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Mechanism of Action
NOTE: Patients are deemed to be at high risk for progressing to severe COVID-19 or requiring hospitalization if they meet at least 1 of the following criteria:
NOTE: Etesevimab MUST be administered in combination with bamlanivimab. Use of etesevimab as a single agent is not authorized.
NOTE: Etesevimab 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.
1,400 mg in combination with 700 mg of bamlanivimab administered together as a single intravenous infusion. Administer the infusion as soon as possible after the positive test for SARS-CoV-2 and within 10 days of symptom onset.
40 kg or more: 1,400 mg IV.
less than 40 kg: Use not authorized.
12 years and weighing 40 kg or more: 1,400 mg IV.
12 years and weighing less than 40 kg: Use not authorized.
1 to 11 years: Use not authorized.
Use not authorized.
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. 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.
For storage information, see the specific product information within the How Supplied section.
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:
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.
Preparation and Dilution:
Adverse reactions that developed in patients treated with a supratherapeutic dose of etesevimab (2,800 mg) in combination with bamlanivimab (2,800 mg) during clinical trials included nausea (1% to 4%), pruritus (2%), fever (1%), dizziness (1%), and rash (1%).
In ongoing, blinded trials, anaphylaxis or anaphylactoid reactions (n = 1) and other cases of serious infusion-related reactions have been reported during treatment with bamlanivimab with and without etesevimab. All cases required treatment, and all resolved. In the phase 2 portion of the BLAZE-1 trial, immediate hypersensitivity events were noted in 2% of patients treated with bamlanivimab and etesevimab. The reported events included pruritus, flushing, hypersensitivity, and 1 case of angioedema (facial swelling). In the phase 3 portion of the BLAZE-1 trial, 1% of patients treated with bamlanivimab and etesevimab experienced immediate hypersensitivity events. These events including infusion-related reactions (n = 2), rash (n = 2), infusion site rash (n = 1), and pruritus (n = 1). All events resolved.
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.
Infusion-related reactions have been observed during treatment with etesevimab plus bamlanivimab; these reactions may be severe or life-threatening. Signs and symptoms of these reactions include fever, chills, nausea, headache, bronchospasm, dyspnea, reduced oxygen saturation, fatigue, arrhythmia exacerbation (e.g., atrial fibrillation, sinus tachycardia, bradycardia), chest pain or discomfort, weakness, altered mental status, hypotension, hypertension, angioedema, throat irritation, rash, urticaria, pruritus, myalgia, dizziness, and diaphoresis. If an infusion-related reaction develops, consider slowing or stopping the infusion and administer appropriate medications and supportive care. Similarly, serious hypersensitivity reactions, including anaphylaxis, have been observed with administration of bamlanivimab with and without etesevimab. If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue administration of the drug and initiate appropriate medications and supportive care.
There are insufficient data regarding the use of etesevimab or bamlanivimab during pregnancy to determine a drug-associated risk for major birth defects, miscarriages, or adverse maternal or fetal outcomes. Human immunoglobulin G1 (IgG1) antibodies are known to cross the placental barrier; therefore, these drugs have the potential to be transferred from the mother to the developing fetus. It is unknown if this potential in utero transfer provides any therapeutic benefit or risk to the fetus. According to the manufacturer, etesevimab plus bamlanivimab should be administered during pregnancy only if the potential benefit outweighs the potential risk for the mother and fetus. The National Institutes of Health (NIH) COVID-19 treatment guidelines recommend that etesevimab plus bamlanivimab not be withheld from a pregnant woman at risk of progressing to severe COVID-19 if the clinician thinks that the potential benefit outweighs potential risk.
There are no data regarding the presence of etesevimab or bamlanivimab in human milk, the effects on the breast-fed infant, or the effects on milk production; however, maternal immunoglobulin G (IgG) is known to be present in human milk. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, the potential for viral transmission to SARS-CoV-2-negative infants, and the risk of an untreated or inadequately treated condition. Lactating mothers are advised to follow clinical guideline recommendations to avoid exposing the infant to COVID-19. If a breast-fed infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.
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.
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:
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.
Etesevimab is administered in combination with bamlanivimab via a single intravenous infusion; there are no changes in the pharmacokinetics of either etesevimab or bamlanivimab when administered alone or together. Once in systemic circulation, the mean volume of distributions for etesevimab are 2.38 L for the central compartment and 1.98 L for the peripheral compartment. The drug is expected to be degraded into small peptides and component amino acids via catabolic pathways similarly to endogenous IgG antibodies. Clearance is 0.128 L/hour and the mean apparent terminal elimination half-life is 25.1 days.
Affected cytochrome P450 isoenzymes: none
Following a single intravenous infusion, the pharmacokinetic profile of etesevimab is linear and dose-proportional between the range of 700 mg and 7,000 mg. The mean maximum plasma concentration (Cmax) from a 1,400 mg etesevimab dose is 504 mcg/mL (90% CI: 262 to 974 mcg/mL). Etesevimab is quantifiable for at least 29 days post-dose, with a mean concentration of 111 mcg/mL (90% CI: 57.4 to 199 mcg/mL) on Day 29.
Based on population pharmacokinetic analysis, there is no difference in the pharmacokinetics of etesevimab in patients with mild hepatic impairment as compared to patients with normal hepatic function. Etesevimab has not been studied in patients with moderate or severe hepatic impairment.
Etesevimab is not eliminated intact in the urine. The pharmacokinetics of etesevimab are not expected to be affected by renal function or the presence of dialysis.
The pharmacokinetics of etesevimab in pediatric patients have not been evaluated. Using pharmacokinetic modeling and simulation, the recommended dosing regimen is expected to result in plasma drug exposures (AUC) in pediatric patients 12 years and older weighing at least 40 kg that are comparable to those observed in adult patients.
Based on population pharmacokinetic analysis, there is no difference in the pharmacokinetics of etesevimab in geriatric patients as compared to younger patients.
Based on population pharmacokinetic analysis, gender does not affect the pharmacokinetics of etesevimab.
Based on population pharmacokinetic analysis, ethnicity does not affect the pharmacokinetics of etesevimab.
Body weight has no clinically relevant effect on the pharmacokinetics of etesevimab in adults with COVID-19 who weigh between 41 kg to 173 kg.
Based on population pharmacokinetic analysis, disease severity does not affect the pharmacokinetics of etesevimab. There were no differences in the pharmacokinetics of etesevimab between mild to moderate ambulatory patients and healthy subjects.
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