Caution: Federal (USA) law prohibits dispensing without prescription.

Rabies Immune Globulin (Human) USP, Imogam® Rabies - HT, is a sterile solution of antirabies immunoglobulin (10-18% protein) for intramuscular administration. It is prepared by cold alcohol fractionation from pooled venous plasma of individuals immunized with Rabies Vaccine prepared from human diploid cells (HDCV). The product is stabilized with 0.3 M glycine. The globulin solution has a pH of 6.8 ± 0.4 adjusted with sodium hydroxide or hydrochloric acid. No preservatives are added. Imogam® Rabies - HT is a colorless to light opalescent liquid.

A heat-treatment process step (58° to 60°C, 10 hours) to inactivate viruses has been added to further reduce any risk of blood-borne viral transmission. The inactivation and removal of model and laboratory strains of enveloped and non-enveloped viruses during the manufacturing and heat treatment processes for Imogam® Rabies - HT has been validated by spiking experiments. Human immunodeficiency virus, type 1 (HIV-1) and type 2 (HIV-2) were selected as relevant viruses for plasma derived products. Bovine viral diarrhea virus and Sindbis virus were chosen to model hepatitis C virus. Porcine pseudorabies virus was selected to model hepatitis B virus and herpes virus. Avian reovirus was used to model non-enveloped RNA viruses and for its relative resistance to inactivation by chemical and physical methods. Finally, porcine parvovirus was selected to model human parvovirus B19 and its notable resistance to inactivation by heat treatment.

Removal and/or inactivation of the studied enveloped and non-enveloped model viruses was demonstrated at the precipitation III stage of manufacturing. In addition, inactivation was demonstrated to occur during the 10-hour (58° to 60°C) heat treatment process for the studied enveloped and non-enveloped viruses.

The product is standardized against the United States (US) Standard Rabies Immune Globulin. The US unit of potency is equivalent to the International Unit (IU) for Rabies antibody. The average potency is 150 IU/mL.

Following the marked decrease of rabies cases among domestic animals in the US in the 1940s and 1950s, indigenously acquired rabies among humans decreased to fewer than two cases per year in the 1960s and 1970s and fewer than one case per year during the 1980s. 1,2 In 1950, for example, 4,979 cases of rabies were reported among dogs and 18 were reported among human populations; in 1989, 160 cases were reported among dogs and one was reported among humans. Thus, the likelihood of human exposure to a rabid domestic animal has decreased greatly; however, the many possible exposures that result from frequent contact between domestic dogs and humans continue to be the basis of most antirabies treatments. 1,3

Rabies among wild animals--especially skunks, raccoons, and bats--has become more prevalent since the 1950s accounting for > 85% of all reported cases of animal rabies every year since 1976. 1,2 Rabies among animals occurs throughout the continental US; only Hawaii remains consistently rabies-free. Wild animals now constitute the most important potential source of infection for both humans and domestic animals in the US. In much of the rest of the world, including most of Asia, Africa, and Latin America, the dog remains the major species with rabies and the major source of rabies among humans. Nine of the 13 human rabies deaths reported to CDC from 1980 through 1990 appear to have been related to exposure to rabid animals outside of the US. 1,4-10

Although rabies among humans is rare in the US, every year approximately 18,000 persons receive rabies pre-exposure prophylaxis and an additional 10,000 receive postexposure prophylaxis. Appropriate management of persons possibly exposed to rabies depends on the interpretation of the risk of infection. Decisions about management must be made immediately. All available methods of systemic prophylactic treatment are complicated by occasional adverse reactions, but these are rarely severe. 1,11-15

Data on the efficacy of active and passive rabies immunization have come from both human and animal studies. Evidence from laboratory and field experience in many areas of the world indicates that postexposure prophylaxis combining local wound treatment, passive immunization, and vaccination is uniformly effective when appropriately applied. 1,16-21

