Rabies Post-Exposure Prophylaxis Guide to Vaccine and Immune Globulin

HRIG provides passive antibodies at the wound to neutralize virus present now; vaccine triggers active immunity that takes ~7 days to develop. Using both prevents early replication and provides durable protection. Do not exceed the HRIG dose, and never co-administer in the same syringe/site.

The rabies vaccine used for post-exposure prophylaxis (PEP) is typically a cell-culture rabies vaccine, such as:

• Imovax Rabies (HDCV, Human Diploid Cell Vaccine)
• RabAvert (PCECV, Purified Chick Embryo Cell Vaccine)

These vaccines are the standard approved vaccines for rabies PEP globally and in the U.S. They are given as a series of intramuscular doses to stimulate active immunity after exposure.​

PEP Vaccine Regimen:

• For individuals who have never been vaccinated against rabies:
• • Start rabies vaccine on Day 0 (first medical visit),
  • then additional doses on Days 3, 7, and 14,
  • totaling 4 doses.​
• For immunocompromised patients, a 5-dose schedule is recommended with an additional dose on Day 28.​
• For individuals who have previously received a complete rabies vaccination series (either pre-exposure or post-exposure), only 2 booster doses of vaccine are needed on Days 0 and 3; HRIG is not required.​

Injection Site:

• The vaccine is given intramuscularly in the deltoid muscle (or anterolateral thigh in infants).
• Avoid gluteal injection sites because vaccine efficacy may be reduced in that location.​

This vaccination schedule, combined with HRIG administration and wound care, effectively prevents development of rabies after exposure

For patients previously vaccinated against rabies, the post-exposure prophylaxis (PEP) dose and schedule differ compared to unvaccinated persons:

Previously Vaccinated Patients (prior complete rabies vaccine series or pre-exposure prophylaxis)

• Rabies Immune Globulin (HRIG) is NOT given, regardless of type of exposure.​
• Rabies vaccine dose: Two doses of rabies vaccine, each 1 mL IM (Imovax or RabAvert), given on:
• • Day 0 (the first visit)
  • Day 3
• This is a shortened vaccine regimen to boost immunity.​

Unvaccinated Patients

• HRIG is given once at day 0 (20 IU/kg) and infiltrated around wounds if possible.
• Rabies vaccine is given as 4 doses IM (1 mL each) on:
• • Days 0, 3, 7, and 14
• Immunocompromised individuals get a fifth vaccine dose on day 28.​

This tailored approach ensures optimal use of HRIG and vaccine based on immune memory and exposure risk.

HRIG provides immediate passive protection by directly neutralizing the rabies virus shortly after exposure, while the rabies vaccine induces the patient’s own immune response to create long-term protection. Both are essential components of post-exposure prophylaxis for unvaccinated patients to prevent rabies.

The recommended Human Rabies Immune Globulin (HRIG) for rabies post-exposure prophylaxis is:

• Dose: 20 IU/kg body weight for all ages, including children.​
• Administration: Given once at the start of the post-exposure prophylaxis (PEP) regimen, ideally on Day 0 with the first rabies vaccine dose.​
• Method:
• • Infiltrate as much of the HRIG dose as possible into and around the bite or exposure wound(s).
  • Inject any remaining volume intramuscularly (IM) at a site distant from the vaccine administration site, typically the deltoid or quadriceps muscle.​
• Products: Various HRIG products are available worldwide, including HyperRAB and KEDRAB, which differ primarily in formulation and concentration but have the same dosing principles.

Dose (IU) = 20 × weight(kg). Convert to mL using product strength (e.g., HyperRAB 300 IU/mL; KEDRAB 150 IU/mL). Infiltrate as much as anatomically feasible into/around all wounds; inject any remainder IM at a site distant from the vaccine. Do not mix in the same syringe or site.

If exposure is judged credible (e.g., bat in a room with a sleeping person or a child, or contact where a bite can’t be ruled out), PEP including HRIG is indicated. With no identifiable wound, give the entire HRIG dose IM in large muscle(s) distant from the vaccine site.

Divide the full dose IM in large muscles (e.g., vastus lateralis or deltoids) contralateral to the vaccine.

Vaccine: never in the gluteal area (reduced immunogenicity, nerve risk). HRIG: give remainder IM in a large muscle away from the vaccine. Many state/health-dept guides advise avoiding gluteal for HRIG as well due to sciatic risk—prefer deltoid or thigh when feasible.

Split the infiltrated volume across multiple wound areas; split the IM “remainder” across multiple distant muscles as needed. Do not exceed 20 IU/kg total.

Yes—CDC allows dilution with normal saline if needed to infiltrate all wounds. Exception: HyperRAB 300 IU/mL labeling specifies do not dilute with normal saline; use D5W if dilution is required. Follow product labeling for the specific HRIG used.

