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    Rabies Vaccines

    DEA CLASS

    Rx

    DESCRIPTION

    Inactivated vaccine containing rabies antigen.
    For preexposure and postexposure vaccination against rabies infection in all age groups.
    High effectiveness post-exposure when given according to defined treatment protocols along with rabies immune globulin (RIG); pre-exposure vaccination recommended for high-risk groups, such as veterinarians.

    COMMON BRAND NAMES

    Imovax, RabAvert

    HOW SUPPLIED

    Imovax/RabAvert Intramuscular Inj Pwd F/Susp: 2.5U, 2.5IU

    DOSAGE & INDICATIONS

    For rabies prophylaxis.
    For preexposure immunization and booster doses in high-risk groups.
    NOTE: Pre-exposure vaccination does not negate the need for post-exposure treatment should a potential rabies exposure occur, it simply reduces the doses of treatment needed post-exposure.
    Intramuscular dosage (RabAvert or IMOVAX)
    Adults, Adolescents, Children, and Infants

    The Advisory Committee on Immunization Practices (ACIP) recommends a primary series of three 1 ml IM injections administered on days 0, 7, and 21 or 28.
    In certain populations, a 1 ml IM booster doses should be administered to maintain a serum titer corresponding to at least complete neutralization at a 1:5 serum dilution by the rapid fluorescent focus inhibition test (RFFIT). Persons who have continuous risk of exposure to live rabies should have their serum antibody titers checked every 6 months and be given a booster dose if the titer is inadequate. Patients at continuous risk of exposure include rabies research laboratory workers and rabies biologics production workers. Persons at frequent risk of exposure should have their serum checked for antibody titer every 2 years with administration of a booster dose if the titer is inadequate. Patients at frequent risk of exposure usually have episodic exposure with a recognized source and include rabies diagnostic lab workers, cavers, veterinarians and staff, animal control and wildlife workers in areas where rabies is enzootic, and all persons who frequently handle bats. Veterinarians, veterinary students, and animal-control and wildlife officers working in areas with low rabies rates and at-risk international travelers do not require routine preexposure booster doses after completion of primary preexposure vaccination.

    For postexposure vaccination of previously unvaccinated persons with altered immunocompetence.
    Intramuscular dosage (RabAvert)
    Adults, Adolescents, Children, and Infants

    The ACIP recommends 1 ml IM on days 0, 3, 7, 14, and 28 in conjunction with RIG on day 0. If RIG is not immediately available at the start of therapy, RIG may be given through the seventh treatment day (i.e., <= 7 days after first vaccine dose).

    For postexposure vaccination of previously vaccinated persons.
    NOTE: Previously vaccinated patients include those who received a complete vaccination series (pre- or postexposure prophylaxis) with a cell-culture vaccine or who previously had a documented adequate rabies virus-neutralizing antibody titer after vaccination with other types of vaccines. If the immune status of a previously vaccinated person is not known, the full post-exposure series is recommended; in such cases, if a protective serum titer (from a sample collected before vaccine administration ) can be demonstrated, then the treatment can be discontinued after at least 2 doses.
    Intramuscular dosage (RabAvert or IMOVAX)
    Adults, Adolescents, Children, and Infants

    1 ml IM on days 0 and 3; do NOT administer RIG.

    Neonates

    The need for post-exposure prophylaxis in a previously vaccinated neonate is an unlikely use scenario; no data are available.

    For postexposure vaccination of previously unvaccinated immunocompetent persons.
    Intramuscular dosage (RabAvert or IMOVAX)
    Adults, Adolescents, Children, and Infants

    The ACIP currently recommends a 4-dose series of 1 ml IM on days 0, 3, 7, and 14 in conjunction with RIG on day 0. If RIG is not immediately available at the start of therapy, RIG may be given through the seventh treatment day (i.e., <= 7 days after first vaccine dose). Previous recommendations of the ACIP, as well as the approved product labels, included a 5-dose regimen of 1 ml IM on days 0, 3, 7, 14, and 28.

    Neonates

    Limited data are available in neonates. However, the data suggest that if needed for post-exposure prophylaxis in an emergent situation, a 1 ml IM dose, given as the traditional 5-dose series (see infants) may be effective.

    MAXIMUM DOSAGE

    Adults

    1 ml/dose IM.

    Geriatric

    1 ml/dose IM.

