Myqorzo

Treatment should be initiated under the supervision of a physician experienced in the management of patients with cardiomyopathy. 4). Initiation or up-titration of MYQORZO in patients with LVEF < 55% is not recommended. Regular LVEF and Valsalva left ventricular outflow tract gradient (LVOT-G) assessment should be performed during titration to achieve an appropriate target Valsalva LVOT-G, while maintaining LVEF ≥ 50%.

Posology The dose range is 5 mg to 20 mg (either 5 mg, 10 mg, 15 mg, or 20 mg). The recommended starting dose is 5 mg orally once daily. A starting dose of 10 mg should be considered for patients with LVOT-G ≥ 100 mmHg. The dose should be increased every 2 to 8 weeks by 5 mg until a maintenance dose or the maximum dose of 20 mg is achieved.

The maintenance dose is individualised based on the patient’s LVEF and LVOT-G. Recommendations for dosing based on LVEF and LVOT-G criteria are in Table 1.

Table 1:

Dose adjustment of aficamten LVEF Valsalva LVOT-G Dose adjustment ≥ 55% ≥ 30 mmHg Increase dose by 5 mg (up to the maximum dose of 20 mg once daily) ≥ 55% < 30 mmHg Maintain dose < 55% and ≥ 50% Any Maintain dose < 50% and ≥ 40% Any Decrease dose by 5 mg1 Interrupt treatment for 7 days for 5 mg dose < 40% Any Interrupt treatment for at least 7 days.

1 Dose decrease as follows: from 20 mg to 15 mg; from 15 mg to 10 mg; from 10 mg to 5 mg An echocardiographic assessment should be performed 2 to 8 weeks after initiation of treatment, any dose adjustment, or treatment interruption.

After a treatment interruption when LVEF < 40%, treatment should be resumed with a dose reduced by 5 mg when LVEF ≥ 55%. If at 5 mg and LVEF < 50%, treatment should be interrupted for 7 days, and treatment can be resumed at 5 mg when LVEF ≥ 55% (see Table 1).

After the maintenance dose has been established, LVEF and Valsalva LVOT-G should be assessed every 6 months, or every 3 months in patients with LVEF ≥ 50% to < 55%. g. g. new or uncontrolled atrial fibrillation or other uncontrolled tachyarrhythmia) or any other conditions that may impair systolic function.

Dose increases are not recommended until intercurrent illness or new arrythmia has resolved or stabilised. Discontinuation of aficamten may result in recurrence of HCM symptoms. 4). g. g. 3). Concomitant use of aficamten with strong CYP2C9 inhibitors should be avoided.

7%). 4 weeks). The adverse reactions included in Table 4 are listed according to system organ class in MedDRA. Within each system organ class, the adverse reactions are presented in order of decreasing frequency and seriousness. In addition, the corresponding frequency category for each adverse reaction is defined as: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1 000 to < 1/100); rare (≥ 1/10 000 to < 1/1 000); very rare (< 1/10 000).

11 Table 4: Adverse reactions System organ class Adverse reaction Frequency Nervous system disorders Dizziness Common Cardiac disorders Systolic dysfunction1 Common Palpitations Common Vascular disorders Hypertension Common 1 Defined as LVEF < 50% with or without symptoms.

5% patients in the aficamten group experienced a reversible dose related reduction in LVEF to < 50% (median 47%; range 34% to 49%). One patient in the aficamten group experienced an asymptomatic LVEF < 40%. 4). 1%). 1 mmHg for diastolic blood pressure.

Most reports of hypertension were in patients with a history of hypertension, and all reports were non-serious and mild or moderate in severity. Aficamten-associated increases in blood pressure are thought to be a consequence of relief of LVOT obstruction with improved cardiac output.

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

Systolic dysfunction defined as LVEF < 50% Aficamten reduces cardiac contractility and LVEF. 8). g. g. new or uncontrolled atrial fibrillation) may be at greater risk of developing systolic dysfunction and heart failure. 2). The patient’s clinical status and LVEF should be assessed prior to and regularly during treatment and the dose should be adjusted accordingly.

New or worsening arrhythmia, dyspnoea, chest pain, fatigue, leg oedema, or elevations in N-terminal pro-B-type natriuretic peptide (NT-proBNP) may be signs and symptoms of heart failure and should also prompt an evaluation of cardiac function.

Heart failure or loss of response to aficamten due to interactions Aficamten is metabolised by CYP2C9, CYP2D6 and CYP3A enzymes. g. 5). Discontinuation of moderate-to-strong CYP3A inducers and moderate-to-strong CYP2C9 inducers may lead to increased blood concentrations of aficamten, and increase the risk of heart failure due to systolic dysfunction.

g. 5). Patients should be advised of the potential for drug interactions and to inform their healthcare professional of all concomitant medicinal products prior to and during MYQORZO treatment. Pregnancy There is no evidence for the use of aficamten in pregnant women, and animal studies are insufficient to inform maternal or embryo-foetal risk in humans.

3). 7 Recurrence of HCM symptoms with discontinuation Discontinuation of aficamten may result in recurrence of HCM symptoms. 5%)], 3 had serious events of worsening HCM when stopping aficamten. Careful monitoring during discontinuation is recommended.

2). Excipient with known effect Sodium This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.

1. g. 5). • Strong CYP3A4 inducers that are also moderate CYP2C9 inducers: rifampicin and St. 5).