myqorzo

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…

The following adverse reaction is discussed in other sections of labeling: Heart Failure [see Warnings and Precautions (5.1) ] The most common adverse reaction was hypertension (8%). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Cytokinetics at 1-833-633-2986 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of MYQORZO was evaluated in SEQUOIA-HCM, a phase 3, randomized, double-blind, placebo-controlled study [see Clinical Studies (14) ] . Of the 282 adults with oHCM, 142 patients received daily doses of MYQORZO (initiated at 5 mg and titrated up to a maximum dose of 20 mg) and 140 patients received placebo. The median treatment duration for patients receiving MYQORZO was ~24 weeks (range 4 to 29 weeks). Hypertension (8% vs. 2%) was the only adverse reaction occurring in >5% of patients and more commonly on MYQORZO than on placebo. Eligible oHCM patients were able to participate in an ongoing, open-label, single-arm, long-term safety study (FOREST-HCM). Based on available data, the safety profile of MYQORZO in FOREST-HCM was similar to that observed in SEQUOIA-HCM.…

MYQORZO is contraindicated with concomitant use of rifampin [see Warnings and Precautions (5.3) and Drug Interactions (7.1) ] . Rifampin ( 4 )

Clinical Experience and Effects There have been no reports of overdose with MYQORZO. Cardiovascular effects of overdose may include reduced LVEF, heart failure, and hypotension. Signs and symptoms of heart failure such as dyspnea, fatigue, leg edema, or elevations in NT-proBNP should prompt an evaluation of cardiac function [see Warnings and Precautions (5.1) ]. Management Discontinue MYQORZO treatment. Provide medically supportive measures to maintain hemodynamic stability and monitor left ventricular function. Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations.

U.S. Poison Control: call or text 1-800-222-1222 (free, 24/7). In an emergency call 911. From the FDA label; not medical advice.

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. Concomitant administration of drugs that inhibit multiple P450 pathways of aficamten elimination, strong inhibitors of CYP2C9, and moderate-to-strong inducers of CYP3A, may affect the exposure of aficamten [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3) ] (see Table 2 ). Table 2: Established and Potentially Significant Pharmacokinetic Drug-Drug Interactions with MYQORZO Inhibitors of Multiple CYPs Fluvoxamine Clinical Impact Fluvoxamine is a strong CYP2C19 inhibitor, weak to moderate CYP3A inhibitor, weak CYP2C9 inhibitor, and weak CYP2D6 inhibitor. Coadministration of fluvoxamine is predicted to increase aficamten exposure, which may increase the risk of developing heart failure due to systolic dysfunction. Prevention or Management Initiate MYQORZO at 5 mg in patients on stable therapy with fluvoxamine. In patients who are on MYQORZO treatment and intend to initiate fluvoxamine: Reduce dose of MYQORZO (i.e., 20 mg to 10 mg, 15 mg to 5 mg, or 10 mg to 5 mg) or continue 5 mg [see Dosage and Administration (2.3) ] . Fluconazole or Voriconazole Clinical Impact Fluconazole is a moderate CYP2C9 inhibitor, moderate CYP3A inhibitor, and strong CYP2C19 inhibitor. Voriconazole is a strong CYP3A inhibitor, moderate CYP2C19 inhibitor, and weak CYP2C9 inhibitor. Coadministration with fluconazole is observed, and voriconazole is predicted, to increase aficamten exposure, which may increase the risk of developing heart failure due to systolic dysfunction [see Clinical Pharmacology (12.3) ] . Prevention or Management Initiate MYQORZO at 5 mg in patients on stable therapy with fluconazole or voriconazole. In patients currently receiving MYQORZO who intend to initiate fluconazole (if used more than 3 days) or voriconazole: Reduce dose of MYQORZO to 5 mg if they are currently receiving MYQORZO 15 mg or 20 mg. Avoid concomitant use if currently receiving MYQORZO 5 mg or 10 mg [see Dosage and Administration (2.3) ] . Strong CYP2C9 inhibitors Clinical Impact Coadministration with a strong CYP2C9 inhibitor is predicted to increase the exposure of aficamten, which may increase the risk of developing heart failure due to systolic dysfunction [see Clinical Pharmacology (12.3) ] . Prevention or Management Initiate MYQORZO at 5 mg in patients who are on stable therapy with a strong CYP2C9 inhibitor. In patients who are on MYQORZO treatment and intend to initiate a strong CYP2C9 inhibitor: Reduce dose of MYQORZO (i.e., 20 mg to 10 mg, 15 mg to 5 mg, or 10 mg to 5 mg) or continue 5 mg [see Dosage and administration (2.3) ]. CYP Inducers Rifampin Clinical Impact Rifampin is a strong CYP3A inducer, strong CYP2C19 inducer, and moderate CYP2C9 inducer. Coadministration of rifampin decreases aficamten exposure, which may reduce the effectiveness of MYQORZO [see Contraindications (4) and Clinical Pharmacology (12.3) ]. Prevention of Management Concomitant use with rifampin is contraindicated. Other moderate-to-strong CYP3A inducers Clinical Impact Concomitant use with a moderate to strong CYP3A inducer decreases aficamten exposure, which may reduce MYQORZO effectiveness [see Clinical Pharmacology (12.3) ] . The risk of heart failure due to systolic dysfunction may increase with discontinuation of these inducers. Prevention or Management In patients who intend to discontinue a moderate to strong CYP3A Inducer: Reduce dose of MYQORZO (20 mg to 10 mg; 15 mg to 5 mg; 10 mg to 5 mg) or continue 5 mg [see Dosage and Administration (2.3) ].