Rabies Post-Exposure Prophylaxis Regimen
Animal Bites and Rabies Risk: A Guide for Health Professionals
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 1.0 mL rabies vaccinations (Table 3). 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).
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, even if the pre- or post-exposure rabies prophylaxis regimen was given many years prior (Table 3; Table 4).
Human rabies immune globulin (HRIG)
Human rabies immune globulin (HRIG) is infiltrated around the site of the bite(s), and provides rapid passive immune protection with a half life of approximately 21 days. It is administered only once, on the first day of the PEP regimen (designated day 0). No more than the recommended dosage of HRIG should be given because excessive HRIG can partially suppress active production of antibody. 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 occurs in that timeframe.
- 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 measels- or varicella-containing vaccines if four months. CDC has provided a chart for more information: http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/appendices/A/mmr_ig.pdf Attention: Non-MDH link.
A 1.0 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). The first vaccination is given concurrently with the HRIG at a site distant from the HRIG. An additional fifth dose of rabies vaccine is given on day 28 to immunocompromised patients (Table 4). Rabies vaccine must NOT be given in the gluteals 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 for distribution from CDC at: http://www.cdc.gov/vaccines/hcp/vis/vis-statements/rabies.html Attention: Non-MDH link.
Previously vaccinated persons
Previously vaccinated individuals are those who have completed a pre-exposure or post-exposure regimen of human diploid cell vaccine (HDCV) and 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) (Reference 7). Following an exposure, previously vaccinated persons are given two 1.0 mL doses of vaccine intramuscularly in the deltoid area on days 0 and 3. No HRIG is administered. Please consult with MDH epidemiologists if the patient’s previous pre- or post-exposure vaccination regimen was administered more than 20 years prior to the current exposure.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, especially the first two days of treatment, days 0 and 3. After day 3 of the regimen, deviations of a few days are acceptable. 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.
- Table 3: Rabies Post-Exposure Prophylaxis Healthy, Immunocompetent Persons, Including Pregnant Women (PDF: 112KB/1 page)
- Table 4: Rabies Post-Exposure Prophylaxis Immunocompromised Persons (PDF: 114KB/1 page)
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
www.vaccineshoppe.com Attention: Non-MDH link.
Bayer Biological Products
http://www.hypermunes.com Attention: Non-MDH link.
Human rabies vaccines
Human Diploid Cell Vaccine (HDCV)
Imovax IM® (pre- and post-exposure)
www.vaccineshoppe.com Attention: Non-MDH link.
Purified Chick Embryo Cell Vaccine (PCEC)
RabAvert® (pre- and post-exposure)
www.gsksource.com Attention: Non-MDH link.
Patient assistance programs
Both rabies vaccine manufacturers have patient assistance programs that provide biologics to qualifying underinsured or uninsured patients.
An application form and information about Sanofi Pasteur’s Patient Assistance Program (providing Imogam® Rabies HT and Imovax® IM) can be found at: www.needymeds.org/papforms/sanofi0312.pdf (PDF: 116KB/3 pages) or by phone at 888-847-4877. Attention: Non-MDH link.
GlaxoSmithKline Patient Assistance Program (providing RabAvert®) is available at: www.gsk-vap.com or phone at 800-589-0837. Attention: Non-MDH link.
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 Disease 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.