Tixagevimab + Cilgavimab

by Editorial Board last updated 2021-12-11 10:05:12.147709-05:00
Evusheld
  • EUA issued on 8 December 2021 for tixagevimab co-packaged with cilgavimab and administered together for the pre-exposure prophylaxis of COVID-19 in certain adults and pediatric individuals (≥12 years of age weighing ≥40 kg).  Of note, tixagevimab + cilgavimab is NOT approved for post-exposure prophylaxis nor as treatment of active SARS-CoV-2 infection.  
  • Authorization is only for individuals who are not currently infected with SARS-CoV-2 and who have not recently been exposed to an infected individual.
  • The EUA also requires that individuals either have a moderate to severely compromised immune system or a history of severe adverse reaction to vaccination.
  • In individuals who have received a COVID-19 vaccine, tixagevimab + cilgavimab should be administered at least two weeks after vaccination.
  • Tixagevimab 150 mg/1.5 mL IM (single dose) + Cilgavimab 150 mg/1.5 mL IM (single dose).
  • Administer the injections at different injection sites, preferably one in each of the gluteal muscles, one after the other.
  • Consider redosing every six months, but note that there are no safety and efficacy data available with repeat dosing.
  • 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.
  • ≥12 years of age, weighing ≥40 kg: same dosage as adults.
  • Renal impairment, including dialysis, is not expected to impact the pharmacokinetics of tixagevimab and cilgavimab.
  • The effect of hepatic impairment on the pharmacokinetics of tixagevimab and cilgavimab is not known.
  • 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.
  Tixagevimab Cilgavimab
Class IgG1 MoAb IgG1 MoAb
PK/PD Index  No data No data
Pharmaceutical
Preparation		  Injection Injection
Usual Adult Dose  150 mg IM 150 mg IM
Pregnancy Risk Summary
 No human data No human data
Food Effect1  N/A N/A
Absorption2 (%) 68.5 65.8
Tmax (days) 14.0 14.0
Peak Serum Level3
(μg/mL)		  16.5 15.3
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
AUCinf9
(μg*day/mL)		 2529 2133
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
  • 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.