Generic Name: rabies vaccine

Uses

Prevention of Rabies

Prevention of rabies in children, adolescents, and adults exposed to or at risk of exposure to rabies disease or virus.

Rabies is a viral infection transmitted by saliva of infected mammals, most commonly wild, terrestrial carnivores (e.g., skunks, raccoons, foxes, coyotes) or bats. In the US, the greatest risk for naturally acquired rabies is from contact with and bites from insectivorous bats. Following exposure and infection, rabies virus usually moves along a neural pathway and enters the CNS. After entrance into the CNS, the virus is unlikely to be affected by antirabies antibodies and encephalomyelitis usually develops and is almost always fatal. In the US, approximately 16,000–39,000 individuals receive rabies postexposure prophylaxis each year. Between 1990 and 2004, there were 47 rabies-related deaths in the US. Worldwide, rabies is much more common and about 40,000–100,000 rabies-related deaths occur each year.

USPHS Advisory Committee on Immunization Practices (ACIP) and AAP recommend preexposure vaccination with rabies vaccine (series of 3 doses with booster doses when indicated) in children, adolescents, and adults who are or will be at risk of exposure to the virus. (See Preexposure Vaccination Against Rabies in High-risk Groups under Uses.)

Postexposure prophylaxis with a combined regimen of rabies vaccine (series of 5 doses) and a single dose of rabies immune globulin (RIG) is recommend for previously unvaccinated children, adolescents, and adults following potential rabies exposure. Postexposure prophylaxis with a series of 2 booster doses of rabies vaccine (without RIG) is recommended for previously vaccinated children, adolescents, and adults following potential rabies exposure. (See Postexposure Prophylaxis of Rabies under Uses.)

Preexposure Vaccination Against Rabies in High-risk Groups

Preexposure vaccination in children, adolescents, and adults who are or will be at risk of exposure to rabies virus.

Preexposure vaccination does not eliminate the need for prompt postexposure prophylaxis if an exposure to rabies occurs. (See Postexposure Prophylaxis of Rabies under Uses.)

Need for rabies preexposure vaccination depends on the nature of risk and associated level of potential exposure. Consider preexposure vaccination for individuals whose risk of rabies exposure is greater than that of the general population (e.g., veterinarians and their staff, animal-control and wildlife workers, field biologists, spelunkers, missionaries, rabies researchers, certain laboratory workers). Also consider preexposure vaccination for individuals whose activities bring them into frequent contact with rabies virus or potentially rabid bats, raccoons, skunks, cats, dogs, or other species at risk for having rabies. (For ACIP definitions of risk categories and recommendations regarding preexposure vaccination for each category, see the table.)

Travelers to areas where rabies is endemic may be at risk, especially if they are likely to come in contact with animals in areas where dog or other animal rabies is enzootic and immediate access to appropriate medical care (including rabies vaccine and RIG) is unlikely. CDC recommends preexposure vaccination based on local incidence of rabies in the country to be visited, availability of appropriate agents for rabies postexposure prophylaxis, and intended activity and duration of stay. Immunization against rabies is not a requirement for entry into any country.

Postexposure Prophylaxis of Rabies

Postexposure prophylaxis of rabies in previously vaccinated and unvaccinated children, adolescents, and adults following potential exposure to rabies disease or virus.

History of previous vaccination against rabies simplifies the postexposure prophylaxis regimen, but does not eliminate the need for prompt postexposure prophylaxis if an exposure to rabies occurs.

Following possible exposure to rabies, base decisions regarding need for postexposure prophylaxis on vaccination status of exposed individual, type of exposure (bite, nonbite), information about the animal involved (type, vaccination status, condition at time of attack), and rabies epidemiology in the specific geographic region. Whenever possible, consult local or state public health officials regarding the need for postexposure prophylaxis.

Bite exposures include any skin penetration by teeth; all bite exposures from an animal known or suspected to be rabid, regardless of bite location, pose a potential risk of rabies transmission and require postexposure prophylaxis. Risk of transmission varies in part based on species of biting animal, anatomic site of bite, and severity of wound. Rabies transmission can occur from bites of some animals (e.g., bats) that inflict rather minor injury and wounds that are difficult to detect.

Any potential exposure to a bat requires thorough evaluation. If possible, the bat should be submitted for rabies diagnosis. Postexposure prophylaxis is not necessary if the individual can be reasonably certain a bite, scratch, or mucous membrane exposure did not occur or if the bat is available for testing and is negative for rabies virus. Situations that might qualify as exposures include finding a bat in the same room as a person who might be unaware that a bite or direct contact occurred (e.g., a deeply sleeping individual awakened to find a bat in the room or an adult observes a bat in the room with a previously unattended child, mentally disabled person, or intoxicated person). Other household members who do not have direct contact with the bat or were awake and aware when in the room with the bat should not be considered as having exposure to rabies.

