Bamlanivimab + Etesevimab

by Douglas Black, Pharm.D. last updated 2021-02-11 19:27:28.375245-05:00 © Antimicrobial Therapy, Inc.
  • 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. Emergency Use is authorized for combination therapy for mild to moderate COVID-19 in adults and children (age ≥12 yrs and wt ≥40 kg) who are at risk for severe disease or hospitalization.
  • Early Use Authorization by FDA issued for Bamlanivimab on 10 Nov 2020; (Prescribing information here) and for Etesevimab on 9 Feb 2021 (EUA letter and FDA fact sheet). Specifically, EUA issued for those who are defined as high risk (defined as patients who meet at least one of the following criteria:
    • Body mass index (BMI) ≥35
    • Chronic kidney disease
    • Diabetes
    • Immunosuppressive disease
    • Age ≥65 years
    • Age ≥55 years and at least one of the following:
      • Cardiovascular disease
      • Hypertension
      • Chronic obstructive pulmonary disease/other chronic respiratory disease
    • Age 12-17 years and at least one of the following:
      • BMI ≥85th percentile for their age and gender based on CDC growth charts
      • Sickle cell disease
      • Congenital or acquired heart disease
      • Medical-related technological dependence, for example, tracheostomy, gastrostomy, or positive pressure ventilation (not related to COVID-19)
      • Asthma, reactive airway or other chronic respiratory disease that requires daily medication for control
  • Co-administration as a single IV infusion:
    • Bamlanivimab 700 mg
    • Etesevimab 1400 mg
  • Product availability: single-dose vials (bamlanivimab 700 mg/20 mL, etesevimab 700 mg/20 mL).
  • Remove one vial of bamlanivimab and two vials of etesevimab from the refrigerator, allow to equilibrate at room temperature for 20 minutes before preparing. Do not shake vials. 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). Administer through an IV line with a 0.20/0.22 micron polyethersulfone filter. Administer the entire infusion solution due to potential overfill of prefilled NS bags.
Size of Prefilled NS Bag (mL) Maximum infusion rate (mL/hr) Minimum infusion time (min)
50 310 (all patients) 21
100 310 (all patients) 31
150 310 (all patients) 41
250
310 (pt wt ≥50 kg)
266 (pt wt <50 kg)
60
70

 

  • The minimum infusion time is extended in patients weighing <50 kg using the 250 mL bag of NS to ensure safe use (endotoxin load).
  • Compatibility with other infusion solutions or medications is not known.
  • Administer the diluted infusion solution immediately. If this is not possible, 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).
  • ≥12 years of age, weight ≥40 kg: same as adult dose.
  • No adjustment recommended.
  • No adjustment recommended in mild hepatic impairment.
  • Not studied in patients with moderate or severe impairment.
  • 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.
  Bamlanivimab Etesevimab
 Class IgG1 mAb IgG1 mAb 
PK/PD Index No data No data
Pharmaceutical
Preparation
Injection Injection
Usual Dose
(Co-administer)
700 mg IV single infusion 1400 mg IV single infusion
Pregnancy
Category
No human data No human data
Food Effect1 Not applicable Not applicable
Oral
Absorption2 (%)
Not applicable  Not applicabale
Mean Serum Level3
(μg/mL)
196 (SD) 504 (SD)
Protein Binding
(%)
No data  No data
Average Serum
Half-life4
17.6 days 25.1 days
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)
2.87 L (central)
2.71 L (peripheral)
2.38 L (central)
1.98 L (peripheral)
AUC
(μg*DAY/mL)
No data No data
CYP450, Transporter
Interactions
No known interactions No known interactions
  • 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
  • No clinically significant interactions known.
  • Storage: refrigerate unopened vials at 2-8°C, protected from light. Allow to equilibrate to room temperature for 20 minutes before preparation. 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.