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Rabies Vaccine (Systemic)

This monograph includes information on the following:

1) Rabies Vaccine Adsorbed  
2) Rabies Vaccine, Human Diploid Cell

VA CLASSIFICATION
Primary: IM100

Commonly used brand name(s): Imovax2; Imovax I.D2.

Other commonly used names are:
HDCV — Rabies Vaccine, Human Diploid Cell
{01} {02} {04} {05} RVA —Rabies Vaccine Adsorbed
{03}
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

Not commercially available in Canada.



Category:


Immunizing agent (active)—

Indications

Accepted

Rabies (prophylaxis)—Rabies vaccine is indicated for post-exposure immunization against rabies infection. Rabies vaccine is also indicated for pre-exposure immunization of persons with a high risk of rabies infection, such as veterinarians, animal handlers, certain laboratory workers, persons spending more than 1 month in areas of foreign countries where rabies (usually canine) is endemic, and other persons whose activities bring them into frequent contact with rabies virus or potentially rabid animals, such as dogs, cats, skunks, raccoons, and bats. Pre-exposure immunization is also recommended for persons who frequently handle or administer modified live rabies virus (MLV) vaccines intended for animals because of the possibility of exposure via needle sticks or sprays. Pre-exposure immunization is indicated for several reasons. It may protect persons whose post-exposure therapy may be delayed and it simplifies post-exposure therapy, both of which may be important for persons in areas where immunizing products may not be available or where available products may carry a high risk of adverse reactions. In addition, pre-exposure immunization may protect persons with inapparent exposure to rabies. {01} {02} {03} {04} {05} {06} {13} {15} {17}

Unaccepted
Post-exposure prophylaxis is not recommended for persons inadvertently exposed to modified live rabies virus (MLV) vaccines intended for animals. Although vaccine-induced rabies has occurred in animals administered these vaccines, there have been no reported rabies cases among humans resulting from exposure to needle sticks or sprays with licensed MLV vaccines. {06}

Rabies vaccine is not intended for use in persons who exhibit clinical manifestation of rabies infection. {03}


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Source—
    Human diploid cell vaccine (HDCV): Most HDCV products are prepared from Wistar's Pitman-Moore strain of rabies virus grown in MRC-5 human diploid cell culture. {01} {02} {05} {06} The vaccine virus is concentrated and then inactivated by betapropiolactone. {01} {02} {05} {06} One Canadian product is prepared from the CL-77 strain of rabies virus grown in MRC-5 human diploid cell culture. This vaccine undergoes a unique purification process. It is also inactivated by betapropiolactone. {04}
    Rabies vaccine adsorbed (RVA): RVA is prepared from the CVS Kissling/MDPH strain of rabies virus grown in a diploid cell line derived from fetal rhesus monkey lung cells. The vaccine virus is inactivated by betapropiolactone and concentrated by adsorption to aluminum phosphate. {03} {06} {11}


Description
    HDCV: Solid, having a creamy white to orange color, and having the characteristic appearance of substances dried from the frozen state. The reconstituted suspension is a pinkish-yellow to red color because of the presence of phenol red. {01} {02} {04} {05} {06}
    RVA: Suspension, having a pink color because of the presence of phenol red. {03} {06}

Mechanism of action/Effect:

Following intradermal or intramuscular administration, rabies vaccine induces the formation of protective antibodies to rabies virus, thereby providing active immunity to rabies virus. {06}


Protective effect

HDCV and RVA are considered equally effective and safe. When the post-exposure prophylaxis regimen has included local wound treatment, passive immunization, and active immunization, 100% effectiveness has been shown. However, rabies has occasionally developed in persons when key elements of the rabies post-exposure prophylaxis regimen were omitted or incorrectly administered. This has occurred outside the United States in cases in which patients' wounds were not cleansed with soap and water or other antiviral agents, rabies vaccine was not administered in the deltoid area, but rather in the gluteal area, and passive immunization was not administered around the wound site. {06}

