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Sep.17.2021

Bamlanivimab; Etesevimab

Indications/Dosage

Labeled

    Off-Label

    • coronavirus disease 2019 (COVID-19)
    • prevention of coronavirus disease 2019 (COVID-19)
    • severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection
    † Off-label indication

    INVESTIGATIONAL USE: For the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection† resulting in mild to moderate coronavirus disease 2019 (COVID-19)† in patients who are at high risk for progressing to severe COVID-19, including hospitalization or death

    NOTE: Bamlanivimab and etesevimab 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. Use of these drugs in hospitalized patients with COVID-19 who require high flow oxygen or mechanical ventilation may be associated with worsening clinical outcomes.[66394]

    NOTE: The National Institutes of Health (NIH) COVID-19 treatment guidelines recommend anti-SARS-CoV-2 antibodies be considered for use in high risk persons with mild to moderate COVID-19 who are hospitalized for a reason other than COVID-19. Additionally, although these antibodies are not authorized for use in patients hospitalized due to severe COVID-19, the NIH states that they may be available through expanded access programs for patients who have not developed an antibody response or who are not expected to mount an effective immune response to SARS-CoV-2 infection.[65314]

    Intravenous dosage

    Adults weighing 40 kg or more

    Administer 700 mg of bamlanivimab and 1,400 mg of etesevimab 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.[66394]

    Children and Adolescents 12 years and older weighing 40 kg or more

    Administer 700 mg of bamlanivimab and 1,400 mg of etesevimab 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.[66394] According to the National Institutes of Health (NIH) COVID-19 treatment guidelines, there are insufficient pediatric data to recommend either for or against the routine use of anti-SARS-CoV-2 antibodies in high risk pediatric patients with mild to moderate COVID-19. The NIH recommends the use of these antibodies be considered on a case-by-case basis in consultation with a pediatric infectious diseases specialist.[65314]

    INVESTIGATIONAL USE: For the post-exposure prevention of coronavirus disease 2019 (COVID-19)† in patients who are at high risk for progressing to severe COVID-19, including hospitalization or death

    NOTE: Post-exposure prophylaxis may be considered in high risk patients who are either not fully vaccinated (i.e., at least 2 weeks after completing the dosing series) OR not expected to mount an adequate immune response to the SARS-CoV-2 vaccination (e.g., immunocompromised condition, immunosuppressive medications) AND 1 of the following:

    • exposed to an individual infected with SARS-CoV-2 consistent with close contact criteria per the Centers for Disease Control and Prevention (CDC)
    • at high risk of exposure to individual(s) infected with SARS-CoV-2 because the infection(s) occurred within the same institutional setting (e.g., nursing homes, prisons)[66394]

    NOTE: Bamlanivimab and etesevimab are not authorized for pre-exposure prophylaxis, nor should they be used as a substitute for the COVID-19 vaccines.[66394]

    Intravenous dosage

    Adults weighing 40 kg or more

    Administer 700 mg of bamlanivimab and 1,400 mg of etesevimab together as a single intravenous infusion. Administer the infusion as soon as possible after exposure to SARS-CoV-2.[66394]

    Children and Adolescents 12 years and older weighing 40 kg or more

    Administer 700 mg of bamlanivimab and 1,400 mg of etesevimab together as a single intravenous infusion. Administer the infusion as soon as possible after exposure to SARS-CoV-2.[66394] According to the National Institutes of Health (NIH) COVID-19 treatment guidelines, there are insufficient pediatric data to recommend either for or against the routine use of anti-SARS-CoV-2 antibodies in high risk pediatric patients. The NIH recommends the use of these antibodies be considered on a case-by-case basis.[65314]

    Therapeutic Drug Monitoring

    Maximum Dosage Limits

    • Adults

      40 kg or more: 700 mg bamlanivimab and 1,400 mg etesevimab IV.

      less than 40 kg: Use not authorized.

    • Geriatric

      40 kg or more: 700 mg bamlanivimab and 1,400 mg etesevimab IV.

      less than 40 kg: Use not authorized.

    • Adolescents

      40 kg or more: 700 mg bamlanivimab and 1,400 mg etesevimab IV.

      less than 40 kg: Use not authorized.

    • Children

      12 years and weighing 40 kg or more: 700 mg bamlanivimab and 1,400 mg etesevimab IV.

      12 years and weighing less than 40 kg: Use not authorized.

