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Rabies Post-Exposure Prophylaxis Regimen and Wound Care
Animal Bites and Rabies Risk:
A Guide for Health Professionals
On this page:
Wound Care
Rabies PEP overview
Human rabies immune globulin (HRIG)
Rabies vaccine
Human rabies biologics
Adverse reactions
Wound Care
Wound cleansing is especially important in rabies prevention. In animal studies, thorough wound cleansing alone without other medical treatments (e.g., PEP) has been shown to markedly reduce the likelihood of rabies. Wounds should be promptly irrigated with water, or a povidone-iodine solution. In addition to decreasing the risk of rabies, it also decreases the risk for bacterial infection. Patients should receive a tetanus booster if their last vaccine was more than 5 years ago. The need for antibiotic prophylaxis should also be assessed.
Rabies PEP overview
The rabies PEP regimen involves administration of human rabies immune globulin (HRIG), which is given only once, and a series of four 1 mL rabies vaccinations (Table 3: Rabies Post-Exposure Prophylaxis Healthy, Immunocompetent Persons, Including Pregnant Women (PDF)). HRIG and the first vaccination are given on the first day of treatment (designated Day 0) and three additional rabies vaccinations are given on Days 3, 7, and 14.
Immunocompromised persons receive a fifth vaccination on Day 28 and should be tested for seroconversion 7 to 14 days following completion of the PEP regimen (Table 4: Rabies Post-Exposure Prophylaxis Immunocompromised Persons (PDF)). For this regimen, pregnancy is not considered to be an immunocompromising condition.
Patients who have previously received either pre- or post-exposure rabies prophylaxis should receive only two rabies vaccine boosters following an exposure, given on Days 0 and 3. Patients who have been previously vaccinated SHOULD NOT receive HRIG.
- Table 3: Rabies Post-Exposure Prophylaxis Healthy, Immunocompetent Persons, Including Pregnant Women (PDF)
- Table 4: Rabies Post-Exposure Prophylaxis Immunocompromised Persons (PDF)
Human rabies immune globulin (HRIG)
Human rabies immune globulin (HRIG) is a biologic product prepared from human donors hyper-immunized with rabies vaccine. HRIG must be infiltrated into and around the bite wound site(s), and provides immediate, passive immune protection until the patient produces antibodies through the PEP vaccine series. HRIG has a half-life of approximately 21 days. It is administered only once, preferably on the first day of the PEP regimen (designated Day 0). Providers must be cautious about giving more than the recommended dosage of HRIG, as studies have shown that administering more than twice the recommended dose can reduce the immune response. If the HRIG was not administered on Day 0, it may be administered up to and including Day 7 of the PEP regimen. Beyond Day 7, HRIG is not indicated, as the patient’s antibody response to the vaccine is presumed to have occurred.
- The recommended dosage of HRIG is 20 IU/kg body weight for all ages including children.
- Infiltrate as much of the HRIG as possible into and around the bite wound.
- Administer the remaining HRIG intramuscularly (IM) at a site distant from the first vaccination site, generally in the quadriceps or deltoids.
- If there is no wound, such as following a bat-in-the-bedroom exposure, then administer the entire dose of HRIG in the quadriceps or deltoids.
Interference of HRIG with live virus vaccine administration
HRIG can interfere with live virus vaccines. Therefore, the recommended interval between HRIG and measles- or varicella-containing vaccines is four months. Refer to table 3.6 in CDC’s Timing and Spacing of Immunobiologics: Vaccines & Immunizations - Table 3.6.
Rabies vaccine
A 1 mL dose of rabies vaccine is given IM in the deltoid area of adults or the anterolateral thigh of young children on Days 0, 3, 7, and 14 of the rabies PEP regimen (Table 3: Rabies Post-Exposure Prophylaxis Healthy, Immunocompetent Persons, Including Pregnant Women (PDF)). The first vaccination is given concurrently with the HRIG at an anatomical site distant from the HRIG. When HRIG and the vaccine are given in the same anatomical site, antibody-vaccine complexes neutralize both products, leaving the patient without protection from infection.
An additional fifth dose of rabies vaccine is given on Day 28 to immunocompromised patients (Table 4: Rabies Post-Exposure Prophylaxis Immunocompromised Persons (PDF)). Rabies vaccine must NOT be given in the gluteal muscles due to the possibility of poor absorption from that site and lower neutralizing antibody titers.
Two inactivated, cell culture rabies vaccines are currently available in the United States: human diploid cell vaccine (HDCV) or purified chick embryo cell vaccine (PCEC). Both are considered equally safe and efficacious. It is recommended that a vaccine series be initiated and completed with the same vaccine product; however, decreased efficacy or increased frequency of adverse reactions have not been documented when the series is initiated with one vaccine product and completed with another. The rabies vaccine series induces an active immune response that requires 7 to 10 days to develop and persists for many years. A rabies vaccine information statement (VIS) is available from the CDC.