Nonbite exposures include contamination of preexisting open wounds, abrasions, mucous membranes, or scratches with saliva or other potentially infectious material (e.g., neural tissue) from an animal known or suspected to be rabid. Although nonbite exposures only rarely cause rabies, such exposures require assessment to determine if sufficient reasons exist to consider postexposure prophylaxis. Nonbite exposures of highest risk occur in surgical recipients of corneas, solid organs, and vascular tissue transplanted from patients who died of rabies and individuals exposed to large amounts of aerosolized rabies virus.

Other forms of contact in the absence of a bite or nonbite exposure (e.g., petting a rabid animal or contact with blood, urine, or feces of a rabid animal, contact of saliva with intact skin) are not considered exposure and postexposure prophylaxis is not necessary.

In health-care personnel, routine delivery of health care to a patient with rabies is not an indication for postexposure rabies prophylaxis, unless there was exposure of mucous membranes or nonintact skin to potentially infectious body fluids.

Regardless of immunization status, ACIP and AAP recommend local wound treatment as an essential initial step in rabies postexposure prophylaxis in all individuals. (See General under Dosage and Administration.)

In previously unvaccinated children, adolescents, and adults following potential rabies exposure, a combined regimen of active immunization with a 5-dose regimen of rabies vaccine and passive immunization with a single dose of RIG is recommended as soon as possible.

In previously vaccinated children, adolescents, and adults following potential rabies exposure, a 2-dose booster regimen of rabies vaccine (without RIG) is recommended as soon as possible.

For ACIP recommendations regarding rabies postexposure prophylaxis in the US based on the type and status of the animal involved, see the table.

Because the rabies incubation period can range from 5 days to >1 year, initiate rabies postexposure prophylaxis (regardless of the length of delay) if a documented or likely exposure has occurred and clinical signs of rabies have not appeared in the exposed individual.

Postexposure prophylaxis failures have not been reported in the US when recommended immunization regimens and wound management procedures were followed using commercially available rabies vaccines and RIG. Rare reports of failures in other countries usually involved some deviation from recommended procedures (e.g., failure to adequately cleanse wounds, IM injection into the gluteal rather than deltoid region, failure to passively immunize with RIG by infiltrating the wound site, use of less than the recommended dose of RIG).

Travelers with potential rabies exposure should immediately contact local health authorities for advice regarding postexposure prophylaxis and should also contact their personal clinician or state health department as soon as possible. Travelers in other countries may receive postexposure prophylaxis with regimens and/or preparations not currently recommended by ACIP resulting in the need for additional therapy following return to the US. Consider serologic testing in these travelers to verify efficacy of the regimen used and to ensure an adequate immune response. (See Pre- and Postvaccination Serologic Testing under Cautions.)

Dosage and Administration

General

• Postexposure prophylaxis of rabies in previously unvaccinated individuals involves thorough cleansing of all bite and nonbite wounds followed by active immunization with rabies vaccine and passive immunization with RIG.
• Postexposure prophylaxis of rabies in individuals who previously received rabies vaccine involves thorough cleansing of all bite and nonbite wounds followed by booster doses of rabies vaccine.
• Because rabies virus may remain localized at the site of inoculation, immediately wash all bites and scratches with soap and water; irrigate with a virucidal agent (e.g., povidone-iodine solution). Institute tetanus prophylaxis and measures to control secondary infection as indicated. Consider cosmetic factors and the potential for bacterial infection before deciding to suture large wounds.

Administration

IM Administration

Administer by IM injection.

Do not administer sub-Q, intravascularly, or intradermally. (See Administration Precautions under Cautions.)

Depending on patient age, administer IM into the deltoid muscle or anterolateral thigh.

For infants and children 1–2 years of age, IM injections should preferably be administered into the anterolateral thigh. For children and adolescents 3–18 years of age, the deltoid muscle is preferred.

Avoid use of the gluteal area as a possible IM injection site. (See Administration Precautions under Cautions.)

Avoid injection into or near blood vessels or nerves.

Administer immediately after reconstitution. Use entire volume of reconstituted vaccine; discard any unused portion.

Use separate needles for reconstitution and administration.

Do not mix with any other vaccine or solution.

Reconstitution (Imovax^®)

To reconstitute, add entire contents of vial containing diluent (1 mL of sterile water for injection) provided by the manufacturer to the vial of lyophilized vaccine. Use only the diluent supplied by the manufacturer.

Attach reconstitution needle and plunger to the syringe and inject diluent into vaccine vial. Gently swirl until completely dissolved; withdraw total contents of vial into the syringe.

Reconstituted suspension is pink to red because of the presence of phenolsulfonphthalein. Remove reconstitution needle and discard. Use a suitable needle for IM administration.