    Adolescents

    1 ml/dose IM.

    Children

    1 ml/dose IM.

    Infants

    1 ml/dose IM.

    Neonates

    Limited data in newborns; 1 ml/dose IM.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    No dosage adjustments are needed.

    Renal Impairment

    No dosage adjustments are needed.

    ADMINISTRATION

     
    NOTE: According to U.S. federal laws, the health care provider must record in the patient's permanent record the manufacturer, lot number, administration date, and the name and address of the person administering the vaccine.
    Inform the patient, parent, guardian, or responsible adult of the benefits and risks of the vaccine. Provide the Vaccine Information Statements from the manufacturer to the patient, parent, or guardian before each immunization. The action is required by the National Childhood Vaccine Injury Act of 1986.
    If the rabies vaccine has been previously given, question the patient, parent, or guardian about any symptoms or signs of an adverse reaction.
    Complete a Vaccine Adverse Event Reporting System (VAERS) report form if adverse events have been identified. The reporting of events is required by the National Childhood Vaccine Injury Act of 1986. The toll-free number for VAERS is 1-800-822-7967. Also, report an adverse event to the manufacturer of the specific agent administered. Depending on the adverse reaction, a subsequent dose may be contraindicated.
    Health care professionals administering vaccines should take appropriate precautions to prevent allergic reactions in vaccine recipients. The health care professional should have immediate availability of epinephrine (1 mg/mL) injection and other agents used in the treatment of severe anaphylaxis in the event of a serious allergic reaction.

    Injectable Administration

    Administer only via the intramuscular (IM) route; do not inject intravenously, subcutaneously, or intradermally.
    Visually inspect parenteral products for particulate matter and discoloration prior to administration. If either particulate matter or discoloration are present, discard the vaccine vial.
    Imovax: The freeze-dried vaccine is creamy white to orange. After reconstitution, it is pink to red.
    RabAvert: The freeze-dried vaccine is white. After reconstitution, it is a clear or slightly opaque, colorless suspension.
    Do not mix rabies vaccine with any other vaccine or product in the same syringe.

    Intramuscular Administration

    Reconstitution (Imovax):
    Inspect syringe and package for leakage, premature plunger activation, or faulty tip seal prior to use.
    Attach the manufacturer provided plunger and reconstitution needle to the syringe containing 1 mL of diluent.
    Inject the diluent into vial containing freeze-dried vaccine. Swirl gently to completely dissolve vaccine.
    Withdraw the entire contents of the vial into the syringe.
    Remove and discard reconstitution needle; attach new needle suitable for intramuscular injection.
    Administer reconstituted vaccine immediately.
     
    Reconstitution (RabAvert):
    The manufacturer supplies a vial of freeze-dried vaccine, a syringe containing 1 mL of sterile diluent, a long needle for reconstitution, and a shorter needle for administration.
    Using aseptic technique, attach the longer of 2 needles provided to the syringe containing the diluent.
    Slowly inject the diluent into the vaccine containing vial at a 45 degree angle. Gently mix until the vaccine has completely dissolved.
    Withdraw the total amount of the dissolved vaccine back into the syringe and replace the long needle with the shorter needle.
    Administer reconstituted vaccine immediately.
     
    Intramuscular (IM) injection:
    Prior to administration, clean skin over the injection site with a suitable cleansing agent.
    The preferred administration site for adults and children is the deltoid muscle; infants and younger children should receive the injection into the midlateral muscles of the thigh. Do not inject into the gluteal area.
    Aspirate prior to injection to avoid administering the vaccine into a blood vessel. If blood or discoloration appears in the syringe, do not inject; instead, discard the contents and administer a new vaccine dose at a different injection site.

    STORAGE

    Imovax:
    - Protect from freezing
    - Refrigerate (between 36 and 46 degrees F)
    RabAvert:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Protect from light
    - Reconstituted product should be used immediately. Discard unused portion
    - Store between 36 to 46 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Albumin hypersensitivity, bovine protein hypersensitivity, egg hypersensitivity, neomycin hypersensitivity

