FDA label 85338960-904b-44df-908f-b74b62902779

WARNING: RISK OF HEART FAILURE CAMZYOS reduces left ventricular ejection fraction (LVEF) and can cause heart failure due to systolic dysfunction [see Warnings and Precautions (5.1) ] . Echocardiogram assessments of LVEF are required prior to and during treatment with CAMZYOS. Initiation of CAMZYOS in patients with LVEF <55% is not recommended. Interrupt CAMZYOS if LVEF is <50% at any visit or if the patient experiences heart failure symptoms or worsening clinical status [see Dosage and Administration (2.1) and Warnings and Precautions (5.1) ] . Concomitant use of CAMZYOS with certain cytochrome P450 inhibitors or discontinuation of certain cytochrome P450 inducers may increase the risk of heart failure due to systolic dysfunction; therefore, the use of CAMZYOS is contraindicated with the following [see Contraindications (4) and Warnings and Precautions (5.2) ] : • Strong CYP2C19 inhibitors • Moderate to strong CYP2C19 inducers or moderate to strong CYP3A4 inducers Because of the risk of heart failure due to systolic dysfunction, CAMZYOS is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called CAMZYOS REMS PROGRAM [see Warnings and Precautions (5.3) ]. WARNING: RISK OF HEART FAILURE See full prescribing information for complete boxed warning. • CAMZYOS can cause heart failure due to systolic dysfunction. ( 5.1 ) • Echocardiogram assessments of left ventricular ejection fraction (LVEF) required before and during CAMZYOS use. ( 2.1 ) • Initiation in patients with LVEF <55% not recommended. Interrupt if LVEF <50% or if worsening clinical status. ( 2.1 , 5.1 ) • Certain CYP450 inhibitors and inducers are contraindicated in patients taking CAMZYOS because of an increased risk of heart failure. ( 4 , 5.2 , 7 ) • CAMZYOS is available only through a restricted program called the CAMZYOS REMS Program. ( 5.3 )

5 WARNINGS AND PRECAUTIONS • Heart Failure : Consider interruption of CAMZYOS in patients with intercurrent illness. ( 2.1 , 5.1 ) • Drug Interactions Leading to Heart Failure or Loss of Effectiveness : Advise patients of the potential for drug interactions including with over-the-counter medications. ( 4 , 5.2 , 17 ) • Embryo-Fetal Toxicity : May cause fetal harm. Advise females of reproductive potential to use effective contraception until 4 months after the last dose. Avoid concomitant use with a combined hormonal contraceptive that contains a progestin other than norethindrone. ( 5.4 , 7.2 , 8.1 , 8.3 ) 5.1 Heart Failure CAMZYOS reduces systolic contraction and can cause heart failure or significantly reduce ventricular function. Patients who experience a serious intercurrent illness (e.g., serious infection) or arrhythmia (e.g., atrial fibrillation or other uncontrolled tachyarrhythmia) are at greater risk of developing systolic dysfunction and heart failure [see Clinical Trial Experience (6.1) ] . Assess the patient’s clinical status and LVEF prior to and regularly during treatment and adjust the CAMZYOS dose accordingly [see Dosage and Administration (2.1) ] . New or worsening arrhythmia, dyspnea, chest pain, fatigue, palpitations, leg edema, or elevations in N-terminal pro-B-type natriuretic peptide (NT-proBNP) may be signs and symptoms of heart failure and should also prompt an evaluation of cardiac function. Asymptomatic LVEF reduction, intercurrent illnesses, and arrhythmias require additional dosing considerations [see Dosage and Administration (2.1 , 2.2 )] . Initiation of CAMZYOS in patients with LVEF <55% is not recommended. Avoid concomitant use of CAMZYOS in patients on disopyramide, ranolazine, verapamil with a beta blocker, or diltiazem with a beta blocker as these medications and combinations increase the risk of left ventricular systolic dysfunction and heart failure symptoms and clinical experience is limited [see Drug Interactions (7) ] . 5.2 CYP450 Drug Interactions Leading to Heart Failure or Loss of Effectiveness CAMZYOS is primarily metabolized by CYP2C19 and CYP3A4 enzymes. Concomitant use of CAMZYOS and drugs that interact with these enzymes may lead to life-threatening drug interactions such as heart failure or loss of effectiveness [see Contraindications (4) , Warnings and Precautions (5.1) , and Drug Interactions (7.1) ] . Advise patients of the potential for drug interactions, including with over-the-counter medications (such as omeprazole, esomeprazole, or cimetidine). Advise patients to inform their healthcare provider of all concomitant products prior to and during CAMZYOS treatment [see Drug Interactions (7.1) , Patient Counseling Information (17) ] . 5.3 CAMZYOS REMS Program CAMZYOS is only available through a restricted program called the CAMZYOS REMS Program because of the risk of heart failure due to systolic dysfunction [see Warnings and Precautions (5.1 , 5.2 )] . Notable requirements of the CAMZYOS REMS Program include the following: • Prescribers must be certified by enrolling in the CAMZYOS REMS Program. • Patients must enroll in the CAMZYOS REMS Program and comply with ongoing monitoring requirements [see Dosage and Administration (2.1) ] . • Pharmacies must be certified by enrolling in the CAMZYOS REMS Program and must only dispense to patients who are authorized to receive CAMZYOS. • Wholesalers and distributors must only distribute to certified pharmacies. Further information is available at www.CAMZYOSREMS.com or by telephone at 1-833-628-7367. 5.4 Embryo-Fetal Toxicity CAMZYOS may cause fetal toxicity when administered to a pregnant female, based on findings in animal studies. Confirm absence of pregnancy in females of reproductive potential prior to treatment and advise patients to use effective contraception during treatment with CAMZYOS and for 4 months after the last dose. Combined hormonal contraceptives (CHCs) containing a combination of ethinyl estradiol and norethindrone may be used with mavacamten. However, CAMZYOS may reduce the effectiveness of certain other CHCs. If these CHCs are used, advise patients to add nonhormonal contraception (such as condoms) during concomitant use and for 4 months after the last dose of CAMZYOS [see Drug Interactions (7.2) and Use in Specific Populations (8.1 , 8.3 )] .