Reconstitution (RabAvert^®)

To reconstitute, add entire contents of vial containing diluent (1 mL of sterile water for injection) provided by the manufacturer to the vial of lyophilized vaccine. Use only the diluent supplied by the manufacturer.

Withdraw entire contents of the diluent into the syringe. Insert the needle at a 45° angle; slowly inject entire contents of diluent vial into the vaccine vial. Mix gently to avoid foaming.

Reconstituted suspension is clear or slightly opaque. Withdraw entire amount of dissolved vaccine into the syringe and replace the long needle with the smaller one for IM injection.

Dosage

Whenever possible, the rabies vaccine (Imovax^®, RabAvert^®) used for the initial dose should be used for subsequent doses in the same individual. Although only limited data available to date, most experts state that rabies vaccines currently available in the US may be considered interchangeable. ACIP states clinical studies not available to date showing differences in efficacy or safety if the vaccine series is completed with a different preparation. One manufacturer recommends that serologic testing be performed to document a protective antibody response if different rabies vaccines are used during a primary vaccine series. (See Pre- and Postvaccination Serologic Testing under Cautions.)

Adhere to the recommended vaccination schedule as closely as possible. If a minor deviation from the schedule occurs (e.g., a dose is delayed by a few days), give the dose and resume the vaccination schedule using the same interval between doses. If a substantial deviation from the schedule occurs, perform serologic testing 7–10 days after the final vaccine dose to assess immune status. (See Pre- and Postvaccination Serologic Testing under Cautions.)

Pediatric Patients

Preexposure Vaccination Against Rabies in High-risk Groups

Primary Immunization in Children and Adolescents

IM

Primary immunization consists of a series of 3 doses. Each dose consists of the entire contents (1 mL) of a reconstituted single-dose vial.

Give first dose on a selected date; give second and third doses 7 and 21 (or 28) days, respectively, after first dose.

Completion of the primary series before an expected exposure to rabies virus ensures the highest level of protection.

Duration of immunity following the recommended 3-dose primary series is ≥2 years. (See Duration of Immunity under Cautions.) Need for additional (booster) doses depends on the category of risk for rabies infection and levels of antirabies antibody. (See Booster Doses in Children and Adolescents under Dosage and Administration.)

Booster Doses in Children and Adolescents

IM

Each booster dose consists of the entire contents (1 mL) of a reconstituted single-dose vial.

Give a booster dose if indicated to maintain protective levels of antirabies antibody. Booster doses may be indicated in those at continuous or frequent risk of rabies, but not in those at infrequent or rare risk. (For information on ACIP definitions of risk categories, see the table under Uses.)

In those at continuous risk of rabies, perform serologic testing every 6 months and administer booster dose if necessary.

In those at frequent risk, perform serologic testing every 2 years and administer booster dose if necessary.

Postexposure Prophylaxis of Rabies

Previously Unvaccinated Children and Adolescents

IM

Postexposure prophylaxis in previously unvaccinated individuals consists of active immunization with a series of 5 doses of rabies vaccine in conjunction with passive immunization with a single dose of RIG.

Give first vaccine dose as soon as possible after exposure (day 0); give 4 remaining doses on days 3, 7, 14, and 28, respectively, after first dose. If rabies vaccine is not immediately available, administer RIG dose and start the vaccine series as soon as possible.

Administer RIG dose preferably at the time of the first dose of rabies vaccine. If RIG is not immediately available, it may be administered at any time through day 7 following the first vaccine dose. RIG is not necessary after day 7 since sufficient vaccine-induced rabies antibody will be present in most vaccine recipients. (See Specific Drugs under Interactions.)

Previously Vaccinated Children and Adolescents

IM

Postexposure prophylaxis in previously vaccinated individuals consists of a series of 2 booster doses of rabies vaccine (without RIG).

Each booster dose consists of the entire contents (1 mL) of a reconstituted single-dose vial.

Give first dose as soon as possible after exposure (day 0); give second dose 3 days later.

This 2-dose regimen can be used in those who previously received a preexposure or postexposure vaccination regimen with Imovax^® Rabies, RabAvert^®, Imovax^® Rabies I.D. (no longer commercially available in the US), or rabies vaccine adsorbed (RVA; no longer commercially available in the US) or those who previously received preexposure vaccination with some other vaccine and had documented antirabies antibody titers.

Adults

Preexposure Vaccination Against Rabies in High-risk Groups

Primary Immunization in Adults

IM

Primary immunization consists of a series of 3 doses. Each dose consists of the entire contents (1 mL) of a reconstituted single-dose vial.

Give first dose on a selected date; give second and third doses 7 and 21 (or 28) days, respectively, after first dose.

