FDA label 2c88ee75-7be5-4583-a03f-477a894c4559

Treatment This EUA is for the use of the unapproved products bamlanivimab and etesevimab administered together for the treatment of mild to moderate COVID-19 in adults and pediatric patients, including neonates, with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death [see Limitations of Authorized Use ( 1.1 )] . For treatment of COVID-19, bamlanivimab and etesevimab should be administered together as soon as possible after positive results of direct SARS-CoV-2 viral testing and within 10 days of symptom onset. Post-Exposure Prophylaxis This EUA is for the use of the unapproved products bamlanivimab and etesevimab administered together in adults and pediatric individuals, including neonates, for post-exposure prophylaxis of COVID-19 in individuals who are at high risk for progression to severe COVID-19, including hospitalization or death, and are: not fully vaccinated or who are not expected to mount an adequate immune response to complete SARS-CoV-2 vaccination (for example, individuals with immunocompromising conditions including those taking immunosuppressive medications ) and have been exposed to an individual infected with SARS-CoV-2 consistent with close contact criteria per Centers for Disease Control and Prevention (CDC) or who are at high risk of exposure to an individual infected with SARS-CoV-2 because of occurrence of SARS-CoV-2 infection in other individuals in the same institutional setting (for example, nursing homes, prisons) [see Limitations of Authorized Use ( 1.2 )] . For post-exposure prophylaxis, bamlanivimab and etesevimab should be administered together as soon as possible following exposure to SARS-CoV-2. Criteria for Identifying High Risk Individuals The following medical conditions or other factors may place adults and pediatric patients, including neonates, at higher risk for progression to severe COVID-19: Older age (for example age ≥65 years of age) <1 year old Obesity or being overweight Pregnancy Chronic kidney disease Diabetes Immunosuppressive disease or immunosuppressive treatment Cardiovascular disease (including congenital heart disease) or hypertension Chronic lung diseases (for example, chronic obstructive pulmonary disease, asthma [moderate-to-severe], interstitial lung disease, cystic fibrosis and pulmonary hypertension) Sickle cell disease Neurodevelopmental disorders (for example, cerebral palsy) or other conditions that confer medical complexity (for example, genetic or metabolic syndromes and severe congenital anomalies) Having a medical-related technological dependence (for example, tracheostomy, gastrostomy, or positive pressure ventilation (not related to COVID-19)) Other medical conditions or factors (for example, race or ethnicity) may also place individual patients at high risk for progression to severe COVID-19 and authorization of bamlanivimab and etesevimab under the EUA is not limited to the medical conditions or factors listed above. For additional information on medical conditions and factors associated with increased risk for progression to severe COVID-19, see the CDC website: https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html . Healthcare providers should consider the benefit-risk for an individual patient. Under this EUA, bamlanivimab and etesevimab must be administered together by intravenous (IV) infusion only. Treatment Dosage The authorized dosage for adults (18 years and older) and pediatric patients (<18 years and weighing at least 40 kg) is 700 mg bamlanivimab and 1,400 mg of etesevimab administered together as a single intravenous (IV) infusion [see Dosage and Administration ( 2.2 , 2.4 ) and Clinical Trial Results and Supporting Data for EUA ( 18.1 )] . The authorized dosage for pediatric patients weighing less than 40 kg will vary depending on weight [see Dosage and Administration ( 2.2 , 2.4 )] . Given the similar course of COVID-19, the safety and efficacy of bamlanivimab and etesevimab in younger pediatric patients, including neonates, is supported by safety and efficacy data in adolescents and adults, together with additional pharmacokinetic and safety data from the clinical trial in pediatric patients. The recommended dosing regimen