The presence of acceptable antibody titers following pre-exposure or post-exposure prophylaxis is demonstrated by complete neutralization of the challenge virus at a 1:25 serum dilution (from serum collected 2 to 4 weeks after therapy) by the rapid fluorescent focus inhibition test (RFFIT). This dilution is approximately equivalent to the minimum titer of 0.5 International Units (IU) recommended by the World Health Organization (WHO). {03} {06}

When considering the administration of booster doses of rabies vaccine, the minimum acceptable antibody titer is demonstrated by complete neutralization of the challenge virus at a 1:5 serum dilution by the RFFIT test. {03} {06}


Time to protective effect

Induction of active antibody production begins within 7 to 10 days. {03} {06}


Duration of protective effect

Two or more years. Studies have shown that 2 years after the 3-dose pre-exposure prophylaxis regimen with rabies vaccine, a 1:5 serum dilution failed to neutralize the challenge virus completely by the RFFIT test in 2 to 7% of persons who received the vaccine intramuscularly and 5 to 17% of persons who received the vaccine intradermally. {06} {16}


Precautions to Consider

Pregnancy/Reproduction

Pregnancy—
Studies have not been done in humans. Because of the potential consequences of rabies virus infection, and because there is no indication that fetal abnormalities have been associated with use of rabies vaccine in pregnant women, pregnancy is not considered to be a contraindication to post-exposure prophylaxis. In addition, if there is a substantial risk of exposure to rabies, pre-exposure prophylaxis may also be administered during pregnancy.

Studies have not been done in animals.

FDA Pregnancy Category C. {01} {02} {03} {04} {06} {08}

Breast-feeding

Problems in humans have not been documented.

Pediatrics

HDCV (intradermal)—Appropriate studies on the relationship of age to the effects of rabies vaccine have not been performed in the pediatric population. However, pediatrics-specific problems that would limit the usefulness of this vaccine in children are not expected. {02}

HDCV (intramuscular)—Appropriate studies performed to date have not demonstrated pediatrics-specific problems that would limit the usefulness of rabies vaccine in children. {01}

RVA—Appropriate studies on the relationship of age to the effects of rabies vaccine have not been performed in children up to 6 years of age. However, pediatrics-specific problems that would limit the usefulness of this vaccine in children are not expected. {03}


Geriatrics


No information is available on the relationship of age to the effects of rabies vaccine in geriatric patients.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

» Chloroquine and possibly other related antimalarials, such as mefloquine    (chloroquine, and possibly other related antimalarials, interferes with the antibody response to rabies vaccine. If the intradermal route is used for pre-exposure rabies immunization, rabies prophylaxis should be initiated at least one month prior to travel [i.e., at least 2 weeks before initiation of antimalarial therapy] to allow for the formation of adequate rabies antibodies; if rabies prophylaxis cannot be initiated at least one month prior to travel, the intramuscular route should be used for pre-exposure rabies prophylaxis, since the intramuscular route is considered to have an adequate margin of safety when given within 2 weeks of antimalarial therapy. If post-exposure therapy is required during concurrent use of chloroquine, it is prudent to test for an adequate response to the rabies vaccine {02} {03} {06} {10} {14})


» Corticosteroids or
» Immunosuppressive agents or
» Radiation therapy    (because normal defense mechanisms are suppressed, concurrent use with rabies vaccine may decrease the patient's antibody response to rabies vaccine. During post-exposure prophylaxis against possible rabies infection, these agents should not be administered unless they are essential for the treatment of other conditions. If these agents must be used concurrently, it is important to test for an adequate response to the rabies vaccine. Pre-exposure prophylaxis for rabies should be postponed if possible. If persons are at risk of rabies exposure and must have pre-exposure prophylaxis, the intramuscular, not the intradermal, agent should be administered and the patient should be tested for an adequate response to the rabies vaccine {01} {02} {03} {04} {05} {06})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
» Febrile illness, severe    (to avoid confusing manifestations of illness with possible side/adverse effects of vaccine; minor illnesses, such as upper respiratory infection, do not preclude administration of vaccine. Although pre-exposure prophylaxis may be postponed during severe febrile illness, post-exposure prophylaxis should be initiated on schedule {02})


