bamlanivimab and etesevimab (Investigational)

Brand and Other Names:
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

IV solution

  • Distributed as individual vials
  • Bamlanivimab: 700mg/20mL (35mg/mL)
  • Etesevimab: 700mg/20mL (35mg/mL)

COVID-19 (EUA)

Treatment

  • Emergency use authorization (EUA) issued by the FDA for treatment of mild-to-moderate coronavirus disease 2019 (COVID-19) in patients aged ≥12 years who weigh ≥40 kg with positive results of direct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral testing, and who are at high risk for progressing to severe COVID-19 and/or hospitalization
  • Administer bamlaniviamb and etesevimab only in combination; monotherapy less effective owing to virologic resistance
  • Etesevimab 1400 mg plus bamlanivimab 700 mg as a single IV infusion
  • Administer as soon as possible after positive viral test for SARS-CoV-2 and within 10 days of symptom onset in patients at high risk for progressing to severe COVID-19 and/or hospitalization

Post-exposure prophylaxis

  • September 16, 2021: EUA issued by the FDA for postexposure prophylaxis of COVID-19 in adults and pediatric individuals aged ≥12 years weighing ≥40 kg who are at high risk for progression to severe COVID-19, including hospitalization or death, and are:
  • Not fully vaccinated or are not expected to mount an adequate immune response AND
    • Were exposed to an infected individual with SARS-CoV-2 consistent with close contact criteria per Centers for Disease Control and Prevention (CDC), OR
    • Are at high risk of exposure to an individual infected with SARS-CoV-2 because of occurrence of SARS-CoV-2 infection in other individuals in the same institutional setting (eg, nursing homes, prisons)
  • NOTE: Not authorized for preexposure prophylaxis to prevent COVID-19 before being exposed to the SARS-CoV-2 virus – only after exposure
  • Etesevimab 1400 mg plus bamlanivimab 700 mg as a single IV infusion together as soon as possible following exposure
  • Fully vaccinated definition
    • 2-dose vaccine series: 2 weeks after second vaccine dose (eg, Pfizer or Moderna mRNA vaccines)
    • Single vaccine series: 2 weeks after a single-dose vaccine (eg, Johnson & Johnson’s Janssen vaccine)
  • Close contact with infected individual (CDC definition)
    • Being within 6 feet for a total of >15 minutes
    • Providing care at home to someone who is sick
    • Having direct physical contact (eg, hugging, kissing)
    • Sharing eating or drinking utensils
    • Being exposed to respiratory droplets from an infected person (eg, sneezing, coughing)

Distribution

  • August 27, 2021: Distribution and use resumed in certain US states following a 2 month pause nationwide in which recent data shows the combined frequency of variants resistant to bamlanivimab and etesevimab administered together is less than or equal to 5%
  • As of September 15, 2021, use authorized in all US states and territories

Dosage Modifications

Renal impairment

  • Mild, moderate, or severe: No dose adjustment required

Hepatic impairment

  • Mild: No dose adjustment required
  • Moderate or severe: Not studied

Dosing Considerations

Circulating SARS-CoV-2 viral variants may be associated with resistance to monoclonal antibodies

Limitations of use

  • Benefit of treatment not observed in patients hospitalized due to COVID-19
  • Monoclonal antibodies may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high-flow oxygen or mechanical ventilation
  • Not authorized for use in states, territories, and US jurisdictions in which the combined frequency of variants resistant to bamlanivimab and etesevimab exceeds 5%
  • Not authorized for use in patients
    • Who are hospitalized due to COVID-19, OR
    • Who require oxygen therapy due to COVID-19, OR
    • Who require an increase in baseline oxygen flow rate due to COVID-19 in those on long-term oxygen therapy due to underlying non-COVID-19–related comorbidity

Patient selection

Other medical conditions or factors (for example, race or ethnicity) may also placeindividual patients at high risk for progression to severe COVID-19 and authorizationof bamlanivimab and etesevimab under the EUA is not limited to the medical conditions or factors listed below

