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.
5). g. voriconazole, fluvoxamine). The maintenance dose of aficamten should not exceed 15 mg. For patients who initiate a weak CYP2C9 inhibitor that is also a moderate-to-strong CYP2D6 or CYP3A inhibitor, the dose of MYQORZO should be reduced to 5 mg if they are currently receiving 15 mg or 20 mg.
Concomitant use should be avoided if patients are currently receiving MYQORZO 5 mg or 10 mg. The maintenance dose of aficamten should not exceed 15 mg. 5). g. 5). For patients currently receiving 5 mg, maintain the 5 mg dose. LVEF and LVOT-G should be assessed after inducer discontinuation.
Assessment of LVEF and LVOT-G and dose titration according to Table 1 is recommended. g. sulfaphenazole) Avoid concomitant administration. 5). g. 3). 3). g. Initiate aficamten at the recommended starting dose of 5 mg once daily. Reduce the dose of aficamten from 20 mg No dose adjustment needed.
5 fluvoxamine, voriconazole) to 5 mg, from 15 mg to 5 mg. 5). The maintenance dose of aficamten should not exceed 15 mg. 5). Assess LVEF and LVOT-G, and dose titrate/monitor […]