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Nov.30.2022

Bebtelovimab

Indications/Dosage

Labeled

    Off-Label

    • 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, and for whom alternative COVID-19 treatment options approved or authorized by FDA are not accessible or clinically appropriate

    NOTE: As of November 30, 2022, bebtelovimab is NO LONGER AUTHORIZED for use in any U.S. region. Health care providers are encouraged to consider use of other approved/authorized products when selecting appropriate treatment options for coronavirus diseases 2019 (COVID-19). The Emergency Use Authorization (EUA) for bebtelovimab was revoked because of the increased circulation of two severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants (BQ.1 and BQ.1.1) that are likely to be resistant to bebtelovimab. The Centers for Disease Control and Prevention Nowcast data estimate that the combined proportion of COVID-19 cases caused by these two subvariants is greater than 57% nationally, and already above 50% in all but 1 individual region. The FDA will continue to monitor variant susceptibility and frequency data and provide additional updates as new information becomes available.[68236]

    NOTE: Information on medical conditions and factors associated with an increased risk for progression to severe COVID-19 can be obtained on the Centers for Disease Control and Prevention (CDC) website at www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions. Health care providers are advised to consider the benefit-risk for each individual patient.[67385]

    NOTE: Administer bebtelovimab only in a setting with immediate access to medications used for the treatment of severe infusion or hypersensitivity reactions (e.g., anaphylaxis) and with the ability to activate the emergency medical system (EMS), if necessary. Patients should be monitored during administration and observed for at least 1 hour after the injection is complete.[67385] [65314]

    NOTE: Bebtelovimab is NOT authorized for use in patients who are hospitalized due to COVID-19, who require oxygen therapy or respiratory support for COVID-19, or who require an increase in baseline oxygen flow rate or respiratory support due to COVID-19 if already on chronic oxygen therapy for an underlying condition. Use of monoclonal antibodies in hospitalized patients with COVID-19 who require high flow oxygen or mechanical ventilation may be associated with worsening clinical outcomes.[67385] However, the National Institutes of Health (NIH) state that treatment with anti-SARS-CoV-2 monoclonal antibodies should be considered for patients with mild to moderate COVID-19 if they are hospitalized for a reason other than COVID-19 and they meet the EUA criteria for outpatient therapy.[65314]

    NOTE: Health care providers should choose an authorized therapeutic option with activity against the circulating variants in their state, territory, or US jurisdiction. Current variant frequency data are available at: www.cdc.gov/coronavirus/2019-ncov/cases-updates/variant-proportions. The Centers for Disease Control and Prevention (CDC) has reported a rapid increase in circulation within the United States of two SARS-CoV-2 Omicron subvariants (BQ.1 and BQ.1.1) that are likely to be resistant to bebtelovimab.[65314] [67385]

    NOTE: The NIH has issued a statement to provide guidance on treating nonhospitalized patients with mild to moderate COVID-19 who are at high risk of progressing to severe disease. The NIH recommends using 1 of the following therapeutics:

    • Preferred therapies (Adult and pediatric patients, listed in order of preference)
      • nirmatrelvir; ritonavir
      • remdesivir
    • Alternative therapies (Adults only)
      • molnupiravir OR
      • bebtelovimab (no longer available)

    The NIH recommends using bebtelovimab ONLY if none of the preferred therapies are available, feasible to administer, or clinically appropriate (e.g., due to drug interactions, renal or hepatic dysfunction). However, if the majority of infections in a region (i.e., greater than 50%) are due to the Omicron subvariants BQ.1 or BQ.1.1, the effectiveness of bebtelovimab cannot be expected and use of the drug may no longer be justified.[65314]

    NOTE: There may be logistical or supply constraints that make it impossible to offer the available therapy to all eligible patients, making patient triage necessary. Health care providers should prioritize their use for patients at highest risk of clinical progression. Information on which individuals might receive the greatest benefit from anti-SARS-CoV-2 therapeutics for treatment or prevention can be obtained from www.covid19treatmentguidelines.nih.gov/therapies/statement-on-patient-prioritization-for-outpatient-therapies.[65314]

    Intravenous dosage

    Adults

    175 mg as a single intravenous injection. Administer as soon as possible after the positive test for SARS-CoV-2 and within 7 days of symptom onset.[65314] [67385]

    Children and Adolescents 12 to 17 years weighing 40 kg or more

    175 mg as a single intravenous injection. Administer as soon as possible after the positive test for SARS-CoV-2 and within 7 days of symptom onset.[67385] The NIH states that there is insufficient evidence to recommend either for or against the use of bebtelovimab in pediatric patients.[65314]

    Therapeutic Drug Monitoring

    Maximum Dosage Limits

    • Adults

      175 mg IV.