Although no postexposure vaccine failures have occurred in the US during the 10 years that HDCV has been licensed, seven persons have contracted rabies after receiving postexposure treatment with both HRIG and HDCV outside the US. An additional six persons have contracted the disease after receiving postexposure prophylaxis with other cell culture-derived vaccines and HRIG or ARS (equine antirabies serum). However, in each of these cases, there was some deviation from the recommended postexposure treatment protocol. 1,22-24 Specifically, patients who contracted rabies after postexposure prophylaxis did not have their wounds cleansed with soap and water or other antiviral agents, did not receive their rabies vaccine injections in the deltoid area (i.e., vaccine was administered in the gluteal area), or did not receive passive vaccination around the wound site. 1

Rabies antibody provides passive protection when given immediately to individuals exposed to rabies virus. 25,26 Rabies Immune Globulin (Human) [RIG(H)] of adequate potency 27 was used in conjunction with Rabies Vaccine of duck embryo origin. 27,28 When a globulin dose of 20 IU/kg of rabies antibody was given simultaneously with the first dose of vaccine, levels of passive rabies antibody were detected 24 hours after injection in all individuals. There was minimal or no interference with the immune response to the initial and subsequent doses of vaccine, including booster doses.

Studies of Rabies Immune Globulin (Human) 29 Imogam® Rabies given with the first of five doses of Aventis Pasteur SA HDCV 1 confirmed that passive immunization with 20 IU/kg of Rabies Immune Globulin (Human) provides maximum circulating antibody with minimum interference of active immunization by HDCV.

A double-blind randomized trial 30 was conducted to compare the safety and antibody levels achieved following intramuscular injection of Imogam® Rabies - HT (heat treated) and Rabies Immune Globulin (Human), Imogam® Rabies (non-heat treated). Each immune globulin was administered on day 0, either alone or in combination with the human diploid cell Rabies Vaccine (Imovax® Rabies) using the standard post-exposure prophylactic schedule of day 0, 3, 7, 14, and 28.

Sixty-four healthy veterinary student volunteers were randomized into four parallel groups of 16 each to receive the following immune globulin and vaccine regimens.

Imogam® Rabies - HT
+
Imovax®
Imogam® Rabies
+
Imovax®
Imogam® Rabies - HT
+
Imogam® Rabies
+

The dosage corresponded to the post-exposure recommended dose of 20 IU/kg of rabies immune globulin and was administered in three, equally divided IM injections of under 5 mL in either gluteus. Serum rabies antibody levels were assessed before treatment and on days 3, 7, 14, 28, 35, and 42 by the Rabies Fluorescent Focus Inhibition Test (RFFIT).

Serum antibody levels were similar in the Imogam® Rabies - HT and Imogam® Rabies groups. By day three, 60% of each group had detectable antibody titers of >/= 0.05 IU/mL. By day 14, the geometric mean titers (with 95% confidence interval) were 19 IU/mL (11-38) in the Imogam® Rabies - HT + vaccine group and 31 IU/mL (20-48) in the Imogam® Rabies + vaccine group. These differences were not statistically different.

Two subjects reported severe headaches, one in the Imogam® Rabies - HT + placebo group and one in the Imogam® Rabies + Imovax® Rabies group. One third of the volunteers had moderate systemic (headache and malaise) reactions. These were equally distributed among the 4 treatment groups with no significant differences between the groups.

Both Imogam® Rabies - HT + Imogam® Rabies were safe and without serious adverse events or allergic reactions. The safety profile did not differ between groups, although Imogam® Rabies - HT produced fewer and milder local reactions such as pain or tenderness at the injection site.

