Rabies Immune Globulin (Human) -- BayRab® treated with solvent/detergent is a sterile solution of antirabies immune globulin for intramuscular administration; it contains no preservative. BayRab is prepared by cold ethanol fractionation from the plasma of donors hyperimmunized with rabies vaccine. The immune globulin is isolated from solubilized Cohn Fraction II. The Fraction II solution is adjusted to a final concentration of 0.3% tri-n-butyl phosphate (TNBP) and 0.2% sodium cholate. After the addition of solvent (TNBP) and detergent (sodium cholate), the solution is heated to 30°C and maintained at that temperature for not less than 6 hours. After the viral inactivation step, the reactants are removed by precipitation, filtration and finally ultrafiltration and diafiltration. BayRab is formulated as a 15-18% protein solution at a pH of 6.4-7.2 in 0.21-0.32 M glycine. BayRab is then incubated in the final container for 21-28 days at 20-27°C. The product is standardized against the U.S. Standard Rabies Immune Globulin to contain an average potency value of 150 IU/mL. The U.S. unit of potency is equivalent to the international unit (IU) for rabies antibody.
The removal and inactivation of spiked model enveloped and non-enveloped viruses during the manufacturing process for BayRab has been validated in laboratory studies. Human Immunodeficiency Virus, Type 1 (HIV-1), was chosen as the relevant virus for blood products; Bovine Viral Diarrhea Virus (BVDV) was chosen to model Hepatitis C virus; Pseudorabies virus (PRV) was chosen to model Hepatitis B virus and the Herpes viruses; and Reo virus type 3 (Reo) was chosen to model non-enveloped viruses and for its resistance to physical and chemical inactivation. Significant removal of model enveloped and non-enveloped viruses is achieved at two steps in the Cohn fractionation process leading to the collection of Cohn Fraction II: the precipitation and removal of Fraction III in the processing of Fraction II + IIIW suspension to Effluent III and the filtration step in the processing of Effluent III to Filtrate III. Significant inactivation of enveloped viruses is achieved at the time of treatment of solubilized Cohn Fraction II with TNBP/sodium cholate.
The usefulness of prophylactic rabies antibody in preventing rabies in man when administered immediately after exposure was dramatically demonstrated in a group of persons bitten by a rabid wolf in Iran. 1,2 Similarly, beneficial results were later reported from the U.S.S.R. 3 Studies coordinated by WHO helped determine the optimal conditions under which antirabies serum of equine origin and rabies vaccine can be used in man. 4 - 7 These studies showed that serum can interfere to a variable extent with the active immunity induced by the vaccine, but could be minimized by booster doses of vaccine after the end of the usual dosage series.
Preparation of rabies immune globulin of human origin with adequate potency was reported by Cabasso et al. 8 In carefully controlled clinical studies, this globulin was used in conjunction with rabies vaccine of duck-embryo origin (DEV). 8,9 These studies determined that a human globulin dose of 20 IU/kg of rabies antibody, given simultaneously with the first DEV dose, resulted in amply detectable levels of passive rabies antibody 24 hours after injection in all recipients. The injections produced minimal, if any, interference with the subject' endogenous antibody response to DEV.
More recently, human diploid cell rabies vaccines (HDCV) prepared from tissue culture fluids containing rabies virus have received substantial clinical evaluation in Europe and the United States. 10 - 16 In a study in adult volunteers, the administration of Rabies Immune Globulin (Human) did not interfere with antibody formation induced by HDCV when given in a dose of 20 IU per kilogram body weight simultaneously with the first dose of vaccine. 15
In a clinical study in eight healthy human adults receiving a 20 IU/kg intramuscular dose of Rabies Immune Globulin (Human) treated with solvent/detergent, BayRab, detectable passive rabies antibody titers were observed in the serum of all subjects by 24 hours post injection and persisted through the 21 day study period. These results are consistent with prior studies 17,18 with non-solvent/detergent treated product.
Rabies vaccine and Rabies Immune Globulin (Human), BayRab® should be given to all persons suspected of exposure to rabies with one exception: persons who have been previously immunized with rabies vaccine and have a confirmed adequate rabies antibody titer should receive only vaccine. BayRab should be administered as promptly as possible after exposure, but can be administered up to the eighth day after the first dose of vaccine is given.
Recommendations for use of passive and active immunization after exposure to an animal suspected of having rabies have been detailed by the U.S. Public Health Service Advisory Committee on Immunization Practices (ACIP). 19
Every exposure to possible rabies infection must be individually evaluated. The following factors should be considered before specific antirabies treatment is initiated:
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 vaccination status of the animal, and presence of rabies in the region. Local or state public health officials should be consulted if questions arise about the need for rabies prophylaxis.
Local Treatment of Wounds: Immediate and thorough washing of all bite wounds and scratches with soap and water is perhaps the most effective measure for preventing rabies. In experimental animals, simple local wound cleansing has been shown to reduce markedly the likelihood of rabies.