for pediatric patients ≤12 kg is based on pharmacokinetic modeling and simulation [see Clinical Pharmacology ( 14.3 )] . The youngest participant in the pediatric clinical trial was 10 months of age and weighed 8.6 kg [see Clinical Trials and Supporting Data for EUA ( 18.1 )] . Post-Exposure Prophylaxis Dosage The authorized dosage for adults (18 years and older) and pediatric individuals (<18 years and weighing at least 40 kg) is 700 mg bamlanivimab and 1,400 mg of etesevimab administered together as a single intravenous (IV) infusion [see Dosage and Administration ( 2.2 , 2.4 )] . The authorized dosage for pediatric individuals weighing less than 40 kg will vary depending on weight [see Dosage and Administration ( 2.2 , 2.4 )] . The authorized dosage is based on the totality of the scientific evidence including clinical pharmacology data and clinical trial data [see Clinical Pharmacology ( 14.2 ) and Clinical Trial Results and Supporting Data for EUA ( 18.2 )] . The recommended dosing regimen for pediatric patients ≤12 kg is predicted based on pharmacokinetic modeling and simulation [see Clinical Pharmacology ( 14.3 )] . The clinical data for post-exposure prophylaxis is based on data generated in the Phase 3 study BLAZE-2. While this study only evaluated dosing with bamlanivimab alone, it is reasonable to expect that bamlanivimab and etesevimab together may be safe and effective for post-exposure prophylaxis based on: Phase 3 data from BLAZE-1 demonstrated treatment of COVID-19 with bamlanivimab and etesevimab together showed a statistically significant reduction in progression of severe COVID-19, including hospitalization or death [see Clinical Trial Results and Supporting Data for EUA ( 18.1 )] . Nonclinical and clinical data support that bamlanivimab and etesevimab together will provide an advantage over bamlanivimab alone against certain SARS-CoV-2 viral variants [see Microbiology/Resistance Information ( 15 )] . Use of bamlanivimab and etesevimab together for post-exposure prophylaxis in subjects who meet high-risk criteria is based on a subgroup analysis of high-risk individuals enrolled in BLAZE-2 [see Clinical Trial Results and Supporting Data for EUA ( 18.2 )] . Given the similar course of COVID-19, the safety and efficacy of bamlanivimab and etesevimab in younger pediatric patients, including neonates, is supported by safety and efficacy data in adolescents and adults, together with additional pharmacokinetic and safety data from the clinical trial in pediatric patients studying bamlanivimab and etesevimab for the treatment of mild to moderate COVID-19. Children were not enrolled in the post-exposure prophylaxis trial, BLAZE-2. Intravenous Infusion: Bamlanivimab and etesevimab are both available as solutions in separate vials and must be combined prior to administration. Administer bamlanivimab and etesevimab together as a single intravenous (IV) infusion via pump or gravity [see Table 1 and Table 2 and Dosage and Administration ( 2.4 )] . Clinically monitor patients during administration and observe patients for at least 1 hour after infusion is complete. Repeat dosing of bamlanivimab and etesevimab has not been evaluated. Bamlanivimab and etesevimab may only be administered in settings in which health care providers have immediate access to medications to treat a severe infusion reaction, such as anaphylaxis, and the ability to activate the emergency medical system (EMS), as necessary. Health care providers must submit a report on all medication errors and ALL SERIOUS ADVERSE EVENTS potentially related to bamlanivimab and etesevimab. See Sections 8 and 9 of the Full EUA Prescribing Information for reporting instructions below. Patients treated with bamlanivimab and etesevimab together should continue to self-isolate and use infection control measures (e.g., wear mask, isolate, social distance, avoid sharing personal items, clean and disinfect “high touch” surfaces, and frequent handwashing) according to CDC guidelines. The authorized dosage may be updated as additional data from clinical trials becomes available. For information on clinical trials that are testing the use of bamlanivimab and etesevimab in COVID-19, please see www.clinicaltrials.gov .

