CYP3A4 inhibitors in patients who are on stable treatment with 2.5 mg of Camzyos because a lower dose is not available.

Potential For Camzyos To Affect Plasma Concentrations Of Other Drugs

• Mavacamten is an inducer of CYP3A4, CYP2C9, and CYP2C19. Concomitant use with CYP3A4, CYP2C19, or CYP2C9 substrates may reduce plasma concentration of these drugs. Closely monitor when Camzyos is used in combination with CYP3A4, CYP2C19, or CYP2C9 substrates where decreases in the plasma concentration of these drugs may reduce their activity.

Hormonal Contraceptives

• Progestin and ethinyl estradiol are CYP3A4 substrates. Concomitant use of Camzyos may decrease exposures of ethinyl estradiol and progestin, which may lead to contraceptive failure or an increase in breakthrough bleeding. Advise patients to use a contraceptive method that is not affected by CYP450 enzyme induction (e.g., intrauterine system) or add nonhormonal contraception (such as condoms) during concomitant use and for 4 months after the last dose of Camzyos.

Drugs That Reduce Cardiac Contractility

• Expect additive negative inotropic effects of Camzyos and other drugs that reduce cardiac contractility. In the EXPLORER-HCM trial, 119 of 123 patients who received Camzyos received concomitant therapy with beta blockers (n=94), verapamil (n=19), or diltiazem (n=6).
• Avoid concomitant use of Camzyos with disopyramide in combination with verapamil or diltiazem because such use has been associated with left ventricular systolic dysfunction and heart failure symptoms.
• If concomitant therapy with a negative inotrope is initiated, or if the dose of a negative inotrope is increased, monitor LVEF closely until stable doses and clinical response have been achieved.

Pregnancy and Breastfeeding

• There are no human data on the use of Camzyos during pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.
• The underlying maternal condition during pregnancy poses a risk to the mother and fetus. Advise pregnant females about the potential risk to the fetus with maternal exposure to Camzyos during pregnancy.
• 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 Camzyos and any potential adverse effects on the breastfed child from Camzyos or from the underlying maternal condition.

Summary

Camzyos (mavacamten) is a prescription medication used to treat the symptoms of obstructive hypertrophic cardiomyopathy (HCM). Camzyos reduces left ventricular ejection fraction (LVEF) and can cause heart failure due to systolic dysfunction. Camzyos may cause serious side effects including hives, difficulty breathing, swelling of your face/lips/tongue/throat, fainting, and reduced left ventricular ejection fraction from the heart. Consult your doctor before taking Camzyos if pregnant or breastfeeding.