Postexposure Prophylaxis (PEP) Guidelines for Rabies

An overview of current recommendations for human rabies PEP, including wound care and administration of both human rabies immune globulin (HRIG) and vaccine.

Two female medical professionals discussing the medical chart of a patient who may have been exposed to rabies.

Immediate Protection Against an Imminent Threat1-3

Along with appropriate wound cleansing, a human rabies immune globulin (HRIG) such as HyperRAB® (rabies immune globulin [human]) is recommended by the Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) to be administered at the same time as the rabies vaccine in previously unvaccinated persons immediately following a transdermal bite or scratch by an animal suspected of being rabid. 

Vaccines can protect for years, but they may take weeks to build efficacy.

An HRIG like HyperRAB provides critical protection immediately, allowing the vaccine time to establish active immunity.

For unvaccinated individuals, the combination of HRIG and vaccine is recommended for both bite and nonbite exposures, regardless of the time interval between exposure and initiation of PEP. Persons who have been previously immunized should receive only vaccine.4

CDC Recommendations

The CDC provides recommendations for human rabies PEP, including wound care and administration of both human rabies immune globulin and vaccine.2

Centers for Disease Control and Prevention. Morbidity and Mortality Weekly Report. May 23, 2008.

Centers for Disease Control and Prevention(CDC) recommendations for postexposure prophylaxis.

HRIG + Vaccine

An HRIG like HyperRAB® (rabies immune globulin [human]) provides critical, immediate protection.

Human Rabies Immune Globulin (HRIG) provides critical, immediate protection.

The most common adverse reactions in >5% of subjects taking HyperRAB during clinical trials were injection-site pain, headache, injection site nodule, abdominal pain, diarrhea, flatulence, nasal congestion, and oropharyngeal pain.

HyperRAB Contains High Titers of Rabies Antibodies for PEP, Providing Rapid Immune Protection4

HyperRAB® (rabies immune globulin [human]), in conjunction with a vaccine, is indicated for postexposure prophylaxis for both bite and nonbite exposures regardless of the time interval between exposure and initiation of PEP in previously unvaccinated persons. Rabies vaccine and HyperRAB should be given to all persons suspected of exposure to rabies, with one exception: persons who have been previously immunized with rabies vaccine and have confirmed adequate rabies antibody titer should receive only vaccine. HyperRAB should be administered as promptly as possible after exposure, but must be administered within 7 days after the first dose of rabies vaccine. Beyond 7 days, HyperRAB is not indicated since an antibody response to vaccine is presumed to have occurred.4

Rabies PEP Schedule – United States2,3

Source: Centers for Disease Control and Prevention. Morbidity and Mortality Weekly Report. May 23, 2008.

Not previously vaccinated

Intervention

Wound cleansing

Regimen*

All PEP should begin with immediate, thorough cleansing of all wounds with soap and water. If available, a virucidal agent (eg, povidine-iodine solution) should be used to irrigate the wounds.

Human rabies immune globulin (HRIG)

Regimen*

Administer 20 IU/kg body weight. If anatomically feasible, the full dose should be infiltrated around and into the wound(s), and any remaining volume should be administered at an anatomical site (intramuscular [IM]) distant from vaccine administration. Also, HRIG should not be administered in the same syringe as vaccine. Because rabies immune globulin (RIG) might partially suppress active production of rabies virus antibody, no more than the recommended dose should be administered.

Vaccine

Regimen*

Human diploid cell vaccine (HDCV) or purified chick embryo cell vaccine (PCECV) 1.0 mL IM (deltoid area), 1 each on days 0, 3, 7, and 14.§

Intervention Regimen*

Wound cleansing

All PEP should begin with immediate, thorough cleansing of all wounds with soap and water. If available, a virucidal agent (eg, povidine-iodine solution) should be used to irrigate the wounds.

Human rabies immune globulin (HRIG)

Administer 20 IU/kg body weight. If anatomically feasible, the full dose should be infiltrated around and into the wound(s), and any remaining volume should be administered at an anatomical site (intramuscular [IM]) distant from vaccine administration. Also, HRIG should not be administered in the same syringe as vaccine. Because rabies immune globulin (RIG) might partially suppress active production of rabies virus antibody, no more than the recommended dose should be administered.

Vaccine

Human diploid cell vaccine (HDCV) or purified chick embryo cell vaccine (PCECV) 1.0 mL IM (deltoid area), 1 each on days 0, 3, 7, and 14.§

Previously vaccinated||

Intervention

Wound cleansing

Regimen*

All PEP should begin with immediate, thorough cleansing of all wounds with soap and water. If available, a virucidal agent such as povidone-iodine solution should be used to irrigate the wounds.