Completion of the primary series before an expected exposure to rabies virus ensures the highest level of protection.

Duration of immunity following the recommended 3-dose primary series is ≥2 years. (See Duration of Immunity under Cautions.) Need for additional (booster) doses depends on the category of risk for rabies infection and levels of antirabies antibody. (See Booster Doses in Adults under Dosage and Administration.)

Booster Doses in Adults

IM

Each booster dose consists of the entire contents (1 mL) of a reconstituted single-dose vial.

Give a booster dose if indicated to maintain protective levels of antirabies antibody. Booster doses may be indicated in those at continuous or frequent risk of rabies, but not in those at infrequent or rare risk. (For information on ACIP definitions of risk categories, see the table under Uses.)

In those at continuous risk of rabies, perform serologic testing every 6 months and administer booster dose if necessary.

In those at frequent risk, perform serologic testing every 2 years and administer booster dose if necessary.

Postexposure Prophylaxis of Rabies

Previously Unvaccinated Adults

IM

Postexposure prophylaxis consists of active immunization with a series of 5 doses of rabies vaccine in conjunction with passive immunization with a single dose of RIG.

Give first vaccine dose as soon as possible after exposure (day 0); give 4 remaining doses on days 3, 7, 14, and 28, respectively, after first dose. If rabies vaccine is not immediately available, administer RIG dose and start the vaccine series as soon as possible.

Administer RIG dose preferably at the time of the first dose of rabies vaccine. If RIG is not immediately available, it may be administered at any time through day 7 following the first vaccine dose. RIG is not necessary after day 7 since sufficient vaccine-induced rabies antibody will be present in most vaccine recipients. (See Specific Drugs under Interactions.)

Previously Vaccinated Adults

IM

Postexposure prophylaxis in previously vaccinated individuals consists of a series of 2 booster doses of rabies vaccine (without RIG).

Each booster dose consists of the entire contents (1 mL) of a reconstituted single-dose vial.

Give first dose as soon as possible after exposure (day 0); give second dose 3 days later.

This 2-dose regimen can be used in those who previously received a preexposure or postexposure vaccination regimen with Imovax^® Rabies, RabAvert^®, Imovax^® Rabies I.D. (no longer commercially available in the US), or rabies vaccine adsorbed (RVA; no longer commercially available in the US) or those who previously received preexposure vaccination with some other vaccine and had documented antirabies antibody titers.

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

No specific dosage recommendations.

Geriatric Patients

No specific dosage recommendations.

Cautions

Contraindications

• Imovax^® (preexposure vaccination): Manufacturer states none known other than situations such as developing febrile illness, etc. (See Concomitant Illness under Cautions.)
• RabAvert^® (preexposure vaccination): History of anaphylactic reactions to the vaccine or any component. (See Sensitivity Reactions under Cautions.)
• Imovax^® and RabAvert^® (postexposure prophylaxis): No known contraindications, including pregnancy, because of the almost invariably fatal outcome of rabies infection. (See Pregnancy under Cautions.)

Warnings/Precautions

Warnings

Neurologic Effects

Neurologic effects, sometimes serious (e.g., Guillain-Barré syndrome, transient neuroparalysis, myelitis, retrobulbar neuritis, multiple sclerosis, subacute peripheral and focal CNS disorders) temporally associated with Imovax^® and RabAvert^®.

If neurologic effects occur, carefully consider the individual's risk of acquiring rabies when deciding whether to discontinue the vaccination series. Contact state health departments or CDC for advice and assistance regarding management of these individuals.

Use of corticosteroids to treat life-threatening neuroparalytic reactions may interfere with the immune response to rabies vaccine. (See Specific Drugs under Interactions.) Perform serologic testing in individuals receiving corticosteroids to verify seroconversion following vaccination. (See Pre- and Postvaccination Serologic Testing under Cautions.)

Immediately report all serious vaccine-associated neuroparalytic reactions to the manufacturer and to the Vaccine Adverse Event Reporting System (VAERS) at 800-822-7967 or http://www.vaers.hhs.gov/.

Administration Precautions

Administer IM preferably into the anterolateral thigh in infants and young children and into the deltoid muscle in adults, adolescents, and older children. (See Administration under Dosage and Administration.)

Do not administer into gluteal muscle; suboptimal immunologic response may occur. Reason for suboptimal response unclear; may occur because of inadvertent sub-Q injection or administration into fatty tissue instead of muscle. Fatal rabies paralysis and encephalitis reported in several individuals who received Imovax^® by IM injection into the gluteal area.

Inadvertent intravascular injection of RabAvert^® may result in systemic reactions (e.g., shock); immediate countermeasures include use of catecholamines, volume replacement, high doses of corticosteroids, and oxygen.