Rabies Immune Globulin (Human) Imogam® Rabies - HT is indicated for individuals suspected of exposure to rabies, particularly severe exposure, with one exception: persons who have been previously immunized with HDCV Rabies Vaccine in a pre or postexposure treatment series should receive only vaccine. Persons who have received Rabies Vaccines other than HDCV or RVA vaccines should have confirmed adequate rabies antibody titers if they are to receive only vaccine. 1

Imogam® Rabies - HT should be injected as promptly as possible after exposure along with the first dose of vaccine. If initiation of treatment is delayed for any reason, Imogam® Rabies - HT and the first dose of vaccine should still be given, regardless of the interval between exposure and treatment Imogam® Rabies - HT may be given up to eight days after the first dose of vaccine was given.

Rabies virus is usually transmitted by the bite of a rabid animal but can occasionally penetrate abraded skin contaminated with the saliva of infected animals. Progress of the virus after exposure is believed to follow a neural pathway and the time between exposure and clinical rabies is a function of the proximity of the bite (or abrasion) to the central nervous system and the dose of virus injected. The incubation is usually 2 to 6 weeks but can be longer. After severe bites about the face and neck and arms, it may be as short as 10 days. After initiation of the vaccine series (human diploid cell origin), it takes approximately one week for development of immunity to rabies; therefore, the value of immediate passive immunization with rabies antibodies in the form of Rabies Immune Globulin (Human) cannot be overemphasized.

Recommendations for passive and/or active immunization after exposure to an animal suspected of having rabies have been outlined by the WHO 31 and by the Centers for Disease Control Service Advisory Committee on Immunization Practices (ACIP). 1

I. Rationale of Treatment

In the United States and Canada the following factors should be considered before specific antirabies treatment is indicated:

  1. Species of Biting Animal
    Carnivorous animals (especially skunks, foxes, coyotes, raccoons, dogs, bobcats, and cats) and bats are more likely to be infected with rabies than other animals. Rats, mice, squirrels, hamsters, guinea pigs, gerbils, chipmunks and other rodents or rabbits and hares are rarely infected with rabies and have not been known to cause human rabies in the United States. Their bites almost never call for antirabies prophylaxis; therefore, before initiating antirabies prophylaxis, the local state health department should be consulted.
    Because some bat bites may be less severe, and therefore more difficult to recognize, than bites inflicted by larger mammalian carnivores, rabies postexposure treatment should be considered for any physical contact with bats when bite or mucous membrane contact cannot be excluded. 32,33
  2. Circumstances of Biting Incident
    An UNPROVOKED attack is more likely than a provoked attack to indicate that the animal is rabid. Bites inflicted on a person attempting to feed or handle an apparently healthy animal should generally be regarded as PROVOKED.
  3. Type of Exposure
    Rabies is commonly transmitted by inoculation with infectious saliva. The likelihood that rabies infection will result from exposure to a rabid animal varies with the nature and extent of the exposure. Two categories of exposure should be considered:
    Bite   Any penetration of the skin by teeth.
    Nonbite:   Scratches, abrasions, open wounds or mucous membranes contaminated with saliva or other potentially infectious material such as brain tissue from a rabid animal.
    In addition, two cases of rabies have been attributed to airborne exposures in laboratories and two cases of rabies have been attributed to probable exposures to a bat-infested cave (Frio Cave, Texas). 1,34-36 Casual contact with a rabid animal, such as petting the animal (without a bite or nonbite exposure as described above) does not constitute an exposure and is not an indication for prophylaxis.
    The only documented cases of rabies due to human-to-human transmission occurred in patients who received corneas transplanted from persons who died of rabies undiagnosed at the time of death. 1,37
    Each exposure to possible rabies infection must be individually evaluated. Local or state public health officials should be consulted if questions arise about the need for rabies prophylaxis.
  4. Vaccination Status of Biting Animal
    A properly immunized animal has only a minimal chance of developing rabies and transmitting the virus.

