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Rabavert

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Rabavert

INDICATIONS

RabAvert (rabies vaccine) is indicated for pre-exposure immunization, in both primary series and booster dose, and for post-exposure prophylaxis against rabies.

There are no data on the interchangeable use of different rabies vaccines in a single pre- or post-exposure series. Therefore the vaccine from a single manufacturer should be used for the complete series whenever possible. If vaccines from other manufacturers are administered during the immunization series, an adequate antibody response should be confirmed by appropriate serologic tests. However, for booster immunization, RabAvert (rabies vaccine) was shown to elicit satisfactory antibody level responses in 41 persons who received a primary series with HDCV (3, 10).

Pre-exposure Immunization - See Table 1

Pre-exposure Immunization Schedule

Pre-exposure immunization consists of three doses of RabAvert (rabies vaccine) 1.0 mL, intramuscularly (deltoid region), one each on days 0, 7, and 21 or 28 ([23] see also Table 1 for criteria for pre-exposure immunization).

Pre-exposure immunization should be offered to persons in high-risk groups, such as veterinarians, animal handlers, wildlife officers, certain laboratory workers, and persons spending time in foreign countries where rabies is endemic. Persons whose activities bring them into contact with potentially rabid dogs, cats, foxes, skunks, bats, or other species at risk of having rabies should also be considered for pre-exposure prophylaxis.

Pre-exposure immunization is given for several reasons. First, it may provide protection to persons with inapparent exposure to rabies. Second, it may protect persons whose post-exposure therapy might be expected to be delayed. Finally, although it does not eliminate the need for prompt therapy after a rabies exposure, it simplifies therapy by eliminating the need for globulin and decreasing the number of doses of vaccine needed. This is of particular importance for persons at high risk of being exposed in countries where the available rabies immunizing products may carry a higher risk of adverse reactions.

In some instances, pre-exposure immunization should be boosted periodically in an effort to provide continuous protection (see Table 1); each booster immunization consists of a single dose. See CLINICAL PHARMACOLOGY. Serum antibody determinations before and after booster immunization may be helpful in determining both the need for a booster dose and the timing of such a dose.

Table 1: Criteria for Pre-exposure Immunization

Risk Category and Nature of Risk Typical Populations Pre-exposure regimen
Continuous.Virus present continuously, often in high concentrations. Aerosol, mucous membrane, bite, or nonbite exposures may go unrecognized. Rabies research lab workers,* rabies biologics production workers. Primary course. Serologic testing every 6 months; booster vaccination when antibody level falls below acceptable level.*
Frequent. Exposure usually episodic, with source recognized, but exposure may also be unrecognized. Aerosol, mucous membrane, bite or nonbite exposure. Rabies diagnostic lab workers,* spelunkers, veterinarians and staff, and animal-control and wildlife workers in rabies enzootic areas. Travelers visiting foreign areas of enzootic rabies for more than 30 days. Primary course. Booster vaccination or serologic testing every 2 years.**
Infrequent (greater than population-at-large). Exposure nearly always episodic with source recognized. Mucous membrane, bite, or nonbite exposure. Veterinarians and animal-control and wildlife workers in areas of low rabies enzooticity. Veterinary students. Primary course. No routine booster vaccination or serologic testing.**
Rare (population-at-large). Exposures always episodic. Mucous membrane, or bite with source unrecognized. US population-at-large, including individuals in rabies epizootic areas. No vaccination necessary.
Adapted from the recommendations of the Immunization Practices Advisory Committee (ACIP) on rabies prevention.
MMWR, 1991; 40 (Suppl. RR-3): 1-19.
* Judgment of relative risk and extra monitoring of vaccination status of laboratory workers is the responsibility of the laboratory supervisor (see US Department of Health and Human Service's Biosafety in Microbiological and Biomedical Laboratories, 1984).
** Minimal acceptable antibody level is complete virus neutralization at a 1:5 serum dilution by RFFIT. Booster dose should be administered if the titer falls below this level.

 

Post-exposure Immunization - See Table 2

The following recommendations are only a guide. In applying them, take into account the animal species involved, the circumstances of the bite or other exposure, the immunization status of the animal, and presence of rabies in the region (as outlined below). Local or state public health officials should be consulted if questions arise about the need for rabies prophylaxis (23).