  • Medical conditions or other factors placing patients at higher risk for progressing to severe COVID-19
    • Older age (eg, ≥65 yr)
    • Obesity/overweight (BMI ≥25 kg/m2 [adults]; BMI ≥85th percentile for age/gender based on CDC growth charts [if aged 12-17 yr])
    • Pregnancy
    • Chronic kidney disease
    • Diabetes
    • Immunosuppressive disease or immunosuppressive treatment
    • Cardiovascular disease (including congenital heart disease) or hypertension
    • Chronic lung diseases (eg, COPD, moderate-to-severe asthma, interstitial lung disease, cystic fibrosis, pulmonary hypertension)
    • Sickle cell disease
    • Neurodevelopmental disorders (eg, cerebral palsy) or other conditions that confer medical complexity (eg, genetic or metabolic syndromes, severe congenital anomalies)
    • Having a medical-related technological dependence (eg, tracheostomy, gastrostomy, positive pressure ventilation [not related to COVID 19])
    • EUA is not limited to the medical conditions or factors listed above; for additional information on medical conditions and factors associated with increased risk for progression to severe COVID, see the CDC website

Dosage Forms & Strengths

IV solution

  • Distributed as individual vials
  • Bamlanivimab: 700mg/20mL (35mg/mL)
  • Etesevimab: 700mg/20mL (35mg/mL)

COVID-19 (EUA)

Treatment

  • Emergency use authorization (EUA) issued by the FDA for treatment of mild-to-moderate coronavirus disease 2019 (COVID-19) in patients aged ≥12 years who weigh ≥40 kg with positive results of direct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral testing, and who are at high risk for progressing to severe COVID-19 and/or hospitalization
  • Administer bamlaniviamb and etesevimab only in combination; monotherapy less effective owing to virologic resistance
  • Etesevimab 1400 mg plus bamlanivimab 700 mg as a single IV infusion
  • Administer as soon as possible after positive viral test for SARS-CoV-2 and within 10 days of symptom onset in patients at high risk for progressing to severe COVID-19 and/or hospitalization

Post-exposure prophylaxis

  • September 16, 2021: EUA issued by the FDA for postexposure prophylaxis of COVID-19 in adults and pediatric individuals aged ≥12 years weighing ≥40 kg who are at high risk for progression to severe COVID-19, including hospitalization or death, and are:
  • Not fully vaccinated or are not expected to mount an adequate immune response AND
    • Were exposed to an infected individual with SARS-CoV-2 consistent with close contact criteria per Centers for Disease Control and Prevention (CDC), OR
    • Are at high risk of exposure to an individual infected with SARS-CoV-2 because of occurrence of SARS-CoV-2 infection in other individuals in the same institutional setting (eg, nursing homes, prisons)
  • NOTE: Not authorized for preexposure prophylaxis to prevent COVID-19 before being exposed to the SARS-CoV-2 virus – only after exposure
  • Etesevimab 1400 mg plus bamlanivimab 700 mg as a single IV infusion together as soon as possible following exposure
  • Fully vaccinated definition
    • 2-dose vaccine series: 2 weeks after second vaccine dose (eg, Pfizer or Moderna mRNA vaccines)
    • Single vaccine series: 2 weeks after a single-dose vaccine (eg, Johnson & Johnson’s Janssen vaccine)
  • Close contact with infected individual (CDC definition)
    • Being within 6 feet for a total of >15 minutes
    • Providing care at home to someone who is sick
    • Having direct physical contact (eg, hugging, kissing)
    • Sharing eating or drinking utensils
    • Being exposed to respiratory droplets from an infected person (eg, sneezing, coughing)

Distribution

  • August 27, 2021: Distribution and use resumed in certain US states following a 2 month pause nationwide in which recent data shows the combined frequency of variants resistant to bamlanivimab and etesevimab administered together is less than or equal to 5%
  • As of September 15, 2021, use authorized in all US states and territories

Dosage Modifications

Renal impairment

  • Mild, moderate, or severe: No dose adjustment required

Hepatic impairment

  • Mild: No dose adjustment required
  • Moderate or severe: Not studied

Dosing Considerations

Circulating SARS-CoV-2 viral variants may be associated with resistance to monoclonal antibodies

Limitations of use

  • Benefit of treatment not observed in patients hospitalized due to COVID-19
  • Monoclonal antibodies may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high-flow oxygen or mechanical ventilation
  • Not authorized for use in states, territories, and US jurisdictions in which the combined frequency of variants resistant to bamlanivimab and etesevimab exceeds 5%
  • Not authorized for use in patients
    • Who are hospitalized due to COVID-19, OR
    • Who require oxygen therapy due to COVID-19, OR
    • Who require an increase in baseline oxygen flow rate due to COVID-19 in those on long-term oxygen therapy due to underlying non-COVID-19–related comorbidity