II. Postexposure Treatment of Rabies

  1. Local Treatment of Wounds
    Immediate and thorough local treatment of all bite wounds and scratches is perhaps the most effective preventive measure. The wound should be thoroughly cleansed immediately with soap and water. Tetanus prophylaxis and measures to control bacterial infection should be given as indicated.
  2. Specific Treatment
    Postexposure antirabies treatment should always include both passive (preferably Rabies Immune Globulin--Human) and active (preferably Rabies Vaccine prepared from human diploid cells) immunization with one exception: persons who have been previously immunized with HDCV Rabies Vaccine in a pre or postexposure treatment series should receive only vaccine. Persons who have received Rabies Vaccines other than HDCV or RVA vaccines should have confirmed adequate rabies antibody titers if they are to receive only vaccine. 1 The combination of globulin and vaccine is recommended for both bite exposures and nonbite exposures (as described under "Rationale of Treatment") and regardless of the interval between exposure and treatment. The sooner treatment is begun after exposure, the better.
  3. Postexposure Treatment Guide
    The following recommendations are only a guide. They should be applied in conjunction with knowledge of the animal species involved, circumstances of the bite or other exposure, vaccination status of the animal, and presence of rabies in the region. Local and state public health officials should be consulted if questions arise about the need for rabies prophylaxis.

    TABLE 1                 RABIES POSTEXPOSURE PROPHYLAXIS GUIDE, UNITED STATES, 1991 1
    Animal Type
    Evaluation and disposition
    of animal
    Postexposure Prophylaxis Recommendations
    Dogs and cats
    Healthy and available for 10 days observation
    Should not begin prophylaxis unless animal develops symptoms of rabies *
    Rabid or suspected rabid
    Immediate vaccination
    Unknown (escaped)
    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 vaccination
    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 HDCV or RVA 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.

CONTRAINDICATIONS

Imogam® Rabies - HT should NOT be administered in repeated doses once vaccine treatment has been initiated. Repeating the dose may interfere with maximum active immunity expected from the vaccine.

Rabies Immune Globulin (Human) USP, Imogam® Rabies - HT, is made from human plasma. Products made from human plasma may contain infectious agents, such as viruses, that can cause disease. The risk that such products will transmit an infectious agent has been reduced by screening plasma donors for prior exposure to certain viruses, by testing for the presence of certain current virus infections, and by inactivating and/or removing certain viruses. An alcohol fractionation procedure used to purify the immunoglobulin component removes and/or inactivates both enveloped and non-enveloped viruses. An added heat treatment process (60°C, 10 hours) further inactivates both enveloped and non-enveloped viruses. Despite these measures, it is still theoretically possible that known or unknown infectious agents may be present. All infections thought by a physician possibly to have been transmitted by this product should be reported by the physician or other health-care provider to the Director of Scientific and Medical Affairs, Aventis Pasteur Inc., telephone 1-800-822-2463. The physician should discuss the risks and benefits of this product with the patient.

Imogam® Rabies - HT should be given with caution to patients with a history of prior systemic allergic reactions following the administration of human immune globulin.

Persons with specific IgA deficiency have increased potential for developing antibodies to IgA and could have anaphylactic reactions to subsequent administration of blood products containing IgA. 38,39

PRECAUTIONS

GENERAL

Care is to be taken by the health-care provider for the safe and effective use of this product.

EPINEPHRINE INJECTION (1:1000) MUST BE IMMEDIATELY AVAILABLE SHOULD AN ACUTE ANAPHYLACTIC REACTION OCCUR DUE TO ANY COMPONENT OF THIS PRODUCT.

Imogam® Rabies - HT should not be administered intravenously because of the potential for serious reactions. Injection should be made intramuscularly and care should be taken to draw back on the plunger of the syringe before injection in order to be certain that the needle is not in a blood vessel. Although systemic reactions to immunoglobulin preparations are rare, epinephrine should be available for treatment of acute anaphylactoid reactions. As with all preparations given intramuscularly, bleeding complications may be encountered in patients with bleeding disorders.