Table 2: Rabies Post-exposure Prophylaxis Guide (Advisory Committee on Immunization Practices [ACIP]) (23)

Animal type Evaluation and disposition of animal Post-exposure prophylaxis recommendations
Dogs and cats Healthy and available for 10 days observation

Rabid or suspected rabid

Unknown (escaped)
Should not begin prophylaxis unless animal develops symptoms of rabies*

Immediate immunization

Consult public health officials
Skunks, raccoons, bats, foxes, and most other carnivores; woodchucks Regarded as rabid unless geographic area is known to be free of rabies or until animal proven negative by laboratory tests** Immediate immunization
Livestock, rodents, and lagomorphs (rabbits and hares) Consider individually Consult public health officials. Bites of squirrels, hamsters, guinea pigs, gerbils, chipmunks, rats, mice, other rodents, rabbits, and hares almost never require antirabies treatment
* During the 10-day holding period, begin treatment with HRIG and RabAvert rabies vaccine at first sign of rabies in a dog or cat that has bitten someone. The symptomatic animal should be killed immediately and tested.
** The animal should be killed and tested as soon as possible. Holding for observation is not recommended. Discontinue vaccine if immunofluorescence test results of the animal are negative.

In the United States, the following factors should be considered before antirabies treatment is initiated.

Species of Biting Animal

Carnivorous wild animals (especially skunks, raccoons, foxes and coyotes) and bats are the animals most commonly infected with rabies and have caused most of the indigenous cases of human rabies in the United States since 1960. Unless an animal is tested and shown not to be rabid, post-exposure prophylaxis should be initiated upon bite or nonbite exposure to the animals. (See definition in “Type of Exposure” below) If treatment has been initiated and subsequent testing in a qualified laboratory shows the exposing animal is not rabid, treatment can be discontinued (23).

The likelihood that a domestic dog or cat is infected with rabies varies from region to region; hence the need for post-exposure prophylaxis also varies (23).

Rodents (such as squirrels, hamsters, guinea pigs, gerbils, chipmunks, rats, and mice) and lagomorphs (including rabbits and hares) are rarely found to be infected with rabies and have not been known to cause human rabies in the United States. In these cases, the state or local health department should be consulted before a decision is made to initiate post-exposure antirabies prophylaxis (23).

Circumstances of Biting Incident

An UNPROVOKED attack is more likely than a provoked attack to indicate the animal is rabid. Bites inflicted on a person attempting to feed or handle an apparently healthy animal should generally be regarded as PROVOKED.

Type of Exposure

Rabies is transmitted by introducing the virus into open cuts or wounds in skin or via mucous membranes. The likelihood of rabies infection varies with the nature and extent of exposure. Two categories of exposure should be considered:

Bite: Any penetration of the skin by teeth. Bites to the face and hands carry the highest risk, but the site of the bite should not influence the decision to begin treatment (23).

Nonbite: Scratches, abrasions, open wounds, or mucous membranes contaminated with saliva or other potentially infectious material, such as brain tissue, from a rabid animal. Casual contact, such as petting a rabid animal (without a bite or nonbite exposure as described above), does not constitute an exposure and is not an indication for prophylaxis. There have been two instances of airborne rabies acquired in laboratories and two probable airborne rabies cases acquired in a bat-infested cave in Texas (23).

The only documented cases for rabies from human-to-human transmission occurred in four patients in the United States and overseas who received corneas transplanted from persons who died of rabies undiagnosed at the time of death (2). Stringent guidelines for acceptance of donor corneas should reduce this risk.

Bite and nonbite exposure from humans with rabies theoretically could transmit rabies, although no cases of rabies acquired this way have been documented. Each potential exposure to human rabies should be carefully evaluated to minimize unnecessary rabies prophylaxis (23).

Post-exposure Immunization Schedule

The essential components of rabies post-exposure prophylaxis are prompt local treatment of wounds and immunization, including administration, in most instances of both globulin and vaccine (Table 2).

A complete course of post-exposure immunization for previously unvaccinated adults and children consists of a total of 5 doses, each 1.0 mL: one IM injection on each of days 0, 3, 7, 14 and 28.

Local Treatment of Wounds

Immediate and thorough washing of all bite wounds and scratches with soap and water is an important measure for preventing rabies. In animal studies, simple local wound cleansing has been shown to reduce markedly the likelihood of rabies. Whenever possible, bite injuries should not be sutured to avoid further and/or deeper contamination. Tetanus prophylaxis and measures to control bacterial infection should be given as indicated (23).