    Use of the rabies vaccine for preexposure prophylaxis is contraindicated in persons with a history of anaphylaxis to the vaccine or any of the vaccine components; there are no contraindications to the use of the rabies vaccine for postexposure prophylaxis. Products involved in the manufacturing process of RabAvert include chicken fibroblasts, human albumin, bovine gelatin, and antibiotics (neomycin, amphotericin B, and chlortetracycline); therefore, administer RabAvert cautiously to individuals with albumin hypersensitivity, bovine protein hypersensitivity, egg hypersensitivity, and/or neomycin hypersensitivity. Imovax is harvested from infected human cells and thus are not processed with chicken fibroblasts or bovine gelatin; however, Imovax does contain albumin and neomycin and should be used with caution in neomycin or albumin allergic patients. With any biologic product, the prescriber or health care professional should take precautions to prevent allergic reactions. The healthcare professional should have immediate availability of epinephrine (1:1000) injection and other agents used in the treatment of severe anaphylaxis in the event of a serious allergic reaction to the vaccine. Prior to the administration of the vaccine, the healthcare personnel should inform the patient, parent, guardian, or responsible adult of the benefits and risks to the patient. This should include the provision of the vaccine information statement from the manufacturer. The patient or responsible adult should report any adverse reaction following vaccine administration to the healthcare provider. The U.S. Department of Health and Human Services has established a Vaccine Adverse Event Reporting System (VAERS) to accept all reports of suspected adverse events after the administration of any vaccine. This includes, but is not limited to, the reporting of events required by the National Childhood Vaccine Injury Act of 1986. The toll-free number for VAERS is 800—822—7967.

    Intraarterial administration, intravenous administration, subcutaneous administration

    The rabies vaccine is only indicated for intramuscular administration; do not give via intravenous administration, intraarterial administration, or subcutaneous administration. Systemic adverse reactions, including shock, may occur if the rabies vaccine is accidentally administered intravascularly. Prior to administration, health care personnel should inform the patient, parent, guardian, or responsible adult of the vaccine's benefits and risks. This should include the provision of the vaccine information statement from the manufacturer. The patient or responsible adult should report any adverse reaction following vaccine administration to the health care provider. The US Department of Health and Human Services has established a Vaccine Adverse Event Reporting System (VAERS) to accept all reports of suspected adverse events after the administration of any vaccine. This includes, but is not limited to, the reporting of events required by the National Childhood Vaccine Injury Act of 1986. The toll-free number for VAERS is 800—822—7967.

    Viral infection

    RabAvert contains albumin, a derivative of human blood. The risk of transmitting infectious agents associated with the albumin formulated rabies vaccine is remote due to effective plasma donor screening for prior exposure to certain viruses, testing for the presence of viruses, and manufacturing processes designed to reduce the risk of transmitting viral infection. However, none of the processes are completely effective. There is also the possibility that unknown infectious agents may be present. A theoretical risk of the transmission of Creutzfeldt-Jakob disease (CJD) is also considered remote. No cases of transmission of viral infections or CJD have ever been identified from albumin.

    Acquired immunodeficiency syndrome (AIDS), agammaglobulinemia, corticosteroid therapy, human immunodeficiency virus (HIV) infection, hypogammaglobulinemia, immunosuppression, neoplastic disease, radiation therapy, severe combined immunodeficiency (SCID)

    Patients suffering significant immunosuppression may not have an adequate antibody response to the rabies vaccine. Immunosuppressed persons may include patients with asymptomatic or symptomatic human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS); severe combined immunodeficiency (SCID); hypogammaglobulinemia; agammaglobulinemia; altered immune states due to diseases such as generalized neoplastic disease; or an immune system compromised by corticosteroid therapy with greater than physiologic doses, alkylating drugs, antimetabolites, or radiation therapy. Short-term (< 2 weeks) corticosteroid therapy or intra-articular, bursal, or tendon injections with corticosteroids should not be immunosuppressive. Avoid use of immunosuppressive agents during postexposure prophylaxis if possible. If postexposure prophylaxis is initiated in an immunosuppressed person, serum antibody titers are recommended on treatment day 14 (day of the 4th vaccination). Preexposure prophylaxis should be given prior to initiation of immunosuppressive therapy or at least 3 months after therapy is discontinued if immune competence has been restored.

    Anticoagulant therapy, coagulopathy, hemophilia, thrombocytopenia, vitamin K deficiency

    The rabies vaccine is indicated for intramuscular administration and, thus, should be given cautiously to persons receiving anticoagulant therapy. Also, patients with thrombocytopenia, coagulopathy (e.g., hemophilia), other bleeding disorders, or vitamin K deficiency should be monitored closely for bleeding at the IM injection site. All steps to avoid hematoma formation are recommended.