HRIG should never be administered in the same syringe or into the same anatomical site as vaccine. Because HRIG may partially suppress active production of antibody, no more than the recommended dose should be given. 1

A separate, sterile syringe and needle or a sterile disposable unit should be used for each patient to prevent transmission of hepatitis or other infectious agents from person to person. Needles should not be recapped and should be disposed of according to biohazard waste guidelines.

INFORMATION FOR PATIENT

Patients, parents or guardians should be fully informed by their health-care provider of the benefits and risks of administration of Imogam® Rabies - HT.

Patients, parents or guardians should be instructed to report any serious adverse reactions to their health-care provider.

DRUG INTERACTIONS

Live virus vaccine such as measles vaccines should not be given close to the time of Imogam® Rabies - HT administration because antibodies in the globulin preparation may interfere with the immune response to the vaccination. Immunization with live vaccines should not be given within three months after Imogam® Rabies - HT administration.

PREGNANCY

REPRODUCTIVE STUDIES--PREGNANCY CATEGORY C

Animal reproduction studies have not been conducted with Imogam® Rabies - HT. It is also not known whether Imogam® Rabies - HT can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Imogam® Rabies - HT should be given to a pregnant woman only if clearly needed.

ADVERSE REACTIONS

In a recent clinical trial involving 16 volunteers in 4 treatment groups, two subjects reported severe headaches, one in the Imogam® Rabies - HT + placebo group and one in the Imogam® Rabies + Imovax® Rabies group, and one third of the volunteers reported moderate systemic (headache and malaise) reactions. These were equally distributed among the 4 treatment groups with no significant differences between the groups. 30

Local adverse reactions such as tenderness, pain, soreness or stiffness of the muscles may occur at the injection site and may persist for several hours after injection. These may be treated symptomatically. Mild systemic adverse reactions to the globulin after intramuscular injection are uncommon. 30,40,41

Although not reported specifically for HRIG, angioneurotic edema, nephrotic syndrome, and anaphylaxis have been reported after injection of immune globulin (IG). These reactions occur so rarely that a causal relationship between IG and these reactions is not clear. 1

Reporting of Adverse Events

The National Vaccine Injury Compensation Program, established by the National Childhood Vaccine Injury Act of 1986, requires physicians and other health-care providers who administer vaccines to maintain permanent vaccination records and to report occurrences of certain adverse events to the US Department of Health and Human Services. Reportable events include those listed in the Act for each vaccine and events specified in the package insert as contraindications to further doses of that vaccine. 42,43,44

Reporting by patients, parents or guardians of all adverse events occurring after HRIG administration should be encouraged. Adverse events following treatment with HRIG should be reported by the health-care provider to the US Department of Health and Human Services (DHHS) Vaccine Adverse Event Reporting Systems (VAERS). Reporting forms and information about reporting requirements or completion of the form can be obtained from VAERS through a toll-free number 1-800-822-7967. 42,43,44

The health-care provider also should report these events to the Director of Scientific and Medical Affairs, Aventis Pasteur Inc., Discovery Drive, Swiftwater, PA 18370 or call 1-800-822-2463.

DOSAGE AND ADMINISTRATION

Parenteral drug products should be inspected visually for particulate matter and/or discoloration prior to administration, whenever solution and container permit. If either of these conditions exist, the vaccine should not be administered.

Imogam® Rabies - HT should be used in conjunction with Rabies Vaccine such as Rabies Vaccine Imovax® Rabies, for intramuscular immunization, vaccine prepared from human diploid cell cultures. The recommended dose of Imogam® Rabies - HT is 20 IU/kg (0.133 mL/kg) or 9 IU/lb (0.06 mL/lb) of body weight administered at time of the first vaccine dose. 27,28 As much as possible of the recommended dose should be infiltrated around the wound if anatomically feasible and the remaining HRIG should be administered intramuscularly in the gluteal region. 45 Two injections would be given in the gluteal region if the volume is greater than 5 mL.

