MYQORZO Film-coated tablet Ref.[116279] Active ingredients: Aficamten

Treatment should be initiated under the supervision of a physician experienced in the management of patients with cardiomyopathy.

Before treatment initiation, left ventricular ejection fraction (LVEF) should be assessed by echocardiography (see section 4.4). 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:

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%. Consider monitoring LVEF and adjust dose per Table 1, as needed, in patients with intercurrent illness (e.g. severe infection or COVID-19), new arrhythmia (e.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. Gradual dose reduction may attenuate the rate of symptom recurrence following treatment discontinuation (see section 4.4).

Dose modification with concomitant medicinal products

Concomitant use with moderate CYP2C9 inhibitors that are also moderate-to-strong inhibitors of CYP2D6 or CYP3A e.g. more than a single dose of fluconazole or strong inducers e.g. rifampicin is contraindicated (see section 4.3).

Concomitant use of aficamten with strong CYP2C9 inhibitors should be avoided. If coadministration cannot be avoided, the dose of aficamten should be reduced to 5 mg and LVEF and LVOT-G assessed every 4 to 8 weeks until a new maintenance dose of aficamten in presence of the inhibitor has been reached (see section 4.5).

The recommended starting dose is 5 mg once daily in patients who are on stable therapy with a weak CYP2C9 inhibitor that is also a moderate-to-strong CYP2D6 or CYP3A inhibitor (e.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. LVEF and LVOT-G should be assessed every 4 to 8 weeks until a new maintenance dose of aficamten in presence of the inhibitor has been reached (see section 4.5).

For patients who intend to discontinue a moderate-to-strong CYP2C9 or CYP3A inducer (e.g. carbamazepine), the dose should be reduced (from 20 mg to 10 mg; from 15 mg to 5 mg; from 10 mg to 5 mg) according to Table 2 (see also section 4.5). 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.

Table 2. Dose modification of aficamten with concomitant medicinal products:

Missed doses

If a dose is missed, it should be taken as soon as possible on the same day. The next scheduled dose should be taken at the usual time the following day. Two doses should not be taken the same day.

Elderly

No dose adjustment is required for patients aged 65 years and older (see section 5.2).

Renal impairment

No dose adjustment to the standard recommended dose and titration schedule is required for patients with mild (estimated glomerular filtration rate [eGFR] 60 to 89 mL/min) to moderate (eGFR 30 to 59 mL/min) renal impairment. No dose recommendation can be made for patients with severe (eGFR <30 mL/min) renal impairment because aficamten has not been studied in patients with severe renal impairment (see section 5.2).

Hepatic impairment

No dose adjustment to the standard recommended dose and titration schedule is required for patients with mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment. No dose recommendation can be made for patients with severe hepatic impairment (Child-Pugh class C) because aficamten has not been studied in patients with severe hepatic impairment (see section 5.2).

Paediatric population

The safety and efficacy of aficamten in children and adolescents below 18 years have not been established. No data are available.

Method of administration

For oral use.

Treatment should be taken once daily with or without meals. The tablet should be swallowed whole with water and not split, crushed, or chewed as these methods have not been studied.

The highest single dose of aficamten 75 mg was administered to 1 healthy participant and resulted in LVEF of 35% at 1.5 hours post-dose that was asymptomatic, with recovery to LVEF of 52% at 4 hours post-dose. Treatment of overdose with consists of discontinuation of aficamten as well as medically supportive measures to maintain hemodynamic stability, including close monitoring of vital signs and LVEF and management of the clinical status of the patient. Overdose in humans can be life-threatening and result in asystole refractory to any medical intervention.

30 months.

Store below 30°C.

Polyvinylchloride (PVC)/Aluminium foil blister containing 14 film-coated tablets.

Pack size of 28 tablets.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.