» Immune complex–like hypersensitivity reaction to rabies vaccine, history of    (persons who have experienced an immune complex–like hypersensitivity reaction following immunization with either human diploid cell vaccine [HDCV] or rabies vaccine adsorbed [RVA] should not receive further doses of the same type of rabies vaccine; although it is not known whether cross-sensitivity exists between the two types of rabies vaccine, it may be helpful to administer the other type of rabies vaccine if additional treatment is necessary; in addition, one specially purified Canadian HDCV vaccine [Rabies Vaccine Inactivated, Diploid Cell Origin, Dried—Connaught] has not been associated with this reaction [see Side/Adverse Effects ]; additional doses of the same type of rabies vaccine should be administered only if the other types of rabies vaccine are not available and prophylaxis is essential [e.g., patient requires post-exposure prophylaxis or patient requires pre-exposure prophylaxis because of a high risk of rabies exposure and inadequate antibody titers] {01} {03} {04} {06})


» Immune deficiency conditions, congenital or hereditary, family history of, or
» Immune deficiency conditions, primary or acquired    (because normal defense mechanisms are suppressed or reduced, there may be a decrease in the patient's antibody response to rabies vaccine. Following post-exposure prophylaxis, it is essential to test for an adequate response to the rabies vaccine. Pre-exposure prophylaxis should use the intramuscular, not the intradermal, route of administration and the patient should be tested for an adequate response to the rabies vaccine {01} {02} {03} {04} {05} {06})


Sensitivity to bovine serum,{04}{05} human albumin,{01}{02}{04}{05} kanamycin,{05}{18} monkey proteins,{03} neomycin,{01}{02}{04}{05} polymyxin B,{04} or thimerosal{03}{04}    (the rabies vaccines available in the U.S. and Canada contain one or more of these ingredients; it may be possible to select a product not having the agent causing sensitivity {03})


Sensitivity to rabies vaccine{06}

Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Rabies antibody titer, serum    (may be determined when there is doubt as to whether an adequate antibody response has occurred following pre-exposure or post-exposure prophylaxis; the acceptable antibody titer is demonstrated by complete neutralization of the challenge virus at a 1:25 serum dilution [from serum collected 2 to 4 weeks after therapy] by the rapid fluorescent focus inhibition test [RFFIT]. This dilution is approximately equivalent to the minimum titer of 0.5 International Units [IU] recommended by the World Health Organization (WHO). Determination of the need for a booster dose of rabies vaccine is based on the minimum acceptable antibody titer, which is demonstrated by complete neutralization of the challenge virus at a 1:5 serum dilution by the RFFIT test {06})




Side/Adverse Effects

Note: All available methods of systemic prophylaxis against rabies are complicated by occasional adverse effects; however, these adverse effects are rarely severe. {06}
If necessary, physicians should consult with the state public health department, the Centers for Disease Control (CDC), Canadian National Advisory Committee on Immunization (NACI), and/or the World Health Organization (WHO) regarding the management of serious adverse reactions. {06}
In approximately 6% of persons receiving a booster dose of human diploid cell vaccine (HDCV), a non–life-threatening immune complex–like reaction occurs 2 to 21 days later. Patients develop a generalized urticaria or rash, which is sometimes accompanied by arthralgia, arthritis, angioedema, nausea, vomiting, fever, or malaise. The reaction occurs much less frequently among persons receiving a primary immunization series, and rarely, if at all, after the first dose of a primary series. The reaction is thought to be caused by human serum albumin present in the product that has become allergenic by interaction with betapropiolactone. A similar reaction occurs after 7 to 14 days in less than 1% of persons receiving a booster, but not a primary, dose of rabies virus adsorbed (RVA), even though human serum albumin is not used in the production of RVA. However, RVA also is inactivated by betapropiolactone. It is not known whether a person hypersensitive to HDCV is hypersensitive to RVA also, or vice versa. Administration of booster doses of a specially purified HDCV vaccine, currently available in Canada (Rabies Vaccine Inactivated, Diploid Cell Origin, Dried—Connaught), has not been associated with this reaction. {01} {03} {04} {06} {07}
Three cases of neurologic illness resembling Guillain-Barré syndrome that resolved without sequelae in 12 weeks have been reported following administration of rabies vaccine. In addition, a few other subacute central and peripheral nervous system disorders have been temporally associated with the vaccine, but a causal relationship has not been established. {01} {04} {06} {12}

