TRANSFORM HOW YOU USE DRUG INFORMATION

No dosage adjustments are needed for patients with mild hepatic impairment. Treatment of patients with moderate to severe hepatic impairment has not been evaluated.

No dosage adjustments are needed.

Etesevimab is an investigational human immunoglobulin G-1 (IgG1) monoclonal antibody with activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is not an FDA-approved medication; however, the drug has been authorized by the FDA for emergency use in combination with another unapproved monoclonal antibody, bamlanivimab. Etesevimab, in combination with bamlanivimab, is used to treat mild to moderate coronavirus disease 2019 (COVID-19) in patients (12 years and older weighing at least 40 kg) with positive SARS-CoV-2 viral testing, and who are at high risk for progressing to severe COVID-19 or hospitalization. The drug is NOT authorized for use in patients who are hospitalized due to COVID-19, who require oxygen therapy for COVID-19, or who require an increase in baseline oxygen flow rate due to COVID-19 if already on chronic oxygen therapy for an underlying condition. Use of the drug in hospitalized patients with COVID-19 who require high flow oxygen or mechanism ventilation may be associated with worsening clinical outcomes.[66394] The National Institutes of Health (NIH) COVID-19 treatment guidelines recommend using combination anti-SARS-CoV-2 monoclonal antibodies (including etesevimab plus bamlanivimab) to treat outpatients with mild to moderate COVID-19 who are at high risk of clinical progression as defined by the Emergency Use Authorization (EUA) criteria. The NIH emphasizes that anti-SARS-CoV-2 antibodies should NOT be used to treat patients hospitalized due to COVID-19, except in a clinical trial; however, their use should be considered for high risk persons with mild to moderate COVID-19 who are hospitalized for a reason other than COVID-19. Anti-SARS-CoV-2 antibodies should be started as soon as possible after positive test results for SARS-CoV-2 and within 10 days of symptom onset. For patients who receive anti-SARS-CoV-2 antibodies, defer administration of the COVID-19 vaccination for at least 90 days as a precaution to avoid interference with vaccine-induced immune responses. Conversely, the use and timing of treatment with anti-SARS-CoV-2 antibodies should not be affected by prior vaccinations in patients who develop COVID-19 after receiving the vaccine.[65314]

For storage information, see the specific product information within the How Supplied section.

NOTE: Etesevimab MUST be administered in combination with bamlanivimab. Use of etesevimab as a single agent is not authorized.

NOTE: Etesevimab is not an FDA-approved medication; however, the drug has been authorized for use under an Emergency Use Authorization (EUA) to treat mild to moderate COVID-19 in patients with positive SARS-CoV-2 viral testing who are at high risk for progressing to severe COVID-19 or hospitalization. Under the EUA, health care providers are required to communicate to the patient, parent, or caregiver information consistent with the "Fact Sheet for Patients, Parents and Caregivers" prior to the patient receiving treatment; such information includes the following:

• The option to accept or refuse etesevimab and bamlanivimab
• The significant known and potential risks and benefits of etesevimab and bamlanivimab, and the extent to which such potential risks and benefits are unknown
• Available alternative treatments and the risk and benefits of those alternatives
• The need to 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, frequent hand washing) according to CDC guidelines

NOTE: Under the EUA, health care providers are required to report all medication errors and serious adverse events potentially related to etesevimab and bamlanivimab therapy within 7 calendar days from the onset of the event.[66394]

Etesevimab MUST be administered in combination with bamlanivimab; clinical worsening of COVID-19 has been reported after bamlanivimab administration. Signs and symptoms included fever, hypoxia or increased respiratory difficulty, arrythmia exacerbation (e.g., atrial fibrillation, sinus tachycardia, bradycardia), fatigue, and altered mental status. Some of these events have required hospitalization. It is not known if these events were related to bamlanivimab treatment or were due to the progression of COVID-19. Additionally, monoclonal antibodies (such as etesevimab and bamlanivimab) may be associated with worsening clinical outcomes when administered to hospitalized patients with COVID-19 who require high flow oxygen or mechanism ventilation. Therefore, these drugs are not authorized for use in patients who are hospitalized due to COVID-19, who require oxygen therapy for COVID-19, or who require an increase in baseline oxygen flow rate due to COVID-19 if already on chronic oxygen therapy for an underlying condition.[66100][66394]

Etesevimab is a recombinant human immunoglobulin G-1 (IgG1) monoclonal antibody used in combination with another IgG1 monoclonal antibody (bamlanivimab) to treat infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Both etesevimab and bamlanivimab target the spike protein of SARS-CoV-2; however, they bind to different but overlapping epitopes in the receptor binding domain (RBD) of the S-protein. By binding to the spike protein, these monoclonal antibodies block the attachment of SARS-CoV-2 to the human ACE2 receptor. Both etesevimab and bamlanivimab are neutralizing antibodies. Bamlanivimab demonstrates antibody-dependent cell-mediated cytotoxicity, but does not elicit complement-dependent cytotoxicity activity. Etesevimab does not demonstrate detectable antibody-dependent cell-mediated cytotoxicity or elicit complement-dependent cytotoxicity. The estimated 50% effective concentration (EC₅₀) against SARS-CoV-2 in Vero cells of bamlanivimab, etesevimab, and a 1:1 ratio of bamlanivimab and etesevimab is 0.02 mcg/mL, 0.14 mcg/mL, and 0.02 mcg/mL, respectively.[66394]

There is a potential for treatment failure due to the development of viral variants that are resistant to both etesevimab and bamlanivimab; however, the use of these antibodies together is expected to reduce the risk of viral resistance. Health care providers are advised to consider the prevalence of SARS-CoV-2 variants in their area when considering treatment options. Data from non-clinical studies have associated E484D/K/Q, F490S, Q493R, and S494P amino acid substitutions in the spike protein with reduced susceptibility to bamlanivimab. Viral variants with reduced susceptibility to etesevimab include substitutions K417N, D420N, and N460K/S/T. All variants maintained susceptibility to bamlanivimab and etesevimab together, except for those with E484K, E484Q, and Q493R substitutions, which had reduced susceptibilities of 17-fold, 22-fold, and more than 100-fold, respectively. An evaluation of susceptibility data from SARS-CoV-2 variants identified through global surveillance in patients treated with etesevimab and bamlanivimab is ongoing. As of February 2021, data for variant substitutions with etesevimab and bamlanivimab together show:

• United Kingdom B.1.1.7 variant: N501Y (no change or less than 5-fold reduction in susceptibility)
• South Africa B.1.351 variant: K417N + E484K + N501Y (more than 45-fold reduced susceptibility)
• Brazil P.1 variant: K417T + E484K + N501Y (more than 511-fold reduced susceptibility)
• California B.1.427/B.1.429 variant: L452R (7.4-fold reduced susceptibility)
• New York B.1.526 variant: E484K (17-fold reduced susceptibility)
  • NOTE: Not all New York B.1.526 isolates harbored the E484K substitution

Although it is still unknown how these data correlate with clinical outcomes, it is unlikely etesevimab and bamlanivimab together will be active against South Africa B.1.351 or Brazil P.1 variants.[66394]