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Bamlanivimab

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 or requiring hospitalization

    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:

    • Body mass index (BMI) greater than or equal to 35
    • Chronic kidney disease
    • Diabetes
    • Immunosuppressive disease or receiving immunosuppressive therapy
    • 65 years or older
    • 55 years or older AND have:
      • Cardiovascular disease OR
      • Hypertension OR
      • Chronic obstructive pulmonary disease (COPD) or other chronic respiratory disease
    • 12 to 17 years of age AND have:
      • BMI greater than or equal to 85th percentile for age and gender based on CDC growth charts OR
      • Sickle cell disease OR
      • Congenital or acquired heart disease OR
      • Neurodevelopmental disorder (e.g., cerebral palsy) OR
      • Medical-related technological dependency (e.g., tracheostomy, gastrostomy, positive pressure ventilation not related to COVID-19) OR
      • Asthma, restrictive airway, or other chronic respiratory disease that requires daily medication to control

    NOTE: Bamlanivimab 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.[66100]

    Intravenous dosage

    Adults weighing 40 kg or more

    700 mg via a single intravenous infusion over at least 60 minutes. Administer the infusion as soon as possible after the positive test for SARS-CoV-2 and within 10 days of symptom onset.[66100]

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

    700 mg via a single intravenous infusion over at least 60 minutes. Administer the infusion as soon as possible after the positive test for SARS-CoV-2 and within 10 days of symptom onset.[66100]

    Therapeutic Drug Monitoring

    Maximum Dosage Limits

    • Adults <p><em>40 kg or more: </em>700 mg IV.</p> <p><em>less than 40 kg:</em> Use not authorized.</p>
    • Geriatric <p><em>40 kg or more: </em>700 mg IV.</p> <p><em>less than 40 kg:</em> Use not authorized.</p>
    • Adolescents <p><em>40 kg or more: </em>700 mg IV.</p> <p><em>less than 40 kg:</em> Use not authorized.</p>
    • Children <p><em>12 years and weighing 40 kg or more: </em>700 mg IV.</p> <p><em>12 years and weighing less than 40 kg:</em> Use not authorized.</p> <p><em>1 to 11 years:</em> Use not authorized.</p>
    • Infants <p>Use not authorized.</p>
    • Neonates <p>Use not authorized.</p>

    Patients with Hepatic Impairment Dosing

    No dosage adjustments are needed for patients with mild hepatic impairment. Treatment of 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: 11/11/2020, 10:42:30 AM

    References

    66100 - Food and Drug Administration (FDA). Fact sheet for health care providers: emergency use authorization (EUA) of bamlanivimab. Retrieved November 10, 2020. Available on the World Wide Web at http://pi.lilly.com/eua/bamlanivimab-eua-factsheet-hcp.pdf.

    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

    Description/Classification

    Description

    Bamlanivimab is an investigational neutralizing human immunoglobulin G-1 (IgG1) monoclonal antibody with activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Bamlanivimab 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 (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 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.[66100] The National Institutes of Health (NIH) COVID-19 treatment guidelines state there are insufficient data to recommend either for or against the use of bamlanivimab in outpatients with mild to moderate COVID-19. However, the NIH emphasizes that the drug should NOT be considered standard of care, nor should it be used to treat hospitalized patients outside of a clinical trial. Due to the possibility of limited supply, the NIH recommends that health care providers prioritize use of the drug in patients at highest risk for COVID-19 progression and ensure communities most affected by COVID-19 have equitable access to bamlanivimab.[65314]

    Classifications

    • General Anti-infectives Systemic
      • Antivirals For Systemic Use
        • Antiviral Monoclonal Antibodies for SARS-CoV-2
    Revision Date: 11/19/2020, 11:20:40 AM

    References

    65314 - COVID-19 Treatment Guidelines Panel. Coronavirus Diseases 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Accessed November 18, 2020. Available at on the World Wide Web at: https://covid19treatmentguidelines.nih.gov/.66100 - Food and Drug Administration (FDA). Fact sheet for health care providers: emergency use authorization (EUA) of bamlanivimab. Retrieved November 10, 2020. Available on the World Wide Web at http://pi.lilly.com/eua/bamlanivimab-eua-factsheet-hcp.pdf.

