Rabies Vaccine

Anaphylaxis, encephalitis including death, meningitis, neuroparalytic events such as encephalitis, transient paralysis, Guillain-Barre Syndrome, myelitis, and retrobulbar neuritis; and multiple sclerosis have been reported to be temporally associated with the use of RabAvert. See PRECAUTIONS and ADVERSE EVENTS sections. A patient's risk of developing rabies must be carefully considered, however, before deciding to discontinue immunization.

RABAVERT MUST NOT BE USED SUBCUTANEOUSLY OR INTRADERMALLY.

RabAvert must be injected intramuscularly. For adults, the deltoid area is the preferred site of immunization; for small children and infants, administration into the anterolateral zone of the thigh is preferred. The use of the gluteal region should be avoided, since administration in this area may result in lower neutralizing antibody titers1.

DO NOT INJECT INTRAVASCULARLY.

Unintentional intravascular injection may result in systemic reactions, including shock. Immediate measures include catecholamines, volume replacement, high doses of corticosteroids, and oxygen.

Development of active immunity after vaccination may be impaired in immune-compromised individuals. Please refer to Drug Interactions, under Precautions.

This product contains albumin, a derivative of human blood. It is present in RabAvert at concentrations of less than 0.3 mg/dose. Based on effective donor screening and product manufacturing processes, it carries an extremely remote risk for transmission of viral diseases. A theoretical risk for transmission of Creutzfeld-Jakob disease (CJD) also is considered extremely remote. No cases of transmission of viral diseases or CJD have ever been identified for albumin.

No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.

Prevention of Rabies

Prevention of rabies in children, adolescents, and adults exposed to or at increased risk of exposure to rabies disease or virus.208 213 234 236 250

Rabies is a viral infection transmitted by saliva of infected mammals, most commonly wild, terrestrial carnivores (e.g., skunks, raccoons, foxes, coyotes) or bats.213 236 In the US, the greatest risk for naturally acquired rabies is from contact with and bites from insectivorous bats.222 236 242 Following exposure and infection, rabies virus usually moves along a neural pathway and enters the CNS.234 236 After entrance into the CNS, the virus is unlikely to be affected by antirabies antibodies and encephalomyelitis usually develops and almost always is fatal.234 236 In the US, approximately 16,000–39,000 individuals receive rabies postexposure prophylaxis each year.234 236 250 Although there were 27 rabies cases reported in the US during 2000–2008,250 these individuals evidently did not receive rabies postexposure prophylaxis.250 Rabies prevention and control strategies and elimination of canine rabies virus variants and enzootic transmission among dogs have lowered the number of rabies cases in the US to an average of 1–2 per year.250 However, worldwide, rabies is much more common and at least 55,000 rabies-related deaths occur each year.249 250

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 increased risk of exposure to the virus.213 236 (See Preexposure Vaccination Against Rabies in High-risk Groups under Uses.)

Postexposure prophylaxis with a regimen that includes local wound treatment, rabies vaccine (series of 4 or 5 doses), and a single dose of rabies immune globulin (RIG) is recommend for previously unvaccinated children, adolescents, and adults following potential rabies exposure.213 236 Postexposure prophylaxis with a regimen that includes local wound treatment and a series of 2 booster doses of rabies vaccine (without RIG) is recommended for previously vaccinated children, adolescents, and adults following potential rabies exposure.213 236 (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.208 213 234 236

Preexposure vaccination does not eliminate the need for prompt postexposure prophylaxis if an exposure to rabies occurs.208 213 234 236 250 (See Postexposure Prophylaxis of Rabies under Uses.)

Need for rabies preexposure vaccination depends on the nature of risk and associated level of potential exposure.236 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).212 236 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.236 (For ACIP definitions of risk categories and recommendations regarding preexposure vaccination for each category, see Table 1.)

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.212 236 237 249 Canine rabies remains highly endemic in certain areas of the world (e.g., parts of Africa, Asia, Central and South America).212 237 CDC recommends preexposure vaccination based on local incidence of rabies in the country to be visited, availability of appropriate agents for rabies postexposure prophylaxis in that country, and intended activity and duration of stay.212

Minimum acceptable antibody titer is complete virus neutralization at a 1:5 serum dilution by the rapid fluorescent focus inhibition test (RFFIT). Give booster dose of rabies vaccine if titer falls below this level.

