General MedicationsORALBlack Box

MYQORZO

AFICAMTEN

Standard Dose

2 DOSAGE AND ADMINISTRATION Recommended starting dose is 5 mg orally once daily. ( 2.1 ) Dosage is individualized based on echocardiographic assessments and clinical status. Refer to Full Prescribing Information for instructions on dosage modification. ( 2.1 , 2.2 ) 2.1 Evaluation Before and During Use of MYQORZO Initiation or up-titration of MYQORZO in patients with LVEF <55% is not recommended. Patients may develop heart failure while taking MYQORZO. Regular LVEF and Valsalva left ventricular outflow tract gradient (LVOT-G) assessment is needed for titration to achieve an appropriate target Valsalva LVOT-G, while maintaining LVEF ≥50% and avoiding heart failure symptoms. 2.2 Recommended Dosage and Administration The recommended starting dose of MYQORZO is 5 mg orally once daily. Increase the dose every 2 to 8 weeks by 5 mg until a maintenance dose or the maximum recommended dose of 20 mg once daily is achieved. The maintenance dose of MYQORZO is individualized based on the patient's LVEF and LVOT-G. Recommendations for dosing based on LVEF and LVOT-G criteria are provided in Table 1. Table 1: Dose Adjustment of MYQORZO 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 mg Decrease dose as follows: 20 mg to 15 mg; 15 mg to 10 mg; 10 mg to 5 mg If already on 5 mg, interrupt treatment for at least 7 days <40% Any Interrupt treatment for at least 7 days Perform an echocardiographic assessment 2 to 8 weeks after initiation of treatment or any dose adjustment (e.g., due to LVEF and LVOT-G criteria or drug interaction). After a treatment interruption due to low LVEF, resume treatment, no earlier than 7 days, when LVEF ≥55% and re-initiate dose titration at the starting dose of 5 mg (see Table 1 ). After the maintenance dose has been established, assess LVEF and Valsalva LVOT-G every 6 months, or every 3 months in patients with LVEF <55% to ≥50%. Consider monitoring LVEF and adjust the dose per Table 1 as needed, in patients with an 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. Do not increase the dose until the intercurrent illness or new arrhythmia has resolved or stabilized. MYQORZO should be taken once daily with or without meals at about the same time every day. Swallow tablets whole. 2.3 Dosage Modifications for Drug Interactions Initiate MYQORZO at the recommended starting dose of 5 mg once daily in patients who are on stable therapy with fluconazole, voriconazole, fluvoxamine, strong CYP2C9 inhibitors, or in patients discontinuing a moderate to strong CYP3A inducer. Concomitant Administration with Fluconazole or Voriconazole In patients who initiate fluconazole (if used for more than 3 days) or voriconazole, reduce the dose of MYQORZO to 5 mg if they are currently receiving 15 mg or 20 mg. Avoid concomitant use if patients are currently receiving MYQORZO 5 mg or 10 mg. Assess LVEF and LVOT-G 2 to 8 weeks after initiation of fluconazole or voriconazole and titrate the dose of MYQORZO according to Table 1 [see Dosage and Administration (2.2) , Warnings and Precautions (5.3) and Drug Interactions (7.1) ] . Concomitant Administration with Fluvoxamine or Strong CYP2C9 Inhibitors In patients who initiate fluvoxamine or a strong CYP2C9 inhibitor, reduce the dose of MYQORZO (20 mg to 10 mg; 15 mg to 5 mg; 10 mg to 5 mg). For patients currently receiving MYQORZO 5 mg, maintain the 5 mg dose. Assess LVEF and LVOT-G 2 to 8 weeks after inhibitor initiation and titrate the dose of MYQORZO according to Table 1 [see Dosage and Administration (2.2) , Warnings and Precautions (5.3) and Drug Interactions (7.1) ] . Concomitant Administration with Moderate to Strong CYP3A Inducers In patients who are on stable therapy with moderate to strong CYP3A inducers (e.g., carbamazepine), when discontinuing these medications, reduce the dose of MYQORZO (20 mg to 10 mg; 15 mg to 5 mg; 10 mg to 5 mg). For patients currently receiving MYQORZO 5 mg, maintain the 5 mg dose. Assess LVEF and LVOT-G 2 to 8 weeks after inducer discontinuation and titrate the dose of MYQORZO according to Table 1 [see Dosage and Administration (2.2) , Warnings and Precautions (5.3) and Drug Interactions (7.1) ]. 2.4 Missed Dose 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 of MYQORZO should not be taken on the same day.