Patient selection

Other medical conditions or factors (for example, race or ethnicity) may also placeindividual patients at high risk for progression to severe COVID-19 and authorizationof bamlanivimab and etesevimab under the EUA is not limited to the medical conditions or factors listed below

  • Medical conditions or other factors placing patients at higher risk for progressing to severe COVID-19
    • BMI ≥85th percentile for age/gender based on CDC growth charts (if aged 12-17 yr)
    • Pregnancy
    • Chronic kidney disease
    • Diabetes
    • Immunosuppressive disease or immunosuppressive treatment
    • Cardiovascular disease (including congenital heart disease) or hypertension
    • Chronic lung diseases (eg, COPD, moderate-to-severe asthma, interstitial lung disease, cystic fibrosis, pulmonary hypertension)
    • Sickle cell disease
    • Neurodevelopmental disorders (eg, cerebral palsy) or other conditions that confer medical complexity (eg, genetic or metabolic syndromes, severe congenital anomalies)
    • Having a medical-related technological dependence (eg, tracheostomy, gastrostomy, positive pressure ventilation [not related to COVID 19])
    • EUA is not limited to the medical conditions or factors listed above; for additional information on medical conditions and factors associated with increased risk for progression to severe COVID, see the CDC website
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Adverse Effects

EUA requirement

Completion of FDA MedWatch Form to report all medication errors and serious adverse events is mandatory

1-10%

Infusion-related reactions (1.1%)

<1%

Nausea (<1%)

Dizziness (<1%)

Pruritus (<1%)

Anaphylaxis (0.07%)

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Warnings

Contraindications

None

Cautions

Hypersensitivity

  • Potential for serious hypersensitivity reaction, including anaphylaxis
  • If signs and symptoms occur, immediately discontinue IV infusion and initiate appropriate medications and/or supportive care
  • Infusion-related reactions reported, including fever, difficulty breathing, reduced oxygen saturation, chills, fatigue, arrhythmia (eg, atrial fibrillation, sinus tachycardia, bradycardia), chest pain or discomfort, weakness, altered mental status, nausea, headache, bronchospasm, hypotension, angioedema, throat irritation, rash including urticaria, pruritus, myalgia, dizziness, diaphoresis

Clinical worsening after administration

  • Clinical worsening of COVID-19 after administration reported; signs or symptoms may include fever, hypoxia or increased respiratory difficulty, arrhythmia (eg, atrial fibrillation, sinus tachycardia, bradycardia), fatigue, and altered mental status
  • Some of these events required hospitalization
  • Unknown if these events were related to monoclonal antibodies or were due to progression of COVID-19

Severe COVID-19

  • Treatment benefit not observed in patients hospitalized due to COVID-19
  • Monoclonal antibodies may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high-flow oxygen or mechanical ventilation
  • Not authorized for use in patients
    • Who are hospitalized due to COVID-19, OR
    • Who require oxygen therapy due to COVID-19, OR
    • Who require an increase in baseline oxygen flow rate due to COVID-19 in those on long-term oxygen therapy due to underlying non-COVID-19–related comorbidity

Viral variants

  • Circulating SARS-CoV-2 viral variants may be associated with resistance to monoclonal antibodies
  • Prescribing clinicians should consider prevalence of resistant variants in their area
  • Health care providers should review antiviral resistance information provided by state and local health departments
  • Variant proportions circulating in the US can be monitored at the CDC website

Fold reduction in susceptibility

  • Pseudotyped virus-like particle neutralization data of etesevimab plus bamlanivimab together (September 2021) B.1.1.7 - Alpha (UK origin): No change
    • B.1.351 - Beta (South Africa origin): 431
    • P.1 - Gamma (Brazil origin): 252
    • B.1.617.2/AY.3 - Delta (India origin): No change
    • B.1.617.2 AY1/AY.2 – Delta sublineages (India origin): 1,235
    • B.1.427/B.1.429 - Epsilon (California origin): 9
    • B.1.526 - Iota (New York origin): 30
    • B.1.517.1 - Kappa (India origin): 6
    • C.37 - Lambda (Peru origin): No change
    • B.1.621 - Mu (Colombia origin): 116
  • Authentica SARS-CoV-2 neutralization data of etesevimab plus bamlanivimab together (September 2021)
    • B.1.1.7 - Alpha (UK origin): No change
    • B.1.351 - Beta (South Africa origin): >325
    • B.1.617.2/AY.3 - Delta (India origin): No change
    • B.1.427/B.1.429 - Epsilon (California origin): 11
    • B.1.526 (New York origin): 11

