Camzoy2.5 mg

Established / FDA-Approved Indication

• Camzoy 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 reduce symptoms such as exertional dyspnoea, chest discomfort, palpitations, and pre-syncope/syncope.

Evidence Basis

Efficacy of Camzoy in this population is based on randomized, double-blind, placebo-controlled trials (e.g. EXPLORER-HCM) demonstrating improvement in peak oxygen uptake, post-exercise left ventricular outflow tract (LVOT) gradient, NYHA functional class, and patient-reported symptom burden.

Not Indicated / Off-Label

Camzoy is not indicated for non-obstructive HCM, for HCM in children, or for other forms of heart failure. It is a first-in-class, highly specialised agent intended only for use within a restricted access program by physicians experienced in the management of HCM; it is not a general-practice medication.

Each capsule contains Mavacamten as the active pharmaceutical ingredient, available in strengths of 2.5 mg, 5 mg, 10 mg, and 15 mg, along with standard pharmaceutical excipients used in oral capsule formulations.

Camzoy is a first-in-class, oral, allosteric and reversible inhibitor of cardiac myosin. It is used to treat symptomatic obstructive hypertrophic cardiomyopathy, a genetic heart-muscle disease in which thickened heart muscle obstructs blood flow out of the heart.

Camzoy is currently available only through a restricted distribution program and requires specialist cardiology prescribing and monitoring; it is not marketed as a routinely stocked retail product in Bangladesh at this time, and availability should be confirmed with a treating cardiology centre.

Camzoy belongs to the therapeutic class of cardiac myosin inhibitors, a novel first-in-class category of drugs used specifically in the management of obstructive hypertrophic cardiomyopathy.

Mechanism of Action

Mavacamten is a selective, allosteric, and reversible inhibitor of cardiac myosin ATPase. By reducing the number of active actin-myosin cross-bridges, it decreases excessive cardiac muscle contractility, improves left ventricular relaxation, and reduces the dynamic left ventricular outflow tract (LVOT) obstruction that characterizes obstructive HCM.

Pharmacokinetics

Mavacamten is well absorbed orally, is extensively metabolized in the liver predominantly via CYP2C19 (with a smaller contribution from CYP3A4), and its metabolism is markedly affected by CYP2C19 genotype (poor metabolizers achieve higher exposure). Its long elimination half-life supports once-daily dosing.

Camzoy capsules should be swallowed whole with water, taken on an empty stomach at a consistent time each day, at least 2 hours before or after food. See Dosage and Administration for full instructions.

CYP2C19 and CYP3A4 Interactions (Clinically Significant)

Camzoy is metabolized primarily by CYP2C19 and, to a lesser extent, CYP3A4. Concomitant use with drugs that alter these enzymes significantly changes Camzoy exposure and cardiac risk:

• Moderate-to-strong CYP3A4 inhibitors (e.g. diltiazem, verapamil, certain azole antifungals, some macrolides) increase Camzoy levels and heart-failure risk; dose reduction and closer echocardiographic monitoring are required.
• Strong CYP2C19 inhibitors (e.g. fluconazole, fluvoxamine) and moderate-to-strong CYP2C19 or CYP3A4 inducers (e.g. rifampin, St. John's wort, carbamazepine) are contraindicated (see Contraindications) because they cause clinically important changes in Camzoy exposure.
• Weak-to-moderate CYP2C19 inhibitors require dose adjustment and increased monitoring frequency.

Negative Inotropes

Concurrent use with other negative inotropic agents (e.g. verapamil, diltiazem, disopyramide) may have additive effects on cardiac contractility and requires cautious specialist co-management.

CYP2C19 Genotype

Genotype-guided dosing may be used in some protocols, as CYP2C19 poor metabolizers are at higher risk of elevated exposure and reduced LVEF.

Always disclose all prescription, over-the-counter, and herbal products to the prescribing cardiologist before starting Camzoy.

Common

• Dizziness (reported in roughly a quarter of patients)
• Syncope (fainting)
• Fatigue
• Palpitations

Serious

• Reduced left ventricular ejection fraction and heart failure due to systolic dysfunction — the principal safety concern with Camzoy; see Precautions and Warnings for the boxed warning and required monitoring.