    • Geriatric

      175 mg IV.

    • Adolescents

      weight 40 kg or more: 175 mg IV.

      weight less than 40 kg: Safety and efficacy have not been established.

    • Children

      12 years and weight 40 kg or more: 175 mg IV.

      12 years and weight less than 40 kg: Safety and efficacy have not been established.

      1 to 11 years: Safety and efficacy have not been established.

    • Infants

      Safety and efficacy have not been established.

    • Neonates

      Safety and efficacy have not been established.

    Patients with Hepatic Impairment Dosing

    No dosage adjustment is recommended in patients with mild hepatic impairment. Bebtelovimab has not been studied in patients with moderate or severe hepatic impairment.[67385]

    Patients with Renal Impairment Dosing

    No dosage adjustment is recommended in patients with renal impairment.[67385]

    † Off-label indication
    Revision Date: 11/30/2022, 03:46:09 PM

    References

    65314 - COVID-19 Treatment Guidelines Panel. Coronavirus Diseases 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Accessed November 10, 2022. Available at on the World Wide Web at: https://covid19treatmentguidelines.nih.gov/.67385 - Food and Drug Administration (FDA). Fact sheet for healthcare providers: Emergency use authorization (EUA) for bebtelovimab. Retrieved November 4, 2022. Available on the World Wide Web at https://www.fda.gov/media/156152/download?utm_medium=email&utm_source=govdelivery.68236 - Center for Drug Evaluation and Research Division of Drug Information. FDA Announces Bebtelovimab is Not Currently Authorized in Any US Region. Food and Drug Administration. November 30, 2022. Available at https://www.fda.gov/drugs/drug-safety-and-availability/fda-announces-bebtelovimab-not-currently-authorized-any-us-region. Accessed on November 30, 2022.

    How Supplied

    Bebtelovimab Solution for injection

    Bebtelovimab 175mg/2mL Solution for Injection (00002-7589) (Eli Lilly and Co) (off market)

    Description/Classification

    Description

    NOTE: As of November 30, 2022, bebtelovimab is NO LONGER AUTHORIZED for use in any U.S. region. Health care providers are encouraged to consider use of other approved/authorized products when selecting appropriate treatment options for coronavirus diseases 2019 (COVID-19). The Emergency Use Authorization (EUA) for bebtelovimab was revoked because of the increased circulation of two severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants (BQ.1 and BQ.1.1) that are likely to be resistant to bebtelovimab. The Centers for Disease Control and Prevention Nowcast data estimate that the combined proportion of COVID-19 cases caused by these two subvariants is greater than 57% nationally, and already above 50% in all but 1 individual region. The FDA will continue to monitor variant susceptibility and frequency data and provide additional updates as new information becomes available.[68236]

     

    Bebtelovimab is an investigational monoclonal antibody with activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is not FDA-approved for any indication; however, it has been authorized for emergency use for the treatment of mild to moderate coronavirus disease 2019 (COVID-19) in adults and pediatric patients 12 years of age and older weighing at least 40 kg with a positive SARS-CoV-2 test, and who are at high risk for progression to severe disease, including hospitalization or death, and for whom approved or authorized alternative COVID-19 treatment options are not accessible or clinically appropriate. Bebtelovimab is not authorized for use in patients who are hospitalized due to COVID-19, who require oxygen therapy or respiratory support for COVID-19, or who require an increase in baseline oxygen flow rate or respiratory support due to COVID-19 if already on chronic oxygen therapy for an underlying condition. Use of monoclonal antibodies in hospitalized patients with COVID-19 who require high flow oxygen or mechanical ventilation may be associated with worsening clinical outcomes.[67385]

     