Adapted from the Recommendations of the Advisory Committee on Immunization Practices (ACIP) on Human Rabies Prevention. MMWR Recomm Rep. 2008; 57 (RR-3):1-28.

Postexposure Prophylaxis of Rabies

Postexposure prophylaxis of rabies in previously vaccinated and unvaccinated children, adolescents, and adults following exposure to rabies disease or virus.208 213 234 236 250

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.208 234 236 250

Whenever a possible human exposure to rabies occurs, the risk of infection must be accurately assessed to determine the need for postexposure prophylaxis.236 250 Base decisions regarding the need for postexposure prophylaxis on vaccination status of exposed individual (see Table 2), type of exposure (bite, nonbite), information about the animal involved (type, vaccination status, condition at time of attack) (see Table 3), and rabies epidemiology in the specific geographic region.213 236 250 Consult local or state public health officials for assistance when evaluating rabies exposures and the need for postexposure prophylaxis.213 236 250

Any person with a history of a complete preexposure or postexposure vaccination regimen with HDCV, PCECV, or rabies vaccine adsorbed (RVA; not commercially available in the US), or previous vaccination with any other type of rabies vaccine and a documented history of antibody response to the prior vaccination

Individuals with immunosuppression should receive a 5-dose regimen of rabies vaccine; give 1 mL (HDCV or PCECV) IM once on days 0, 3, 7, 14, and 28.

Deltoid area is the only acceptable site for IM administration of rabies vaccine in adults, adolescents, and older children. For younger children, deltoid or anterolateral thigh should be used. Never administer in gluteal area.

Day 0 is the day the first dose of rabies vaccine is administered.

Adapted from Use of a Reduced (4-Dose) Vaccine Schedule for Postexposure Prophylaxis to Prevent Human Rabies. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2010; 59 (RR-2):1-9.

Regardless of rabies immunization status, ACIP and AAP recommend that postexposure prophylaxis of rabies begin immediately with thorough cleansing of all bite wounds and scratches using soap and water and, if available, irrigation with a virucidal agent such as povidone-iodine solution.213 236 250 Local wound treatment is an essential initial step in rabies postexposure prophylaxis in all individuals.213 236 250 (See General under Dosage and Administration.)

In previously unvaccinatedchildren, adolescents, and adults following potential rabies exposure, a postexposure prophylaxis regimen of active immunization with a 4- or 5-dose regimen of rabies vaccine and passive immunization with a single dose of RIG is recommended as soon as possible.208 213 234 236 250 The ACIP states that a 4-dose regimen of rabies vaccine in conjunction with RIG is sufficient for postexposure prophylaxis in previously unvaccinated individuals who are immunocompetent; however, a 5-dose vaccine regimen in conjunction with RIG should be used in those with altered immunocompetence.250

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.213 236 250

During the 10-day observation period, begin postexposure prophylaxis in the exposed individual at the first sign of rabies in a dog, cat, or ferret that has bitten them. If the animal exhibits clinical signs of rabies, euthanize it immediately and perform appropriate testing.

Initiate postexposure prophylaxis as soon as possible following exposure to such wildlife, unless animal is available for testing and public health authorities are facilitating expeditious laboratory testing or it is already known that brain material from the animal has tested negative. Other factors that might influence urgency of decision-making regarding initiation of postexposure prophylaxis before diagnostic results are known include the animal species, general appearance and behavior of the animal, whether encounter was provoked by a human, and the severity and location of bites. Discontinue postexposure prophylaxis if appropriate laboratory tests (i.e., direct fluorescent antibody test) are negative.

Euthanize the animal and test as soon as possible. Holding for observation is not recommended.

Adapted from the Recommendations of the Advisory Committee on Immunization Practices (ACIP) on Human Rabies Prevention. MMWR Recomm Rep. 2008; 57 (RR-3):1-28.