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence rare
    
Immune complex–like reaction (hives or skin rash)—less frequent with booster doses{01}{02}{03}{04}{05}{06}



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Abdominal pain (stomach or abdomen pain)
    
chills
    
dizziness
    
fatigue (tiredness or weakness)
    
fever
    
headache
    
itching, pain, redness, or swelling at the place of injection
    
malaise (general feeling of discomfort or illness)
    
muscle or joint aches
    
nausea{01}{02}{03}{04}{05}{06}





Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Rabies Vaccine (Systemic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to rabies vaccine or to bovine serum, human albumin, kanamycin, monkey proteins, neomycin, polymyxin B, or thimerosal, which may also be present in the vaccine
Other medications, especially chloroquine and possibly other related antimalarials, such as mefloquine; corticosteroids; immunosuppressive agents; or radiation therapy
Other medical problems, especially febrile illness, severe; immune complex–like hypersensitivity reaction to rabies vaccine, history of; immune deficiency conditions, congenital or hereditary, family history of; or immune deficiency conditions, primary or acquired

Proper use of this medication
» Importance of not missing doses; keeping appointments with physician

» Proper dosing
Missed dose: Contacting physician as soon as possible

Precautions while using this medication
» Caution if dizziness occurs; not driving, using machines, or doing anything else that requires alertness while receiving rabies vaccine


Side/adverse effects
Signs of potential side effects, especially immune complex–like reaction


General Dosing Information
The dosage is the same for all persons, children and adults. {06}

Rabies vaccine is administered either intramuscularly or intradermally, depending on the product and the indication. The products are not interchangable with respect to the route of administration. Care should be taken to avoid injection of the vaccine into or near blood vessels or nerves. {01} {03} {06}

Rabies vaccine should not be administered into the gluteal area (buttocks), since administration into this area of the body results in lower antibody titers. {01} {03} {06}

It is not considered necessary to document seroconversion by testing serum samples from patients completing pre- or post-exposure prophylaxis except under unusual instances, such as when the person is known to be immunosuppressed. Studies at the Centers for Disease Control (CDC) have shown that persons tested 2 to 4 weeks after completion of pre- or post-exposure rabies prophylaxis, administered according to Immunization Practices Advisory Committee (ACIP) guidelines, developed adequate antibody response to rabies. If documentation of seroconversion is required, serum collected 2 to 4 weeks after pre-exposure or post-exposure prophylaxis, and diluted 1:25, should completely neutralize the challenge virus by the rapid fluorescent focus inhibition test (RFFIT). This dilution is approximately equivalent to the minimum titer of 0.5 International Units (IU) recommended by the World Health Organization (WHO). {01} {03} {06}

For pre-exposure immunization only
For pre-exposure immunization, either the intradermal or intramuscular product may be used. {06} If the intradermal vaccine is used and is inadvertently injected subcutaneously, another dose of intradermal vaccine should be administered at a different site. {02}

Pre-exposure immunization does not eliminate the need for prompt post-exposure prophylaxis following an exposure. However, pre-exposure immunization eliminates the need for administration of rabies immune globulin and reduces the number of injections of rabies vaccine needed for post-exposure prophylaxis. {03}