    Administration Information

    General Administration Information

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

     

    NOTE: Bamlanivimab 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 bamlanivimab
    • The significant known and potential risks and benefits of 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, 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 bamlanivimab therapy within 7 calendar days from the onset of the event.[66100]

    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. Bamlanivimab is a clear to slightly opalescent and colorless to slightly yellow to slightly brown solution.[66100]

    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.
    • Remove the vial from refrigerated storage and allow it to equilibrate to room temperature (approximately 20 minutes). DO NOT expose the vial to direct heat.
    • Gently invert the vial by hand approximately 10 times. DO NOT shake.
    • Using a 250 mL prefilled 0.9% Sodium Chloride Injection bag, withdraw and discard 70 mL from the bag to obtain 180 mL of diluent.
    • Withdraw 20 mL of the bamlanivimab solution from the vial using an appropriately sized syringe. Discard any remaining product in the vial.
    • Transfer the 20 mL of bamlanivimab solution to the 0.9% Sodium Chloride Injection bag containing 180 mL of diluent to produce a total volume for infusion of 200 mL.
    • 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.[66100]

     

    Intravenous Infusion:

    • Obtain a polyvinyl chloride (PVC) infusion set containing a 0.20/0.22 micron in-line polyethersulfone (PES) filter.
    • Attach the infusion set to the IV infusion bag.
    • Prime the infusion set.
    • Administer over at least 60 minutes via pump or gravity.
    • Once the infusion is complete, flush the infusion line to ensure delivery of the required dose.
    • Clinically monitor patients during the infusion and for at least 1 hour after the infusion is complete.[66100]

    Clinical Pharmaceutics Information

    From Trissel's 2‚Ñ¢ Clinical Pharmaceutics Database

    Bamlanivimab

      Revision Date: 11/23/2020, 10:29:06 AMCopyright 2004-2020 by Lawrence A. Trissel. All Rights Reserved.

      References

      66100 - Food and Drug Administration (FDA). Fact sheet for health care providers: emergency use authorization (EUA) of bamlanivimab. Retrieved November 10, 2020. Available on the World Wide Web at http://pi.lilly.com/eua/bamlanivimab-eua-factsheet-hcp.pdf.

      Adverse Reactions

      Mild

      • diarrhea
      • dizziness
      • flushing
      • headache
      • nausea
      • pruritus
      • vomiting

      Severe

      • anaphylactoid reactions

      Moderate

      • infusion-related reactions

      Gastrointestinal adverse reactions that developed in patients treated with the recommended 700 mg dose of bamlanivimab during clinical trials included nausea (3%), diarrhea (1%), and vomiting (1%). The incidence of these reactions were similar to those observed in patients who received a placebo [nausea (4%), diarrhea (5%), vomiting (3%)] and those who received supratherapeutic doses (2,800 mg and 7,000 mg) of bamlanivimab [nausea (4% to 5%), diarrhea (2% to 7%), vomiting (1% to 3%)].[66100]

      Neurologic adverse reactions that developed in patients treated with the recommended 700 mg dose of bamlanivimab during clinical trials included dizziness (3%) and headache (3%). The incidence of these reactions were similar to those observed in patients who received a placebo [dizziness (2%), headache (2%)] and those who received supratherapeutic doses (2,800 mg and 7,000 mg) of bamlanivimab [dizziness (3%), headache (2%)].[66100]

      Pruritus was reported by 2% of patients treated with the recommended 700 mg dose of bamlanivimab during clinical trials. The incidence of pruritus was similar to those observed in patients who received a placebo (1%) and those who received supratherapeutic doses (2,800 mg and 7,000 mg) of bamlanivimab (3%).[66100]