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.213 236 Risk of transmission varies in part based on species of biting animal, anatomic site of bite, and severity of wound.236 Rabies transmission can occur from bites of some animals (e.g., bats) that inflict rather minor injury and wounds that are difficult to detect.236

Any potential exposure to a bat requires thorough evaluation.236 If possible, the bat should be submitted for rabies diagnosis.236 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.236 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).236 Other household members who did 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.236

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.213 236 Although nonbite exposures only rarely cause rabies, such exposures require assessment to determine if sufficient reasons exist to consider postexposure prophylaxis.213 236 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.236

Transmission of rabies to individuals performing autopsies not reported to date;251 no confirmed cases of rabies reported in individuals performing postmortem examinations of humans or animals.251 CDC recommends that personnel performing autopsies on decedents with confirmed or suspected rabies use appropriate personal protective equipment, wear heavy or chain mail gloves, minimize aerosol generation by using a handsaw rather than oscillating saw, limit the number of individuals participating in the procedure and collection of specimens, and use ample amounts of 10% sodium hypochlorite solution during and after the procedure to ensure decontamination of all exposed surfaces.251 CDC states that preexposure vaccination against rabies usually is not required for individuals performing autopsies and that rabies postexposure prophylaxis is recommended in autopsy personnel only if a wound or mucous membrane gets contaminated with the patient's saliva or other potentially infectious material (e.g., neural tissue) during the procedure.251

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.236

In health-care personnel, routine delivery of health care to a patient with rabies is not an indication for postexposure rabies prophylaxis; postexposure prophylaxis in such personnel is indicated if they have been bitten by the patient or if they have mucous membranes or nonintact skin (e.g., open wounds) that were contaminated with the patient's saliva or other potentially infectious material (e.g., neural tissue).236

Because the rabies incubation period in humans can range from days to years (usually 1–3 months),212 213 234 236 250 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.236

Postexposure prophylaxis failures have not been reported in the US when recommended wound management and postexposure regimens were followed using commercially available rabies vaccines and RIG.236 250 ACIP states that rabies pathogenesis data, animal data, clinical studies, and epidemiologic surveillance indicate that a 4-dose vaccine series is as effective as a 5-dose vaccine series when used in conjunction with wound management and RIG.250 Rare reports of postexposure prophylaxis failures in other countries usually involved some deviation from recommended procedures (e.g., postexposure prophylaxis not given or substantially delayed, wounds not adequately cleansed, rabies vaccine given IM 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, use of less than the recommended number of vaccine doses).234 236 250

Travelers to rabies-endemic countries should be warned about the risk of acquiring rabies and educated in bite prevention strategies (e.g., avoiding contact with bats, avoiding stray dogs, monkeys, or cats).212 Because appropriate preparations of RIG or rabies vaccine may be not available for postexposure prophylaxis in the destination country, CDC recommends that travelers to such countries have a preplanned strategy in place that may involve identifying a different country where appropriate postexposure prophylaxis can be obtained if necessary.212 CDC states that rabies vaccines grown in animal brains (nerve tissue vaccines; NTV) may still be used in some developing countries; if offered such a vaccine (identified by a regimen that requires 5-mL injections once daily for 14–21 days), travelers should refuse the vaccine and travel to a country where an acceptable rabies vaccine and RIG are available.212 If travelers in other countries receive postexposure prophylaxis with regimens and/or preparations not recommended by ACIP (or not used in the US), additional therapy may be necessary following return to the US.212 236 In such cases, consult state and local health authorities for advice regarding the need for additional postexposure prophylaxis.236 Consider serologic testing in these travelers to verify efficacy of the regimen used and to ensure an adequate immune response.236 (See Pre- and Postvaccination Serologic Testing under Cautions.)

Contraindications

• HDCV (Imovax) for preexposure vaccination: Manufacturer states none known other than situations such as developing febrile illness, etc.208 (See Concomitant Illness under Cautions.)

• PCECV (RabAvert) for preexposure vaccination: History of anaphylactic reactions to the vaccine or any component.234 (See Sensitivity Reactions under Cautions.)

• HDCV (Imovax) and PCECV (RabAvert) for postexposure prophylaxis: No known contraindications, including pregnancy, because of the almost invariably fatal outcome of rabies infection.208 234 (See Pregnancy under Cautions.)