Pre-exposure booster immunization is administered to persons who have received the pre-exposure immunization series, who remain at risk of rabies exposure by reasons of occupation or avocation, and whose 1:5 diluted serum does not completely neutralize the challenge virus by the RFFIT test. Depending on the person's degree of risk of rabies exposure, serum testing should be performed every 6 months to 2 years. As an alternative to serum testing for those persons who, based on their degree of risk, would require serum testing every 2 years, a booster can be administered every 2 years. {06}

For post-exposure immunization only
All post-exposure therapy should begin with immediate and thorough cleansing of all the patient's wounds with soap and water. Studies have shown that wound cleansing greatly reduces the likelihood of rabies. {01} {03} {06}

For post-exposure immunization, the intramuscular vaccine, not the intradermal vaccine, should be used. {01} {02} {06}

Appropriate management of persons who may have been exposed to rabies depends on the assessment of the risk of infection. The incubation period for rabies infection varies with respect to the location and severity of the bite. For bites to the face or extensive bites elsewhere on the body, the incubation period may be as short as 17 days. Decisions about management should be made promptly. Persons who have been bitten by animals suspected of being, or proven, rabid should begin therapy within 24 hours. If necessary, physicians should consult with the local or state public health department, CDC, the Canadian National Advisory Commitee on Immunization (NACI), and/or WHO regarding the need for rabies prophylaxis. {01} {03} {04} {05} {06}

The essential components of the rabies post-exposure prophylaxis regimen are local wound treatment, passive immunization with rabies immune globulin (RIG) (unless the patient has been previously immunized against rabies), and active immunization with rabies vaccine. Rabies has occasionally developed in persons when key elements of this regimen were omitted or incorrectly performed. In addition, tetanus prophylaxis and antibacterial medications may be administered as required. Both passive immunization with RIG (except for patients who have been previously immunized against rabies) and active immunization with rabies vaccine are required regardless of the interval between exposure and initiation of therapy. {01} {02} {03} {04} {05} {06}

Persons are considered to have been previously immunized against rabies (and as such should not receive RIG as part of the post-exposure therapy) if they have previously received complete regimens of pre- or post-exposure rabies prophylaxis with human diploid cell rabies vaccine (HDCV) or rabies vaccine adsorbed (RVA) or if they have been documented to have had an adequate antibody response to another rabies vaccine, such as duck embryo rabies vaccine. Regardless of the antibody titer that is present before post-exposure therapy occurs, an anamnestic antibody response should occur following the administration of the next dose of rabies vaccine. {01} {03} {06}

RIG, when indicated, is administered only once, usually at the beginning of the post-exposure therapy regimen. RIG provides immediate passive antibodies until the patient can produce active antibodies from the rabies vaccine. If not given on the first day, RIG may be given any time up through the 7th day of the therapy regimen. Beyond the 7th day, RIG is not indicated, since an active antibody response to the rabies vaccine is presumed to have begun. RIG should not be administered in the same syringe or into the same body site as the rabies vaccine. In addition, since RIG may partially suppress active production of rabies antibody, it is recommended that no more than the recommended dose be administered. {03} {04} {06}

WHO recommends a 6-dose series (administered on Days 0, 3, 7, 14, 30, and 90) of HDCV, and probably RVA, for persons not previously immunized with rabies vaccine. The WHO regimen is considered safe and effective. However, studies conducted at CDC have shown that a 5-dose regimen of HDCV or RVA was also safe and effective and induced an adequate antibody response in all recipients tested. {01} {06}

If post-exposure prophylaxis is administered outside the U.S., additional prophylaxis may be desirable when the patient returns to the U.S. Physicians should contact the state public health department or the CDC for specific advice. This is important, since treatment regimens and products vary from country to country. {01} {03} {06}

For treatment of adverse effects {01} {03} {04} {06}
Recommended treatment consists of the following:

   • Antihistamines may be administered for mild hypersensitivity reactions.
   • Anti-inflammatory and antipyretic agents (e.g., aspirin) may be administered for local or mild systemic adverse reactions.
   • Epinephrine may be administered to treat severe hypersensitivity or anaphylactic reaction.
   • If possible, corticosteroids should not be administered, because when given in immunosuppressive doses, they may reduce the production of rabies antibodies. If corticosteroids are administered, it is important to test for an adequate response to the rabies vaccine, especially during post-exposure prophylaxis.

