hepatitis B immune globulin

INDICATIONS AND USAGE Nabi-HB, Hepatitis B Immune Globulin (Human), is indicated for treatment of acute exposure to blood containing HBsAg, perinatal exposure of infants born to HBsAg-positive mothers, sexual exposure to HBsAg-positive persons and household exposure to persons with acute HBV infec- tion in the following settings: Acute Exposure to Blood Containing HBsAg: Following either parenteral exposure (needlestick, bite, sharps), direct mucous membrane contact (accidental splash), or oral ingestion (pipetting accident), involving HBsAg-positive materials such as blood, plasma, or serum. Perinatal Exposure of Infants Born to HBsAg-positive Mothers: Infants born to mothers positive for HBsAg with or without HBeAg 12 . Sexual Exposure to HBsAg-positive Persons: Sexual partners of HBsAg-positive persons. Household Exposure to Persons with Acute HBV Infection: Infants less than 12 months old whose mother or primary caregiver is positive for HBsAg. Other household contacts with an identifiable blood exposure to the index patient. Nabi-HB is indicated for intramuscular use only.

CLINICAL PHARMACOLOGY Hepatitis B Immune Globulin (Human) products provide passive immunization for individuals exposed to the hepatitis B virus as evidenced by a reduction in the attack rate of hepatitis B following use 6-9 . Clinical studies 10,11 conducted prior to 1983 with hepatitis B immune globulins similar to Nabi-HB indicate the advantage of simultaneous administration of hepatitis B vaccine and Hepatitis B Immune Globulin (Human). The Centers for Disease Control and Prevention Advisory Committee on Immunization Practices (ACIP) advises that the combination prophylaxis be provided in certain instances of exposure based upon the increased efficacy found with that regimen in neonates 12 . Cases of hepatitis B are rarely seen following exposure to HBV in persons with preexisting anti-HBs. However, no prospective studies have been performed on the efficacy of concurrent hepatitis B vaccine and Hepatitis B Immune Globulin (Human) administration following parenteral exposure, mucous membrane contact, or oral ingestion in adults. Infants born to HBsAg-positive mothers are at risk of being infected with HBV and becoming chronic carriers 13 . The risk is especially great if the mother is also HBeAg-positive 14 . Studies conducted with hepatitis B immune globulins similar to Nabi-HB indicated that for an infant with perinatal exposure to an HBsAg-positive and HBeAg-positive mother, a regimen combining one dose of Hepatitis B Immune Globulin (Human) at birth with the hepatitis B vaccine series started soon after birth is 85-98% effective in preventing development of the HBV carrier state 15-17 . Regimens involving either multiple doses of Hepatitis B Immune Globulin (Human) alone or the vaccine series alone have a 70-90% efficacy, while a single dose of Hepatitis B Immune Globulin (Human) alone has 50% efficacy 18 . Since infants have close contact with primary caregivers and they have a higher risk of becoming HBV carriers after acute HBV infection, prophylaxis of an infant less than 12 months of age with Hepatitis B Immune Globulin (Human) and hepatitis B vaccine is indicated if the mother or primary caregiver has acute HBV infection 19 . Sexual partners of HBsAg-positive persons are at increased risk of acquiring HBV infection. A single dose of Hepatitis B Immune Globulin (Human) is 75% effective if administered within two weeks of the last sexual exposure to a person with acute hepatitis B 19 . Pharmacokinetics Pharmacokinetics trials 20 of Nabi-HB, Hepatitis B Immune Globulin (Human), given intramuscularly to 50 healthy volunteers demonstrated pharmacokinetic parameters similar to those reported by Scheiermann and Kuwert 21 . The half-life for Nabi-HB was 23.1 ± 5.5 days. The clearance rate was 0.35 ± 0.12 L/day and the volume of distribution was 11.2 ± 3.4 L. Maximum concentration of Nabi-HB was reached in 6.5 ± 4.3 days. The maximum concentration of anti-HBs and the area under the time-concentration curve achieved by Nabi-HB were bioequivale