      1 to 11 years: Use not authorized.

    • Infants

      Use not authorized.

    • Neonates

      Use not authorized.

    Patients with Hepatic Impairment Dosing

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

    Patients with Renal Impairment Dosing

    No dosage adjustments are needed.

    † Off-label indication
    Revision Date: 09/17/2021, 02:36:16 PM

    References

    65314 - COVID-19 Treatment Guidelines Panel. Coronavirus Diseases 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Accessed September 15, 2021. Available at on the World Wide Web at: https://covid19treatmentguidelines.nih.gov/.66394 - Food and Drug Administration (FDA). Fact sheet for health care providers: emergency use authorization (EUA) of bamlanivimab and etesevimab. Retrieved September 17, 2021. Available on the World Wide Web at https://www.fda.gov/media/145802/download

    How Supplied

    Bamlanivimab Solution for injection

    Bamlanivimab 700mg/20mL Solution for Injection (00002-7910) (Eli Lilly and Co) nullBamlanivimab 700mg/20mL Solution for Injection package photo

    Etesevimab Solution for injection

    Etesevimab 700mg/20mL Solution for Injection (00002-7950) (Eli Lilly and Co) null

    Description/Classification

    Description

    Bamlanivimab and etesevimab are investigational human immunoglobulin G-1 (IgG1) monoclonal antibodies with activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). They are not FDA-approved drugs; however, their use in combination has been authorized by the FDA for emergency treatment of 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 who are at high risk for progressing to severe COVID-19, including hospitalization or death. They are also authorized for use as post-exposure prophylaxis of COVID-19 in persons (12 years and older weighing at least 40 kg) exposed to SARS-CoV-2 who are at high risk for progressing to severe COVID-19 and are not fully vaccinated or are not expected to mount an adequate immune response to the complete COVID-19 vaccination. These drugs are NOT authorized for treatment of 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 these drugs in hospitalized patients with COVID-19 who require high flow oxygen or mechanical ventilation may be associated with worsening clinical outcomes. Additionally, the combination is not authorized for pre-exposure prophylaxis, nor should it be used as a substitute for the COVID-19 vaccines. Bamlanivimab and etesevimab must NOT be used in states, territories, and US jurisdictions in which the combined frequency of variants resistant to bamlanivimab and etesevimab exceeds 5%. A list of areas where these drugs are and are not currently authorized for use can be obtained online at www.FDA.gov.[66394] The National Institutes of Health (NIH) COVID-19 treatment guidelines recommend using anti-SARS-CoV-2 monoclonal antibodies (including bamlanivimab and etesevimab) to treat nonhospitalized patients with mild to moderate COVID-19 who are at high risk of clinical progression as defined by the Emergency Use Authorization (EUA) criteria; however, the use of bamlanivimab and etesevimab is restricted to regions where the combined frequency of potentially resistant variants is low. Anti-SARS-CoV-2 antibodies should also be considered for use in high risk persons with mild to moderate COVID-19 who are hospitalized for a reason other than COVID-19. While these antibodies are not authorized for use in patients hospitalized due to severe COVID-19, they may be available through expanded access programs for patients who have not developed an antibody response or who are not expected to mount an effective immune response to SARS-CoV-2 infection. 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. In situations where it is necessary to triage eligible patients (i.e., antibody shortages, logistical constraints), the NIH suggests prioritizing treatment dosing over post-exposure prophylaxis and prioritizing to unvaccinated/incompletely vaccinated high risk individuals or vaccinated individuals not expected to mount an adequate immune response over vaccinated individuals who are expected to have developed an adequate immune response. These considerations should NOT limit the use of anti-SARS-CoV-2 antibodies when there are no logistical constraints. 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]

    Classifications

    • General Anti-infectives Systemic
      • Antivirals For Systemic Use
        • Antiviral Monoclonal Antibodies for SARS-CoV-2
    Revision Date: 09/17/2021, 01:38:07 PM

    References

    65314 - COVID-19 Treatment Guidelines Panel. Coronavirus Diseases 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Accessed September 15, 2021. Available at on the World Wide Web at: https://covid19treatmentguidelines.nih.gov/.66394 - Food and Drug Administration (FDA). Fact sheet for health care providers: emergency use authorization (EUA) of bamlanivimab and etesevimab. Retrieved September 17, 2021. Available on the World Wide Web at https://www.fda.gov/media/145802/download

    Administration Information

    General Administration Information

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

     

    NOTE: Bamlanivimab and etesevimab MUST be administered in combination. Neither drug is authorized for administration as a single agent (i.e., monotherapy).