How to split HRIG dose across multiple injection sites (practical steps):

1. Calculate total volume; 2) Map all wounds; 3) Allocate most volume to highest-risk sites (hands/face/fingers) and distribute proportionally by wound length/area; 4) Infiltrate gently in a fan pattern; 5) Any leftover volume → IM in distant muscle(s). Document volumes per site (see template).

Total mL (dose ÷ product IU/mL) − sum of mL infiltrated into/around wounds = mL to give IM at site(s) distant from vaccine. (Do not round dose; use additional vials as needed.) Single-use vials are discarded after use.

Do not round down. Open the combination of single-use vials needed to reach the calculated dose; discard any unused portion per labeling.

PEP is a medical urgency. If risk is meaningful and lab confirmation/observation will be delayed (e.g., weekends, logistics), initiate PEP now; you can stop if results return negative. Many jurisdictions allow short delays (often ≤48–72 hours) when risk is low and testing/observation is imminent. Coordinate with public health.

Start as soon as possible—even after delays of days to weeks—as long as the patient has no rabies symptoms. (Once symptomatic, rabies is almost uniformly fatal.)

Yes. Vaccine can be started at any time post-exposure if the patient is asymptomatic. The 7-day limit applies only to HRIG (see next).

Any time post-exposure before symptom onset; do not withhold for long while risk remains. Begin immediately once the decision is made.

Low-risk scenarios where the animal is healthy/available for 10-day observation (dogs/cats/ferrets) or where testing will be completed within a short window (commonly ≤5 days) and bite severity/site are not high risk (e.g., not face/hand/neck). Public-health consultation is recommended.

If the animal cannot be located/tested promptly—or if exposure involves high-risk wildlife (bats/raccoons/skunks/foxes) or severe/cranial bites—start PEP. Stop if the animal later tests negative.

If Human Rabies Immune Globulin (HRIG) is inadvertently given in the same anatomical site as the rabies vaccine (or very close proximity), the following steps are recommended:

• Re-administer the rabies vaccine dose at a different, distant injection site as soon as possible. This is necessary because HRIG can neutralize the vaccine virus at the same site, potentially reducing the vaccine's immunogenicity and effectiveness.​
• You may also need to consider repeating or re-administering HRIG, but do not exceed the total recommended HRIG dose of 20 IU/kg, as higher doses may blunt the immune response to the vaccine.​
• For subsequent vaccine doses (days 3, 7, 14), it is acceptable to administer them in the same site where HRIG was initially given since HRIG is only given once.​
• Prevent this by always administering HRIG and the first rabies vaccine dose at different anatomical sites (e.g., opposite deltoids or a deltoid and quadriceps).

HRIG can neutralize vaccine antigen if colocated; separate sites.

Prioritize high-risk wounds, distribute by wound size/location, then split IM remainder across large muscles.

22–25G; 1–1.5" for most teens/adults; consider 22G for viscous/large volumes; choose site-appropriate length.

No fixed national limits—use judgment; split doses and consider thigh for larger volumes; ensure correct needle length to reach muscle.

HRIG and rabies vaccine can be given in either order on Day 0 of post-exposure prophylaxis, but with important considerations:

• Both HRIG and the first dose of rabies vaccine should ideally be administered during the same visit (Day 0) to provide passive and active immunity simultaneously as soon as possible after exposure.
• If HRIG is administered first, the vaccine can be given immediately after but in a different anatomical site; similarly, if the vaccine is administered first, HRIG should not be given at the same site immediately after.​
• If HRIG was not given at the first vaccine dose, it may still be administered up to 7 days after starting vaccine series—but not later, as the vaccine-induced antibodies would have developed.

This administration practice optimizes passive and active immunity to prevent rabies after exposure.

The side effects associated with rabies biologics—Human Rabies Immune Globulin (HRIG) and rabies vaccine—are generally mild and temporary but can include both local and systemic reactions.

HRIG Side Effects

• Common local reactions:
• • Pain, redness, swelling, soreness, or tenderness at the injection site
  • Bruising or irritation
• Common systemic reactions:
• • Headache
  • Fever
  • Body aches or muscle pain
  • Malaise or unusual tiredness
  • Chills, nasal congestion, runny nose, sore throat
• Rare but serious:
• • Severe allergic reactions (anaphylaxis, rash, itching, swelling)
  • Blood complications like clotting disorders or hemolysis (very rare)
• Most adverse events (AEs) with HRIG are mild and resolve without complications.​

Rabies Vaccine Side Effects

• Common local reactions:
• • Injection site pain, redness, swelling
• Common systemic reactions:
• • Headache
  • Nausea, vomiting
  • Fatigue
  • Muscle aches
  • Fever and chills
• These side effects are generally mild, transient, and self-limited.