    The National Institutes of Health (NIH) COVID-19 treatment guidelines recommend bebtelovimab as an alternative treatment option for nonhospitalized adult patients with mild to moderate COVID-19 who are at high risk of progressing to severe disease. Bebtelovimab should ONLY be prescribed when preferred treatment options cannot be used. According to the NIH, bebtelovimab may also be considered for use in patients with mild to moderate COVID-19 who are hospitalized for a reason other than COVID-19 if they meet the EUA criteria for outpatient therapy. The NIH states that there is insufficient evidence to recommend either for or against the use of bebtelovimab in pediatric patients. Start bebtelovimab as soon as possible after positive test results for SARS-CoV-2 and within 7 days of symptom onset. The use and timing of anti-SARS-CoV-2 antibodies, such as bebtelovimab, should not be affected by prior exposure to the COVID-19 vaccine.[65314] Similarly, the Centers for Disease Control and Prevention (CDC) state that although some reduction in vaccine-induced antibody titers have been observed in persons who previously received antibody products, the benefits versus risks favor proceeding with vaccination; and thus, COVID-19 vaccination does not need to be delayed after receipt of anti-SARS-CoV-2 antibodies.[66175]

    Classifications

    • General Anti-infectives Systemic
      • Antivirals For Systemic Use
        • SARS-CoV-2 Antivirals
          • Antiviral Monoclonal Antibodies for SARS-CoV-2
    Revision Date: 12/01/2022, 01:39:17 PM

    References

    65314 - COVID-19 Treatment Guidelines Panel. Coronavirus Diseases 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Accessed November 10, 2022. Available at on the World Wide Web at: https://covid19treatmentguidelines.nih.gov/.66175 - Center for Disease Control and Prevention. Interim clinical considerations for use of COVID-19 vaccines currently approved or authorized in the United States. Updated August 22, 2022. Accessed August 22, 2022. Available at: https://www.cdc.gov/vaccines/covid-19/info-by-product/clinical-considerations.html.67385 - Food and Drug Administration (FDA). Fact sheet for healthcare providers: Emergency use authorization (EUA) for bebtelovimab. Retrieved November 4, 2022. Available on the World Wide Web at https://www.fda.gov/media/156152/download?utm_medium=email&utm_source=govdelivery.68236 - Center for Drug Evaluation and Research Division of Drug Information. FDA Announces Bebtelovimab is Not Currently Authorized in Any US Region. Food and Drug Administration. November 30, 2022. Available at https://www.fda.gov/drugs/drug-safety-and-availability/fda-announces-bebtelovimab-not-currently-authorized-any-us-region. Accessed on November 30, 2022.

    Administration Information

    General Administration Information

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

    NOTE: Bebtelovimab is not an FDA-approved medication; however, it has been authorized for emergency use 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. Under the Emergency Use Authorization (EUA), health care providers are required to communicate to the patient, parent, or caregiver information consistent with the "Fact Sheet for Patients, Parents or Caregivers" and provide them with a copy of this Fact Sheet prior to the patient receiving treatment.[67385]

    NOTE: Under the EUA, health care providers are required to report all medication errors and serious adverse events potentially related to bebtelovimab therapy within 7 calendar days from the onset of the event.[67385]

    Route-Specific Administration

    Injectable Administration

    • Administer bebtelovimab only in a setting with immediate access to medications used for the treatment of severe infusion or hypersensitivity reactions (e.g., anaphylaxis) and with the ability to activate the emergency medical system (EMS), if necessary.
    • Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Bebtelovimab is clear to opalescent and colorless to slightly yellow to slightly brown solution. Discard the vial if the solution is cloudy, discolored or visible particles are observed.[67385]

    Intravenous Administration

    Preparation

    • Obtain the following:
      • 1 bebtelovimab vial (175 mg/2 mL)
      • 1 disposable polypropylene dosing syringe capable of holding 2 mL
      • 0.9% Sodium Chloride Injection for flushing
      • Optional: 1 syringe extension set made of polyethylene or polyvinylchloride with or without diethylhexylphthalate (DEHP)
    • Remove bebtelovimab vial from refrigerated storage and allow it to equilibrate to room temperature for approximately 20 minutes before preparation. Do not expose to direct heat. Do not shake vial.
    • Withdraw 2 mL from the vial into the disposable syringe. Discard any product remaining in the vial.
    • The product is preservative-free and therefore, should be administered immediately.
    • If immediate administration is not possible, store the syringe for up to 24 hours at refrigerated temperature (2 to 8 degrees C [36 to 46 degrees F]) and up to 7 hours at room temperature (20 to 25 degrees C [68 to 77 degrees F]). If refrigerated, allow the prepared syringe to equilibrate to room temperature for approximately 20 minutes prior to administration.[67385]

