What is the protocol for rabies post-exposure prophylaxis (PEP) with rabies immunoglobulin (RIG)?

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Last updated: November 16, 2025View editorial policy

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Rabies Post-Exposure Prophylaxis with RIG Protocol

For previously unvaccinated persons with rabies exposure, administer human rabies immunoglobulin (HRIG) at 20 IU/kg body weight on day 0 along with a 4-dose vaccine series on days 0,3,7, and 14, with the full HRIG dose infiltrated around and into all wounds when anatomically feasible. 1, 2, 3

Immediate Wound Management

  • Thoroughly wash all wounds with soap and water for 15 minutes immediately upon presentation — this single intervention markedly reduces rabies likelihood in animal studies and is perhaps the most effective preventive measure. 1, 2, 4, 5
  • Apply a virucidal agent such as povidone-iodine solution to irrigate wounds after washing when available. 2, 3
  • Assess for tetanus prophylaxis needs and bacterial infection risk. 1

HRIG Administration Protocol

Dosing and Timing

  • Calculate HRIG dose at exactly 20 IU/kg (0.133 mL/kg) body weight — this formula applies to all age groups including children. 1, 2, 3
  • Administer HRIG on day 0 (same day as first vaccine dose) ideally, but it can be given up to and including day 7 of the vaccine series. 1, 3
  • Beyond day 7, do not administer HRIG because vaccine-induced antibody response is presumed to have occurred. 1

Anatomical Administration Technique

  • Infiltrate the full calculated HRIG dose thoroughly around and into all wound sites when anatomically feasible — failure to adequately infiltrate wounds has been associated with rare PEP failures. 1, 2, 3, 6
  • Inject any remaining HRIG volume intramuscularly at a site distant from vaccine administration (deltoid or lateral thigh, never gluteal region). 1, 3
  • Never administer HRIG in the same syringe or at the same anatomical site as the first vaccine dose. 1, 3
  • Do not exceed the recommended 20 IU/kg dose, as higher doses can partially suppress active antibody production. 1, 2

Vaccine Administration Protocol

Standard 4-Dose Regimen (Previously Unvaccinated)

  • Administer 1.0 mL doses of human diploid cell vaccine (HDCV) or purified chick embryo cell vaccine (PCECV) intramuscularly on days 0,3,7, and 14. 1, 2, 4
  • Day 0 is defined as the day the first vaccine dose is administered, not necessarily the exposure date. 1, 4
  • Inject in the deltoid muscle for adults and older children; use anterolateral thigh for young children and infants. 1, 3
  • Never use the gluteal area — this produces inadequate antibody response. 1, 7, 4

Modified Regimen for Immunocompromised Patients

  • Administer a 5-dose regimen on days 0,3,7,14, and 28 for immunosuppressed individuals. 2, 4
  • Consider serologic testing 7-14 days after the final dose to confirm adequate antibody response in this population. 1, 4

Previously Vaccinated Persons

  • Administer only 2 vaccine doses (1.0 mL each) on days 0 and 3 — do not give HRIG. 1, 7, 4
  • This applies to persons with documented prior complete pre-exposure or post-exposure vaccination with cell culture vaccines. 1
  • HRIG administration in previously vaccinated persons may interfere with the anamnestic antibody response. 1, 7

Critical Timing Considerations

  • Initiate PEP as soon as possible after exposure, ideally within 24 hours — rabies is nearly 100% fatal once clinical symptoms develop. 4, 3
  • PEP remains indicated regardless of delay, even if weeks or months have elapsed since exposure, provided the patient shows no clinical signs of rabies. 1, 4
  • Minor delays of a few days between individual vaccine doses are acceptable and do not require restarting the series. 4
  • For substantial schedule deviations (weeks or more), assess immune status by serologic testing 7-14 days after the final dose. 4

Common Pitfalls to Avoid

  • Insufficient wound infiltration: Only 56% of eligible patients receive proper HRIG infiltration at wound sites in real-world practice — ensure the full dose reaches all wounds. 6
  • Incorrect anatomical site: Never administer vaccine in the gluteal region due to risk of sciatic nerve injury and diminished immune response. 1, 4, 3
  • Excessive HRIG dosing: Do not exceed 20 IU/kg as this suppresses active antibody production. 1, 2
  • Administering HRIG to previously vaccinated persons: This is unnecessary and may inhibit the anamnestic response. 1, 7
  • Delaying treatment for animal observation: Begin PEP immediately for high-risk exposures (bats, wild carnivores) without waiting for animal testing results. 1, 3
  • Missing bat exposures: Bat bites may be minor and undetected — consider PEP for any physical bat contact when bite cannot be excluded. 7, 3

Exposure Category Assessment

When administered correctly and promptly, this combined HRIG and vaccine regimen is nearly 100% effective in preventing human rabies. 4, 8 No PEP failures have been documented in the United States when current biologics are properly administered. 1

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Rabies Post-Exposure Prophylaxis Protocol

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Current Rabies Post-Exposure Prophylaxis Recommendations

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Rabies Exposure Categories and Post-Exposure Prophylaxis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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