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

Rabies Post-Exposure Prophylaxis Dosing

For previously unvaccinated persons, administer 4 doses of rabies vaccine (1.0 mL intramuscularly) on days 0,3,7, and 14, combined with rabies immune globulin (RIG) at 20 IU/kg on day 0. 1, 2

Vaccination Regimen for Unvaccinated Persons

The current ACIP recommendation represents a reduction from the historical 5-dose schedule, based on evidence demonstrating that 4 doses in combination with RIG elicit adequate immune responses without the need for a fifth dose. 1

Key dosing parameters:

• Vaccine type: Human diploid cell vaccine (HDCV) or purified chick embryo cell vaccine (PCECV) 1
• Dose volume: 1.0 mL per dose 1, 2
• Schedule: Days 0,3,7, and 14 (day 0 = day first dose is given) 1, 2
• Route: Intramuscular in deltoid area for adults and older children; anterolateral thigh for young children 1, 2
• Critical caveat: Never use the gluteal area—this produces inadequate antibody response 1, 2

Rabies Immune Globulin Administration

RIG is a critical component of PEP for unvaccinated persons and must be given correctly to avoid treatment failure. 1

RIG dosing specifics:

• Dose: 20 IU/kg body weight 1, 2
• Timing: Administered on day 0 with the first vaccine dose 1, 2
• Late administration: Can be given up to and including day 7 if not given initially 2
• Anatomical placement: Infiltrate the full dose around and into the wound(s) if anatomically feasible; any remaining volume should be given intramuscularly at a site distant from vaccine administration 1, 2
• Critical warning: Do not exceed the recommended dose, as RIG may partially suppress active antibody production 1
• Never mix: RIG should not be administered in the same syringe or at the same anatomical site as the vaccine 1, 2

Previously Vaccinated Persons

Previously vaccinated individuals require only 2 doses of vaccine (days 0 and 3) and do NOT need RIG. 1, 3

This simplified regimen applies to anyone who previously received a complete ACIP-recommended pre-exposure or post-exposure prophylaxis regimen with cell-culture vaccines, regardless of how long ago vaccination occurred. 3

Immunocompromised Patients

Immunocompromised individuals must receive the full 5-dose regimen (days 0,3,7,14, and 28) plus RIG at 20 IU/kg. 1, 2, 3

This population requires the older, more intensive schedule because their immune response may be inadequate with the standard 4-dose regimen. 1 Conditions causing immunosuppression include corticosteroid use, other immunosuppressive medications, antimalarials, HIV/AIDS, and other immunosuppressive illnesses. 3 Serologic testing to confirm adequate antibody response is recommended for these patients. 3

Essential Wound Care

Immediate thorough washing of all wounds with soap and water for 15 minutes is perhaps the most effective single measure for preventing rabies and should be performed before any other intervention. 2

If available, irrigate wounds with a virucidal agent such as povidone-iodine solution. 1, 2 This local wound treatment has been shown in animal studies to markedly reduce the likelihood of rabies infection. 2

Timing Considerations

Initiate PEP as soon as possible after exposure—delays of even hours matter significantly. 2

However, there is no absolute cutoff beyond which PEP should be withheld. 2 Treatment remains indicated even if weeks or months have elapsed since exposure, as rabies is nearly 100% fatal once clinical symptoms develop. 2 Treatment decisions have been successfully implemented many months after exposure when recognition was delayed. 2

Managing Schedule Deviations

Delays of a few days for individual doses are unimportant. 2, 4 For most minor deviations, simply administer the missed dose when the patient presents and resume the schedule from that point, maintaining the same intervals between remaining doses. 4 Most interruptions do not require restarting the entire series. 2, 4

For substantial deviations (lapses of weeks or more), immune status should be assessed by serologic testing 7-14 days after the final dose. 2, 4

Common Pitfalls to Avoid

• Never administer vaccine in the gluteal area—this is associated with vaccine failure due to inadequate antibody response 1, 2
• Do not give RIG to previously vaccinated persons—this is unnecessary and wastes resources 1, 3
• Do not exceed the recommended RIG dose—excess RIG suppresses active antibody production 1
• Do not forget immunocompromised patients need 5 doses, not 4—the standard regimen is inadequate for this population 1, 2, 3
• Do not delay treatment waiting for animal testing results—initiate PEP immediately if exposure is suspected 2

Efficacy

When administered promptly and appropriately, rabies PEP combining wound care, RIG infiltration, and the vaccine series is nearly 100% effective in preventing human rabies. 2 The reduction from 5 to 4 doses was estimated to save approximately $16.6 million annually in the U.S. healthcare system without compromising efficacy. 1