Specific Treatment of Rabies

The injection schedule for post-exposure prophylaxis depends on whether the patient has had or has not had previous immunization against rabies. For persons who have not previously been immunized against rabies, the schedule consists of an initial injection IM of HRIG exactly 20 IU per kilogram body weight in total. If anatomically feasible, up to half of the dose of HRIG should be thoroughly infiltrated in and around the wound(s) and the remainder should be administered IM in the gluteal region. HRIG is administered only once (for specific instructions for HRIG use, see the product package insert). The HRIG injection is followed by a series of 5 individual injections of RabAvert (rabies vaccine) (1.0 mL each) given IM on days 0, 3, 7, 14 and 28. Administration of HRIG and RabAvert (rabies vaccine) should be given at separate sites using separate syringes. Post-exposure rabies prophylaxis should begin the same day exposure occurred or as soon after exposure as possible. The combined use of HRIG and RabAvert (rabies vaccine) is recommended for both bite and non-bite exposures, regardless of the interval between exposure and initiation of treatment. In the event that HRIG is not readily available for the initiation of treatment, it can be given through the seventh day after administration of the first dose of vaccine. HRIG is not indicated beyond the seventh day because an antibody response to RabAvert (rabies vaccine) is presumed to have begun by that time (23). The sooner treatment is begun after exposure, the better. However, there have been instances in which the decision to begin treatment was made as late as 6 months or longer after exposure due to delay in recognition that an exposure had occurred. Post-exposure antirabies immunization should always include administration of both passive antibody and immunization with the exception of persons who have previously received complete immunization regimens (pre-exposure or post-exposure) with a cell culture vaccine, or persons who have been immunized with other types of vaccines and have had documented rabies antibody titers. Persons who have previously received rabies immunization should receive 2 IM doses of RabAvert (rabies vaccine) : 1 on day 0 and another on day 3. They should not be given HRIG.

Treatment Outside the United States

If post-exposure immunization is begun outside the United States with regimens or products that are not used in the United States, it may be desirable to provide additional treatment when the patient reaches the USA. State or local health departments should be contacted for specific advice in such cases (23).

DOSAGE AND ADMINISTRATION

The individual dose is 1 mL, given intramuscularly.

Administer in adults by IM injection into the deltoid muscle or, in the case of small children, into the anterolateral zone of the thigh. The gluteal area should be avoided for vaccine injections, since administration in this area may result in lower neutralizing antibody titers. Care should be taken to avoid injection into or near blood vessels and nerves. After aspiration, if blood or any suspicious discoloration appears in the syringe, do not inject but discard contents and repeat procedure using a new dose of vaccine, at a different site.

Instructions for Reconstituting RabAvert (rabies vaccine)

Using the longer of the 2 needles supplied, transfer the entire contents of the diluent vial into the vaccine vial. Mix gently to avoid foaming. The white, freeze-dried vaccine dissolves to give a clear or slightly opaque suspension. Withdraw the total amount of dissolved vaccine into the syringe and replace the long needle with the smaller needle for IM injection. The reconstituted vaccine should be used immediately.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. If either of these conditions exists, the vaccine should not be administered. A separate, sterile syringe and needle or a sterile disposable unit should be used for each patient to prevent transmission of hepatitis and other infectious agents from person to person. Needles should not be recapped and should be properly disposed of.

No data are available regarding the concurrent administration of RabAvert (rabies vaccine) rabies vaccine with other vaccines.

Pediatric Use

Children and adults receive the same dose of 1 mL, given IM.

Only limited data on the safety and efficacy of RabAvert (rabies vaccine) in the pediatric age group are available. However, in four studies some pre-exposure and post-exposure experience has been gained (17, 31, 32, 33).

Pre-exposure

Pre-exposure administration of RabAvert (rabies vaccine) in 11 Thai children from the age of 2 years and older resulted in antibody levels higher than 0.5 IU/mL on day 14 in all children (32). In another study in Mexico, 15/21 children aged 7 - 18 years had antibody titers of ≥ 0.5 IU/mL on day 14, and all 21 children had antibody titers of ≥ 0.5 IU/mL on day 30. Only mild local pain was noted in approximately one quarter of the children (33).

Post-exposure

In a 10-year serosurveillance study, RabAvert (rabies vaccine) has been administered to 91 children aged 1 to 5 years and 436 children and adolescents aged 6 to 20 years (17). The vaccine was effective in both age groups. None of these patients developed rabies.

One newborn has received RabAvert (rabies vaccine) on an immunization schedule of days 0, 3, 7, 14 and 30; the antibody concentration on day 37 was 2.34 IU/mL. There were no clinically significant adverse events (31).

Pre-exposure Dosage

Primary Immunization

In the United States, the Advisory Committee on Immunization Practices (ACIP) recommends three injections of 1.0 mL each: one injection on day 0 and one on day 7, and one either on day 21 or 28 (for criteria for pre-exposure immunization, see Table 1).

Booster Immunization

The individual booster dose is 1 mL, given intramuscularly.

Booster immunization is given to persons who have received previous rabies immunization and remain at increased risk of rabies exposure by reasons of occupation.