    Guillain-Barre syndrome

    Cases of Guillain-Barre syndrome, as well as transient paralysis, neuritis, myelitis, and other neuroparalytic events have been reported during post-marketing use of the rabies vaccine; however, because of the uncontrolled nature of post-marketing reports, a definitive causal relationship to the vaccine cannot be established. Consider the risk to benefit ratio when deciding to vaccinate individuals with a history of Guillain-Barre; advice and assistance may be obtained from the state health department or the Centers for Disease Control (CDC). A patient's risk for developing rabies should be carefully considered before deciding to discontinue immunization.

    Pregnancy

    The rabies vaccine is classified as FDA pregnancy risk category C. There are no adequate, well controlled studies in pregnant humans; animal reproduction studies have not been conducted. It is not known if administration of the vaccine can cause fetal harm or affect the reproductive system. Rabies vaccine should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus. Because of the potential consequences of inadequately treated rabies exposure, pregnancy is not considered a contraindication to postexposure prophylaxis. If the risk of exposure to rabies is substantial, preexposure prophylaxis might be indicated during pregnancy.

    Breast-feeding

    It is not known whether rabies vaccine is excreted in human breast milk; however, because of the potential consequences of inadequately treated rabies exposure, the manufacturer does not consider breast-feeding to be a contraindication for postexposure prophylaxis. Additionally, if the risk of exposure to rabies is substantial, preexposure vaccination might also be indicated during nursing. According to the Advisory Committee on Immunization Practices (ACIP), inactivated virus vaccines pose no risk to mothers or their infants. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.

    Infants, neonates

    The safety and efficacy of Imovax and RabAvert have not been established in neonates. There is a single case report of one newborn treated with the vaccine post-exposure. Limited safety and efficacy data are available on the use of rabies vaccines in non-newborn infants for pre- and postexposure rabies prophylaxis. Pre-exposure use has been primarily limited to those infants living in select global areas where rabies is enzootic; treatment in infants is usually otherwise reserved for post-exposure use when necessary. The safety and efficacy of both vaccines have been established in children.

    ADVERSE REACTIONS

    Severe

    muscle paralysis / Delayed / Incidence not known
    Guillain-Barre syndrome / Delayed / Incidence not known
    myelitis / Delayed / Incidence not known
    angioedema / Rapid / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    bronchospasm / Rapid / Incidence not known
    visual impairment / Early / Incidence not known

    Moderate

    lymphadenopathy / Delayed / 15.0
    erythema / Early / Incidence not known
    neuritis / Delayed / Incidence not known
    meningitis / Delayed / Incidence not known
    edema / Delayed / Incidence not known
    hot flashes / Early / Incidence not known
    palpitations / Early / Incidence not known

    Mild

    myalgia / Early / 20.0-53.0
    headache / Early / 20.0-52.0
    injection site reaction / Rapid / 25.0-45.0
    malaise / Early / 15.0-25.0
    dizziness / Early / 10.0-15.0
    arthralgia / Delayed / 0-6.0
    pruritus / Rapid / Incidence not known
    chills / Rapid / Incidence not known
    rash (unspecified) / Early / Incidence not known
    abdominal pain / Early / Incidence not known
    paresthesias / Delayed / Incidence not known
    asthenia / Delayed / Incidence not known
    nausea / Early / Incidence not known
    fever / Early / Incidence not known
    fatigue / Early / Incidence not known
    urticaria / Rapid / Incidence not known
    vertigo / Early / Incidence not known