Individuals with Altered Immunocompetence

May be administered to individuals immunosuppressed as the result of disease or immunosuppressive therapy. Consider possibility that the immune response to rabies vaccine and efficacy may be reduced in these individuals.

ACIP states that recommendations concerning use of rabies vaccine in individuals with altered immunocompetence (e.g., patients with HIV infection, congenital immunodeficiency, leukemia, lymphoma, aplastic anemia, generalized malignancy, solid organ transplant, asplenia, renal failure, diabetes, alcoholism, or alcoholic cirrhosis, or in those receiving therapy with alkylating agents, antimetabolites, radiation, corticosteroids, or other chronic immunosuppressive therapy) are the same as those for patients who are not immunocompromised.

Postpone preexposure vaccination (3-dose series) in immunocompromised individuals and advise them to avoid activities for which rabies preexposure vaccination is indicated. If this is not possible, administer preexposure vaccination and perform serologic testing to document seroconversion. (See Pre- and Postvaccination Serologic Testing under Cautions.) Individuals who fail to seroconvert after the third vaccine dose should be managed in consultation with appropriate public health officials.

If rabies postexposure prophylaxis is indicated in an immunocompromised individual, serologic testing is considered essential to confirm than an adequate antibody response is obtained. Perform serologic testing 14 days after the postexposure prophylaxis regimen is initiated (i.e., day of the fourth vaccine dose) to document seroconversion. (See Pre- and Postvaccination Serologic Testing under Cautions.)

Avoid use of immunosuppressive agents during postexposure prophylaxis unless considered essential for the treatment of other conditions. (See Specific Drugs under Interactions.)

Risk of Transmissible Agents in Preparations Containing Albumin

Imovax^® and RabAvert^® contain albumin human.

Since albumin is prepared from pooled human plasma, it is a potential vehicle for transmission of human viruses, including the causative agents of viral hepatitis and HIV infection, and theoretically may carry a risk of transmitting the causative agent of Creutzfeldt-Jakob disease (CJD) or variant CJD (vCJD).

Improved donor screening, viral-inactivation procedures (e.g., solvent/detergent treatment), and/or filtration procedures have reduced, but not completely eliminated, risk of pathogen transmission with plasma-derived preparations.

Sensitivity Reactions

Hypersensitivity Reactions

Allergic reactions, including anaphylaxis, reported in association with RabAvert^®. Bronchospasm, edema, pruritus, and urticaria also reported during postmarketing surveillance.

Serious anaphylactic reactions during rabies vaccination pose a serious therapeutic dilemma. Carefully consider the individual's risk of acquiring rabies when deciding whether to discontinue the vaccination series. Contact state health departments or CDC for advice and assistance regarding management of these individuals.

When rabies vaccine is indicated in an individual with a history of hypersensitivity to the vaccine or any ingredient, observe patient closely following each dose and ensure that appropriate therapy (e.g., epinephrine, corticosteroids, oxygen) is readily available to treat a reaction if it occurs. Use of prophylactic antihistamines is acceptable.

Immediately report all serious anaphylactic reactions associated with rabies vaccine to the manufacturer and the Vaccine Adverse Event Reporting System (VAERS) at 800-822-7967 or http://www.vaers.hhs.gov/.

Immune Complex-like Reactions

Immune complex (serum sickness)-like (type III hypersensitivity) reactions reported in up to 6% of individuals 2–21 days following booster doses of Imovax^®. Similar reactions also reported following primary immunization with Imovax^®, but much less frequently.

These reactions involved generalized urticaria with or without arthralgia, arthritis, angioedema, nausea, vomiting, fever, and malaise and were not life-threatening.

May be caused by propiolactone-altered albumin human formed as a result of the manufacturing process for Imovax^®; propiolactone is thought to render the albumin allergenic resulting in development of IgE antibodies to the allergen.

Do not administer additional doses of Imovax^® in individuals who experienced immune complex-like reactions to a previous dose, unless postexposure prophylaxis with the vaccine is considered necessary.

Allergy to Neomycin or Other Anti-infectives

Imovax^® contains <150 mcg of neomycin sulfate. RabAvert^® contains <1 mcg of neomycin and trace amounts of chlortetracycline and amphotericin B.

Use caution in individuals sensitive to these antibiotics. Weigh possibility of an allergic reaction against the potential risk of contracting rabies if the vaccine is not given.

Neomycin allergy usually results in delayed-type (cell-mediated) hypersensitivity reactions manifested as contact dermatitis. ACIP and AAP state that vaccines containing trace amounts of neomycin should not be used in individuals with a history of anaphylactic reaction to neomycin, but use of such vaccines may be considered in those with a history of delayed-type neomycin hypersensitivity if benefits of vaccination outweigh the risks.