Previously vaccinated persons
Previously vaccinated individuals are those who have completed a pre-exposure or post-exposure regimen of human diploid cell vaccine (HDCV) or purified chick embryo cell vaccine (PCEC), or who have received a different vaccine outside of the U.S. and have a documented serum titer corresponding to complete neutralization at >1:5 serum dilution (or its equivalent, approximately 0.1-0.2 IU/mL) by the rapid fluorescent focus inhibition test (RFFIT). Following an exposure, previously vaccinated persons are given two 1 mL doses of vaccine intramuscularly in the deltoid area on Days 0 and 3. No HRIG is administered because it might inhibit the strength or speed of the expected anamnestic response.
If the patient’s previous pre- or post-exposure vaccination regimen was administered prior to 1985 then the person is considered unvaccinated due to a change in vaccine biologics. Vaccines prior to 1985 were derived from animal nerve tissues and vaccines after 1985 are derived from human diploid cells or chick embryos. Administer the full rabies PEP regimen including HRIG.
Deviations from recommended PEP vaccination schedule
Once the decision to initiate rabies PEP has been made, the PEP regimen should be started as soon as possible. Every effort should be made to adhere to the recommended PEP regimen schedule. However, given that the PEP regimen requires multiple visits, deviations from the recommended schedule occur frequently. Minor delays in the PEP schedule do not affect the efficacy of the vaccinations. Longer delays of weeks or months are not well studied and could lead to a reduced immune response that could be fatal to a patient exposed to the rabies virus. Restarting the series is reserved for situations when the vaccine has been delayed significantly. For most minor delays or interruptions, the vaccination schedule can be shifted and resumed as though the patient were on schedule. For example, if a patient misses the dose scheduled for Day 7 and presents for vaccination on Day 10, the Day 7 dose should be administered that day, and the final dose given one week later on Day 17.
Please consult MDH epidemiologists for advice when substantial deviations from the recommended schedule have occurred.
Note: Doses should not be administered prior to their scheduled date. For more guidance on how to approach rabies PEP deviations, please see Rabies experts on demand: A cross-sectional study describing the use of a rabies telehealth service.” Public Health Chall. 2023 Aug 1;2(3):10.1002/puh2.109 PMID: 38192571 | National Library of Medicine
Human rabies biologics
Rabies products are commercially available through pharmaceutical distributors or may be obtained directly from the manufacturers using the toll-free numbers listed below. The Minnesota Department of Health does not provide rabies biologics. Check with your pharmacy to determine availability.
Human rabies immune globulin (HRIG) products
(Note: potency varies between products)
KEDRAB™
Kedrion Biopharma and Kamada Ltd
Potency 150 IU/ml
1-855-353-7466
HyperRab™*
Grifols Therapeutics
Bayer Biological Products
Potency 300 IU/ml
1-800-243-4153
*Note: HyperRab has a different concentration compared to the other immunoglobulin products and requires a lower volume to administer the recommended dose of 20 IU/kg. Care should be taken to ensure the correct dose of immunoglobulin is administered to ensure an adequate immune response.
Human rabies vaccines
Human Diploid Cell Vaccine (HDCV)
Imovax IM® (pre- and post-exposure)
Sanofi Pasteur
1-800-822-2463
Purified Chick Embryo Cell Vaccine (PCEC)
RabAvert® (pre- and post-exposure)
Bavarian Nordic
1-866-378-5237
Patient assistance programs
Patient assistance programs may be available from individual biologics manufacturers. Please refer to the websites listed in the above section for current programs.
Adverse reactions
In general, there is a very low frequency of serious adverse reactions to the rabies PEP regimen. Local pain, headache and low-grade fever may follow administration of HRIG. Pain, erythema, swelling, itching, and other mild local reactions are reported among 11-90% of vaccines. Rabies PEP should not be interrupted or discontinued because of local or mild systemic adverse reactions to rabies vaccine. Non-steroidal anti-inflammatory drugs and antipyretic agents, such as ibuprofen or acetaminophen, may be used to control mild adverse reactions.
An immune-complex-like reaction (generalized urticaria, sometimes accompanied by arthralgia, arthritis, angioedema, nausea, vomiting, fever, and malaise) occurs in approximately 6% of pre-exposure vaccinated individuals receiving a booster dose of rabies vaccine after primary vaccination. Although it is rare, this reaction can occur in persons receiving their primary vaccination regimen. No deaths resulting from these reactions have been reported.
When a person with a history of serious hypersensitivity to rabies vaccine must be revaccinated, antihistamines may be administered concomitant with vaccine, and the patient should be observed for development of anaphylaxis immediately following vaccination. The Zoonotic Diseases Unit is available at 651-201-5414 for consultation about the management of possible rabies exposure and PEP in patients with a history of serious adverse reactions to rabies vaccine.
For more information regarding the safety of rabies biologics, please consult Manning, SE., et al., Human rabies prevention--United States, 2008: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep, 2008. 57(RR-3): p.9-10.