HRIG should never be administered in the same syringe or into the same anatomical site as vaccine. Because HRIG may partially suppress active production of antibody, no more than the recommended dose should be given. 1

HOW SUPPLIED

Imogam® Rabies - HT is supplied in 2 mL and 10 mL vials with average potency of 150 International Units per milliliter (IU/mL). The 2 mL vial contains 300 IU which is sufficient for a child weighing 15 kg (33 lb). Product No. 49281-190-20. The 10 mL vial contains a total of 1,500 IU which is sufficient for an adult weighing 75 kg (165 lb). Product No. 49281-190-10

STORAGE

Imogam® Rabies - HT should be stored in the refrigerator between 2° and 8°C (35° and 46°F). Do not freeze.

Imogam® Rabies - HT CONTAINS NO PRESERVATIVE AND UNUSED PORTION MUST BE DISCARDED IMMEDIATELY.

REFERENCES

  1. Recommendation of the Advisory Committee on Immunization Practices (ACIP). Rabies prevention--United States, 1991. MMWR 40: No. RR-3, 1991
  2. Reid-Sanden FL, et al. Rabies surveillance, United States during 1989. J Am Vet Med Assoc 197: 1571-1583, 1990
  3. Helmick CG. The epidemiology of human rabies postexposure prophylaxis, 1980-1981. JAMA 250: 1990-1996, 1983
  4. CDC. Human rabies diagnosed 2 months postmortem--Texas. MMWR 34: 700, 705-707, 1985
  5. CDC. Human rabies acquired outside the United States. MMWR 34: 235-236, 1985
  6. CDC. Human rabies--California, 1987. MMWR 37: 305-308, 1988
  7. CDC. Human rabies--Oregon, 1989. MMWR 38: 335-337, 1989
  8. CDC. Human rabies--Texas. MMWR 33: 469-470, 1984
  9. CDC. Imported human rabies. MMWR 32: 78-80, 85-86, 1983
  10. CDC. Human rabies acquired outside the United States from a dog bite. MMWR 30: 537-540, 1981
  11. Bernard, KW, et al. Neuroparalytic illness and human diploid cell rabies vaccine. JAMA 248: 3136-3138, 1982
  12. CDC. Systemic allergic reactions following immunization with human diploid cell rabies vaccine. MMWR 33: 185-187, 1984
  13. Dreesen EW, et al. Immune complex-like disease in 23 persons following a booster dose of rabies human diploid cell vaccine. Vaccine 4: 45-49, 1986
  14. Aoki FY, et al. Immunogenicity and acceptability of a human diploid-cell culture rabies vaccine in volunteers. Lancet 1: 660-662, 1975
  15. Cox JH, et al. Prophylactic immunization of humans against rabies by intradermal inoculation of human diploid cell culture vaccine. J Clin Microbiol 3: 96-101, 1976
  16. Anderson LJ, et al. Postexposure trial of a human diploid cell strain rabies vaccine. J Infect Dis 142: 133-138, 1980
  17. Bahmanyar M, et al. Successful protection of humans exposed to rabies infection. Postexposure treatment with the new human diploid cell rabies vaccine and antirabies serum. JAMA 236: 2751-2754, 1976
  18. Hattwick MAW. Human rabies. Public Health Rev 3: 229-274, 1974
  19. Wiktor TJ, et al. Development and clinical trials of the new human rabies vaccine of tissue culture (human diploid cell) origin. Dev. Biol Stand 40: 3-9, 1978
  20. World Health Organization. WHO expert committee on rabies. WHO Tech Rep Ser 709: 1-104, 1984
  21. Kuwert EK, et al. Immunization against rabies with rabies immune globulin, human (RIGH) and a human diploid cell strain (HDCS) rabies vaccine. J Biol Stand 6: 211-219, 1978
  22. CDC. Human rabies despite treatment with rabies immune globulin and human diploid cell rabies vaccine - Thailand. MMWR 36: 759-760, 765, 1987