    DRUG INTERACTIONS

    Adalimumab: (Major) If administered concurrently, adalimumab can impair the immunologic response to the rabies vaccine, thereby, decreasing its protective effect. If possible, administration of immunosuppressive mediations, such as adalimumab, should be avoided during use of the rabies vaccine for postexposure prophylaxis. When immunosuppressive therapies must be administered to persons also receiving the rabies vaccine for postexposure prophylaxis, a serum rabies antibody titer should be obtained on day 14 (day of the 4th vaccination) to ensure an acceptable antibody response has been induced.
    Antimalarials: (Major) If administered concurrently, antimalarials can impair the immunologic response to the rabies vaccine, thereby, decreasing its protective effect. If possible, administration of antimalarials should be avoided during use of the rabies vaccine for postexposure prophylaxis. When antimalarials must be administered to persons also receiving the rabies vaccine for postexposure prophylaxis, a serum rabies antibody titer should be obtained on day 14 (day of the 4th vaccination) to ensure an acceptable antibody response has been induced.
    Artemether; Lumefantrine: (Major) If administered concurrently, antimalarials can impair the immunologic response to the rabies vaccine, thereby, decreasing its protective effect. If possible, administration of antimalarials should be avoided during use of the rabies vaccine for postexposure prophylaxis. When antimalarials must be administered to persons also receiving the rabies vaccine for postexposure prophylaxis, a serum rabies antibody titer should be obtained on day 14 (day of the 4th vaccination) to ensure an acceptable antibody response has been induced.
    Atovaquone: (Major) If administered concurrently, antimalarials can impair the immunologic response to the rabies vaccine, thereby, decreasing its protective effect. If possible, administration of antimalarials should be avoided during use of the rabies vaccine for postexposure prophylaxis. When antimalarials must be administered to persons also receiving the rabies vaccine for postexposure prophylaxis, a serum rabies antibody titer should be obtained on day 14 (day of the 4th vaccination) to ensure an acceptable antibody response has been induced.
    Atovaquone; Proguanil: (Major) If administered concurrently, antimalarials can impair the immunologic response to the rabies vaccine, thereby, decreasing its protective effect. If possible, administration of antimalarials should be avoided during use of the rabies vaccine for postexposure prophylaxis. When antimalarials must be administered to persons also receiving the rabies vaccine for postexposure prophylaxis, a serum rabies antibody titer should be obtained on day 14 (day of the 4th vaccination) to ensure an acceptable antibody response has been induced.
    Chloroquine: (Major) If administered concurrently, antimalarials can impair the immunologic response to the rabies vaccine, thereby, decreasing its protective effect. If possible, administration of antimalarials should be avoided during use of the rabies vaccine for postexposure prophylaxis. When antimalarials must be administered to persons also receiving the rabies vaccine for postexposure prophylaxis, a serum rabies antibody titer should be obtained on day 14 (day of the 4th vaccination) to ensure an acceptable antibody response has been induced.
    Etanercept: (Major) Etanercept has not been found to act as a general immunosuppressant; however, the patient's underlying disease state may result in the immunosuppression of the patient, thereby, impairing the immunologic response to the rabies vaccine. If possible, administration of etanercept should be avoided during use of the rabies vaccine for postexposure prophylaxis. When etanercept must be administered to persons also receiving the rabies vaccine for postexposure prophylaxis, a serum rabies antibody titer should be obtained on day 14 (day of the 4th vaccination) to ensure an acceptable antibody response has been induced.
    Halofantrine: (Major) If administered concurrently, antimalarials can impair the immunologic response to the rabies vaccine, thereby, decreasing its protective effect. If possible, administration of antimalarials should be avoided during use of the rabies vaccine for postexposure prophylaxis. When antimalarials must be administered to persons also receiving the rabies vaccine for postexposure prophylaxis, a serum rabies antibody titer should be obtained on day 14 (day of the 4th vaccination) to ensure an acceptable antibody response has been induced.
    Mefloquine: (Major) If administered concurrently, antimalarials can impair the immunologic response to the rabies vaccine, thereby, decreasing its protective effect. If possible, administration of antimalarials should be avoided during use of the rabies vaccine for postexposure prophylaxis. When antimalarials must be administered to persons also receiving the rabies vaccine for postexposure prophylaxis, a serum rabies antibody titer should be obtained on day 14 (day of the 4th vaccination) to ensure an acceptable antibody response has been induced.
    Primaquine: (Major) If administered concurrently, antimalarials can impair the immunologic response to the rabies vaccine, thereby, decreasing its protective effect. If possible, administration of antimalarials should be avoided during use of the rabies vaccine for postexposure prophylaxis. When antimalarials must be administered to persons also receiving the rabies vaccine for postexposure prophylaxis, a serum rabies antibody titer should be obtained on day 14 (day of the 4th vaccination) to ensure an acceptable antibody response has been induced.
    Pyrimethamine: (Major) If administered concurrently, antimalarials can impair the immunologic response to the rabies vaccine, thereby, decreasing its protective effect. If possible, administration of antimalarials should be avoided during use of the rabies vaccine for postexposure prophylaxis. When antimalarials must be administered to persons also receiving the rabies vaccine for postexposure prophylaxis, a serum rabies antibody titer should be obtained on day 14 (day of the 4th vaccination) to ensure an acceptable antibody response has been induced.
    Pyrimethamine; Sulfadoxine: (Major) If administered concurrently, antimalarials can impair the immunologic response to the rabies vaccine, thereby, decreasing its protective effect. If possible, administration of antimalarials should be avoided during use of the rabies vaccine for postexposure prophylaxis. When antimalarials must be administered to persons also receiving the rabies vaccine for postexposure prophylaxis, a serum rabies antibody titer should be obtained on day 14 (day of the 4th vaccination) to ensure an acceptable antibody response has been induced.
    Quinine: (Major) If administered concurrently, antimalarials can impair the immunologic response to the rabies vaccine, thereby, decreasing its protective effect. If possible, administration of antimalarials should be avoided during use of the rabies vaccine for postexposure prophylaxis. When antimalarials must be administered to persons also receiving the rabies vaccine for postexposure prophylaxis, a serum rabies antibody titer should be obtained on day 14 (day of the 4th vaccination) to ensure an acceptable antibody response has been induced.
    Rabies Immune Globulin, human RIG: (Minor) The rabies immune globulin, human RIG may be administered concurrently with, and up to 8 days after the rabies vaccine. The RIG and the rabies vaccine must be administered via separate syringes and at different anatomical site. Avoid administering RIG if more than 7 days have elapsed since administration of the rabies vaccine as this may impair rabies vaccine-induced active immunity. Additionally, RIG doses greater than the recommended 20 International Units/kg and repeat RIG doses should also be avoided as these too may partially suppress active production of antibodies by the rabies vaccine.