      In ongoing, blinded trials, anaphylaxis or anaphylactoid reactions (n = 1) and serious infusion-related reactions (n = 1) have been reported during treatment with bamlanivimab. Both cases required treatment, and both resolved. In the BLAZE-1 trial, immediate non-serious hypersensitivity events were noted in 2% of bamlanivimab recipients and 1% of patients who received a placebo. The reported events included pruritus, flushing, hypersensitivity, and 1 case of facial swelling. All events resolved.[66100]

      Revision Date: 11/11/2020, 10:49:10 AM

      References

      66100 - Food and Drug Administration (FDA). Fact sheet for health care providers: emergency use authorization (EUA) of bamlanivimab. Retrieved November 10, 2020. Available on the World Wide Web at http://pi.lilly.com/eua/bamlanivimab-eua-factsheet-hcp.pdf.

      Contraindications/Precautions

      Absolute contraindications are italicized.

      • breast-feeding
      • infusion-related reactions
      • pregnancy

      Monoclonal antibodies, such as 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, 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.[66100]

      Infusion-related reactions have been observed during treatment with bamlanivimab. Signs and symptoms of these reactions include fever, chills, nausea, headache, bronchospasm, hypotension, angioedema, throat irritation, rash, urticaria, pruritus, myalgia, and dizziness. If an infusion-related reaction develops, consider slowing or stopping the infusion and administer appropriate medications and supportive care. Similarly, there is a potential for serious hypersensitivity reactions, including anaphylaxis, with bamlanivimab. 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.[66100]

      There are insufficient data regarding the use of 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, bamlanivimab has the potential to be transferred from the mother to the developing fetus. It is unknown if this potential in utero transfer of bamlanivimab provides any therapeutic benefit or risk to the fetus. According to the manufacturer, bamlanivimab should be administered during pregnancy only if the potential benefit outweighs the potential risk for the mother and fetus.[66100] The National Institutes of Health (NIH) COVID-19 treatment guidelines recommend that 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.[65314]

      There are no data regarding the presence of 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 practices according to clinical guidelines to avoid exposing the infant to COVID-19. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.[66100]

      Revision Date: 11/19/2020, 08:25:08 AM

      References

      65314 - COVID-19 Treatment Guidelines Panel. Coronavirus Diseases 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Accessed November 18, 2020. Available at on the World Wide Web at: https://covid19treatmentguidelines.nih.gov/.66100 - Food and Drug Administration (FDA). Fact sheet for health care providers: emergency use authorization (EUA) of bamlanivimab. Retrieved November 10, 2020. Available on the World Wide Web at http://pi.lilly.com/eua/bamlanivimab-eua-factsheet-hcp.pdf.

      Mechanism of Action

      Bamlanivimab is a recombinant human immunoglobulin G-1 (IgG1) monoclonal antibody used as an antiviral medication to target the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). By binding to the spike protein, bamlanivimab blocks the attachment of SARS-CoV-2 to the human ACE2 receptor. Bamlanivimab is a neutralizing antibody that, when bound to the target cell expressing the spike protein, demonstrates antibody-dependent cell-mediated cytotoxicity. It does not elicit complement-dependent cytotoxicity activity. The estimated 50% effective concentration (EC50) against SARS-CoV-2 in Vero cells is 0.03 mcg/mL and the estimated EC90 is 0.09 mcg/mL.[66100]

       

      There is a potential for treatment failure due to the development of viral variants that are resistant to bamlanivimab. Non-clinical studies have associated E484K, F490S, Q493R, and S494P amino acid substitutions in the spike protein receptor binding domain with reduced susceptibility to bamlanivimab. In the BLAZE-1 clinical trial, known bamlanivimab-resistant variants at baseline were observed in 1 of 375 patients (0.27%). In the same study, treatment-emergent variants were detected at spike protein amino acid positions E484, F490, and S494. The clinical significance of these substitutions is not known.[66100]

      Revision Date: 11/11/2020, 11:07:31 AM

      References

      66100 - Food and Drug Administration (FDA). Fact sheet for health care providers: emergency use authorization (EUA) of bamlanivimab. Retrieved November 10, 2020. Available on the World Wide Web at http://pi.lilly.com/eua/bamlanivimab-eua-factsheet-hcp.pdf.