Gelatin Allergy

RabAvert^® contains 12 mg of polygeline (bovine gelatin). Consider possibility of allergic reactions in individuals sensitive to bovine gelatin.

Allergy to Egg-related Antigens

RabAvert^® is produced in chick embryo cell culture and may contain minimal amounts of chicken protein. Imovax^® is produced in human diploid cells and does not contain chicken protein.

Consider possibility that an allergic reaction may occur if RabAvert^® is used in individuals allergic to chicken protein.

Safety data regarding use of RabAvert^® in individuals with egg allergy not available. Experience with other vaccines produced using primary cultures of chick embryo fibroblasts indicate that documented egg hypersensitivity does not necessarily predict an increased likelihood of adverse reactions.

No evidence to date that individuals with allergies to chickens or feathers are at increased risk of reaction to vaccines produced in chick embryo fibroblasts.

General Precautions

Local or Systemic Adverse Effects

Once initiated, postexposure prophylaxis for rabies should not be interrupted or discontinued because of local or mild systemic adverse reactions to rabies vaccine. These reactions generally can be managed with NSAIAs or antipyretic agents (ibuprofen, acetaminophen).

Serious systemic, anaphylactic, or neuroparalytic reactions pose a therapeutic dilemma. Contact state health departments or CDC for advice and assistance regarding management of these individuals.

Limitations of Vaccine Effectiveness

May not protect all vaccine recipients against rabies.

May not prevent rabies in individuals who do not achieve protective antibody titers. (For information on protective antibody levels, see Pre- and Postvaccination Serologic Testing under Cautions.)

Duration of Immunity

Duration of immunity following the recommended 3-dose preexposure vaccine series is ≥2 years. Need for additional (booster) doses depends on the nature of risk for rabies infection and an individual's associated level of potential exposure. (See Booster Doses in Children and Adolescents and also see Booster Doses in Adults under Dosage and Administration)

Concomitant Illness

A decision to administer or delay vaccination in an individual with current or recent febrile illness depends on the severity of symptoms and etiology of the illness.

ACIP states that minor acute illness, such as mild diarrhea or mild upper respiratory tract infection (with or without fever) generally does not preclude vaccination.

The manufacturers and ACIP state that preexposure rabies vaccination (but not postexposure prophylaxis) with rabies vaccine (Imovax^®, RabAvert^®) generally should be deferred in individuals with moderate or severe acute illness until improvement of the condition is noted.

Individuals with Bleeding Disorders

Because bleeding may occur following IM administration in individuals with thrombocytopenia or a bleeding disorder (e.g., hemophilia) or in those receiving anticoagulant therapy, use caution in such individuals.

ACIP states that vaccines may be given IM to individuals who have bleeding disorders or are receiving anticoagulant therapy if a clinician familiar with the patient's bleeding risk determines that the vaccine can be administered with reasonable safety. In these cases, use a fine needle (23 gauge) to administer the vaccine and apply firm pressure to the injection site (without rubbing) for ≥2 minutes. If patient is receiving antihemophilia therapy, administer the IM vaccine shortly after a scheduled dose of such therapy.

Advise the individual and/or their family about the risk of hematoma from IM injections.

Pre- and Postvaccination Serologic Testing

If serologic testing for serum antirabies antibody is performed 2–4 weeks after preexposure vaccination or postexposure prophylaxis, the minimum antibody titer needed to confer rabies immunity as defined by the CDC is complete virus neutralization at a 1:5 serum dilution when determined by rapid fluorescent-focus inhibition test (RFFIT). WHO considers an antirabies antibody titer of ≥0.5 international units/mL as a protective level of rabies immunity.

Serologic confirmation of rabies immunity following preexposure vaccination (3-dose primary series) is not necessary in most individuals because of the high rate of response in immunocompetent adults and children when the recommended vaccine regimen is used.

Postvaccination serologic testing may be particularly important in immunocompromised individuals since these individuals may have impaired immune response to vaccination. Manage individuals who fail to seroconvert after the third vaccine dose in consultation with appropriate public health officials. (See Individuals with Altered Immunocompetence under Cautions.)

To determine the need for preexposure booster doses of rabies vaccine in individuals who received preexposure vaccination with a primary vaccine series, serum antirabies antibody titers should be measured every 6 months in those at continuous risk of rabies exposure and every 2 years for those at frequent risk of rabies exposure. (For ACIP definitions of risk categories, see the table under Uses.)

Serologic testing is not indicated prior to postexposure prophylaxis in previously vaccinated individuals who are exposed to rabies. Such testing is inappropriate because it would delay postexposure prophylaxis and, although antirabies neutralizing antibodies are an important component of immunity, other immune effectors also play a role in disease prevention.

Serologic confirmation of rabies immunity following postexposure prophylaxis (5-dose series of rabies vaccine) is not necessary in most individuals because of the high rate of vaccine response among immunocompetent adults and children when the recommended regimen is used.