Warnings/Precautions

Warnings

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 HDCV (Imovax) and PCECV (RabAvert).208 234

If neurologic effects occur, carefully consider the individual's risk of acquiring rabies when deciding whether to discontinue the vaccination series.208 234 Contact state health departments or CDC for advice and assistance regarding management of these individuals.208 236

Use of corticosteroids to treat life-threatening neuroparalytic reactions may interfere with the immune response to rabies vaccine.208 234 (See Specific Drugs under Interactions.) Perform serologic testing in individuals receiving corticosteroids to verify seroconversion following vaccination.208 (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 .208 234

Administer IM into the deltoid or anterolateral thigh in infants and young children and into the deltoid in adults, adolescents, and older children.211 213 236 250 (See Administration under Dosage and Administration.)

Do not administer into gluteal muscle; suboptimal immunologic response may occur.208 209 210 211 212 213 216 221 234 250 Reason for suboptimal response unclear; may occur because of inadvertent sub-Q injection or administration into fatty tissue instead of muscle.209 210 211 221 Fatal rabies paralysis and encephalitis reported in several individuals who received HDCV (Imovax) by IM injection into the gluteal area.210 216 221

Inadvertent intravascular injection of PCECV (RabAvert) may result in systemic reactions (e.g., shock); immediate countermeasures include use of catecholamines, volume replacement, high doses of corticosteroids, and oxygen.234

Do not administer RIG in the same syringe or simultaneously at the same injection site as rabies vaccine.213 236 246 250 (See Specific Drugs under Interactions.)

May be administered to individuals immunosuppressed as the result of disease or immunosuppressive therapy.211 233 236 250 Consider possibility that the immune response to rabies vaccine and efficacy may be reduced in these individuals.208 213 234 236 250

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) generally are the same as those for patients who are not immunocompromised.233 236 250 However, the ACIP states that a 5-dose vaccine series (not a 4-dose series) of HDCV (Imovax) or PCECV (RabAvert) should be used when rabies postexposure prophylaxis is indicated in previously unvaccinated individuals with altered immunocompetence.250 (See Previously Unvaccinated Children and Adolescents and also see Previously Unvaccinated Adults under Dosage and Administration.)

Postpone preexposure vaccination (3-dose primary series) in immunocompromised individuals and advise them to avoid activities for which rabies preexposure vaccination is indicated.212 236 If this is not possible, administer preexposure vaccination and perform serologic testing to document seroconversion.212 236 (See Pre- and Postvaccination Serologic Testing under Cautions.) Individuals who fail to seroconvert after the third vaccine dose should be managed in consultation with their clinician and appropriate public health officials.236

Avoid use of immunosuppressive agents during rabies postexposure prophylaxis, unless considered essential for the treatment of other conditions.233 234 236 250 (See Specific Drugs under Interactions.)

If rabies postexposure prophylaxis is indicated in an immunocompromised individual, serologic testing is considered essential after completion of the postexposure prophylaxis regimen to confirm than an adequate antibody response is obtained.234 236 250 If an acceptable antibody response is not detected after the final vaccine dose of the postexposure prophylaxis series, the patient should be managed in consultation with their clinician and appropriate public health officials.216 250 (See Pre- and Postvaccination Serologic Testing under Cautions.)

HDCV (Imovax) and PCECV (RabAvert) contain albumin human.208 234

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).234 245

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.234

Sensitivity Reactions

Allergic reactions, including anaphylaxis and immune complex-like reactions, reported in association with HDCV (Imovax) or PCECV (RabAvert).208 219 234 236 Bronchospasm, edema, pruritus, and urticaria also reported during postmarketing surveillance.234

Serious anaphylactic reactions during rabies vaccination pose a serious therapeutic dilemma.208 234 236 Carefully consider the individual's risk of acquiring rabies when deciding whether to discontinue the vaccination series.208 236 Contact state health departments or CDC for advice and assistance regarding management of these individuals.208 236

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.208 234 236 Use of prophylactic antihistamines is acceptable.234 236

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 .213 234 236

Immune complex (serum sickness)-like (type III hypersensitivity) reactions reported in up to 6% of individuals 2–21 days following booster doses of HDCV (Imovax).208 219 236 Similar reactions also reported following primary immunization with HDCV (Imovax), but much less frequently.208 219 236

These reactions involved generalized urticaria with or without arthralgia, arthritis, angioedema, nausea, vomiting, fever, and malaise and were not life-threatening.208 219 236

May be caused by β-propiolactone-altered albumin human formed as a result of the manufacturing process for HDCV (Imovax); β-propiolactone is thought to render the albumin allergenic resulting in development of IgE antibodies to the allergen.236

