Introduction
Evusheld (tixagevimab co-packaged with cilgavimab) is a long-acting monoclonal antibody combination developed by AstraZeneca for pre-exposure prophylaxis of COVID-19. It represents a significant advancement in protecting immunocompromised individuals who may not mount an adequate immune response to COVID-19 vaccination. The combination received Emergency Use Authorization (EUA) from the FDA in December 2021 for specific high-risk populations.
Mechanism of Action
Evusheld consists of two fully human monoclonal antibodies (tixagevimab and cilgavimab) derived from B-cells donated by convalescent patients who recovered from SARS-CoV-2 infection. These antibodies bind to non-overlapping epitopes on the receptor-binding domain of the SARS-CoV-2 spike protein with high affinity. This dual-target mechanism effectively neutralizes the virus by blocking its attachment to the human ACE2 receptor, thereby preventing viral entry into host cells. The antibodies have been engineered with a YTE mutation in the Fc region to extend their half-life approximately three to four times longer than conventional antibodies.
Indications
Evusheld is authorized for the pre-exposure prophylaxis of COVID-19 in adults and pediatric individuals (12 years of age and older weighing at least 40 kg) who:
- Are not currently infected with SARS-CoV-2 and have not had recent known exposure to an infected individual
- Have moderate to severe immune compromise due to a medical condition or immunosuppressive medications
- May not mount an adequate immune response to COVID-19 vaccination
- For whom COVID-19 vaccination is not recommended due to history of severe adverse reaction
Dosage and Administration
Standard dosing: 300 mg of tixagevimab and 300 mg of cilgavimab (total 600 mg) administered as two separate consecutive intramuscular injections Route: Intramuscular injection preferably in the gluteal muscles Frequency: Single dose for pre-exposure prophylaxis (repeat dosing may be considered every 6 months based on epidemiological factors and individual risk) Administration: Must be administered by a healthcare provider Special populations: No dosage adjustment recommended for renal or hepatic impairment Storage: Refrigerate at 2°C to 8°C in original carton to protect from lightPharmacokinetics
Absorption: Following IM administration, peak serum concentrations are achieved in approximately 7-14 days Distribution: Volume of distribution approximately 5-7 L for both components Metabolism: Expected to be degraded via proteolytic enzymes throughout the body similarly to endogenous IgG antibodies Elimination: Mean elimination half-life is approximately 90 days for both antibodies Excretion: Cleared via catabolic pathways in the reticuloendothelial systemContraindications
- History of severe hypersensitivity reaction, including anaphylaxis, to any component of Evusheld
- Current active SARS-CoV-2 infection
- Recent exposure to someone with SARS-CoV-2 infection (consider post-exposure prophylaxis alternatives)
Warnings and Precautions
Cardiac events: Monitor for clinical signs and symptoms of cardiac events, particularly in individuals with cardiovascular risk factors Hypersensitivity reactions: Anaphylaxis and other hypersensitivity reactions have been reported; appropriate medical support must be available during administration COVID-19 risk: Not a substitute for vaccination; individuals for whom COVID-19 vaccination is recommended should receive vaccination Viral variants: Effectiveness may be reduced against certain SARS-CoV-2 variants; consider current variant susceptibility data Duration of protection: Protection may decrease over time; consider repeat dosing based on individual risk factors and circulating variantsDrug Interactions
Immunosuppressants: Concurrent use may diminish the efficacy of Evusheld COVID-19 vaccines: Administration may interfere with the immune response to live virus vaccines; separate administration by appropriate timing Other monoclonal antibodies: Potential for interference with other monoclonal antibody therapies; clinical significance unknown No expected interactions with cytochrome P450 substrates, inhibitors, or inducersAdverse Effects
Common reactions (≥1%):- Injection site reactions (pain, erythema, induration)
- Fatigue
- Headache
- Nausea
- Diarrhea
- Hypersensitivity reactions including anaphylaxis
- Cardiac events (rare cases of myocardial infarction and heart failure reported in clinical trials)
- Bleeding events at injection site (in patients on anticoagulants)
Monitoring Parameters
- Signs and symptoms of hypersensitivity during and following administration
- Cardiac symptoms in patients with cardiovascular risk factors
- Signs and symptoms of COVID-19 infection
- Injection site reactions
- Adverse events for up to 24 hours post-administration
- Serum antibody levels in special circumstances (not routinely required)
Patient Education
- Evusheld is not a substitute for vaccination when vaccination is recommended
- Continue following all recommended infection prevention measures
- Seek immediate medical attention if symptoms of COVID-19 develop
- Report any cardiac symptoms (chest pain, shortness of breath, palpitations) promptly
- Inform healthcare providers about Evusheld administration when receiving medical care
- Understand that protection is not absolute and may decrease over time
- Be aware of potential side effects and report any concerning symptoms
References
1. FDA Emergency Use Authorization Fact Sheet for Evusheld. December 2021. 2. Levin MJ, et al. Intramuscular AZD7442 (Tixagevimab-Cilgavimab) for Prevention of COVID-19. NEJM. 2022;386:2188-2200. 3. AstraZeneca EVUSHELD™ (tixagevimab co-packaged with cilgavimab) prescribing information. 4. COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. 5. Dong J, et al. Genetic and structural basis for SARS-CoV-2 variant neutralization by a two-antibody cocktail. Nature Microbiology. 2021;6:1233-1244. 6. CDC Interim Clinical Considerations for COVID-19 Treatment in Outpatients.