    NOTE: Bamlanivimab and etesevimab are not FDA-approved medications; however, they have 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, including hospitalization or death. They are also authorized for use as post-exposure prophylaxis of COVID-19 in persons exposed to SARS-CoV-2 who are at high risk for progressing to severe COVID-19 and are not fully vaccinated or are not expected to mount an adequate immune response to the complete COVID-19 vaccination. 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 bamlanivimab and etesevimab
    • The significant known and potential risks and benefits of bamlanivimab and etesevimab, 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 handwashing) 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 bamlanivimab and etesevimab therapy within 7 calendar days from the onset of the event.[66394]

    Route-Specific Administration

    Injectable Administration

    • Must be administered in a setting in which health care providers have immediate access to medications used to treat a severe infusion reaction and the ability to activate the emergency medical system, as necessary.
    • Visually inspect parenteral products for particulate matter and discoloration prior to drug administration. Both bamlanivimab and etesevimab are clear to opalescent and colorless to slightly yellow to slightly brown solutions.[66394]

    Intravenous Administration

    Preparation and Dilution:

    • The infusion should be prepared and administered by a qualified health care professional using aseptic technique. The product does not contain a preservative.
    • Obtain required materials:
      • ONE BAMLANIVIMAB 20 mL vial and TWO ETESEVIMAB 20 mL vials
      • Polyvinyl chloride (PVC) or polyethylene (PE)-lined PVC, sterile prefilled infusion bag. Choose 1 of the following sizes:
        • Prefilled 50 mL, 100 mL, 150 mL, or 250 mL infusion bag containing 0.9% Sodium Chloride Injection
    • Remove 1 bamlanivimab vial and 2 etesevimab vials from refrigerated storage and allow them to equilibrate to room temperature (approximately 20 minutes). DO NOT expose the vials to direct heat. DO NOT shake the vials.
    • Withdraw 20 mL from 1 bamlanivimab vial and 40 mL from 2 etesevimab vials and inject all 60 mL into the prefilled infusion bag containing 0.9% Sodium Chloride Injection. Discard any remaining product in the vials.
    • Gently invert the infusion bag by hand approximately 10 times to mix. DO NOT shake.
    • Storage: Use immediately after dilution. If immediate administration is not possible, the diluted solution may be stored at room temperature 20 to 25 degrees C (68 to 77 degrees F) for up to 7 hours or under refrigeration at 2 to 8 degrees C (36 to 46 degrees F) for up to 24 hours (including infusion time). If refrigerated, allow the infusion solution to equilibrate to room temperature for approximately 20 minutes before administration.

     

    Intravenous Infusion:

    • Obtain a polyvinyl chloride (PVC) or polyethylene (PE)-lined PVC infusion set. Use of an in-line or add-on 0.2/0.22 micron polyethersulfone (PES) filter is strongly recommended.
    • Attach the infusion set to the IV infusion bag.
    • Prime the infusion set.
    • Administer the entire infusion solution in the bag via pump or gravity. Due to potential overfill of prefilled saline bags, the entire infusion solution in the bag should be administered to avoid underdosage. The minimum infusion duration is dependent on the size of the infusion bag used.
      • Patients weighing 40 to 49 kg:
        • 20 mL bamlanivimab and 40 mL etesevimab added to a 50 mL prefilled 0.9% Sodium Chloride infusion bag (110 mL total) given over at least 21 minutes
        • 20 mL bamlanivimab and 40 mL etesevimab added to a 100 mL prefilled 0.9% Sodium Chloride infusion bag (160 mL total) given over at least 31 minutes
        • 20 mL bamlanivimab and 40 mL etesevimab added to a 150 mL prefilled 0.9% Sodium Chloride infusion bag (210 mL total) given over at least 41 minutes
        • 20 mL bamlanivimab and 40 mL etesevimab added to a 250 mL prefilled 0.9% Sodium Chloride infusion bag (310 mL total) given over at least 70 minutes
      • Patients weighing 50 kg or more:
        • 20 mL bamlanivimab and 40 mL etesevimab added to a 50 mL prefilled 0.9% Sodium Chloride infusion bag (110 mL total) given over at least 21 minutes
        • 20 mL bamlanivimab and 40 mL etesevimab added to a 100 mL prefilled 0.9% Sodium Chloride infusion bag (160 mL total) given over at least 31 minutes
        • 20 mL bamlanivimab and 40 mL etesevimab added to a 150 mL prefilled 0.9% Sodium Chloride infusion bag (210 mL total) given over at least 41 minutes
        • 20 mL bamlanivimab and 40 mL etesevimab added to a 250 mL prefilled 0.9% Sodium Chloride infusion bag (310 mL total) given over at least 60 minutes
    • The prepared infusion solution should not be administered simultaneously with other medications. The compatibility of etesevimab and bamlanivimab with solutions or medications other than 0.9% Sodium Chloride Injection is not known.
    • Once the infusion is complete, flush the infusion line with 0.9% Sodium Chloride to ensure delivery of the required dose.
    • Clinically monitor patients during the infusion and for at least 1 hour after the infusion is complete.
    • If the infusion must be discontinued due to an infusion reaction, discard any unused product.
    • The use of closed system transfer devices (CSTDs), elastomeric pumps, and pneumatic transport has not been studied.[66394]

