Bamlanivimab + Etesevimab

by Douglas Black, Pharm.D. last updated 2022-11-28 11:20:28.384300-05:00 © Antimicrobial Therapy, Inc.

Usage and Dosing

  • Bamlanivimab and Etesevimab (Lilly) are neutralizing IgG1 monoclonal antibodies that bind to distinct but overlapping epitopes within the receptor binding domain of the spike protein of SARS-CoV-2. They are administered together as a single IV infusion. The information on this page reflects pre-Omicron data.
  • No activity vs. Omicron variant, hence, DO NOT USE.
  • Outpatient clinical trial data
    • BLAZE-1: N Engl J Med. 2020 Oct 28;NEJMoa2029849: Reduction in hospitalizations and ER visits for the bamlanivimab treated subjects (e.g., 1.6% in bamlanivimab recipients vs 6.3% Placebo), more rapid improvement in symptoms with bamlanivimab and a favorable safety profile. There were no deaths in the trial.
    • No significant effect on viral load unless used in combination with a second monoclonal antibody, Etesevimab (JAMA. 2021 Jan 21;e210202).
  • Hospitalized patients  (ACTIV-3: N Engl J Med. 2020 Published Online Dec 22; DOI: 10.1056/NEJMoa2033130): Study terminated on the recommendation of the data and safety monitoring board due to futility in meeting the primary efficacy outcomes of time to sustained recovery and ordinal outcome scores at 5 days.
  • EUA updated December 2021 (fact sheet here):
    • For the treatment of mild to moderate COVID-19 in adults and pediatric patients, including neonates, with positive results of direct SARS-CoV-2 testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death.
    • For post-exposure prophylaxis of COVID-19 in adults and pediatric individuals, including neonates, who are at high risk for progression to severe COVID-19, including hospitalization or death, and a) are not fully vaccinated, or not expected to mount an adequate immune response to complete vaccination, and b) have had close contact with an individual infected with SARS-CoV-2 OR are at high risk of exposure to an individual infected with SARS-CoV-2.
  • Dosage for treatment and PEP is the same. PEP should be administered as soon as possible after exposure
  • Bamlanivimab and Etesevimab are not authorized for use in these situations:
    • In states, territories, and US jurisdictions where the combined frequency of resistant variants exceeds 5%.
    • In patients 2 years of age and older who are hospitalized due to COVID-19 (the authorization allows for young children of age 0 to 2 years who are hospitalized with mild to moderate COVID-19 at the time of treatment).
    • In patients, regardless of age, who require oxygen therapy and/or respiratory support due to COVID-19, or require an increase in baseline oxygen flow rate and/or respiratory support due to COVID-19 and are on chronic oxygen or respiratory support due to an underlying non-COVID-19 related comorbidity.
    • As pre-exposure prophylaxis.

Adult Dose

  • Co-administration as a single IV infusion:
    • Bamlanivimab 700 mg
    • Etesevimab 1400 mg
  • Preparation instructions: Add 20 mL of bamlanivimab (one vial) and 40 mL of etesevimab (two vials) to a selected bag of normal saline (see chart). Mix by gently inverting bag about ten times (do not shake).
  • Immediately administer IV through a 0.2/0.22 micron polyethersulfone filter. Administer the entire infusion solution due to overfill of prefilled bags. Flush tubing with NS afterward. Compatibility with other infusion solutions or medications is not known.
  • If necessary, the diluted solution may be stored in the refrigerator (2-8ºC) for up to 24 hours, or at room temperature (20-25ºC) for up to seven hours (including infusion time).
  • Dilution and administration instructions for adults and pediatric patients (<18 years, weight ≥40 kg):
Size of Prefilled NS Bag
(mL)
 Maximum infusion rate (mL/hr) Minimum infusion time (min)
50 310 21
100 310 31
150 310 41
250 (pt wt ≥50 kg)
310
60
250 (pt wt ≥40 to <50 kg)
266
70

Pediatric Dose

  • Weight-based dosage for patients <18 years:
Body weight Bamlanivimab Etesevimab
≥40 kg 700 mg 1400 mg
<20 to <40 kg 350 mg 700 mg
>12 to 20 kg 175 mg 350 mg
1 to 12 kg 12 mg/kg 24 mg/kg

 