Warnings There are limited clinical data available for bamlanivimab and etesevimab. Serious and unexpected adverse events may occur that have not been previously reported with use of bamlanivimab and etesevimab together. Hypersensitivity Including Anaphylaxis and Infusion-Related Reactions Serious hypersensitivity reactions, including anaphylaxis, have been observed with administration of bamlanivimab and etesevimab. If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue administration and initiate appropriate medications and/or supportive therapy. Infusion-related reactions, occurring during the infusion and up to 24 hours after the infusion, have been observed with administration of bamlanivimab and etesevimab together. These reactions may be severe or life threatening. Signs and symptoms of infusion related reactions may include: fever, difficulty breathing, reduced oxygen saturation, chills, fatigue, arrhythmia (e.g., atrial fibrillation, sinus tachycardia, bradycardia), chest pain or discomfort, weakness, altered mental status, nausea, headache, bronchospasm, hypotension, hypertension, angioedema, throat irritation, rash including urticaria, pruritus, myalgia, vasovagal reactions (e.g., pre-syncope, syncope), dizziness and diaphoresis. Consider slowing or stopping the infusion and administer appropriate medications and/or supportive care if an infusion-related reaction occurs. Hypersensitivity reactions occurring more than 24 hours after the infusion have also been reported with the use of bamlanivimab and etesevimab under Emergency Use Authorization. Clinical Worsening After Bamlanivimab and Etesevimab Administration Clinical worsening of COVID-19 after administration of bamlanivimab and etesevimab together has been reported and may include signs or symptoms of fever, hypoxia or increased respiratory difficulty, arrhythmia (e.g., atrial fibrillation, sinus tachycardia, bradycardia), fatigue, and altered mental status. Some of these events required hospitalization. It is not known if these events were related to bamlanivimab and etesevimab use or were due to progression of COVID-19. Limitations of Benefit and Potential for Risk in Patients with Severe COVID-19 Treatment with bamlanivimab and etesevimab has not been studied in patients hospitalized due to COVID-19. Monoclonal antibodies, such as bamlanivimab and etesevimab, may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high flow oxygen or mechanical ventilation. Therefore, [see Limitations of Authorized Use ( 1.1 )] : Bamlanivimab and etesevimab are not authorized for use in patients 2 years and older who are hospitalized due to COVID-19 , Bamlanivimab and etesevimab are not authorized for use in patients, regardless of age, who: require oxygen therapy and/or respiratory support due to COVID-19, OR require an increase in baseline oxygen flow rate and/or respiratory support due to COVID-19 and are on chronic oxygen therapy and/or respiratory support due to underlying non-COVID-19 related comorbidity.

5 WARNINGS AND PRECAUTIONS There are limited clinical data available for bamlanivimab and etesevimab. Serious and unexpected adverse events may occur that have not been previously reported with use of bamlanivimab and etesevimab together. 5.1 Hypersensitivity Including Anaphylaxis and Infusion-Related Reactions Serious hypersensitivity reactions, including anaphylaxis, have been observed with administration of bamlanivimab and etesevimab. If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue administration and initiate appropriate medications and/or supportive care. Infusion-related reactions, occurring during the infusion and up to 24 hours after the infusion, have been observed with administration of bamlanivimab and etesevimab together. These reactions may be severe or life threatening. Signs and symptoms of infusion related reactions may include [see Overall Safety Summary ( 6.1 )] : fever, difficulty breathing, reduced oxygen saturation, chills, fatigue, arrhythmia (e.g., atrial fibrillation, sinus tachycardia, bradycardia), chest pain or discomfort, weakness, altered mental status, nausea, headache, bronchospasm, hypotension, hypertension, angioedema, throat irritation, rash including urticaria, pruritus, myalgia, vasovagal reactions (e.g., pre-syncope, syncope), dizziness and diaphoresis. Consider slowing or stopping the infusion and administer appropriate medications and/or supportive care if an infusion-related reaction occurs. Hypersensitivity reactions occurring more than 24 hours after the infusion have also been reported with the use of bamlanivimab and etesevimab under Emergency Use Authorization. 