Do not administer additional doses of HDCV (Imovax) in individuals who experienced immune complex-like reactions to a previous dose, unless postexposure prophylaxis with the vaccine is considered necessary.208

Each dose of HDCV (Imovax) contains <150 mcg of neomycin sulfate.208 Each dose of PCECV (RabAvert) contains <1 mcg of neomycin and trace amounts of chlortetracycline (<20 ng) and amphotericin B (<2 ng).234

Use caution in individuals sensitive to these antibiotics.234 Weigh possibility of an allergic reaction against the potential risk of contracting rabies if the vaccine is not given.208 234

Neomycin allergy usually results in delayed-type (cell-mediated) hypersensitivity reactions manifested as contact dermatitis.211 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.211 213

PCECV (RabAvert) contains <12 mg of polygeline (bovine gelatin).234 Consider possibility of allergic reactions in individuals sensitive to bovine gelatin.211 234 Bovine components of the vaccine originate only in the US, Australia, and New Zealand.234

PCECV (RabAvert) is produced in chick embryo cell culture and may contain minimal amounts of chicken protein.234 HDCV (Imovax) is produced in human diploid cells and does not contain chicken protein.208

Consider possibility that an allergic reaction may occur if PCECV (RabAvert) is used in individuals allergic to chicken protein.234

Safety data regarding use of PCECV (RabAvert) in individuals with egg allergy not available.234 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.234

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.234

General Precautions

Once initiated, postexposure prophylaxis for rabies should not be interrupted or discontinued because of local or mild systemic adverse reactions to rabies vaccine.208 234 236 These reactions generally can be managed with NSAIAs or antipyretic agents (e.g., ibuprofen, acetaminophen).208 234 236

Serious systemic, anaphylactic, or neuroparalytic reactions pose a therapeutic dilemma.208 236 Contact state health departments or CDC for advice and assistance regarding management of these individuals.208 236

May not protect all vaccine recipients against rabies.234

May not prevent rabies in individuals who do not achieve adequate antibody titers.234 236 (For information on adequate antibody titers, see Pre- and Postvaccination Serologic Testing under Cautions.)

Duration of immunity following the recommended 3-dose preexposure vaccine series (primary immunization) of HDCV (Imovax) or PCECV (RabAvert) is ≥2 years.213 234 236

Need for additional (booster) doses after primary immunization depends on the nature and category of risk associated with the potential exposure.236 (See Booster Doses in Children and Adolescents and also see Booster Doses in Adults under Dosage and Administration)

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.211

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.211 212 213

The manufacturers and ACIP state that preexposure rabies vaccination (but not postexposure prophylaxis) with HDCV (Imovax) or PCECV (RabAvert) generally should be deferred in individuals with moderate or severe acute illness until improvement of the condition is noted.208 211 234

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.211

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.211 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.211 If patient is receiving antihemophilia therapy, administer the IM vaccine shortly after a scheduled dose of such therapy.211

Advise the individual and/or their family about the risk of hematoma from IM injections.211

If serologic testing for serum antirabies antibody is performed 1–2 weeks after preexposure vaccination or postexposure prophylaxis, ACIP defines an adequate antibody response as complete virus neutralization at a 1:5 serum dilution when determined by rapid fluorescent-focus inhibition test (RFFIT).236 250 WHO states that an antirabies antibody titer of ≥0.5 international units/mL can be considered protective.249

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, adolescents, and children when the recommended vaccine regimen is used.208 212 213 234 236

Postvaccination serologic testing may be particularly important in immunocompromised individuals who receive preexposure vaccination since these individuals may have impaired immune response to vaccination.208 213 234 236 Manage individuals who fail to seroconvert after the third vaccine dose in the primary series in consultation with appropriate public health officials.236 (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.208 212 213 236 (For ACIP definitions of risk categories and recommendations regarding preexposure vaccination for each category, see Table 1 under Uses.)