Tetanus prophylaxis and measures to control bacterial infection should be given as indicated.
Active Immunization: Active immunization should be initiated as soon as possible after exposure. Many dosage schedules have been evaluated for the currently available rabies vaccines and their respective manufacturers' literature should be consulted.
Passive Immunization: A combination of active and passive immunization (vaccine and immune globulin) is considered the acceptable postexposure prophylaxis except for those persons who have been previously immunized with rabies vaccine and who have documented adequate rabies antibody titer. These individuals should receive vaccine only. For passive immunization, Rabies Immune Globulin (Human) is preferred over antirabies serum, equine. 16,17 It is recommended both for treatment of all bites by animals suspected of having rabies and for nonbite exposure inflicted by animals suspected of being rabid. Rabies Immune Globulin (Human) should be used in conjunction with rabies vaccine and can be administered through the seventh day after the first dose of vaccine is given. Beyond the seventh day, Rabies Immune Globulin (Human) is not indicated since an antibody response to cell culture vaccine is presumed to have occurred.
Rabies Immune Globulin (Human)--BayRab® 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. Despite these measures, such products can still potentially transmit disease. There is also the possibility that unknown infectious agents may be present in such products. Individuals who receive infusions of blood or plasma products may develop signs and/or symptoms of some viral infections, particularly hepatitis C. ALL infections thought by a physician possibly to have been transmitted by this product should be reported by the physician or other healthcare provider to Bayer Corporation [1-800-765-3203].
The physician should discuss the risks and benefits of this product with the patient, before prescribing or administering it to the patient.
Rabies Immune Globulin (Human) - BayRab® should be given with caution to patients with a history of prior systemic allergic reactions following the administration of human immunoglobulin preparations.
The attending physician who wishes to administer BayRab to persons with isolated immunoglobulin A (IgA) deficiency must weigh the benefits of immunization against the potential risks of hypersensitivity reactions. Such persons have increased potential for developing antibodies to IgA and could have anaphylactic reactions to subsequent administration of blood products that contain IgA. 25
As with all preparations administered by the intramuscular route, bleeding complications may be encountered in patients with thrombocytopenia or other bleeding disorders.
BayRab should not be administered intravenously because of the potential for serious reactions. Although systemic reactions to immunoglobulin preparations are rare, epinephrine should be available for treatment of acute anaphylactoid symptoms.
Repeated doses of Rabies Immune Globulin (Human) - BayRab® should not be administered once vaccine treatment has been initiated as this could prevent the full expression of active immunity expected from the rabies vaccine.
Other antibodies in the BayRab preparation may interfere with the response to live vaccines such as measles, mumps, polio or rubella. Therefore, immunization with live vaccines should not be given within 3 months after BayRab administration.
Animal reproduction studies have not been conducted with BayRab. It is also not known whether BayRab can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. BayRab should be given to a pregnant woman only if clearly needed.
Safety and effectiveness in the pediatric population have not been established.
Soreness at the site of injection and mild temperature elevations may be observed at times. Sensitization to repeated injections has occurred occasionally in immunoglobulin-deficient patients. Angioneurotic edema, skin rash, nephrotic syndrome, and anaphylactic shock have rarely been reported after intramuscular injection, so that a causal relationship between immunoglobulin and these reactions is not clear.
The recommended dose for BayRab is 20 IU/kg (0.133 mL/ kg) of body weight given preferably at the time of the first vaccine dose. 8,9 If anatomically feasible, up to the full dose of BayRab should be thoroughly infiltrated in the area around the wound and the rest should be administered intramuscularly in the gluteal area. Because of risk of injury to the sciatic nerve, the central region of the gluteal area MUST be avoided; only the upper, outer quadrant should be used. 26 BayRab should never be administered in the same syringe or into the same anatomical site as vaccine.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
BayRab is packaged in 2 mL and 10 mL single dose vials with an average potency value of 150 International Units per mL (IU/ mL). The 2 mL vial contains a total of 300 IU which is sufficient for a child weighing 15 kg. The 10 mL vial contains a total of 1500 IU which is sufficient for an adult weighing 75 kg.
NDC Number Size
0026-0618-02 2 mL vial
0026-0618-10 10 mL vial
BayRab should be stored under refrigeration (2°-8°C, 36°-46°F). Solution that has been frozen should not be used.
U.S. federal law prohibits dispensing without prescription.
A number of factors beyond our control could reduce the efficacy of this product or even result in an ill effect following its use. These include improper storage and handling of the product after it leaves our hands, diagnosis, dosage, method of administration, and biological differences in individual patients. Because of these factors, it is important that this product be stored properly and that the directions be followed carefully during use.
No warranty, express or implied, including any warranty of merchantability or fitness is made. Representatives of the Company are not authorized to vary the terms or the contents of the printed labeling, including the package insert for this product, except by printed notice from the Company's headquarters. The prescriber and user of this product must accept the terms hereof.