Drug interaction overview

  • Not renally excreted or metabolized by CYP450 enzymes
  • Interactions with concomitant renally excreted drugs or drugs that are CYP450 substrates, inducers, or inhibitors are unlikely
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Pregnancy & Lactation

Pregnancy

Insufficient data to evaluate drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes

Use during pregnancy only if potential benefit outweighs the potential risk for the mother and fetus

Pregnancy is a risk factor for severe COVID-19 disease

No dosage adjustment recommended by the manufacturer

Lactation

Data are unknown regarding presence in human or animal milk, effects on breastfed infants, or effects on milk production

Maternal IgG is known to be present in human milk

Breastfeeding females with COVID-19 should follow practices according to clinical guidelines to avoid exposing the infant to COVID-19

No dosage adjustment recommended by the manufacturer

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

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Pharmacology

Mechanism of Action

Bamlaniviamb and etesevimab are recombinant neutralizing human IgG1-kappa monoclonal antibodies (mAb) to the spike protein of SARS-CoV-2, and are unmodified in the Fc region

Etesevimab and bamlanivimab bind to different but overlapping epitopes in the receptor-binding domain of the S-protein; using both antibodies together is expected to reduce the risk of viral resistance

Binding sites

  • Etesevimab binds to spike protein with a dissociation constant KD = 6.45 nM and blocks spike protein attachment to human ACE2 receptor with an IC50 value of 0.046 mcg/mL
  • Bamlanivimab binds to spike protein with a dissociation constant KD = 0.071 nM and blocks spike protein attachment to human ACE2 receptor with an IC50 value of 0.025 mcg/mL

Pharmacogenomics

Genotypic and phenotypic testing are ongoing to monitor for potential bamlanivimab resistance-associated spike variations in clinical trials

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Administration

IV Preparation

Remove drugs (2 vials etesevimab and 1 vial bamlanivimab) from refrigerator and allow drug to equilibrate to room temperature (~20 min) before preparation; do not expose to direct heat; do not shake

Inspect for particulate matter and discoloration; solution should appear clear to slightly opalescent and colorless to slightly yellow to brown

Dilution

  • Withdraw 20 mL from 1 bamlanivimab vial and 40 mL from 2 etesevimab vials and inject all 60 mL into a prefilled infusion bag (ie, 50-250 mL) containing 0.9% NaCl
  • Discard any product remaining in vials
  • Gently invert IV bag by hand ~10 times to mix; do not shake
  • Administer immediately after preparation; if unable to administer immediately, store according to directions

IV Administration

If solution refrigerated, allow to equilibrate to room temperature for ~20 minutes

Administer IV via pump or gravity according to size of infusion bag used

Infuse by PVC infusion set containing 0.20/0.22-micron in-line polyethersulfone (PES) filter

Attach infusion set to IV bag and prime infusion set

Owing to potential overfill of prefilled saline bags, administer entire infusion solution in bag to avoid underdosage

Flush line with 0.9% NaCl after infusion completed to ensure entire dose delivered

Discard unused product

Monitor during infusion and observe patients for at least 1 hr after infusion completed

Use of closed system transfer devices, elastomeric pumps, and pneumatic transport with bamlanivimab has not been studied

Infusion rates

  • Maximum infusion rate for all infusion bags: 310 mL/hr
  • 50-mL bag: Infuse over at least 21 min; maximum infusion rate 310 mL/hr
  • 100-mL bag: Infuse over at least 31 min; maximum infusion rate 310 mL/hr
  • 150-mL bag: Infuse over at least 41 min; maximum infusion rate 310 mL/hr
  • 250-mL bag (weight <50 kg): Infuse over at least 70 min; maximum infusion rate 266 mL/hr
  • 250-mL bag (weight ≥50 kg): Infuse over at least 60 min; maximum infusion rate 310 mL/hr

Storage

Preservative-free product

Unopened vials

  • Refrigerate at 2-8ºC (36-46ºF) in original carton to protect from light
  • Do not freeze, shake, or expose to direct light

Diluted solution

  • Refrigerate at 2-8ºC (36-46ºF) for up to 24 hr OR
  • Store at room temperature 20-25ºC (68-77ºF) for up to 7 hr
  • These storage times include the infusion time
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Images

No images available for this drug.
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Patient Handout

A Patient Handout is not currently available for this monograph.
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Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.