RABIES VACCINE ADSORBED


Parenteral Dosage Forms

RABIES VACCINE ADSORBED SUSPENSION (RVA) USP

Usual adult and adolescent dose
Immunizing agent (active)
Intramuscular, into the deltoid muscle:


Pre-exposure immunization:
1 mL on Days 0, 7, and 21 or 28, for a total of three doses. {03}



Pre-exposure booster immunization, if required:
1 mL as a single dose. {03}

Note: See General Dosing Information for the parameters for administering booster doses.




Post-exposure immunization of persons who have been previously immunized against rabies:
1 mL on Days 0 and 3, for a total of two doses. {03}



Post-exposure immunization of persons who have not been previously immunized against rabies:
1 mL on Days 0, 3, 7, 14, and 28, for a total of five doses. {03}

Note: For persons who have not been previously immunized against rabies, rabies immune globulin (RIG) should be administered on Day 0 along with the first dose of the vaccine. See General Dosing Information. {03}




Usual pediatric dose
See Usual adult and adolescent dose. {03}

Note: The vaccine may be administered into the anterolateral aspect of the thigh if the child does not have sufficient deltoid muscle mass. {03}


Strength(s) usually available
U.S.—


Greater than or equal to 2.5 International Units (IU) of rabies antigen per mL (Rx)[Generic](no more than 2 mg aluminum phosphate per mL; 0.01% thimerosal){03}

Canada—
Not commercially available.

Packaging and storage:
Store between 2 and 8 °C (35 and 46 °F), unless otherwise specified by manufacturer. Do not freeze. {03} {09}

Preparation of dosage form:
The vial should be shaken gently to ensure complete suspension of the aluminum phosphate adjuvant before withdrawing the dose into a syringe. {03}

Stability:
The suspension should be discarded if it has been frozen. {03}

The suspension should not be used if it is discolored or contains particulate matter. {03}

Auxiliary labeling:
   • Do not freeze. {03}
   • Discard if vaccine has been frozen. {03}
   • Store in refrigerator {03}

Note: The suspension is a light pink color because of the presence of phenol red indicator. {03}



RABIES VACCINE, HUMAN DIPLOID CELL


Parenteral Dosage Forms

RABIES VACCINE, HUMAN DIPLOID CELL(FOR INTRADERMAL INJECTION) (HDCV)

Usual adult and adolescent dose
Immunizing agent (active)
Intradermal, on the deltoid muscle:


Pre-exposure immunization:
0.1 mL on Days 0, 7, and 21 or 28, for a total of three doses. {02}



Pre-exposure booster immunization, if required:
0.1 mL as a single dose. {02}

Note: See General Dosing Information for the parameters for administering booster doses.




Usual pediatric dose
See Usual adult and adolescent dose. {02}

Strength(s) usually available
U.S.—


Greater than or equal to 2.5 International Units (IU) of rabies antigen per mL of reconstituted suspension (Rx) [Imovax I.D (contains no preservatives or stabilizers)]{02}

Canada—
Not commercially available.

