Mavacamten, as an innovative cardiac myosin inhibitor, has brought a new treatment option to patients with obstructive hypertrophic cardiomyopathy (HCM).

1. Drug name

Mavacamten

II. Indications

It is used to treat symptomatic adult patients with New York Heart Association (NYHA) class II-III obstructive hypertrophic cardiomyopathy (HCM) to improve functional capacity and symptoms.

III. Specifications and Characteristics

Specification: 2.5mg, capsule form.

IV. Main components

Active ingredient: Mavacamten.

V. Usage and Dosage

1. Recommended starting dose: 5mg orally once daily.

2. Allowed subsequent doses: The titration doses are 2.5mg, 5mg, 10mg, or 15mg, taken orally once daily.

3. Maximum recommended dosage: 15mg once daily.

4. Medication must be individualized and adjusted based on the patient's clinical status and echocardiographic evaluation.

5. Ingestion method: Swallow the capsule whole, do not break, open, or chew it.

6. Timing of administration: It can be taken with or without food.

VI. Dose adjustment

1. Adjustment based on LVEF: The left ventricular ejection fraction (LVEF) must be assessed via echocardiography before and after medication administration. Patients with an LVEF <55% at the initiation of medication are not recommended to start or increase the dosage. If LVEF <50%, treatment should be discontinued and re-evaluated according to relevant procedures.

2. Adjustment based on concomitant medication: Drugs are primarily metabolized by CYP2C19 and CYP3A4 enzymes. When concomitant medication is used (especially CYP2C19 or CYP3A4 inhibitors/inducers), the dosage needs to be adjusted. Specific adjustments include:

3. When starting medication: If the patient has been stably taking a weak CYP2C19 inhibitor or moderate CYP3A4 inhibitor, the starting dose remains at 5mg; if taking a moderate CYP2C19 inhibitor or strong CYP3A4 inhibitor, the starting dose should be 2.5mg.

4. During medication: If planning to initiate the aforementioned inhibitor treatment, the dose of CAMZYOS should be reduced to the next lower daily (mg) dosage level (i.e., 15mg to 10mg; 10mg to 5mg; 5mg to 2.5mg). Avoid initiating the aforementioned inhibitors in patients taking a stable dose of 2.5mg CAMZYOS. For short-term (e.g., one week) use of the aforementioned inhibitors, CAMZYOS treatment can be interrupted, and the previous dose can be resumed immediately after the completion of concomitant medication.

VII. Medication Precautions

1. Before and after meals: It can be taken with or without food, with no significant clinical difference.

2. Missed dose: If a dose is missed, it should be taken as soon as possible on the same day, and the regular dose should be taken at the scheduled time the next day. Do not take two doses on the same day.

3. Concurrent diseases: If the patient develops concurrent severe diseases (such as severe infections) or arrhythmias (such as atrial fibrillation), which may impair systolic function, the increase in dosage should be delayed, and consideration should be given to discontinuing CAMZYOS treatment.

4. Regular monitoring: During treatment, LVEF and Valsalva left ventricular outflow tract (LVOT) gradient must be regularly monitored through echocardiography.

VIII. Medication for special populations

1. Pregnant women: May cause fetal harm. Before treatment, it is necessary to confirm that women who are capable of bearing children are not pregnant. It is recommended that they take effective contraceptive measures during treatment and for four months after the last dose.

2. Lactating women: It is not clear whether mawhakatant is secreted in human milk, its impact on breastfed infants, and its effect on milk secretion. The benefits and risks need to be weighed.

3. Women and men of childbearing age: Before treatment, it should be confirmed that the woman is not pregnant. It is recommended that women adopt effective contraceptive measures during treatment and for 4 months after the last dose. The effectiveness of some combined hormonal contraceptives may be reduced, and it is necessary to use non-hormonal contraception (such as condoms) in combination or switch to a contraceptive method that is not affected by CYP450 enzyme induction.

4. Pediatric patients: Safety and efficacy have not been established.

5. Elderly patients: The safety and efficacy in patients aged 65 and above are similar to those in younger patients.

6. Patients with liver injury: Patients with mild (Child-Pugh A) to moderate (Child-Pugh B) liver injury do not require dosage adjustments. The impact of severe (Child-Pugh C) liver injury is not yet clear.

IX. Adverse reactions

1. The most common adverse reactions (incidence rate >5% and higher than that of the placebo group) are dizziness (27%) and syncope (6%).

2. Serious adverse reactions: May lead to heart failure, requiring close monitoring of cardiac function.

3. Other reactions observed in clinical trials that are consistent with the drug's mechanism of action include reversible reductions in left ventricular ejection fraction.

X. Contraindications

Prohibited combination with the following drugs:

1. Strong CYP2C19 inhibitor.

2. Moderate to strong CYP2C19 inducers or moderate to strong CYP3A4 inducers.

XI. Drug Interactions

1. Other drugs affecting CAMZYOS:

Increased risk of heart failure or drug exposure: Inhibitors of CYP2C19 and CYP3A4 (as described in "VI. Dose Adjustment" above) may increase the plasma concentration of mavacantan and the risk of heart failure; inducers of CYP2C19 and CYP3A4 may decrease its plasma concentration, leading to loss of efficacy, and the risk of heart failure may increase after discontinuation of the inducer.

Management: Follow the "Dosage Adjustment" section. Inform patients of the risk of interactions, including the use of non-prescription drugs (such as omeprazole, esomeprazole, cimetidine, etc.).

2. Effects of CAMZYOS on other drugs:

Induction effect: Mavacantane is an inducer of CYP3A4, CYP2C9, and CYP2C19, which may reduce the plasma concentration of such substrate drugs (such as certain drugs metabolized by these enzymes), leading to diminished efficacy.

Combined hormonal contraceptives: May reduce the plasma concentration of certain progestins, leading to contraceptive failure. Combined hormonal contraceptives containing only ethinyl estradiol and norethisterone can be used in combination with maravacant; if other combined hormonal contraceptives are used, non-hormonal contraceptive measures (such as condoms) should be added, or a contraceptive method that is not affected by enzyme induction (such as an intrauterine device system) should be used during the medication period and for four months after the last dose.

Combined use with drugs that inhibit myocardial contractility: Combined use may result in additive negative inotropic effects. Combination use of β-blockers with propafenone, ranolazine, verapamil, and diltiazem should be avoided.

XII. Storage method

Store at room temperature between 20°C to 25°C (68°F to 77°F), with brief excursions permitted to 15°C to 30°C (59°F to 86°F).

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