When postexposure prophylaxis is indicated in an immunocompromised individual, serologic testing is considered essential to confirm that a protective antibody response was obtained. Perform serologic testing 14 days after the postexposure prophylaxis regimen is initiated (i.e., day of the fourth vaccine dose) to document protective antibody levels in individuals receiving immunosuppressive agents (e.g., those receiving corticosteroids for the treatment of life-threatening neuroparalytic reactions to rabies vaccine). (See Individuals with Altered Immunocompetence under Cautions.)

Consider serologic testing to confirm that a protective antibody response was obtained in travelers who received rabies postexposure prophylaxis with regimens and/or preparations not currently recommended by ACIP to confirm a protective immune response. (See Postexposure Prophylaxis of Rabies under Uses.)

Improper Storage and Handling

Improper storage or handling of vaccines may result in loss of vaccine potency and reduced immune response in vaccinees.

Do not administer Imovax^® or RabAvert^® that has been mishandled or has not been stored at the recommended temperature (2–8°C). (See Storage under Stability.)

Inspect all vaccines upon delivery and monitor during storage to ensure that the appropriate temperature is maintained.

Specific Populations

Pregnancy

Category C.

ACIP, AAP, American College of Obstetricians and Gynecologists (ACOG), and the manufacturers state that pregnancy is not considered a contraindication for postexposure prophylaxis with rabies vaccine because of the potential risks of inadequately treated rabies exposure and because there is no evidence of an association between fetal abnormalities and rabies vaccine. ACOG recommends that each pregnant woman be considered individually and that public health authorities be consulted.

Preexposure vaccination may also be indicated during pregnancy when a substantial risk of rabies exposure is present.

Lactation

Not known whether antigens contained in rabies vaccine are distributed into milk. CDC states the vaccine is commonly administered to nursing women without unusual adverse effects.

Because inactivated vaccines do not multiply within the body, they should not pose any unusual problems for nursing women or their infants.

RabAvert^®: Manufacturer states nursing is not considered a contraindication when the vaccine is indicated for postexposure prophylaxis because of the possible risks of inadequately treated rabies exposure. In addition, use of the vaccine for preexposure vaccination may be indicated in nursing women when a substantial risk of rabies exposure is present.

Pediatric Use

Imovax^®: Safety and efficacy in children established.

RabAvert^®: Limited data available regarding safety and efficacy in children. Used effectively for preexposure vaccination in children ≥2 years of age and for postexposure prophylaxis in children ≥1 year of age.

AAP recommends preexposure vaccination in children traveling to areas where they may encounter rabid animals (e.g., dogs in developing countries) or engage in activities involving increased risk of rabies transmission (e.g., spelunking). Children are at higher risk of rabies exposure compared with adults because of increased potential for animal contact and serious bites to the head, face, and neck.

ACIP, AAP, and the manufacturers recommend that postexposure prophylaxis in children follow the same guidelines as in adults.

Geriatric Use

RabAvert^®: Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently to the vaccine than younger adults. Clinical experience with RabAvert^® reveals that there are no overall differences in safety between geriatric and younger individuals.

Common Adverse Effects

Imovax^®: Local effects at injection site (pain, swelling, erythema, itching), mild systemic reactions (headache, nausea, abdominal pain, muscle aches, dizziness).

RabAvert^®: Local effects at injection site (pain, swelling, erythema, itching), influenza-like symptoms (mild to moderate asthenia, fatigue, fever, myalgia, malaise, headache).

Interactions

Other Vaccines

Imovax^® and RabAvert^® rabies vaccines are inactivated viral vaccines; interactions with other inactivated vaccines, live virus vaccines, recombinant vaccines, or toxoids are unlikely. Inactivated vaccines can be administered either simultaneously with or at any time before or after inactivated or live vaccines. However, each vaccine should be administered using a different syringe and a different injection site.

Specific Drugs

Stability

Storage

Parenteral

Suspension for IM Injection

Imovax^®: Prior to reconstitution, 2–8°C; avoid freezing.

RabAvert^®: Prior to reconstitution, 2–8°C; protect from light.

Must be used immediately after reconstitution; discard if not used immediately.

Imovax^® and RabAvert^® do not contain thimerosal or any other preservatives.