     

    IV Push

    • If used, attach and prime the syringe extension set.
    • Administer the entire contents of the syringe via IV injection over at least 30 seconds.
    • After the entire contents of the syringe have been administered, flush the injection line with 0.9% Sodium Chloride Injection to ensure delivery of the required dose.
    • Clinically monitor patients during the infusion and for at least 1 hour after the infusion is complete.[67385]

    Clinical Pharmaceutics Information

    From Trissel's 2‚Ñ¢ Clinical Pharmaceutics Database
      Revision Date: 06/20/2022, 12:57:14 PM

      References

      67385 - Food and Drug Administration (FDA). Fact sheet for healthcare providers: Emergency use authorization (EUA) for bebtelovimab. Retrieved November 4, 2022. Available on the World Wide Web at https://www.fda.gov/media/156152/download?utm_medium=email&utm_source=govdelivery.

      Adverse Reactions

      Moderate

      • infusion-related reactions

      Mild

      • nausea
      • pruritus
      • rash
      • vomiting

      Severe

      • anaphylactoid reactions

      Serious hypersensitivity reactions, including anaphylaxis and anaphylactoid reactions, have been observed with human immunoglobulin G1 (IgG1) monoclonal antibodies, and may occur with bebtelovimab. Infusion-related reactions (0.3%), including rash (0.8%) and pruritus (0.3%), were reported in patients who received bebtelovimab, alone or in combination with bamlanivimab and etesevimab, in the phase 1 and 2 portions of a randomized, single-dose clinical trial (n = 602). Monitor patients for possible infusion-related reactions during administration and for at least 1 hour after the injection is complete.[67385]

      The most common adverse reactions that were reported in patients who received bebtelovimab, alone or in combination with bamlanivimab and etesevimab, in the phase 1 and 2 portions of a randomized, single-dose clinical trial (n = 602) were nausea (0.8%) and vomiting (0.7%).[67385]

      Revision Date: 02/15/2022, 11:28:03 AM

      References

      67385 - Food and Drug Administration (FDA). Fact sheet for healthcare providers: Emergency use authorization (EUA) for bebtelovimab. Retrieved November 4, 2022. Available on the World Wide Web at https://www.fda.gov/media/156152/download?utm_medium=email&utm_source=govdelivery.

      Contraindications/Precautions

      Absolute contraindications are italicized.

      • breast-feeding
      • infusion-related reactions
      • pregnancy

      Clinical worsening of COVID-19 has been reported after administration of SARS-CoV-2 monoclonal antibodies. 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 monoclonal antibody treatment or were due to the progression of COVID-19. Additionally, monoclonal antibodies 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.[67385]

      Serious hypersensitivity reactions, including anaphylaxis, have been observed with administration of other SARS-CoV-2 monoclonal antibodies and could occur with administration of bebtelovimab. 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. Infusion-related reactions, which may occur up to 24 hours after the injection, have been observed in clinical trials of bebtelovimab when administered with other monoclonal antibodies and may occur with use of bebtelovimab alone; 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. Monitor patients for possible infusion-related reactions during administration and for at least 1 hour after the injection is complete. If an infusion-related reaction develops, administer appropriate medications and supportive care. Hypersensitivity reactions have also been reported to occur more than 24 hours after the injection with the use of SARS-CoV-2 monoclonal antibodies under Emergency Use Authorization.[67385]

      Bebtelovimab should be administered during pregnancy only if the potential benefit outweighs the potential risk for the mother and fetus. There are insufficient data regarding the use of bebtelovimab 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, bebtelovimab has 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. There are risks to the mother and fetus associated with untreated COVID-19 in pregnancy. There are also risks of severe hypersensitivity and infusion-related reactions following administration of bebtelovimab, including in pregnant patients. Pregnant patients who develop severe hypersensitivity or infusion-related reactions should be managed appropriately, including obstetrical care.[67385]

      There are no data regarding the presence of bebtelovimab 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 developmental and health benefits of breast-feeding along with the mother's clinical need for bebtelovimab and any potential adverse effects on the breast-fed infant from bebtelovimab or the underlying maternal condition. Lactating mothers are advised to follow practices according to clinical guidelines to avoid exposing the infant to COVID-19.[67385]

      Revision Date: 06/20/2022, 01:52:14 PM

      References

      67385 - Food and Drug Administration (FDA). Fact sheet for healthcare providers: Emergency use authorization (EUA) for bebtelovimab. Retrieved November 4, 2022. Available on the World Wide Web at https://www.fda.gov/media/156152/download?utm_medium=email&utm_source=govdelivery.

