Rabavert

Rabavert

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Questions & Answers

Side Effects & Adverse Reactions

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 titers (1).

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.

Legal Issues

There is currently no legal information available for this drug.

FDA Safety Alerts

There are currently no FDA safety alerts available for this drug.

Manufacturer Warnings

There is currently no manufacturer warning information available for this drug.

FDA Labeling Changes

There are currently no FDA labeling changes available for this drug.

Uses

RabAvert is indicated for preexposure vaccination, in both primary series and booster dose, and for postexposure prophylaxis against rabies in all age groups.

Usually, an immunization series is initiated and completed with one vaccine product. No clinical studies have been conducted that document a change in efficacy or the frequency of adverse reactions when the series is completed with a second vaccine product. However, for booster immunization, RabAvert was shown to elicit protective antibody level responses in persons tested who received a primary series with HDCV (4,11).

A. Preexposure Vaccination - See Table 1

(see also Dosage and Administration section below)

Preexposure vaccination consists of three doses of RabAvert 1.0 mL, intramuscularly (deltoid region), one each on days 0, 7, and 21 or 28 (1) (see also Table 1 for criteria for preexposure vaccination).

Preexposure vaccination does not eliminate the need for additional therapy after a known rabies exposure (see also Dosage and Administration section, subsection C).

Preexposure vaccination should be offered to persons in high-risk groups, such as veterinarians, animal handlers, wildlife officers in areas where animal rabies is enzootic, 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 preexposure vaccination. International travelers might be candidates for preexposure vaccination if they are likely to come in contact with animals in areas where dog rabies is enzootic and immediate access to appropriate medical care, including biologics, might be limited (27, 28)

Preexposure vaccination is given for several reasons. First, it may provide protection to persons with inapparent exposure to rabies. Second, it may protect persons whose postexposure 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, booster doses of vaccine should be administered to maintain a serum titer corresponding to at least complete neutralization at a 1:5 serum dilution by the RFFIT (see Table 1); each booster immunization consists of a single dose. See Clinical Pharmacology. Serum antibody determinations to decide upon the need for a booster dose is suggested by the ACIP and is considered cost-effective.

Table 1: Rabies Preexposure prophylaxis guide – United States, 1999

Adapted from the Recommendations of the Advisory Committee on Immunization Practices: Human Rabies Prevention – United States, 1999. (1)

* Judgment of relative risk and extra monitoring of vaccination status of laboratory workers is the responsibility of the laboratory supervisor (29).

** Minimum acceptable antibody level is complete virus neutralization at a 1:5 serum dilution by RFFIT. A booster dose should be administered if the titer falls below this level.

Risk Category and Nature of RiskTypical PopulationsPreexposure Recommendations
Continuous. Virus present continuously, often in high concentrations. Specific exposures likely to go unrecognized. Bite, nonbite or aerosol exposure.Rabies research lab workers,* rabies biologics production workers.Primary course. Serologic testing every 6 months; booster vaccination if antibody titer is below acceptable level.*
Frequent. Exposure usually episodic, with source recognized, but exposure might be unrecognized. Bite, nonbite or aerosol exposure.Rabies diagnostic lab workers,* spelunkers, veterinarians and staff, and animal-control and wildlife workers in rabies enzootic areas.Primary course. Serologic testing every 2 years; booster vaccination if antibody titer is below acceptable level.**
Infrequent (greater than population-at-large). Exposure nearly always episodic with source recognized. Bite or nonbite exposure.Veterinarians and animal- control and wildlife workers in areas with low rabies rates. Veterinary students. Travelers visiting areas where rabies in enzootic and immediate access to appropriate medical care including biologics is limited.Primary course. No serologic testing or booster vaccination.**
Rare (population-at-large). Exposures always episodic. with source recognized. Bite or nonbite exposure.US population-at-large, including persons in rabies-epizootic areas.No vaccination necessary.
B. Postexposure Treatment - See Table 2

(see also Dosage and Administration section below)

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 (1).

TABLE 2: RABIES POSTEXPOSURE PROPHYLAXIS GUIDE – UNITED STATES, 1999

Adapted from the Recommendations of the Advisory Committee on Immunization Practices: Human Rabies Prevention – United States, 1999. (1)

* During the 10-day observation period, begin postexposure prophylaxis at the first sign of rabies in a dog, cat or ferret that has bitten someone. If the animal exhibits clinical signs of rabies, it should be euthanized immediately and tested.