Persons who work with live rabies virus in research laboratories or vaccine production facilities (continuous-risk category: see Table 1) should have a serum sample tested for rabies antibodies every 6 months. Booster doses of vaccine should be given to maintain a serum titer > 1 : 5 serum dilution by the RFFIT.

The frequent-risk category includes other laboratory workers such as those doing rabies diagnostic testing, spelunkers, veterinarians and staff, animal-control and wildlife officers in areas where rabies is epizootic, and international travelers living or visiting (for > 30 days) in areas where canine rabies is endemic. Persons among this group should have a serum sample tested for rabies antibodies every 2 years and, if the titer is less than complete neutralization at a 1 : 5 serum dilution by RFFIT, should have a booster dose of vaccine. Alternatively, a booster can be administered in the absence of a titer determination.

Veterinarians and animal-control and wildlife officers working in areas of low rabies enzooticity (infrequent-exposure group) do not require routine pre-exposure booster doses of RabAvert (rabies vaccine) after completion of a full primary pre-exposure immunization scheme (Table 1).

Post-exposure Dosage

Immunization should begin as soon as possible after exposure. A complete course of immunization consists of a total of 5 injections of 1 mL each: one injection on each of days 0, 3, 7, 14 and 28 in conjunction with the administration of HRIG on day 0. For children, see Pediatric Use section, above. Begin with the administration of HRIG. Give 20 IU/kg body weight.

This formula is applicable to all age groups, including children. The recommended dosage of HRIG should not exceed 20 IU/kg body weight because it may otherwise interfere with active antibody production. Since vaccine-induced antibody appears within 1 week, HRIG is not indicated more than 7 days after initiating post-exposure immunization with RabAvert (rabies vaccine) . If possible, up to one-half the dose of HRIG should be thoroughly infiltrated in the area around the wound and the rest should be administered IM, in a different site from the rabies vaccine, preferably in the gluteal area.

Because the antibody response following the recommended immunization regimen with RabAvert (rabies vaccine) has been satisfactory, routine post-immunization serologic testing is not recommended. Serologic testing is indicated in unusual circumstances, as when the patient is known to be immunosuppressed. Contact state health department or CDC for recommendations.

Post-exposure Therapy of Previously Immunized Persons

When rabies exposure occurs in an immunized person who was vaccinated according to the recommended regimen with RabAvert (rabies vaccine) or other tissue culture vaccines or who had previously demonstrated rabies antibody, that person should receive two IM doses (1.0 mL each) of RabAvert (rabies vaccine) : one immediately and one 3 days later. HRIG should not be given in these cases. Persons should be considered to have been immunized previously if they received pre- or post-exposure prophylaxis with RabAvert (rabies vaccine) or other tissue culture vaccines or have been documented to have had an adequate antibody response to duck embryo rabies vaccine. If the immune status of a previously vaccinated person is not known, full primary post-exposure antirabies treatment (HRIG plus 5 doses of vaccine) may be necessary. In such cases, if antibodies can be demonstrated in a serum sample collected before vaccine is given, treatment can be discontinued after at least two doses of vaccine.

HOW SUPPLIED

Package with

1 vial of freeze-dried vaccine containing a single dose
1 vial of sterile Water For Injection, USP (1 mL)
1 disposable syringe
1 smaller needle for injection, 25 gauge X 1 “
1 longer needle for reconstitution, 21 gauge X1.5 ”

N.D.C.# 53905-501-01

CAUTION: Federal law prohibits dispensing without a prescription

Storage

RabAvert (rabies vaccine) should be stored protected from light at 2°C to 8°C (36°F to 46°F). After reconstitution the vaccine is to be used immediately. The vaccine may not be used after the expiration date given on package and container.

REFERENCES

2. Eighth Report of the WHO Expert Committee on Rabies. WHO Technical Report Series, no. 824; 1992.

3. Dreesen DW, et al. Two-year comparative trial on the immunogenicity and adverse effects of purified chick embryo cell rabies vaccine for pre-exposure immunization. Vaccine. 1989; 7: 397-400.

10. Bijok U, et al. Clinical trials in healthy volunteers with the new purified chick embryo cell rabies vaccine for man. J Commun Dis. 1984; 16: 61-69.

23. Centers for Disease Control. Rabies Prevention - United States, 1991. Recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR. 1991; 40 (RR-3): 1-19.

Manufactured by: Chiron Behring GmbH & Co, D-35006 Marburg, Germany. Distributed by: Chiron Corporation, Emeryville, CA. 94608, USA. Rev. 10/97.

Last reviewed on RxList: 2/23/2009
This monograph has been modified to include the generic and brand name in many instances.

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