    Clinical Pharmaceutics Information

    From Trissel's 2‚Ñ¢ Clinical Pharmaceutics Database

    Bamlanivimab

    Etesevimab

      Revision Date: 09/17/2021, 01:44:44 PMCopyright 2004-2021 by Lawrence A. Trissel. All Rights Reserved.

      References

      66394 - Food and Drug Administration (FDA). Fact sheet for health care providers: emergency use authorization (EUA) of bamlanivimab and etesevimab. Retrieved September 17, 2021. Available on the World Wide Web at https://www.fda.gov/media/145802/download

      Adverse Reactions

      Mild

      • dizziness
      • nausea
      • pruritus

      Moderate

      • infusion-related reactions

      Severe

      • anaphylactoid reactions

      The most common adverse reactions that developed in patients treated with bamlanivimab and etesevimab during clinical trials included nausea, pruritus, and dizziness. No treatment-emergent adverse event occurred in more than 1% of drug recipients, and the rates were comparable to the placebo group.[66394]

      Anaphylaxis or anaphylactoid reactions (n = 1, less than 1%) and serious infusion-related reactions (n = 16; 1.1%) have been associated with the use of bamlanivimab and etesevimab together at the authorized doses or higher. In all cases, the infusions were stopped and treatment was administered; 1 case required the use of epinephrine. All events resolved.[66394]

      Revision Date: 09/17/2021, 02:33:17 PM

      References

      66394 - Food and Drug Administration (FDA). Fact sheet for health care providers: emergency use authorization (EUA) of bamlanivimab and etesevimab. Retrieved September 17, 2021. Available on the World Wide Web at https://www.fda.gov/media/145802/download

      Contraindications/Precautions

      Absolute contraindications are italicized.

      • breast-feeding
      • infusion-related reactions
      • pregnancy

      Clinical worsening of COVID-19 has been reported after administration of bamlanivimab and etesevimab together. 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 and etesevimab treatment or were due to the progression of COVID-19. Additionally, monoclonal antibodies (such as bamlanivimab and etesevimab) may be associated with worsening clinical outcomes when administered to hospitalized patients with COVID-19 who require high flow oxygen or mechanical 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.[66394]

      Infusion-related reactions, occurring during and up to 24 hours after the infusion, have been reported with bamlanivimab and etesevimab; 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, vasovagal reactions (e.g., pre-syncope, syncope), 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 and 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. Health care providers are advised that hypersensitivity reactions have also been reported to occur more than 24 hours after the infusion.[66394]

      There are insufficient data regarding the use of bamlanivimab and etesevimab 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, bamlanivimab and etesevimab should be administered during pregnancy only if the potential benefit outweighs the potential risk for the mother and fetus.[66394] The National Institutes of Health (NIH) COVID-19 treatment guidelines recommend that bamlanivimab and etesevimab 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.[65314]

      There are no data regarding the presence of bamlanivimab or etesevimab 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.[66394]