** The animal should be euthanized and tested as soon as possible. Holding for observation is not recommended. Discontinue vaccine if immunofluorescence test results of the animal are negative.

Animal typeEvaluation and disposition of animalPostexposure prophylaxis recommendations
Dogs, cats and ferretsHealthy and available for 10 days observation


Rabid or suspected rabid

Unknown (e.g., escaped)
Should not begin prophylaxis unless animal develops clinical signs of rabies*

Immediately vaccinate

Consult public health officials
Skunks, raccoons, bats, foxes, and most other carnivoresRegarded as rabid unless animal proven negative by laboratory tests**Consider immediate vaccination
Livestock, small rodents, lagomorphs (rabbits and hares), large rodents (woodchucks and beavers), and other mammalsConsider individuallyConsult public health officials. Bites of squirrels, hamsters, guinea pigs, gerbils, chipmunks, rats, mice, other small rodents, rabbits, and hares almost never require antirabies postexposure prophylaxis

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

Species of Biting Animal

Wild terrestrial animals (especially skunks, raccoons, foxes and coyotes) and bats are the animals most commonly infected with rabies and are the most important potential source of infection for both humans and domestic animals. Unless a wild animal is tested and shown not to be rabid, postexposure 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, postexposure prophylaxis can be discontinued (1).

The likelihood of rabies in a domestic animal varies from region to region; hence the need for postexposure prophylaxis also varies (1).

Small rodents (such as squirrels, hamsters, guinea pigs, gerbils, chipmunks, rats, and mice) and lagomorphs (including rabbits and hares) are almost never found to be infected with rabies and have not been known to transmit rabies to humans in the United States. Bites from large rodents such as woodchucks (including groundhogs) and beavers, should be considered as possible rabies exposures, especially in regions where rabies is enzootic in raccoons (30). In all cases involving rodents, the state or local health department should be consulted before a decision is made to initiate antirabies postexposure prophylaxis (1).

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. A currently vaccinated dog, cat or ferret is unlikely to become infected with rabies (1).

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 highly innervated areas such as the face and hands carry the highest risk, but the site of the bite should not influence the decision to begin treatment. Recent epidemiologic data suggest that even the very limited injury inflicted by a bat bite (compared to lesions caused by terrestrial carnivores) should prompt consideration of postexposure prophylaxis unless the bat is available for testing and is negative for evidence of rabies (1).

Nonbite: The contamination of open wounds, abrasions, mucous membranes, or theoretically, scratches, with saliva or other potentially infectious material (such as neural tissue) from a rabid animal constitutes a nonbite exposure. In all instances of potential human exposures involving bats, and the bat is not available for testing, postexposure prophylaxis might be appropriate even if a bite, scratch or mucous membrane exposure is not apparent when there is reasonable probability that such exposure might have occurred. Postexposure prophylaxis can be considered for persons who were in the same room as the bat and who might be unaware that a bite or direct contact had occurred (e.g., a sleeping person awakens to find a bat in the room or an adult witnesses a bat in the room with a previously unattended child, mentally disabled person, or intoxicated person) and rabies cannot be ruled out by testing the bat. Other contact by itself, such as petting a rabid animal and contact with blood, urine, or feces (e.g., guano) of a rabid animal, does not constitute an exposure and is not an indication for prophylaxis. Because the rabies virus is inactivated by desiccation and ultraviolet irradiation, in general, if the material containing the virus is dry, the virus can be considered noninfectious. Two cases of rabies have been attributed to probable aerosol exposures in laboratories, and two cases of rabies in Texas could possibly have been due to airborne exposures in caves containing millions of bats (1).

The only documented cases for rabies from human-to-human transmission occurred in eight patients, including two in the USA, who received corneas transplanted from persons who died of rabies undiagnosed at the time of death (1). Stringent guidelines for acceptance of donor corneas have been implemented to reduce this risk.

Bite and nonbite exposure from humans with rabies theoretically could transmit rabies, but no laboratory-diagnosed cases occurring under such situations have been documented. Each potential exposure to human rabies should be carefully evaluated to minimize unnecessary rabies prophylaxis (1).

