⛔ FDA Black Box 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 )
Pregnancy & Breastfeeding
8.1 Pregnancy Risk Summary There are no available data on the use of MYQORZO during pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. The underlying maternal condition during pregnancy poses a risk to the mother and fetus (see Clinical Considerations ) . In embryo-fetal and pre- and postnatal development studies, when pregnant rats were administered aficamten during the period of organogenesis, aficamten increased the incidence of structural malformations at exposures ≥4-times the maximum recommended human dose (MRHD) of 20 mg based on free area under the concentration curve (AUC) . No adverse effects on development were seen at 3-times the MRHD exposure (see Data ) . The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defects, loss, and other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. There is a pregnancy safety study for MYQORZO. If MYQORZO is administered during pregnancy, or if a patient becomes pregnant while receiving MYQORZO or within 3 weeks after the last dose of MYQORZO, healthcare providers should report MYQORZO exposure by contacting Cytokinetics, Inc. at 1-833-633-2986. Clinical Considerations Disease-Associated Maternal and Embryo-Fetal Risk Obstructive HCM in pregnancy has been associated with increased risk for preterm birth. Data Animal Data Aficamten given to pregnant rats (2, 6 and 9 mg/kg/day) during the period of organogenesis was associated with increased external fetal malformations (kinked tail) at aficamten exposures 5-times the clinical exposures at the MRHD based on free AUC, with uncertain human relevance. Increased post-implantation loss (early and late resorptions) and decreased mean fetal body weight occurred