Packaging and storage:
Store between 2 and 8 °C (35 and 46 °F), unless otherwise specified by manufacturer. Do not freeze. {02}

Preparation of dosage form:
The freeze-dried vaccine is contained in the single-dose syringe. The plunger of the syringe should be pushed so that the leading edge of the black stopper is even with the broken blue line on the side of the syringe. The needle should be inserted into the diluent bottle in such a way that both syringe and bottle remain upright. The needle should be in the diluent at all times during withdrawal in order to prevent air bubbles. The diluent should be drawn into the syringe until the end of the syringe's black stopper is at the solid blue line on the side of the syringe. The protective rubber cap should be replaced on the needle, and the freeze-dried vaccine should be allowed to completely dissolve. The syringe may be shaken if necessary. The reconstituted vaccine should be used immediately. {02}

Stability:
The vaccine should be administered immediately following reconstitution, or reconstituted vaccine should be discarded. {02}

The reconstituted vaccine should not be used if it is discolored or contains particulate matter. {02}

Auxiliary labeling:
   • Use reconstituted vaccine immediately. {02}


RABIES VACCINE, HUMAN DIPLOID CELL (FOR INTRAMUSCULAR INJECTION) (HDCV) USP

Usual adult and adolescent dose
Immunizing agent (active)
Intramuscular, into the deltoid muscle:


Pre-exposure immunization:
1 mL on Days 0, 7, and 21 or 28, for a total of three doses. {01} {04} {05}



Pre-exposure booster immunization, if required:
1 mL as a single dose. {01} {04} {05}

Note: See General Dosing Information for the parameters for administering booster doses.




Post-exposure immunization of persons who have been previously immunized against rabies:
l mL on Days 0 and 3, for a total of two doses. {01} {04} {05}



Post-exposure immunization of persons who have not been previously immunized against rabies:
1 mL on Days 0, 3, 7, 14, and 28, for a total of five doses. {01} {04} {05}

Note: For persons who have not been previously immunized against rabies, rabies immune globulin (RIG) should be administered on Day 0 along with the first dose of the vaccine. See General Dosing Information . {01} {04}




Usual pediatric dose
See Usual adult and adolescent dose. {01}

Note: The intramuscular vaccine may be administered into the anterolateral aspect of the thigh if the child does not have sufficient deltoid muscle mass. {01}


Strength(s) usually available
U.S.—


Greater than or equal to 2.5 International Units (IU) of rabies antigen per mL of reconstituted suspension (Rx) [Imovax (contains no preservatives or stabilizers)]{01}

Canada—


Greater than or equal to 2.5 International Units (IU) of rabies antigen per mL of reconstituted suspension (Rx)[Generic](diluent may contain 0.01% thimerosal){04}{05}

Packaging and storage:
Store between 2 and 8 °C (35 and 46 °F), unless otherwise specified by manufacturer. Do not freeze. {01} {04} {05} {09}

Preparation of dosage form:
The freeze-dried vaccine should be reconstituted in its vial by using the 1 mL of diluent supplied in the disposable syringe. The longer of the two needles should be used to introduce the diluent into the vaccine vial. The contents of the vial should be gently swirled until they are completely dissolved. The total amount of dissolved vaccine in the vial should be drawn into the syringe. In order to do this, the vial should be set in an upright position on a table. The needle used for reconstitution should be removed and replaced with the smaller needle that will be used for administration. The reconstituted vaccine should be used immediately. {01}

Stability:
The vaccine should be administered immediately following reconstitution, or the reconstituted vaccine should be discarded. {01} {04} {05}

The reconstituted vaccine should not be used if it is discolored or contains particulate matter. {01} {05}

Auxiliary labeling:
   • Use reconstituted vaccine immediately. {01}



Developed: 08/31/1994



References
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  1. Baevsky RH, Bartfield JM. Human rabies: a review. Am J Emerg Med 1993 May; 11(3): 279-86.
  1. Briggs DJ, Schewnke JR. Longevity of rabies antibody titre in recipients of human diploid cell rabies vaccine. Vaccine 1992; 10(2): 125-9.
  1. Groleau G. Rabies. Emerg Med Clin North Am 1992 May; 10(2): 361-8.
  1. Panel comment, 8/30/94.
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