Serologic testing is not indicated prior to postexposure prophylaxis in previously vaccinated individuals who are exposed to rabies.236 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.236

Serologic confirmation of rabies immunity following postexposure prophylaxis is not necessary in most individuals because of the high rate of vaccine response among immunocompetent adults, adolescents, and children when the recommended rabies postexposure prophylaxis regimen is used (i.e., proper wound care followed by a single dose of RIG and a 4- or 5-dose regimen of a cell culture-derived rabies vaccine).208 212 213 236

When postexposure prophylaxis against rabies is indicated in an immunocompromised individual, serologic testing is considered essential after completion of the postexposure prophylaxis regimen to confirm that an adequate antibody response was obtained.208 213 234 236 This includes individuals receiving immunosuppressive agents (e.g., those receiving corticosteroids for the treatment of life-threatening neuroparalytic reactions to rabies vaccine).236 (See Individuals with Altered Immunocompetence under Cautions.)

Consider serologic testing to confirm that an adequate antibody response was obtained in travelers who received rabies postexposure prophylaxis with regimens and/or preparations not currently recommended by ACIP.236 (See Postexposure Prophylaxis of Rabies under Uses.)

Improper storage or handling of vaccines may result in loss of vaccine potency and reduced immune response in vaccinees.211

Do not administer HDCV (Imovax) or PCECV (RabAvert) that has been mishandled or has not been stored at the recommended temperature.211 (See Storage under Stability.)

Inspect all vaccines upon delivery and monitor during storage to ensure that the appropriate temperature is maintained.211 If there are concerns about mishandling, contact the manufacturer or state or local health departments for guidance on whether the vaccine is usable.211

Specific Populations

Category C.208 234

Manufacturers state that HDCV (Imovax) and PCECV (RabAvert) should be given to pregnant women only if clearly needed.208 234

However, ACIP, CDC, 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.204 208 212 213 234 236 ACOG recommends that each pregnant woman be considered individually and that public health authorities be consulted.204

Preexposure vaccination may also be indicated during pregnancy when a substantial risk of rabies exposure is present.208 236

Not known whether antigens contained in rabies vaccine are distributed into milk.234 CDC states that use of rabies vaccine in nursing women should follow the same guidelines as other adults.212

Because inactivated vaccines do not multiply within the body, the ACIP states that they should not pose any unusual problems for nursing women or their infants.211

PCECV (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.234 In addition, use of the vaccine for preexposure vaccination may be indicated in nursing women when a substantial risk of rabies exposure is present.234

HDCV (Imovax): Safety and efficacy in children established.208

PCECV (RabAvert): Limited data available regarding safety and efficacy in children.234 Used effectively for preexposure vaccination in children ≥2 years of age and for postexposure prophylaxis in children ≥1 year of age.234

Children are at higher risk of rabies exposure compared with adults because of increased potential for animal contact and because they are more likely to be bitten on the head, face, and neck leading to more severe injuries.212 213 237 249

ACIP, CDC, AAP, and the manufacturers recommend that postexposure prophylaxis in children follow the same guidelines as in adults.208 212 213 234 236

PCECV (RabAvert): Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently to the vaccine than younger adults.234 Clinical experience with PCECV (RabAvert) reveals that there are no overall differences in safety between geriatric and younger individuals.234

Common Adverse Effects

HDCV (Imovax): Local effects at injection site (pain, swelling, erythema, itching), mild systemic reactions (headache, nausea, abdominal pain, muscle aches, dizziness).208

PCECV (RabAvert): Local effects at injection site (pain, swelling, erythema, itching), influenza-like symptoms (mild to moderate asthenia, fatigue, fever, myalgia, malaise, headache).234

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

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• This medicine is made from human plasma (part of the blood) and may have viruses that may cause disease. This medicine is screened, tested, and treated to lower the chance that it carries an infection. Talk with the doctor.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• Other drugs may be given before rabies vaccine to help avoid side effects.
• Very bad side effects have rarely happened with this medicine. These include allergic reactions and brain or nervous system problems. Sometimes, brain problems have been deadly. Talk with the doctor.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using rabies vaccine while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as a shot into a muscle.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

• Imovax Rabies
• RabAvert

There are no dosage adjustments provided in the manufacturer’s labeling.

• Discuss specific use of vaccine and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience injection site irritation, flu-like symptoms, nausea, joint pain, muscle pain; or dizziness. Have patient report immediately to prescriber signs of meningitis (headache with fever, stiff neck, nausea, confusion, or sensitivity to light), severe headache, confusion, vision changes, swollen glands, severe loss of strength and energy, facial paralysis, muscle weakness, or difficulty moving (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.