5.2 Clinical Worsening After Bamlanivimab and Etesevimab Administration Clinical worsening of COVID-19 after administration of bamlanivimab and etesevimab together has been reported and may include signs or symptoms of fever, hypoxia or increased respiratory difficulty, arrhythmia (e.g., atrial fibrillation, sinus tachycardia, bradycardia), fatigue, and altered mental status. Some of these events required hospitalization. It is not known if these events were related to bamlanivimab and etesevimab use or were due to progression of COVID-19. 5.3 Limitations of Benefit and Potential for Risk in Patients with Severe COVID-19 Treatment with bamlanivimab and etesevimab has not been studied in patients hospitalized due to COVID-19. Monoclonal antibodies, such bamlanivimab and etesevimab, may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high flow oxygen or mechanical ventilation. Therefore, Bamlanivimab and etesevimab are not authorized for use in patients 2 years and older who are hospitalized due to COVID-19 , Bamlanivimab and etesevimab are not authorized for use in patients, regardless of age, who: require oxygen therapy and/or respiratory support due to COVID-19, OR require an increase in baseline oxygen flow rate and/or respiratory support due to COVID-19 and are on chronic oxygen therapy and/or respiratory support due to underlying non-COVID-19 related comorbidity [see Limitations of Authorized Use ( 1.1 )] .

8 ADVERSE REACTIONS AND MEDICATION ERRORS REPORTING REQUIREMENTS AND INSTRUCTIONS Clinical trials evaluating the safety of bamlanivimab and etesevimab are ongoing [see Overall Safety Summary ( 6 )] . Completion of FDA MedWatch Form to report all medication errors and serious adverse events* occurring during bamlanivimab and etesevimab use and considered to be potentially related to bamlanivimab and etesevimab is mandatory and must be done by the prescribing healthcare provider and/or the provider's designee. These adverse events must be reported within 7 calendar days from the onset of the event: *Serious adverse events are defined as: death; a life-threatening adverse event; inpatient hospitalization or prolongation of existing hospitalization; a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; a congenital anomaly/birth defect; a medical or surgical intervention to prevent death, a life-threatening event, hospitalization, disability, or congenital anomaly. If a serious and unexpected adverse event occurs and appears to be associated with the use of bamlanivimab and etesevimab under this EUA, the prescribing healthcare provider and/or the provider's designee must complete and submit a MedWatch form to FDA using one of the following methods: Complete and submit the report online: www.fda.gov/medwatch/report.htm , or Complete and submit a postage-paid FDA Form 3500 ( https://www.fda.gov/media/76299/download ) and return by: Mail to MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787, or Fax (1-800-FDA- 0178), or Call 1-800-FDA-1088 to request a reporting form IMPORTANT: When reporting adverse events or medication errors to MedWatch, please complete the entire form with detailed information. It is important that the information reported to FDA be as detailed and complete as possible. Information that must be included: Patient demographics (e.g., patient initials, date of birth) Pertinent medical history Pertinent details regarding adverse events and course of illness Concomitant medications Timing of adverse event(s) in relationship to administration of bamlanivimab and etesevimab Pertinent laboratory and virology information Outcome of the event and any additional follow-up information if it is available at the time of the MedWatch report. Subsequent reporting of follow-up information should be completed if additional details become available. The following steps are highlighted to provide the necessary information for safety tracking: In section A, box 1, provide the patient's initials in the Patient Identifier In section A, box 2, provide the patient's date of birth In section B, box 5, description of the event: Write “bamlanivimab and etesevimab use for COVID-19 under Emergency Use Authorization (EUA)” as the first line Provide a detailed report of medication error and/or adverse event. It is important to provide detailed information regarding the patient and adverse event/medication error for ongoing safety evaluation of this unapproved drug. Please see information to include listed above. In section G, box 1, name and address: Provide the name and contact information of the prescribing healthcare provider or institutional designee who is responsible for the report. Provide the address of the treating institution (NOT the healthcare provider's office address).