Report any new or worsening shortness of breath, swelling of the legs/ankles, fatigue, dizziness, or fainting to the prescribing physician immediately.

Pregnancy

Camzoy can cause fetal harm based on animal reproduction studies. A formal FDA pregnancy category has not been assigned. Pregnancy must be excluded before starting treatment, and females of reproductive potential must use effective, non-hormonal contraception during treatment and for 4 months after the final dose (hormonal contraceptive efficacy may be reduced by Camzoy). Camzoy should be used in pregnancy only if clearly needed, and only after the treating physician has weighed the potential benefit against the potential risk to the fetus.

Lactation

There is no data on the presence of Camzoy in human milk or its effects on the breastfed infant. Because of the potential for serious adverse effects in a nursing infant, a decision should be made, in consultation with a physician, whether to discontinue breastfeeding or discontinue Camzoy, taking into account the importance of treatment to the mother.

Boxed Warning: Risk of Heart Failure

Camzoy can cause dose-dependent reductions in left ventricular ejection fraction (LVEF) and has been associated with heart failure due to systolic dysfunction. For this reason, Camzoy is available only through a restricted Risk Evaluation and Mitigation Strategy (REMS)-type program that mandates:

• Baseline echocardiogram to confirm LVEF ≥55% before starting therapy.
• Periodic echocardiographic monitoring of LVEF throughout treatment (initially every 4 weeks, then every 12 weeks, or more frequently with dose changes or interacting medications).
• Interruption of treatment if LVEF falls below 50%, or if the patient develops signs/symptoms of heart failure, with dose adjustment or discontinuation as directed by the specialist.

Specialist Prescribing Requirement

Camzoy must be prescribed and monitored only by cardiologists experienced in the management of hypertrophic cardiomyopathy, within the restricted access program; it is not intended for general-practice initiation given its novel mechanism, narrow therapeutic considerations, and complex CYP2C19/CYP3A4-mediated interaction profile.

Concurrent Illness

Temporarily interrupt Camzoy in patients who develop a concurrent illness affecting cardiac function (e.g. infection with fever, arrhythmia) until the illness resolves, under physician guidance.

Drug Interaction Caution

Careful review of all concurrent medications is required before and during therapy because of significant CYP2C19/CYP3A4-mediated interactions (see Interactions).

Overdose of Camzoy may cause excessive reduction in left ventricular ejection fraction and precipitate heart failure. There is no specific antidote. In case of suspected overdose, seek immediate medical attention or contact a poison control center/emergency services right away; the patient should be monitored, including echocardiographic assessment of cardiac function, and managed supportively under specialist care.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

Pediatric Use

Safety and efficacy of Camzoy have not been established in patients under 18 years of age.

Geriatric Use

No overall dosing differences are required based on age alone; elderly patients should be monitored with the same echocardiographic protocol, with attention to concurrent medications and comorbidities.

Hepatic Impairment

Lower starting dose and slower titration in moderate hepatic impairment; not recommended in severe hepatic impairment (see Dosage and Administration).

Renal Impairment

No adjustment needed for mild-to-moderate impairment; use with caution and limited data in severe renal impairment.

CYP2C19 Poor Metabolizers

Patients who are CYP2C19 poor metabolizers may require a lower starting dose because of higher expected Camzoy exposure.

Camzoy is intended for long-term, continuous use in obstructive HCM, for as long as clinical benefit is demonstrated and monitoring remains favourable. The need for continued therapy, dose, and monitoring interval is reassessed periodically by the treating cardiologist; treatment is not intended for short courses.

Mavacamten is classified as a cardiac myosin inhibitor, the first agent in this novel drug class.

Mavacamten works as a selective, reversible, allosteric inhibitor of cardiac myosin ATPase, reducing the number of myosin heads able to bind actin. This decreases excessive cardiac contractility and dynamic left ventricular outflow tract obstruction, and improves diastolic (relaxation) function in obstructive hypertrophic cardiomyopathy.

Camzoy is not approved for use in children or adolescents; safety and efficacy in patients under 18 years have not been established, and it should not be used in this population outside of a clinical trial.