    PREGNANCY AND LACTATION

    Pregnancy

    The rabies vaccine is classified as FDA pregnancy risk category C. There are no adequate, well controlled studies in pregnant humans; animal reproduction studies have not been conducted. It is not known if administration of the vaccine can cause fetal harm or affect the reproductive system. Rabies vaccine should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus. Because of the potential consequences of inadequately treated rabies exposure, pregnancy is not considered a contraindication to postexposure prophylaxis. If the risk of exposure to rabies is substantial, preexposure prophylaxis might be indicated during pregnancy.

    It is not known whether rabies vaccine is excreted in human breast milk; however, because of the potential consequences of inadequately treated rabies exposure, the manufacturer does not consider breast-feeding to be a contraindication for postexposure prophylaxis. Additionally, if the risk of exposure to rabies is substantial, preexposure vaccination might also be indicated during nursing. According to the Advisory Committee on Immunization Practices (ACIP), inactivated virus vaccines pose no risk to mothers or their infants. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    The rabies vaccine is manufactured from inactivated strains of the rabies virus. Each dose (1 ml) of the vaccines marketed in the US, ImoVax and RabAvert, contains at least 2.5 international units of rabies antigen. When administered intramuscularly, the rabies antigen induces production of specific neutralizing antibodies against the rabies virus, thereby providing active immunity. The active antibody response requires approximately 7 to 10 days to develop, and detectable rabies virus neutralizing antibodies generally persist for several years. Due to the delay in development of antibodies, post-exposure prophylaxis must include administration of Rabies Immune Globulin (see separate monograph).

    PHARMACOKINETICS

    The rabies vaccine is administered intramuscularly. Pre-exposure vaccination does not ensure immunity.
     
    The Centers for Disease Control and Prevention (CDC) defines the minimum antibody titer acceptable for seroconversion as a 1:5 dilution (complete inhibition) by rapid fluorescent focus inhibition test (RFFIT); The World Heath Organization (WHO) recommends a titer of at least 0.5 international units/ml. Immunization with the rabies vaccine has been shown to achieve titers above these minimum concentrations within 14 days of initiating the postexposure prophylaxis series in all age groups. In US clinical trials, administering the rabies vaccine for preexposure prophylaxis has resulted in seroconversion (>= 0.5 international units/ml) in all patients by the end of the 28 day vaccination series. The duration of protection is undefined; therefore, persons with continued exposure to rabies should obtain serum titers every 6 months to 2 years (depending on exposure risk) to ensure acceptable antibody concentrations (see Indications).