      Revision Date: 08/30/2021, 02:23:09 PM

      References

      65314 - COVID-19 Treatment Guidelines Panel. Coronavirus Diseases 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Accessed September 15, 2021. Available at on the World Wide Web at: https://covid19treatmentguidelines.nih.gov/.66394 - Food and Drug Administration (FDA). Fact sheet for health care providers: emergency use authorization (EUA) of bamlanivimab and etesevimab. Retrieved September 17, 2021. Available on the World Wide Web at https://www.fda.gov/media/145802/download

      Mechanism of Action

      Bamlanivimab and etesevimab are recombinant human immunoglobulin G-1 (IgG1) monoclonal antibodies used in combination as an antiviral medication against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Both bamlanivimab and etesevimab 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 bamlanivimab and etesevimab 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 bamlanivimab and etesevimab. Bamlanivimab and etesevimab are NOT authorized for use in states, territories, and US jurisdictions in which the combined frequency of variants resistant to bamlanivimab and etesevimab exceeds 5%. A list of areas where these drugs are and are not currently authorized for use can be obtained online at www.FDA.gov. Other anti-SARS-CoV-2 antibodies should be considered. 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/Y. All variants maintained susceptibility to bamlanivimab and etesevimab together, except for those with E484D, E484K, E484Q, and Q493R substitutions, which had reduced susceptibilities of 145-fold, 24-fold, 17-fold, and 1,054-fold, respectively. An evaluation of susceptibility data from SARS-CoV-2 variants identified through global surveillance in patients treated with bamlanivimab and etesevimab is ongoing. As of September 2021, neutralization data for variant substitutions with bamlanivimab and etesevimab together show:

      • United Kingdom B.1.1.7 variant (Alpha):
        • Key substitution: N501Y
        • No change or less than 5-fold reduction in susceptibility
      • South Africa B.1.351 variant (Beta):
        • Key substitutions: K417N + E484K + N501Y
        • More than 325- to 431-fold reduced susceptibility; bamlanivimab and etesevimab are unlikely to be active against this variant
      • Brazil P.1 variant (Gamma):
        • Key substitutions: K417T + E484K + N501Y
        • 252-fold reduced susceptibility; bamlanivimab and etesevimab are unlikely to be active against this variant
      • California B.1.427/B.1.429 variant (Epsilon):
        • Key substitution: L452R
        • 9- to 11-fold reduced susceptibility; etesevimab retains activity against this variant
      • New York B.1.526 variant (Iota):
        • Key substitution: E484K (not all New York B.1.526 isolates harbored the E484K substitution)
        • 11- to 30-fold reduced susceptibility
      • India B.1.617.2/AY.3 variant (Delta)
        • Key substitutions: L452R + T478K
        • No change or less than 5-fold reduction in susceptibility
      • India B.1.617.2/AY.1/AY.2 variant (Delta Plus)
        • Key substitutions: L452R + T478K + K417N
        • 1,235-fold reduced susceptibility; bamlanivimab and etesevimab are unlikely to be active against this variant
      • India B.1.617.1 variant (Kappa)
        • Key substitutions: L452R + E484Q
        • 6-fold reduced susceptibility; etesevimab retains activity against this variant
      • Peru C.37 variant (Lambda)
        • Key substitutions: L452Q + F490S
        • No change or less than 5-fold reduction in susceptibility
      • Colombia B.1.621 variant (Mu)
        • Key substitutions: R346K + E484K + N501Y
        • 116-fold reduced susceptibility; bamlanivimab and etesevimab are unlikely to be active against this variant[66394]
      Revision Date: 09/17/2021, 01:41:04 PM

      References

      66394 - Food and Drug Administration (FDA). Fact sheet for health care providers: emergency use authorization (EUA) of bamlanivimab and etesevimab. Retrieved September 17, 2021. Available on the World Wide Web at https://www.fda.gov/media/145802/download

      Pharmacokinetics

      Bamlanivimab and etesevimab are administered together via an intravenous infusion; there are no changes in the pharmacokinetics of either drug when administered alone or together. Once in systemic circulation, the mean volume of distributions of the central and peripheral compartments are 2.87 L and 2.71 L, respectively, for bamlanivimab and 2.38 L and 1.98 L, respectively, for etesevimab. Both drugs are expected to be degraded into small peptides and component amino acids via catabolic pathways similarly to endogenous IgG antibodies. Clearance and the mean apparent terminal elimination half-life for bamlanivimab are 0.27 L/hour and 17.6 days, respectively; for etesevimab, the clearance and mean half-life are 0.128 L/hour and 25.1 days, respectively.[66394]