DOSAGE AND ADMINISTRATION This product is for intramuscular use only. The use of this product by the intravenous route is not indicated. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. It is important to use a separate vial, sterile syringe, and needle for each individual patient, in order to prevent transmission of infectious agents from one person to another. Any vial of Nabi-HB, Hepatitis B Immune Globulin (Human) that has been entered should be used promptly. Do not reuse or save for future use. This product contains no preservative; therefore, partially used vials should be discarded immediately. Hepatitis B Immune Globulin (Human) may be administered at the same time (but at a different site), or up to one month preceding hepatitis B vaccination without impairing the active immune response to hepatitis B vaccine 11 . Acute Exposure to Blood Containing HBsAg Table 2 summarizes prophylaxis for percutaneous (needlestick, bite, sharps), ocular, or mucous membrane exposure to blood according to the source of exposure and vaccination status of the exposed person. For greatest effectiveness, passive prophylaxis with Hepatitis B Immune Globulin (Human) should be given as soon as possible after exposure, as its value after seven days following exposure is unclear 12 . An injection of 0.06 mL/kg of body weight should be administered intramuscularly as soon as possible after exposure and within 24 hours, if possible. Consult the hepatitis B vaccine package insert for dosage information regarding the vaccine. For persons who refuse hepatitis B vaccine or are known non-responders to vaccine, a second dose of Hepatitis B Immune Globulin (Human) should be given one month after the first dose 12 . Table 2 Recommendations for Hepatitis B Prophylaxis Following Percutaneous or Permucosal Exposure 12 * Hepatitis B Immune Globulin (Human) dose of 0.06 mL/kg IM. † See manufacturer’s recommendation for appropriate dose. ‡ Less than 10 mIU/mL anti-HBs by radioimmunoassay, negative by enzyme immunoassay. § Two doses of Hepatitis B Immune Globulin (Human) is preferred if no response after at least four doses of vaccine. Exposed Person Source Unvaccinated Vaccinated HBsAg-positive Hepatitis B Immune Globulin (Human) X1 immediately* Initiate HB vaccine series† Test exposed person for anti-HBs If inadequate antibody ‡ , Hepatitis B Immune Globulin (Human) X 1 immediately plus either HB vaccine booster dose or second dose of Hepatitis B Immune Globulin (Human) one month later § Known Source - High Risk for HBsAg-positive Initiate HB vaccine series Test source for HBsAg. If positive, Hepatitis B Immune Globulin (Human) X 1 Test source for HBsAg only if exposed is vaccine nonresponder; if source is HBsAg-positive, give Hepatitis B Immune Globulin (Human) X 1 immediately plus either HB vaccine booster dose or second dose of Hepatitis B Immune Globulin (Human) one month later § . Known Source - Low Risk for HBsAg-positive Initiate HB vaccine series Nothing required Unknown Source Initiate HB vaccine series Nothing required Prophylaxis of Infants Born to Mothers who are Positive for HBsAg with or without HBeAg Table 3 contains the recommended schedule of hepatitis B prophylaxis for infants born to mothers that are either known to be positive for HBsAg or have not been screened. Infants born to mothers known to be HBsAg-positive should receive 0.5 mL Hepatitis B Immune Globulin (Human) after physiologic stabilization of the infant and preferably within 12 hours of birth. The hepatitis B vaccine series should be initiated simultaneously, if not contraindicated, with the first dose of the vaccine given concurrently with the Hepatitis B Immune Globulin (Human), but at a different site. Subsequent doses of the vaccine should be administered in accordance with the recommendations of the manufacturer. Women admitted for delivery, who were not screened for HBsAg during the prenatal period, sh

ADVERSE REACTIONS SECTION Fifty male and female volunteers received Nabi-HB, Hepatitis B Immune Globulin (Human), intramuscularly in pharmacokinetics trials 20 . The number of patients with reactions related to the administration of Nabi-HB included local reactions such as erythema 6 (12%) and ache 2 (4%) at the injection site, as well as systemic reactions such as headache 7 (14%), myalgia 5 (10%), malaise 3 (6%), nausea 2 (4%), and vomiting 1 (2%). The majority (92%) of reactions were reported as mild. The following adverse events were reported in the pharmacokinetics trials and were considered probably related to Nabi-HB: elevated alkaline phosphatase 2 (4%), ecchymosis 1 (2%), joint stiffness 1 (2%), elevated AST 1 (2%), decreased WBC 1 (2%), and elevated creatinine 1 (2%). All adverse events were mild in intensity. There were no serious adverse events. No anaphylactic reactions with Nabi-HB have been reported. However, these reactions, although rare, have been reported following the injection of human immune globulins 23 .

WARNINGS In patients who have severe thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injections, Nabi-HB, Hepatitis B Immune Globulin (Human), should be given only if the expected benefits outweigh the potential risks. Nabi-HB is made from human plasma. Products made from human plasma may contain infectious agents, e.g., viruses, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent. The risk that such products can 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 viral infections, and by inactivating and/or reducing certain viruses. The Nabi-HB manufacturing process includes a solvent/detergent treatment step (using tri- n -butyl phosphate and Triton ® X-100) that is effective in inactivating known enveloped viruses such as HBV, HCV, and HIV. Nabi-HB is filtered using a Planova ® 35 nm Virus Filter that is effective in reducing the levels of some enveloped and non-enveloped viruses. These two processes are designed to increase product safety. 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. 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 ADMA Biologics at 1-800-458-4244. The physician should discuss the risks and benefits of this product with the patient.

CONTRAINDICATIONS Individuals known to have had an anaphylactic or severe systemic reaction to human globulin should not receive Nabi-HB, Hepatitis B Immune Globulin (Human), or any other human immune globulin. Nabi-HB contains not more than 40 micrograms per mL IgA. Individuals who are deficient in IgA have the potential to develop antibodies against IgA and anaphylactic reactions. The physician must weigh the potential benefit of treatment with Nabi-HB against the potential for hypersensitivity reactions.

OVERDOSAGE Although no data are available, clinical experience reported with other human immune globulins suggests that the only manifestations of overdose with Nabi-HB, Hepatitis B Immune Globulin (Human), would be pain and tenderness at the injection site.