HRIG

Regimen*

HRIG should not be administered.

Vaccine

Regimen*

HDCV or PCECV 1.0 mL IM (deltoid area), 1 each on days 0 and 3.

* These regimens are applicable for persons in all age groups, including children.

The deltoid area is the only acceptable site of vaccination for adults and older children. For younger children, the outer aspect of the thigh may be used. 
Vaccine should never be administered in the gluteal area.

Day 0 is the day dose 1 of vaccine is administered.

§ For persons with immunosuppression, rabies PEP should be administered using all 5 doses of vaccine on days 0, 3, 7, 14, and 28.

|| Any person with a history of pre-exposure vaccination with HDCV, PCECV, or rabies vaccine absorbed (RVA); prior PEP with HDCV, PCECV or RVA; or previous vaccination with any other type of rabies vaccine and a documented history of antibody response to the prior vaccination.

Intervention Regimen*

Wound cleansing

All PEP should begin with immediate, thorough cleansing of all wounds with soap and water. If available, a virucidal agent such as povidone-iodine solution should be used to irrigate the wounds.

HRIG

HRIG should not be administered.

Vaccine

HDCV or PCECV 1.0 mL IM (deltoid area), 1 each on days 0 and 3.

A shoulder wound that has received medical attention.

Post-bite Wound Care

All animal bite wounds, regardless of risk for rabies exposure, should undergo treatment for serious injury—which may include nerve or tendon laceration. Wounds should be gently irrigated with water or a water diluted povidone-iodine solution to minimize the risk of infection. Take care to avoid causing any additional damage to surrounding skin or tissue. When at all possible, avoid suturing.2

Administering a tetanus vaccine should also be considered as part of standard wound care.

Discontinuation of PEP

If appropriate diagnostic tests indicate that the animal that caused the exposure was not rabid, any initiated PEP measures may be discontinued.2

Discover What You Need to Know About HRIG Dosing and Administration

Important Safety Information for HyperRAB® (rabies immune globulin [human])

Indication and Usage
HYPERRAB® (rabies immune globulin [human]) is indicated for postexposure prophylaxis, along with rabies vaccine, for all persons suspected of exposure to rabies.

Limitations of Use
Persons who have been previously immunized with rabies vaccine and have a confirmed adequate rabies antibody titer should receive only vaccine. For unvaccinated persons, the combination of HYPERRAB and vaccine is recommended for both bite and nonbite exposures regardless of the time interval between exposure and initiation of postexposure prophylaxis. Beyond 7 days (after the first vaccine dose), HYPERRAB is not indicated since an antibody response to vaccine is presumed to have occurred.

Important Safety Information

For infiltration and intramuscular use only.

Severe hypersensitivity reactions may occur with HYPERRAB. Patients with a history of prior systemic allergic reactions to human immunoglobulin preparations are at a greater risk of developing severe hypersensitivity and anaphylactic reactions. Have epinephrine available for treatment of acute allergic symptoms, should they occur.

HYPERRAB is made from human blood and may carry a risk of transmitting infectious agents, eg, viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent, and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent.

The most common adverse reactions in >5% of subjects during clinical trials were injection-site pain, headache, injection-site nodule, abdominal pain, diarrhea, flatulence, nasal congestion, and oropharyngeal pain.

Do not administer repeated doses of HYPERRAB once vaccine treatment has been initiated as this could prevent the full expression of active immunity expected from the rabies vaccine.

Other antibodies in the HYPERRAB preparation may interfere with the response to live vaccines such as measles, mumps, polio, or rubella. Defer immunization with live vaccines for 4 months after HYPERRAB administration.

Please see full Prescribing Information for HYPERRAB.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088

References

  1. World Health Organization (WHO). Rabies. WHO website. Accessed March 12, 2022. https://www.who.int/news-room/fact-sheets/detail/rabies.
  2. Manning SE, Rupprecht CE, Fishbein D, et al. Human rabies prevention—United States, 2008: recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2008;57(RR-3):1-28.
  3. Rupprecht CE, Briggs D, Brown CM, et al; Centers for Disease Control and Prevention (CDC). Use of a reduced (4-dose) vaccine schedule for postexposure prophylaxis to prevent human rabies: recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2010;59(RR-2):1-9. 
  4. HyperRAB (rabies immune globulin [human]) Prescribing Information. Grifols.