       

      Affected cytochrome P450 isoenzymes: none

      Route-Specific Pharmacokinetics

      Intravenous Route

      Following a single intravenous infusion, the pharmacokinetic profile of bamlanivimab and etesevimab are linear and dose-proportional between the range of 700 mg and 7,000 mg. The mean maximum plasma concentration (Cmax) from a 700 mg bamlanivimab dose is 196 mcg/mL (90% CI: 102 to 378 mcg/mL) and the Cmax from a 1,400 mg etesevimab dose is 504 mcg/mL (90% CI: 262 to 974 mcg/mL). Both bamlanivimab and etesevimab are quantifiable for at least 29 days post-dose. On Day 29, the mean bamlanivimab concentration is 22 mcg/mL (90% CI: 10.7 to 41.6 mcg/mL) and the mean etesevimab concentration is 111 mcg/mL (90% CI: 57.4 to 199 mcg/mL).[66394]

      Special Populations

      Hepatic Impairment

      Based on population pharmacokinetic analysis, there is no difference in the pharmacokinetics of bamlanivimab or etesevimab in patients with mild hepatic impairment as compared to patients with normal hepatic function. These drugs have not been studied in patients with moderate or severe hepatic impairment.[66394]

      Renal Impairment

      Bamlanivimab and etesevimab are not eliminated intact in the urine. The pharmacokinetics of bamlanivimab and etesevimab are not expected to be affected by renal function or the presence of dialysis.[66394]

      Pediatrics

      The pharmacokinetics of bamlanivimab and etesevimab have been evaluated in pediatric patients ages 12 years and older who weigh at least 40 kg (n = 10). Data show plasma exposures are comparable to those observed in adult patients at the authorized dose. The pharmacokinetics in patients younger than 12 years or less than 40 kg have not been evaluated.[66394]

      Geriatric

      Based on population pharmacokinetic analysis, there is no difference in the pharmacokinetics of bamlanivimab or etesevimab in geriatric patients as compared to younger patients.[66394]

      Gender Differences

      Based on population pharmacokinetic analysis, gender does not affect the pharmacokinetics of bamlanivimab or etesevimab.[66394]

      Ethnic Differences

      Based on population pharmacokinetic analysis, ethnicity does not affect the pharmacokinetics of bamlanivimab or etesevimab.[66394]

      Obesity

      Body weight has no clinically relevant effect on the pharmacokinetics of bamlanivimab or etesevimab in adults with COVID-19 who weigh between 41 kg to 173 kg.[66394]

      Other

      Disease Severity

      Based on population pharmacokinetic analysis, disease severity does not affect the pharmacokinetics of bamlanivimab or etesevimab. There were no differences in the pharmacokinetics of these drugs between mild to moderate ambulatory patients and healthy subjects.[66394]

      Revision Date: 05/19/2021, 12:47:12 PM

      References

      66394 - Food and Drug Administration (FDA). Fact sheet for health care providers: emergency use authorization (EUA) of bamlanivimab and etesevimab. Retrieved September 17, 2021. Available on the World Wide Web at https://www.fda.gov/media/145802/download

      Pregnancy/Breast-feeding

      pregnancy

      There are insufficient data regarding the use of bamlanivimab and etesevimab 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, bamlanivimab and etesevimab should be administered during pregnancy only if the potential benefit outweighs the potential risk for the mother and fetus.[66394] The National Institutes of Health (NIH) COVID-19 treatment guidelines recommend that bamlanivimab and etesevimab 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.[65314]

      breast-feeding

      There are no data regarding the presence of bamlanivimab or etesevimab 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.[66394]

      Revision Date: 08/30/2021, 02:23:09 PM

      References

      65314 - COVID-19 Treatment Guidelines Panel. Coronavirus Diseases 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Accessed September 15, 2021. Available at on the World Wide Web at: https://covid19treatmentguidelines.nih.gov/.66394 - Food and Drug Administration (FDA). Fact sheet for health care providers: emergency use authorization (EUA) of bamlanivimab and etesevimab. Retrieved September 17, 2021. Available on the World Wide Web at https://www.fda.gov/media/145802/download

      Interactions

      There are no drug interactions associated with Bamlanivimab; Etesevimab products.
      Revision Date: 04/20/2021, 02:26:00 AM

      References

      Monitoring Parameters

      • laboratory monitoring not necessary
      ;