Actions

• Rabies vaccine is a sterile, freeze-dried vaccine containing inactivated rabies virus antigen (≥2.5 international units/mL).
• Commercially available as human diploid-cell rabies vaccine (HDCV; Imovax^®) or purified chick embryo cell culture rabies vaccine (PCECV; RabAvert^®).
• Imovax^® contains whole-virus antigen prepared from the Wistar Institute Pitman-Moore strain (PM-1503-3M) of rabies virus propagated in MRC-5 strain of human diploid-cell tissue culture. RabAvert^® contains antigens prepared from the fixed-virus strain Flury low egg passage (LEP) of rabies virus propagated in primary cultures of chicken fibroblasts.
• Stimulates active immunity to rabies by inducing production of IgG antirabies neutralizing antibodies. Antirabies antibodies neutralize rabies virus so that spread of the virus is retarded and its infective or pathogenic properties are inhibited.
• Imovax^® and RabAvert^® are highly immunogenic in most children, adolescents, and adults. When administered according to the recommended preexposure immunization schedule in clinical studies, 100% of vaccinees achieved protective levels of antirabies antibody.
• Following IM administration of Imovax^®, antirabies antibody levels are detectable in serum within 7–10 days, peak within 30–60 days, and persist for ≥2 years. In one study following IM administration of Imovax^®, mean rabies antibody titers determined by RFFIT at 0, 3, 7, and 14 days were 0.05, 0.6, 40.2, 16.3, and 2.4 international units/mL at 7, 10, 28, 60, and 150 days, respectively.
• Following rabies exposure and inoculation, the virus remains close to the wound for an indeterminate time, and can be partially neutralized with RIG while at this site. In susceptible individuals, the virus may move along a neural pathway toward the CNS. Following entrance into the CNS, the virus is unlikely to be affected by antirabies antibodies and a fatal encephalomyelitis almost always develops.
• Incubation period for rabies infection varies from 5 days to several years (usually 20–60 days). After severe bites to the face, neck, or arms, the incubation period may be as short as 10 days.
• Common prodromal symptoms of rabies infection include malaise, anorexia, fatigue, headache, and fever followed by pain or paresthesia at the site of exposure. Anxiety, agitation, and irritability may also occur during the prodromal stage followed by hyperactivity, disorientation, seizures, aerophobia, hydrophobia, hypersalivation, and eventually paralysis, coma, and death. Following appearance of clinical symptoms of rabies, use of rabies vaccine or RIG will not improve the prognosis and there is no specific treatment for the disease.
• Development of immunity and protection from rabies infection are determined by appearance of antirabies antibody in serum. Minimum titers of antirabies antibodies conferring protection against rabies have not been definitely established to date (varies among laboratories and by type of test performed). CDC considers antirabies antibody titers ≥1:5 as determined by RFFIT to be indicative of a protective response to rabies immunization. WHO considers a titer of ≥0.5 international units/mL to be protective. However, presence of an adequate antirabies antibody titer may not be an absolute indication of protection against rabies.

Advice to Patients

• Prior to administration of each vaccine dose, provide a copy of the appropriate CDC Vaccine Information Statement (VIS) to the patient or patient's legal representative as required by the National Childhood Vaccine Injury Act (VISs are available at http://www.cdc.gov/vaccines/pubs/vis/default.htm).
• Advise the patient and/or patient's parent or guardian of the risks and benefits of vaccination with rabies vaccine.
• Advise the patient and/or patient's parent or guardian that rabies vaccine is used to prevent rabies and is given to persons at high risk of exposure to rabies as a result of employment, travel, or hobbies (e.g., certain laboratory workers, veterinarians, animal control and wildlife workers, spelunkers, hunters).
• Advise the patient and/or patient's parent or guardian that rabies vaccine is also used to prevent rabies in individuals who have been bitten, scratched, or licked on an open wound by an animal known or suspected of having rabies.
• When rabies preexposure vaccination is indicated, importance of completing the 3-dose primary vaccination series.
• When rabies postexposure prophylaxis is indicated in previously unvaccinated individuals, importance of completing a 5-dose series of rabies vaccine and receiving a single dose of RIG as soon as possible following rabies exposure.
• When rabies postexposure prophylaxis is indicated in previously vaccinated individuals, importance of receiving a 2-dose regimen of rabies vaccine as soon as possible following rabies exposure.
• Importance of informing clinicians if the patient has a weakened immune system (e.g., cancer, HIV/AIDS) or receives treatment that may weaken the immune system (e.g., corticosteroids, cancer treatment).
• Importance of informing clinicians if a patient has a fever or serious illness. Advise patient that preexposure vaccination may be deferred if they are moderately or severely ill, but that rabies postexposure prophylaxis will still be administered, regardless of any other illness they may have.
• Importance of informing clinicians if any serious adverse reactions (e.g., hypersensitivity, neurologic reactions) occur. Clinicians or individuals can report any adverse reactions that occur following vaccination to the Vaccine Adverse Event Reporting System (VAERS) at 800-822-7967 or http://www.vaers.hhs.gov/.
• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, and any concomitant illnesses.
• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

AHFS Drug Information. © Copyright, 1959-2009, Selected Revisions June 2008. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.