Tixagevimab + Cilgavimab, Evusheld

by Michael S. Saag, M.D. last updated 2023-02-07 19:28:48.049136-05:00 © Antimicrobial Therapy, Inc.
Evusheld

Usage and Dosing

  • The U.S. Food and Drug Administration (link here) revised the Emergency Use Authorization (EUA) for Evusheld (tixagevimab co-packaged with cilgavimab) to limit its use to when the combined frequency of non-susceptible SARS-CoV-2 variants nationally is less than or equal to 90%. Based on this revision, Evusheld is not currently authorized for use in the U.S. until further notice by the Agency.
    • NOT approved for post-exposure prophylaxis nor as treatment of active SARS-CoV-2 infection.
    • For information on post-exposure prophylaxis, see Prevention of SARS-CoV-2 and for more information on treatment options, see the COVID-19 treatment.

Adult Dose

  • Tixagevimab 300 mg/3 mL IM (single dose) + Cilgavimab 300 mg/3 mL IM (single dose).
  • Administer the injections at different injection sites, preferably one in each of the gluteal muscles, one after the other.
  • Repeat dosing every six months (EUA update June 2022).
  • Observe recipients for at least one hour after the injections.
  • As with any IM injection, administer with caution to individuals with thrombocytopenia or any coagulation disorder.

Pediatric Dose

  • ≥12 years of age, weighing ≥40 kg: same dosage as adults.

Renal Adjustment

  • Renal impairment, including dialysis, is not expected to impact the pharmacokinetics of tixagevimab and cilgavimab.

Hepatic Adjustment

  • The effect of hepatic impairment on the pharmacokinetics of tixagevimab and cilgavimab is not known.

Adverse Effects

  • Hypersensitivity reactions
  • In one of two ongoing phase 3 trials, there was a higher rate of cardiovascular serious adverse events (SAEs), including myocardial infarction (one fatality) and cardiac failure, in subjects who received tixagevimab + cilgavimab compared to placebo. All subjects who experienced cardiac SAEs had cardiac risk factors and/or a prior history of cardiovascular disease, and there was no clear temporal pattern. A causal relationship has not been established. There was no signal for cardiac toxicity or thrombotic events identified in the nonclinical studies.

Antimicrobial Spectrum

Pharmacology

  Tixagevimab Cilgavimab
Class IgG1 MoAb IgG1 MoAb
PK/PD Index  No data No data
Pharmaceutical
Preparation		  Injection Injection
Usual Adult Dose  300 mg IM 300 mg IM
Pregnancy Risk Summary
 No human data No human data
Food Effect1  N/A N/A
Absorption2 (%) 68.5 65.8
Tmax (days) 14.9 15.0
Peak Serum Level3
(μg/mL)		  21.9 20.3
Protein Binding
(%)		  No data No data
Average Serum
Half-life4		  87.9 days 82.9 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)		 7.7 L 8.7 L
AUC0-849
(μg*day/mL)		 1408 1307
CYP450, Transporter
Interactions		  None known None known
  • Notes:
    • 1 Adult preparations unless otherwise noted.
    • 2 Absorption from an IM site.
    • 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
      • Vss/F = Vd at steady state/oral bioavailability
    • 9 Area under the plasma concentration versus time curve

Major Drug Interactions

  • Tixagevimab and cilgavimab are not renally excreted or metabolized by CYP450 enzymes. Therefore, interactions with concomitant medications that are renally excreted or that are substrates, inducers, or inhibitors of CYP enzymes are unlikely.