Generic Name

Evusheld

Mechanism

• Evusheld is a fixed‑ratio combination of two long‑acting monoclonal antibodies (tixagevimab + cilgavimab) that target the SARS‑CoV‑2 spike protein.
• The antibodies bind non‑overlapping epitopes on the receptor‑binding domain (RBD), blocking virus attachment to ACE2 receptors.
• By occupying the RBD, the drug neutralizes viruses and prevents cellular entry, providing passive immunity without requiring the host to mount an active immune response.

Pharmacokinetics

• Route: Subcutaneous (SC).
• Absorption: Rapid absorption; peak serum concentration (C_max) reached within ~1–2 days.
• Distribution: Restricted to the intravascular compartment; limited penetration into tissues.
• Half‑life: ~45 days (tixagevimab) and ~50 days (cilgavimab) owing to engineered Fc‑region mutations enhancing neonatal Fc receptor recycling.
• Metabolism: Proteolytic catabolism via the reticuloendothelial system, not CYP-mediated.
• Excretion: Catabolized peptides; negligible renal excretion.
• Drug interactions: No clinically relevant interactions identified; no CYP inhibition/induction.

Indications

• Pre‑exposure prophylaxis against COVID‑19 in adults and adolescents ≥ 12 years with:
• Immunocompromising conditions (e.g., HIV‑1 infection, cancer chemotherapy, organ transplantation) *or*
• Inability to mount an adequate immune response to SARS‑CoV‑2 vaccination.
• Reserved for patients who are vaccination‑ineligible or have hypogammaglobulinemia.

Contraindications

• Contraindications
• Known hypersensitivity to any component of Evusheld or to prior mAb therapies.
• Warnings
• Potential for anaphylactic reactions (monitor 15–30 min post‑injection).
• Emergence of resistance: circulating variants may reduce efficacy; ongoing surveillance required.
• Gastrointestinal immunoglobulin deficiency may alter pharmacokinetics.

Dosing

• Dose: 600 mg total (two 300 mg vials) administered once subcutaneously; recommended repeat dose after 6 months if ongoing prophylaxis is desired.
• Technique:
• Dilute each vial in 1 mL of sterile water for injection (if required).
• Inject into the anterolateral thigh; minimal pain expected.
• Do not mix the two antibodies in a single syringe unless pre‑mixed as supplied.
• Special populations: No dose adjustment needed for renal or hepatic impairment.
• Storage: 2–8 °C; protect from light; use within 24 h after reconstitution.

Adverse Effects

• Common (≥ 5%)
• Injection‑site reaction (pain, erythema, swelling)
• Headache
• Fatigue
• Arthralgia
• Serious (≤ 1%)
• Anaphylaxis or hypersensitivity reaction
• Dyspnea, angioedema requiring emergency care
• Gastrointestinal symptoms (rare)
• Monitoring for delayed immune reactions: check CBC, CRP if symptoms develop.

Monitoring

• Baseline labs: CBC, liver enzymes, renal panel (optional).
• Follow‑up:
• Clinical assessment for systemic allergic reactions.
• Periodic review for breakthrough SARS‑CoV‑2 infection.
• Consider anti‑drug antibody testing if therapeutic failure suspected.
• Immunogenicity: Detectable anti‑antibody responses typically low; significant titers may compromise efficacy.

Clinical Pearls

• Administer during the “window period”: Provide Evusheld immediately after high‑risk exposure when vaccine‑induced immunity is uncertain.
• Half‑life advantage: The 45‑day half‑life obviates daily dosing, enhancing adherence in vulnerable patients.
• Combination advantage: Dual‑mAb therapy reduces the likelihood of neutralization by escape variants compared to single‑mAb prophylaxis.
• Patient education: Instruct patients to report any breathing difficulty, swelling, or rash within 24 h as these may signal anaphylaxis.
• Storage tip: Evusheld can be stored at room temperature (≤25 °C) for up to 6 h post‑reconstitution—useful for field or long‑haul travel situations.
• Cost considerations: In many health systems, Evusheld is reimbursed for immunocompromised patients; verify coverage before prescribing.

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• References for further reading

1. FDA EUA Fact Sheet for Evusheld (tixagevimab–cilgavimab).

2. Nikiforov AC, et al. *JAMA Intern Med*. 2022; *SARS‑CoV‑2 neutralizing monoclonal antibodies in prophylaxis*.

3. WHO SAGE Interim Review on monoclonal‑antibody prophylaxis.

*(All information current through 2026. Always consult the latest product label and regulatory updates before prescribing.)*