What is the post-exposure prophylaxis (PEP) vaccination protocol for rabies?

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Last updated: December 21, 2025View editorial policy

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Rabies Post-Exposure Prophylaxis Protocol

Immediate Wound Management (First Priority)

Thoroughly wash all wounds with soap and water for 15 minutes immediately upon presentation—this is the single most effective measure for preventing rabies infection. 1, 2

  • Follow wound washing with irrigation using a virucidal agent such as povidone-iodine solution if available 1, 3
  • Do not delay wound cleaning for any reason—it is the most crucial step in preventing infection 2
  • Avoid suturing wounds unless absolutely necessary for cosmetic reasons or high risk of bacterial infection 2
  • Administer tetanus prophylaxis and antibiotics as clinically indicated 2, 3

Post-Exposure Prophylaxis for Previously Unvaccinated Persons

For individuals who have never received rabies vaccination, administer a 4-dose vaccine regimen on days 0,3,7, and 14, combined with human rabies immune globulin (HRIG) at 20 IU/kg on day 0. 4, 1

Vaccine Administration

  • Use human diploid cell vaccine (HDCV) or purified chick embryo cell vaccine (PCECV), 1.0 mL per dose, administered intramuscularly 1, 5
  • Inject in the deltoid muscle for adults and older children 1, 2
  • Inject in the anterolateral thigh for young children 1, 2
  • Never use the gluteal area—this produces inadequate antibody response and is associated with vaccine failure 1, 5, 3
  • Day 0 is defined as the day the first dose is administered, not necessarily the day of exposure 5

HRIG Administration

  • Administer HRIG at exactly 20 IU/kg body weight on day 0, ideally at the same time as the first vaccine dose 1, 3
  • Infiltrate as much of the calculated dose as anatomically possible directly into and around all wound sites 1, 3
  • Administer any remaining HRIG volume intramuscularly at a site distant from vaccine administration 1, 3
  • Do not exceed 20 IU/kg—higher doses suppress active antibody production 1, 2
  • Never administer HRIG in the same syringe or anatomical location as the vaccine 1, 5
  • HRIG can be given up to and including day 7 after the first vaccine dose if not initially administered 1, 3

Post-Exposure Prophylaxis for Previously Vaccinated Persons

Previously vaccinated individuals require only 2 doses of vaccine (on days 0 and 3) and should NOT receive HRIG. 1, 5

  • "Previously vaccinated" is defined as having received ACIP-recommended pre- or post-exposure prophylaxis with cell-culture vaccines, or documented adequate rabies virus-neutralizing antibody response 1
  • Do not administer HRIG to previously vaccinated persons—it will inhibit the anamnestic immune response 1, 5

Special Populations

Immunocompromised Patients

Immunocompromised individuals must receive a 5-dose vaccine regimen on days 0,3,7,14, and 28, plus HRIG at 20 IU/kg, even if they were previously vaccinated. 1, 2

  • Consider serologic testing 7-14 days after the last dose to ensure seroconversion 2, 5
  • The standard 4-dose schedule is inadequate for this population 5

Pediatric Patients

  • Children receive the same vaccine dose volume (1.0 mL) and HRIG dose (20 IU/kg) as adults 1, 2
  • Use the anterolateral thigh for vaccine administration in young children 1, 2
  • The 4-dose schedule applies to all pediatric age groups 2, 5

Critical Timing Considerations

Initiate PEP as soon as possible after exposure, ideally within 24 hours, though PEP should be administered regardless of time elapsed since exposure. 1, 5

  • Delays of even a few hours matter significantly because rabies is nearly 100% fatal once clinical symptoms develop 5
  • PEP should still be given even if exposure was recognized months later 2, 5
  • When administered promptly and appropriately, PEP is nearly 100% effective in preventing human rabies 5, 6

Managing Schedule Deviations

  • Delays of a few days for individual doses are unimportant 5
  • For substantial deviations (weeks or more), assess immune status by serologic testing 7-14 days after the final dose 5
  • Most interruptions do not require restarting the entire series 5

Common Pitfalls to Avoid

  • Never use the gluteal area for vaccine administration—this is associated with inadequate immune response and vaccine failure 1, 2, 5, 3
  • Never give HRIG to previously vaccinated persons—it inhibits the immune response 1, 5
  • Never administer HRIG and vaccine in the same syringe or anatomical location 1, 5
  • Never exceed the recommended HRIG dose of 20 IU/kg—higher doses suppress active antibody production 1, 2
  • Do not delay wound cleaning for any other intervention 2, 5

References

Guideline

Rabies Post-Exposure Prophylaxis Guidelines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Post-Exposure Prophylaxis for Rabies in Children

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Current Rabies Post-Exposure Prophylaxis Recommendations

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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