      Mechanism of Action

      Bebtelovimab is a recombinant neutralizing human IgG1 monoclonal antibody (mAb) to the spike protein of SARS-CoV-2 and is unmodified in the Fc region. Bebtelovimab binds the spike protein with a dissociation constant KD of 0.046 to 0.075 nM and blocks spike protein attachment to the human ACE2 receptor with an IC50 value of 0.39 nM (0.056 mcg/mL). The cell culture neutralization activity of bebtelovimab against SARS-CoV-2 was measured in a dose-response model quantifying plaque reduction using cultured Vero E6 cells. Bebtelovimab neutralized the USA/WA/1/2020 isolate of SARS-CoV-2 with estimated EC50 value = 0.044 nM (6.4 ng/mL). Bebtelovimab demonstrated antibody-dependent cell-mediated cytotoxicity on Jurkat reporter cells expressing Fc gamma RIIIa following engagement with target cells expressing spike protein. Bebtelovimab did not elicit complement-dependent cytotoxicity activity in cell-based assays.

       

      There is a potential risk of treatment failure due to the development of viral variants that are resistant to bebtelovimab. Health care providers should refer to the CDC website as well as information from state and local health authorities regarding reports of viral variants of importance in their region to guide treatment decisions. Data from non-clinical studies have shown a 5-fold or greater reduction in susceptibility to bebtelovimab of viral variants with the following substitutions: K444E (more than 862-fold), K444N (more than 1,901-fold), K444Q (208-fold), K444T (more than 1,814-fold), V445A (111-fold), V445F (369-fold), V445G (more than 730-fold), G446D (69-fold), G446R (7-fold), G446V (8-fold), P499H (more than 1,606-fold), P499R (more than 1,870-fold), and P499S (25-fold). In the context of Delta spike protein, G446V substitution had reduced susceptibility of 16.4-fold.

       

      Bebtelovimab pseudotyped virus-like particle (VLP) neutralization data for SARS-CoV-2 spike protein variants are as follows:

      • United Kingdom B.1.1.7 variant (Alpha):
        • Key substitution: N501Y
        • less than 5-fold reduced susceptibility
      • South Africa B.1.351 variant (Beta):
        • Key substitutions: K417N + E484K + N501Y
        • less than 5-fold reduced susceptibility
      • Brazil P.1 variant (Gamma):
        • Key substitutions: K417T + E484K + N501Y
        • less than 5-fold reduced susceptibility
      • India B.1.617.2/AY.3 variant (Delta):
        • Key substitutions: L452R + T478K
        • less than 5-fold reduced susceptibility
      • India AY.1/AY.2 (B.1.617.2 sublineages) variant (Delta +K417N):
        • Key substitutions: L452R + T478K + K417N
        • less than 5-fold reduced susceptibility
      • California B.1.427/B.1.429 variant (Epsilon):
        • Key substitution: L452R
        • less than 5-fold reduced susceptibility
      • New York B.1.526 variant (Iota):
        • Key substitution: E484K (not all New York B.1.526 isolates harbored the E484K substitution)
        • less than 5-fold reduced susceptibility
      • India B.1.617.1 variant (Kappa):
        • Key substitution: L452R + E484Q
        • less than 5-fold reduced susceptibility
      • Peru C.37 variant (Lambda):
        • Key substitutions: L452Q + F490S
        • less than 5-fold reduced susceptibility
      • Columbia B.1.621 variant (Mu):
        • Key substitutions: R346K + E484K + N501Y
        • 5.3-fold reduced susceptibility
      • South Africa B.1.1.529/BA.1 variant (Omicron [BA.1]):
        • Key substitutions: G339D + S371L + S373P + S375F + K417N + N440K + G446S + S477N + T478K + E484A + Q493R + G496S + Q498R + N501Y + Y505H
        • less than 5-fold reduced susceptibility
      • South Africa BA.1.1 variant (Omicron [+ R346K]):
        • Key substitutions: G339D + R346K + S371L + S373P + S375F + K417N + N440K + G446S + S477N + T478K + E484A + Q493R + G496S + Q498R + N501Y + Y505H
        • less than 5-fold reduced susceptibility
      • South Africa BA.2 variant (Omicron [BA.2]):
        • Key substitutions: G339D + S371F + S373P + S375F + T376A + D405N + R408S + K417N + N440K + S477N + T478K + E484A + Q493R + Q498R + N501Y + Y505H
        • less than 5-fold reduced susceptibility
      • United States BA.2.12.1 (Omicron [BA.2 + L452Q]):
        • Key substitutions: G339D + S371F + S373P + S375F + T376A + D405N + R408S + K417N + N440K + S477N + T478K + E484A + Q493R + Q498R + N501Y + Y505H + L452Q
        • less than 5-fold reduced susceptibility
      • India BA.2.75 (Omicron [BA.2 + D339H, G446S, N460K, R493Q]
        • Key substitutions: G339D + S371F + S373P + S375F + T376A + D405N + R408S + K417N + N440K + S477N + T478K + E484A + Q493R + Q498R + N501Y + Y505H + D339H + G446S + N460K + R493Q
        • less than 5-fold reduced susceptibility
      • India BA.2.75.2 (Omicron [BA.2.75 + R346T + F486S]
        • Key substitutions: G339D + S371F + S373P + S375F + T376A + D405N + R408S + K417N + N440K + S477N + T478K + E484A + Q493R + Q498R + N501Y + Y505H + D339H + G446S + N460K + R493Q + R346T + F486S
        • less than 5-fold reduced susceptibility
      • South Africa BA.4/BA.5 (Omicron [BA.4/BA.5]):
        • Key substitutions: G339D + S371F + S373P + S375F + T376A + D405N + R408S + K417N + N440K + L452R + S477N + T478K + E484A + F486V + Q498R + N501Y + Y505H
        • less than 5-fold reduced susceptibility
      • United States/Belgium BA.4.6/BF.7 (Omicron [BA.4 + R346T])
        • Key substitutions: G339D + S371F + S373P + S375F + T376A + D405N + R408S + K417N + N440K + L452R + S477N + T478K + E484A + F486V + Q498R + N501Y + Y505H + R346T
        • less than 5-fold reduced susceptibility
      • Nigeria BQ.1 (Omicron [BA.5 + K444T + N460K])
        • Key substitutions: G339D + S371F + S373P + S375F + T376A + D405N + R408S + K417N + N440K + L452R + S477N + T478K + E484A + F486V + Q498R + N501Y + Y505H + K444T + N460K
        • more than 672-fold reduced susceptibility; unlikely to be active against this variant
      • Multiple countries BQ.1.1 (Omicron [BA.5 + R346T + K444T + N460K])
        • Key substitutions: G339D + S371F + S373P + S375F + T376A + D405N + R408S + K417N + N440K + L452R + S477N + T478K + E484A + F486V + Q498R + N501Y + Y505H + R346T + K444T + N460K
        • more than 672-fold reduced susceptibility; unlikely to be active against this variant

       

      In authentic SARS-CoV-2 assays, bebtelovimab retained activity (less than 5-fold reduction) against variant virus isolates from the Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2/AY.3), Omicron (B.1.1.529/BA.1), Omicron [+R346K] (BA.1.1), Omicron BA.2, Omicron BA.2 [+L452Q] (BA.2.12.1), Omicron BA.2 [+D339H, G446S, N460K, R493Q] (BA.2.75), Omicron BA.4, Omicron BA.4 [+R346T] (BA.4.6), and Omicron BA.5 lineages; as well as SARS-CoV-2 (USA/WA/1/2020 isolate) engineered to express the L452R substitution present in the Epsilon (B.1.427/B.1.429) lineage or the E484K substitution present in the Iota (B.1.526) lineage.[67385]

      Revision Date: 11/07/2022, 09:48:23 AM

      References

      67385 - Food and Drug Administration (FDA). Fact sheet for healthcare providers: Emergency use authorization (EUA) for bebtelovimab. Retrieved November 4, 2022. Available on the World Wide Web at https://www.fda.gov/media/156152/download?utm_medium=email&utm_source=govdelivery.