Postexposure Treatment Schedule

(see also Dosage and Administration section below)

The essential components of rabies postexposure prophylaxis are prompt local treatment of wounds and administration of both Human Rabies Immune Globulin (HRIG) and vaccine.

A complete course of postexposure treatment for previously unvaccinated adults and children consists of a total of 5 doses of vaccine, each 1.0 mL: one IM injection (deltoid) on each of days 0, 3, 7, 14 and 28. For previously immunized adults and children, a total of 2 doses of vaccine, each 1.0 mL: one IM injection (deltoid) on each of days 0 and 3. No HRIG should be administered to previously vaccinated persons as it may blunt their rapid memory response to rabies antigen.

1. 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, thorough local wound cleansing alone 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 (1).

2. Postexposure Prophylaxis of Rabies

The regimen for postexposure prophylaxis depends on whether or not the patient has been previously immunized against rabies (see below). 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, the FULL DOSE of HRIG should be thoroughly infiltrated in the area around and into the wounds. Any remaining volume of HRIG should be injected IM at a site distant from rabies vaccine administration. HRIG should never be administered in the same syringe or in the same anatomical site as the rabies vaccine. 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 (1.0 mL each) given IM on days 0, 3, 7, 14 and 28. Postexposure rabies prophylaxis should begin the same day exposure occurred or as soon after exposure as possible. The combined use of HRIG and RabAvert is recommended by the CDC 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 is presumed to have begun by that time (1).

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. Postexposure antirabies treatment should always include administration of both passive antibody (HRIG) and immunization, with the exception of persons who have previously received complete immunization regimens (preexposure or postexposure) 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: 1 on day 0 and another on day 3. They should not be given HRIG as this may blunt their rapid memory response to rabies antigen.

3. Postexposure Prophylaxis Outside the United States

If postexposure treatment is begun outside the United States with regimens or biologics that are not used in the United States, it may be prudent to provide additional treatment when the patient reaches the USA. State or local health departments should be contacted for specific advice in such cases (1).

History

There is currently no drug history available for this drug.

Other Information

RabAvert, Rabies Vaccine, produced by Novartis Vaccines and Diagnostics GmbH is a sterile freeze-dried vaccine obtained by growing the fixed-virus strain Flury LEP in primary cultures of chicken fibroblasts. The strain Flury LEP was obtained from American Type Culture Collection as the 59th egg passage. The growth medium for propagation of the virus is a synthetic cell culture medium with the addition of human albumin, polygeline (processed bovine gelatin) and antibiotics. The virus is inactivated with β-propiolactone, and further processed by zonal centrifugation in a sucrose density-gradient. The vaccine is lyophilized after addition of a stabilizer solution which consists of buffered polygeline and potassium glutamate. One dose of reconstituted vaccine contains less than 12 mg polygeline (processed bovine gelatin), less than 0.3 mg human serum albumin, 1 mg potassium glutamate and 0.3 mg sodium EDTA. Small quantities of bovine serum are used in the cell culture process. Bovine components originate only from the United States, Australia and New Zealand. Minimal amounts of chicken protein may be present in the final product; ovalbumin content is less than 3 ng/dose (1 mL), based on ELISA. Antibiotics (neomycin, chlortetracycline, amphotericin B) added during cell and virus propagation are largely removed during subsequent steps in the manufacturing process. In the final vaccine, neomycin is present at < 1 μg, chlortetracycline at < 20 ng, and amphotericin B at < 2 ng per dose. RabAvert is intended for intramuscular (IM) injection. The vaccine contains no preservative and should be used immediately after reconstitution with the supplied Sterile Diluent for RabAvert (Water For Injection). The potency of the final product is determined by the NIH mouse potency test using the US reference standard. The potency of one dose (1.0 mL) RabAvert is at least 2.5 IU of rabies antigen. RabAvert is a white, freeze-dried vaccine for reconstitution with the diluent prior to use; the reconstituted vaccine is a clear to slightly opaque, colorless suspension.

Rabavert Manufacturers


  • Novartis Vaccines And Diagnostics Gmbh
    Rabavert (Rabies Vaccine) Kit [Novartis Vaccines And Diagnostics Gmbh]

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