Max Dose

See official label

Primary Use

1 INDICATIONS AND USAGE MYQORZO is indicated for the treatment of adults with symptomatic obstructive hypertrophic cardiomyopathy (oHCM) to improve functional capacity and symptoms.

Summary

MYQORZO is a cardiac myosin inhibitor indicated for the treatment of adults with symptomatic obstructive hypertrophic cardiomyopathy (oHCM) to improve functional capacity and symptoms. ( 1 ) Dosage and administration 2 DOSAGE AND ADMINISTRATION Recommended starting dose is 5 mg orally once daily. ( 2.1 ) Dosage is individualized based on echocardiographic assessments and clinical status.

Structured Monograph

Clinical summary

Indications and usage 1 INDICATIONS AND USAGE MYQORZO is indicated for the treatment of adults with symptomatic obstructive hypertrophic cardiomyopathy (oHCM) to improve functional capacity and symptoms. MYQORZO is a cardiac myosin inhibitor indicated for the treatment of adults with symptomatic obstructive hypertrophic cardiomyopathy (oHCM) to improve functional capacity and symptoms. ( 1 ) Dosage and administration 2 DOSAGE AND ADMINISTRATION Recommended starting dose is 5 mg orally once daily. ( 2.1 ) Dosage is individualized based on echocardiographic assessments and clinical status. Refer to Full Prescribing Information for instructions on dosage modification. ( 2.1 , 2.2 ) 2.1 Evaluation Before and During Use of MYQORZO Initiation or up-titration of MYQORZO in patients with LVEF <55% is not recommended. Patients may develop heart failure while taking MYQORZO. Regular LVEF and Valsalva left ventricular outflow tract gradient (LVOT-G) assessment is needed for titration to achieve an appropriate target Valsalva LVOT-G, while maintaining LVEF ≥50% and avoiding heart failure symptoms. 2.2 Recommended Dosage and Administration The recommended starting dose of MYQORZO is 5 mg orally once daily. Increase the dose every 2 to 8 weeks by 5 mg until a maintenance dose or the maximum recommended dose of 20 mg once daily is achieved. The maintenance dose of MYQORZO is individualized based on the patient's LVEF and LVOT-G. Recommendations for dosing based on LVEF and LVOT-G criteria are provided in Table 1. Table 1: Dose Adjustment of MYQORZO 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 mg Decrease dose as follows: 20 mg to 15 mg; 15 mg to 10 mg; 10 mg to 5 mg If already on 5 mg, interrupt treatment for at least 7 days <40% Any Interrupt treatment for at least 7 days Perform an echocardiographic assessment 2 to 8 weeks after initiation of treatment or any dose adjustment (e.g., due to LVEF and LVOT-G criteria or drug interaction). After a treatment interruption due to low LVEF, resume treatment, no earlier than 7 days, when LVEF ≥55% and re-initiate dose titration at the starting dose of 5 mg (see Table 1 ). After the maintenance dose has been established, assess LVEF and Valsalva LVOT-G every 6 months, or every 3 months in patients with LVEF <55% to ≥50%. Consider monitoring LVEF and adjust the dose per Table 1 as needed, in patients with an 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. Do not increase the dose until the intercurrent illness or new arrhythmia has resolved or stabilized. MYQORZO should be taken once daily with or without meals at about the same time every day. Swallow tablets whole. 2.3 Dosage Modifications for Drug Interactions Initiate MYQORZO at the recommended starting dose of 5 mg once daily in patients who are on stable therapy with fluconazole, voriconazole, fluvoxamine, strong CYP2C9 inhibitors, or in patients discontinuing a moderate to strong CYP3A inducer. Concomitant Administration with Fluconazole or Voriconazole In patients who initiate fluconazole (if used for more than 3 days) or voriconazole, reduce the dose of MYQORZO to 5 mg if they are currently receiving 15 mg or 20 mg. Avoid concomitant use if patients are currently receiving MYQORZO 5 mg or 10 mg. Assess LVEF and LVOT-G 2 to 8 weeks after initiation of fluconazole or voriconazole and titrate the dose of MYQORZO according to Table 1 [see Dosage and Administration (2.2) , Warnings and Precautions (5.3) and Drug Interactions (7.1) ] . Concomitant Administration with Fluvoxamine or Strong CYP2C9 Inhibitors In patients who initiate fluvoxamine or a strong CYP2C9 inhibitor, reduce the dose of MYQORZO (20 mg to 10 mg; 15 mg to 5 mg; 10 mg to 5 mg). For patients currently receiving MYQORZO 5 mg, maintain the 5 mg dose. Assess LVEF and LVOT-G 2 to 8 weeks after inhibitor initiation and titrate the dose of MYQORZO according to Table 1 [see Dosage and Administration (2.2) , Warnings and Precautions (5.3) and Drug Interactions (7.1) ] . Concomitant Administration with Moderate to Strong CYP3A Inducers In patients who are on stable therapy with moderate to strong CYP3A inducers (e.g., carbamazepine), when discontinuing these medications, reduce the dose of MYQORZO (20 mg to 10 mg; 15 mg to 5 mg; 10 mg to 5 mg). For patients currently receiving MYQORZO 5 mg, maintain the 5 mg dose. Assess LVEF and LVOT-G 2 to 8 weeks after inducer discontinuation and titrate the dose of MYQORZO according to Table 1 [see Dosage and Administration (2.2) , Warnings and Precautions (5.3) and Drug Interactions (7.1) ]. 2.4 Missed Dose If a dose is missed, it should be taken as soon as possible on the same day. The next sched