6 ADVERSE REACTIONS The following adverse reaction is discussed in other sections of the labeling: • Heart failure [see Warnings and Precautions (5.1) ] Adverse reactions occurring in >5% of patients and more commonly on CAMZYOS than on placebo were dizziness (27%) and syncope (6%). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Bristol-Myers Squibb at 1-800-721-5072 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 CAMZYOS was evaluated in EXPLORER-HCM, a Phase 3, double-blind, randomized, placebo-controlled trial [see Clinical Studies (14) ] . Of the 251 adults with obstructive HCM, 123 patients were treated with CAMZYOS 2.5-15 mg daily and 128 were treated with placebo. CAMZYOS-treated patients had a median duration of exposure of 30 weeks (range: 2-40 weeks). Syncope (0.8%) was the only adverse drug reaction leading to discontinuation in patients receiving CAMZYOS. Adverse reactions occurring in >5% of patients and more commonly on CAMZYOS than on placebo were dizziness (27% vs. 18%) and syncope (6% vs. 2%). The safety of CAMZYOS in patients was further evaluated in VALOR-HCM, a Phase 3, double-blind, randomized, placebo-controlled trial [see Clinical Studies (14) ] . Of the 112 adults with symptomatic obstructive HCM, 56 patients were treated with CAMZYOS 2.5-15 mg daily and 55 were treated with placebo. CAMZYOS-treated patients had a median duration of exposure of 17 weeks (range: 3-19 weeks). There were no new adverse reactions identified in VALOR-HCM. Effects on Systolic Function In the EXPLORER-HCM trial, mean (SD) resting LVEF was 74% (6) at baseline in both treatment groups. Consistent with the mechanism of action of CAMZYOS, mean (SD) absolute change from baseline in LVEF was -4% (8) in the CAMZYOS group and 0% (7) in the placebo group over the 30-week treatment period. At Week 38, following an 8-week interruption of trial drug, mean LVEF was similar to baseline for both treatment groups. In the EXPLORER-HCM trial, 7 (6%) patients in the CAMZYOS group and 2 (2%) patients in the placebo group experienced reversible reductions in LVEF to <50% (median 48%: range 35-49%) while on treatment. In 3 of the 7 CAMZYOS patients and 1 of the 2 placebo patients, these reductions were asymptomatic. In all 7 patients treated with CAMZYOS, LVEF recovered following interruption of CAMZYOS [see Warnings and Precautions (5.1) ] .