      Pharmacokinetics

      Bamlanivimab is administered via intravenous infusion. Data regarding the pharmacokinetics of bamlanivimab are limited; however, the pharmacokinetic profile is expected to be consistent with the profile of other IgG1 monoclonal antibodies. Bamlanivimab is not metabolized by cytochrome P450 enzymes, nor is the drug renally excreted.[66100]

       

      Affected cytochrome P450 isoenzymes: none

      Special Populations

      Hepatic Impairment

      Based on population pharmacokinetic analysis, patients with mild hepatic impairment had approximately 20% higher clearance of bamlanivimab than patients with normal hepatic function. This information is statistically significant, but not clinically relevant. Bamlanivimab has not been studied in patients with moderate or severe hepatic impairment.[66100]

      Renal Impairment

      Bamlanivimab is not eliminated intact in the urine. The pharmacokinetics of bamlanivimab are not expected to be affected by renal function.[66100]

      Pediatrics

      The pharmacokinetics of bamlanivimab in pediatric patients have not been evaluated. Using 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.[66100]

      Geriatric

      Based on population pharmacokinetic analysis, age does not affect the pharmacokinetics of bamlanivimab.[66100]

      Gender Differences

      Based on population pharmacokinetic analysis, gender does not affect the pharmacokinetics of bamlanivimab.[66100]

      Ethnic Differences

      Based on population pharmacokinetic analysis, ethnicity does not affect the pharmacokinetics of bamlanivimab.[66100]

      Obesity

      Body weight has no clinically relevant effect on the pharmacokinetics of bamlanivimab in adults with COVID-19 who weigh between 41 kg to 173 kg.[66100]

      Other

      Disease Severity

      Based on population pharmacokinetic analysis, neither disease severity nor inflammation affects the pharmacokinetics of bamlanivimab.[66100]

      Revision Date: 11/11/2020, 11:01:34 AM

      References

      66100 - Food and Drug Administration (FDA). Fact sheet for health care providers: emergency use authorization (EUA) of bamlanivimab. Retrieved November 10, 2020. Available on the World Wide Web at http://pi.lilly.com/eua/bamlanivimab-eua-factsheet-hcp.pdf.

      Pregnancy/Breast-feeding

      pregnancy

      There are insufficient data regarding the use of 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, bamlanivimab has the potential to be transferred from the mother to the developing fetus. It is unknown if this potential in utero transfer of bamlanivimab provides any therapeutic benefit or risk to the fetus. According to the manufacturer, bamlanivimab should be administered during pregnancy only if the potential benefit outweighs the potential risk for the mother and fetus.[66100] The National Institutes of Health (NIH) COVID-19 treatment guidelines recommend that 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.[65314]

      breast-feeding

      There are no data regarding the presence of 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 practices according to clinical guidelines to avoid exposing the infant to COVID-19. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.[66100]

      Revision Date: 11/19/2020, 08:25:08 AM

      References

      65314 - COVID-19 Treatment Guidelines Panel. Coronavirus Diseases 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Accessed November 18, 2020. Available at on the World Wide Web at: https://covid19treatmentguidelines.nih.gov/.66100 - Food and Drug Administration (FDA). Fact sheet for health care providers: emergency use authorization (EUA) of bamlanivimab. Retrieved November 10, 2020. Available on the World Wide Web at http://pi.lilly.com/eua/bamlanivimab-eua-factsheet-hcp.pdf.

      Interactions

      There are no drug interactions associated with Bamlanivimab products.
      Revision Date: 11/11/2020, 02:38:00 AM

      References

      Monitoring Parameters

      • laboratory monitoring not necessary