  • Preparation instructions for patients weighing ≥40 kg: follow Adult Dose instructions above.
  • Preparation instructions for patients weighing <40 kg:
    • Doses do not require dilution.
    • Withdraw appropriate amounts of bamlanivimab and etesevimab (according to chart below) and inject into an empty infusion bag or draw into a disposable syringe.
  • Immediately administer doses over at least 16 minutes (see chart below). Use of a 0.2/0.22 micron polyethersulfone filter is recommended. Flush afterward with NS.
  • If necessary, may store in the refrigerator (2-8ºC) for up to 24 hours, or at room temperature (20-25ºC) for up to seven hours (including infusion time).
  • Recommended dosing, preparation, and administration instructions for undiluted bamlanivimab (BAM) and etesevimab (ETE) in pediatric patients <40 kg:
Body weight (kg) BAM/ETE dose Amount of BAM (mL) Amount of ETE (mL) Max infusion rate (mL/min)
>20 to <40 350 mg/700 mg 10 20 1.88
>12 to 20 175 mg/350 mg 5 10 0.94
>11 to 12 138 mg/276 mg 3.9 7.9 0.74
>10 to 11 126 mg/252 mg 3.6 7.2 0.68
>9 to 10 114 mg/228 mg 3.3 6.5 0.61
>8 to 9 102 mg/204 mg 2.9 5.8 0.54
>7 to 8 90 mg/180 mg 2.6 5.1 0.48
>6 to 7 78 mg/156 mg 2.2 4.5 0.42
>5 to 6 66 mg/132 mg 1.9 3.8 0.36
>4 to 5 54 mg/108 mg 1.5 3.1 0.29
>3 to 4 42 mg/84 mg 1.2 2.4 0.23
>2 to 3 30 mg/60 mg 0.9 1.7 0.16
>1.5 to 2 21 mg/42 mg 0.6 1.2 0.11
1 to 1.5 15 mg/30 mg 0.4 0.9 0.08

 

Renal Adjustment

  • No dosage adjustment recommended.

Hepatic Adjustment

  • No dosage adjustment recommended in mild hepatic impairment.
  • Not studied in patients with moderate or severe hepatic impairment.

Adverse Effects

  • Monitor patients during infusion and for at least one hour after infusion is complete.
  • Infusion-related adverse effects:
    • Fever, chills, nausea, headache, bronchospasm, hypotension, angioedema, throat irritation, rash including urticaria, pruritus, myalgia, dizziness
  • Serious hypersensitivity reaction, including anaphylaxis.

Antimicrobial Spectrum

Pharmacology

  Bamlanivimab Etesevimab
 Class IgG1 mAb IgG1 mAb 
PK/PD Index No data No data
Pharmaceutical
Preparation		 Injection Injection
Pregnancy
Category		 No human data No human data
Food Effect1 - -
Oral
Absorption2 (%)		 - -
Mean Serum Level3
(μg/mL)
196
(700 mg IV, SD)
504
(1400 mg IV, SD)
Protein Binding
(%)		 No data  No data
Average Serum
Half-life4		 17.6 days 25.1 days
Elimination Catabolized (similar to IgG) Catabolized (similar to IgG)
Biliary Penetration5 (%) No data  No data
CSF/Blood
Penetration6 (%)		 No data  No data
Therapeutic Levels in CSF7 No data No data
Volume of Distribution8
(Vd)		 5.58 (Vss) 4.36 L (Vss)
AUC
(μg*DAY/mL)		 No data No data
CYP450, Transporter
Interactions		 None known None known
  • Notes:
    • 1 Adult preparations unless otherwise noted.
    • 2 Absorption under optimal conditions.
    • 3 Total drug; adjust for protein binding to determine free drug concentration.
      • SD = after single dose
      • SS = steady state after multiple doses
    • 4 Assumes CrCl > 80 mL/min
    • 5 Peak concentration in bile/peak concentration in serum x 100
    • 6 CSF levels with inflammation
    • 7 Judgment based on drug dose & organism susceptibility. CSF concentration ideally ≥10x above MIC.
    • 8 Volume of Distribution (Vd):
      • V/F = Vd/oral bioavailability
      • Vss = Vd at steady state

Major Drug Interactions

  • No clinically significant interactions known.

Comments

  • Product availability: single-dose vials (bamlanivimab 700 mg/20 mL, etesevimab 700 mg/20 mL).
  • Storage: refrigerate unopened vials at 2-8°C, protected from light. Allow to equilibrate to room temperature for 20 minutes before preparation. Do not shake vials. Do not expose to direct heat.
  • Product usually administered at an infusion therapy center.
  • Initiate therapy as early as possible in the course of COVID infection; ideally within days of onset of symptoms (preferably <5 days); can be effective up to 8-10 days after onset of symptoms but outcomes not as good compared to earlier initiation; therefore, all individuals who develop COVID-like symptoms should be tested for SARS-CoV-2 as soon as possible after onset of symptoms.  Those who test positive and who are eligible for BAM-ETES should receive the product within a day or two after testing positive.