Evusheld for pre-exposure prophylaxis of COVID-19
Evusheld for pre-exposure prophylaxis of COVID-19

Evusheld for pre-exposure prophylaxis of COVID-19

Evusheld has been shown to significantly reduce the risk of developing symptomatic COVID-19.

The FDA has approved the use of Evusheld for pre-exposure prophylaxis for the prevention of COVID-19 under an Emergency Use Authorization (EUA).1 Tixagevimab co-packaged with cilgavimab (Evusheld) is a SARS-CoV-2 spike protein-controlled attachment inhibitor.

EUA does not permit tixagevimab / cilgavimab for the treatment of COVID-19 or for the post-exposure prophylaxis of COVID-19.

Adults and children 12 years of age or older who weigh at least 40 kg may receive tixagevimab / cilgavimab. Individuals must not have COVID-19 or have been in contact with a person with COVID-19. They must be moderately to severely immunocompromised with an inadequate immune response to COVID-19 vaccination or unable to complete their vaccination series due to a serious side effect of a COVID-19 vaccine or other components.2

Tixagevimab / cilgavimab is not a substitute for any COVID-19 vaccinations in unvaccinated individuals who are able to receive and respond appropriately to COVID-19 vaccinations.

Clinical Studies

Phase 3 trial PROVENT, supports ERE. PROVENT is a randomized (2: 1), double-blind, placebo-controlled clinical trial studying the efficacy of tixagevimab / cilgavimab for pre-exposure to COVID-19.

All selected subjects had at least 1 increased risk factor for COVID-19, including age (over 60 years), comorbidity, or residential or occupational status. Of the 3441 patients receiving 150 mg tixagevimab plus 150 mg cilgavimab, only 8 (0.2%) developed symptomatic COVID-19. Seventeen (1.0%) of the 1731 patients receiving placebo developed symptomatic COVID-19. The results show a relative risk reduction of 77%.

Detailed results from the pre-exposure prophylaxis trial showed that treatment reduced the risk of developing symptomatic COVID-19 by 77% in the primary analysis and by 83% in the 6-month follow-up analysis compared to placebo. There were no cases of serious illness or COVID-19-related deaths in the tixagevimab / cilgavimab group during the 6-month follow-up.3

Mechanism of action

Tixagevimab and cilgavimab are both human immunoglobulin G1 (IgG1k) monoclonal antibodies. The antibodies are produced in Chinese hamster ovary cells via recombinant DNA technology.

In combination, tixagevimab and cilgavimab bind to the receptor binding domain of the nail protein and block its interaction with human ACE2 (SARS-CoV-2 receptor), preventing virus binding to the receptor.

Dosage and preparation

Tixagevimab / cilgavimab consists of 2 separate consecutive intramuscular injections of 300 mg tixagevimab and 300 mg cilgavimab. Currently, there are no recommendations for repeated doses. A qualified physician should prepare and administer both injections and monitor the patient for at least one hour after injections.

The provider must inspect the vials to ensure proper color and absence of particles prior to withdrawal. The solutions are colorless to pale yellow and clear to opalescent and must not be shaken.

Tixagevimab and cilgavimab are packaged separately in 150 mg / 1.5 ml (100 mg / ml) single-dose vials. The injection requires 2 vials of each medicine for a total of 3 ml (300 mg).

Providers must use a separate syringe for each medicine. Both products contain no preservatives, so they require immediate administration and must be discarded if not administered within 4 hours.

Administration

Providers should administer tixagevimab and cilgavimab as 2 separate, consecutive intramuscular injections. The provider should give the injections at different injection sites, preferably 1 in each gluteal region to account for the appropriate volume of 3 ml per injection.

A healthcare professional should monitor the patient for at least 1 hour after the injections. Patients who have received a COVID-19 vaccination should wait at least 2 weeks before receiving tixagevimab / cilgavimab.

Previous administration

Some people have initially received 150 mg of tixagevimab and 150 mg of cilgavimab from the previously approved dose. These patients should receive a second dose of 150 mg tixagevimab and 150 mg cilgavimab as soon as possible. All other persons should receive a starting dose of 300 mg tixagevimab and 300 mg cilgavimab.

Adverse events (AEs)

The most common side effects include headache, fatigue, and cough. Local reactions at the injection site, including pain, bruising of the skin, and soreness are possible.

Warnings and Precautions

A healthcare professional should monitor the patient for at least one hour after the injections in case of severe hypersensitivity reactions. This includes anaphylaxis, which may occur using IgG1 monoclonal antibody.

Providers should exercise caution when administering to patients with thrombocytopenia or other coagulation disorder. They should consider the benefit / risk balance of patients at high risk for cardiovascular adverse events, as clinical trials have reported a higher proportion of subjects who experienced cardiovascular adverse events.

Pregnancy and breastfeeding

There are insufficient data to assess a drug-associated risk of serious birth defects, miscarriage, or unwanted maternal or fetal outcomes.1 Patients should only use Evusheld during pregnancy if the potential benefit justifies the potential risk factors. It is not known whether tixagevimab or cilgavimab is present in breast milk.

About the author

Greta Staubly is a 2024 PharmD graduate at the University of Connecticut.

References

  1. Fact sheet for healthcare providers: Emergency use permit for Evusheld (tixagevimab packaged with cilgavimab). AstraZeneca. Opened March 7, 2022. https://den8dhaj6zs0e.cloudfront.net/50fd68b9-106b-4550-b5d0-12b045f8b184/6d1d5fea-2532-46e9-a1d4-1504f6dd41b2/6d1d5fea-2532-46e9-a1d4b502f_v.
  2. Prevention of SARS-CoV-2 infection. National Institutes of Health. Available March 7, 2022. https://www.covid19treatmentguidelines.nih.gov/overview/prevention-of-sars-cov-2/
  3. EVUSHELD ™ significantly protected against symptomatic COVID-19 for at least six months in PROVENT phase III trials in high-risk populations. AstraZeneca. April 20, 2022 https://finance.yahoo.com/news/evusheld-significantly-protected-against-symptomatic-221200107.html

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