  23. Shill M, et al. Fatal rabies encephalitis despite appropriate post-exposure prophylaxis. A case report. N Engl J Med 316: 1257-1258, 1987
  24. Wilde H, et al. Failure of rabies postexposure treatment in Thailand. Vaccine 7: 49-52, 1989
  25. Baltazard M, et al. Essai pratique du serum antirabique chez les mordus par loups enrages. Bull WHO 13: 747-772, 1955
  26. Habel K, et al. Laboratory data supporting clinical trial of antirabies serum in persons bitten by rabid wolf. Bull WHO 13: 773-779, 1955
  27. Cabasso VJ, et al. Rabies immune globulin of human origin: preparation and dosage determination in non-exposed volunteer subjects. Bull WHO 45: 303-315, 1971
  28. Loofbourow JC, et al. Rabies immune globulin (human). Clinical trials and dose determination. JAMA 217:1825-1831, 1971
  29. Helmick CG, et al. A clinical study of Mérieux human rabies immune globulin. J Biol Stand 10:357-367 1982
  30. Lang J, et al. A clinical evaluation of a new heat treated Rabies Immune Globulin (Human). VII Annual International Meeting on Research Advances & Rabies Control in the Americas.|7257 Centers for Disease Control & Prevention, Atlanta, Georgia, December 9-13, 1996
  31. WHO Expert Committee on Rabies. WHO Tech Rep Ser 523: 50-51, 1973
  32. ACIP. Human Rabies--California, 1994. MMWR 43: 455-457, 1994
  33. Wilde H, et al. Failure of Postexposure Treatment of Rabies in Children. Clin Infect Dis 22: 228-232, 1996
  34. Afshar A. A review of non-bite transmission of rabies virus infection. Br Vet J 135: 142-148, 1979
  35. Winkler WG, et al. Airborne rabies transmission in a laboratory worker. JAMA 226: 1219-1221, 1973
  36. CDC. Rabies in a laboratory worker--New York. MMWR 26: 183-184, 1977
  37. Gode GR, et al. Two rabies deaths after corneal grafts from one donor {letter}. Lancet 2: 791, 1988
  38. Fudenberg HH. Sensitization to immunoglobulins and hazards of gamma globulin therapy, pp 211-220 in Merler E, Editor Immunoglobulins: biologic aspects and clinical uses. National Academy of Sciences, Wash. DC. 1970
  39. Pineda AA, et al. Transfusion reactions associated with anti-IgA antibodies: report of four cases and review of the literature. Transfusion 15:10-15, 1975
  40. Janeway CA, et al. The gamma globulins. IV. Thera-peutic uses of gamma globulins. N Engl J Med 275: 826-831, 1966
  41. Kjellman H. Adverse reactions to human immune serum globulin in Sweden (1969-1978). pp 143-150. Immunoglobulins: characteristics and uses of intravenous preparations. Alving BM and Finlayson JS, Editors. US Dept. Health & Human Services, DHHS Publ. No. (FDA) 80-9005, Wash. DC. 1980
  42. CDC. Vaccine Adverse Event Reporting System--United States. MMWR 39: 730-733, 1990
  43. CDC. National Childhood Vaccine Injury Act. Requirements for permanent vaccination records and for reporting of selected events after vaccination. MMWR 37: 197-200, 1988
  44. Food and Drug Administration. New Reporting Requirements for Vaccine Adverse Events. FDA Drug Bull 18(2), 16-18, 1988
  45. World Health Organization. WHO expert committee on rabies. WHO Tech Rep Ser 824: 1992

                                                          Product Information
                                                                as of April 1997

Manufactured by:

Aventis Pasteur SA

Lyon France

US Govt License #1279

Distributed by:

Aventis Pasteur Inc.

Swiftwater PA 18370 USA

1-800-VACCINE (1-800-822-2463)

                                                                                4210