Tixagevimab + Cilgavimab, Evusheld
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Tixagevimab + Cilgavimab, Evusheld
Evusheld
- Pre-exposure prophylaxis for COVID-19
- EUA issued on 8 December 2021 for tixagevimab co-packaged with cilgavimab and administered together for pre-exposure prophylaxis of COVID-19 in certain adults and pediatric individuals (≥12 years of age weighing ≥40 kg).
- 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.
- Review: JAMA 2022;327: 384
- For information on post-exposure prophylaxis, see Prevention of SARS-CoV-2 and for more information on treatment options, see the COVID-19 treatment.
- Tixagevimab 300 mg/1.5 mL IM (single dose) + Cilgavimab 300 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.