      Pharmacokinetics

      Bebtelovimab is administered by intravenous injection. Once in systemic circulation, the mean steady state volume of distribution is 4.61 L. Bebtelovimab is expected to be degraded into small peptides and component amino acids via catabolic pathways similarly to endogenous IgG antibodies. The mean clearance and elimination half-life for bebtelovimab are 0.014 L/hour and 11.5 days, respectively.[67385]

       

      Affected cytochrome P450 isoenzymes: none

      Route-Specific Pharmacokinetics

      Intravenous Route

      Following administration of a single dose of 175 mg bebtelovimab, the mean Cmax and AUC were 59.9 mcg/mL and 539 mcg x day/mL, respectively. The mean drug concentration on day 29 was 4.55 mcg/mL.[67385]

      Special Populations

      Hepatic Impairment

      Based on population pharmacokinetic analysis, there is no significant difference in pharmacokinetics of bebtelovimab in patients with mild hepatic impairment compared to patients with normal hepatic function. Bebtelovimab has not been studied in patients with moderate or severe hepatic impairment.[67385]

      Renal Impairment

      Renal impairment is not expected to impact the pharmacokinetics of bebtelovimab, since monoclonal antibodies with molecular weight more than 69 kDa are known not to undergo renal elimination. Similarly, dialysis is not expected to impact the pharmacokinetics of bebtelovimab.[67385]

      Geriatric

      Based on population pharmacokinetic analysis, there is no difference in the pharmacokinetics of bebtelovimab in geriatric patients as compared to younger patients.[67385]

      Gender Differences

      Based on population pharmacokinetic analysis, gender does not affect the pharmacokinetics of bebtelovimab.[67385]

      Ethnic Differences

      Based on population pharmacokinetic analysis, ethnicity does not affect the pharmacokinetics of bebtelovimab.[67385]

      Obesity

      Body weight has no clinically relevant effect on the pharmacokinetics of bebtelovimab in adults with COVID-19 who weigh between 45 kg to 194 kg.[67385]

      Other

      Disease Severity

      Based on population pharmacokinetic analysis, baseline viral load does not affect the pharmacokinetics of bebtelovimab.[67385]

      Revision Date: 06/20/2022, 03:52:17 PM

      References

      67385 - Food and Drug Administration (FDA). Fact sheet for healthcare providers: Emergency use authorization (EUA) for bebtelovimab. Retrieved November 4, 2022. Available on the World Wide Web at https://www.fda.gov/media/156152/download?utm_medium=email&utm_source=govdelivery.

      Pregnancy/Breast-feeding

      pregnancy

      Bebtelovimab should be administered during pregnancy only if the potential benefit outweighs the potential risk for the mother and fetus. There are insufficient data regarding the use of bebtelovimab 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, bebtelovimab has 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. There are risks to the mother and fetus associated with untreated COVID-19 in pregnancy. There are also risks of severe hypersensitivity and infusion-related reactions following administration of bebtelovimab, including in pregnant patients. Pregnant patients who develop severe hypersensitivity or infusion-related reactions should be managed appropriately, including obstetrical care.[67385]

      breast-feeding

      There are no data regarding the presence of bebtelovimab 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 developmental and health benefits of breast-feeding along with the mother's clinical need for bebtelovimab and any potential adverse effects on the breast-fed infant from bebtelovimab or the underlying maternal condition. Lactating mothers are advised to follow practices according to clinical guidelines to avoid exposing the infant to COVID-19.[67385]

      Revision Date: 06/20/2022, 01:52:14 PM

      References

      67385 - Food and Drug Administration (FDA). Fact sheet for healthcare providers: Emergency use authorization (EUA) for bebtelovimab. Retrieved November 4, 2022. Available on the World Wide Web at https://www.fda.gov/media/156152/download?utm_medium=email&utm_source=govdelivery.

      Interactions

      There are no drug interactions associated with Bebtelovimab products.
      Revision Date: 02/15/2022, 02:27:00 AM

      References

      Monitoring Parameters

      • laboratory monitoring not necessary

      US Drug Names

      • Bebtelovimab
      ;