Boxed Warning

WARNING: RISK OF HEART FAILURE MYQORZO reduces left ventricular ejection fraction (LVEF) and can cause heart failure due to systolic dysfunction [see Warnings and Precautions (5.1) ]. Echocardiogram assessments are required prior to and during treatment with MYQORZO to monitor for systolic dysfunction. Initiation of MYQORZO in patients with LVEF <55% is not recommended. Decrease the dose of MYQORZO if LVEF is <50% and ≥40% [see Dosage and Administration (2.2) and Warnings and Precautions (5.1) ] . Interrupt the dose of MYQORZO if LVEF <40% or if the patient experiences heart failure symptoms or worsening clinical status due to systolic dysfunction [see Dosage and Administration (2.2) ]. Because of the risk of heart failure due to systolic dysfunction, MYQORZO is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the MYQORZO REMS Program [see Warnings and Precautions (5.2) ]. WARNING: RISK OF HEART FAILURE See full prescribing information for complete boxed warning. MYQORZO can cause heart failure due to systolic dysfunction. ( 5.1 ) Echocardiogram assessments of left ventricular ejection fraction (LVEF) are required before and during MYQORZO use. ( 2.1 ) Initiation in patients with left ventricular ejection fraction (LVEF) <55% is not recommended. ( 2.1 ) Decrease dose if LVEF <50% and ≥40%. Interrupt dosing if LVEF <40% or if worsening clinical status. ( 2.2 ) MYQORZO is available only through a restricted program called the MYQORZO REMS Program. ( 5.2 )

Monitoring

• 5 WARNINGS AND PRECAUTIONS Risk of Heart Failure : Consider decreasing dose or dose interruption in patients with serious intercurrent illness.
• ( 2.2 , 5.1 ) Drug Interactions Leading to Increased Risk of Heart Failure or Loss of Effectiveness: Advise patients of the potential for drug interactions.
• ( 2.3 , 5.3 , 17 ) 5.1 Heart Failure MYQORZO reduces cardiac contractility, which can reduce LVEF and cause heart failure.
• Patients who experience a serious intercurrent illness (e.g., serious infection) or arrhythmia (e.g., new or uncontrolled atrial fibrillation) may be at greater risk of developing systolic dysfunction and heart failure [see Clinical Trial Experience (6.1) ] .

Interaction Notes

• 7 DRUG INTERACTIONS Drugs that inhibit multiple pathways of MYQORZO elimination, strong CYP2C9 inhibitors, or moderate-to-strong CYP3A inducers may increase risk of heart failure.
• MYQORZO dose reduction and additional monitoring may be required when initiating or discontinuing these drugs.
• ( 2.3 , 7.1 ) 7.1.
• Potential for Other Drugs to Affect Plasma Concentrations of MYQORZO Aficamten is primarily metabolized by CYP2C9 and, to a lesser extent by CYP3A, CYP2D6, and CYP2C19.