NABI-HB

Biotest Pharmaceuticals Corporation
Biotest Pharmaceuticals Corporation

Hepatitis B Immune Globulin (Human) Nabi-HB Solvent Detergent Treated and Filtered

FULL PRESCRIBING INFORMATION

DESCRIPTION Hepatitis B Immune Globulin (Human), Nabi-HB, is a sterile solution of immunoglobulin (5 1 percent protein) containing antibodies to hepatitis B surface antigen (anti-HBs). It is prepared from plasma donated by individuals with high titers of anti-HBs. The plasma is processed using a modified Cohn 6 Oncley 9 cold-alcohol fractionation process1, 2 with two added viral reduction steps described below. Nabi-HB is formulated in 0.042-0.108 M sodium chloride, 0.10-0.20 M glycine, and 0.005-0.050 percent polysorbate 80, at pH 5.8-6.5. The product is supplied as a nonturbid sterile liquid in single dose vials and appears as clear to opalescent. It contains no preservative and is intended for single use by the intramuscular route only. Each plasma donation used for the manufacture of Nabi-HB is tested for the presence of hepatitis B virus (HBV) surface antigen (HBsAg), human immunodeficiency viruses (HIV) 1/2, and hepatitis C virus (HCV) antibodies. In addition, pooled samples of Source Plasma used in the manufacture of this product are tested by FDA licensed Nucleic Acid Testing (NAT) for HIV and HCV and found to be negative. Investigational NAT for hepatitis A virus (HAV) and HBV is also performed on pooled samples of all Source Plasma used, and found to be negative; however, the significance of a negative result has not been established. Investigational NAT for parvovirus B19 (B19) is also performed on pooled samples of all Source Plasma and the limit for B19 DNA in a manufacturing pool is set not to exceed 104 IU/mL. The manufacturing steps for Nabi-HB are designed to reduce the risk of transmission of viral disease. The solvent/detergent treatment step, using tri-n-butyl phosphate and Triton X-100, is effective in inactivating known enveloped viruses such as hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) 3. Virus filtration, using a Planova 35 nm Virus Filter, is effective in reducing some known enveloped and non-enveloped viruses4. The inactivation and reduction of known enveloped and non-enveloped model viruses were validated in laboratory studies as summarized in the following table

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 use6-9. Clinical studies10,11 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 neonates12. 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 carriers13. The risk is especially great if the mother is also HBeAg-positive14. 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 85-98percent effective in preventing development of the HBV carrier state15-17. Regimens involving either multiple doses of Hepatitis B Immune Globulin (Human) alone or the vaccine series alone have a 70-90percent efficacy, while a single dose of Hepatitis B Immune Globulin (Human) alone has 50percent efficacy18. 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 infection19. Sexual partners of HBsAg-positive persons are at increased risk of acquiring HBV infection. A single dose of Hepatitis B Immune Globulin (Human) is 75percent effective if administered within two weeks of the last sexual exposure to a person with acute hepatitis B19.

Uses

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.

PRECAUTIONS General Nabi-HB, Hepatitis B Immune Globulin (Human), must be administered only intramuscularly for post-exposure prophylaxis. The preferred sites for intramuscular injections are the anterolateral aspect of the upper thigh and the deltoid muscle. If the buttock is used due to the volume to be injected, the central region should be avoided only the upper, outer quadrant should be used, and the needle should be directed anterior (i.e., not inferior or perpendicular to the skin) to minimize the possibility of involvement with the sciatic nerve22. The 50 healthy volunteers who received Nabi-HB in pharmacokinetic studies were followed for 84 days for possible development of anti-HCV antibodies. No subject seroconverted.

Pregnancy Category C Animal reproduction studies have not been conducted with Nabi-HB. It is also not known whether Nabi-HB can cause fetal harm when administered to a pregnant woman or can affect a woman's ability to conceive. Nabi-HB should be given to a pregnant woman only if clearly indicated.

Nursing Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Nabi-HB is administered to a nursing mother.

Pediatric Use Safety and effectiveness in the pediatric population have not been established for Nabi-HB. However, the safety and effectiveness of similar hepatitis B immune globulins have been demonstrated in infants and children12.

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.

HOW SUPPLIED Nabi-HB, Hepatitis B Immune Globulin (Human), is supplied as:

NDC Number Contents 59730-4202-1 a carton containing a 1 mL dose in a single-use vial (>312 IU) and package insert

59730-4203-1 a carton containing a 5 mL dose in a single-use vial (>1560 IU) and package insert

STORAGE

Refrigerate between 2 to 8 C (36 to 46 F). Do not freeze. Do not use after expiration date. Use within 6 hours after the vial has been entered.

REFERENCES

1. Cohn E.J., Strong W.L., Mulford D.J., Ashworth J.N., Melin M., Taylor H.L. Preparation and Properties of Serum and Plasma Proteins IV. A system for the separation into fractions of the protein and lipoprotein components of biological tissues and fluids. J Am Chem Soc 1946, 68: 459-475.

2. Oncley J.L, Melin M, Richert D.A, Cameron J. W, Gross P.M. The separation of antibodies, isoagglutinins, prothrombin, plasminogen and b1-lipoproteins into sub-fractions of human plasma. J Am Chem Soc 1949, 71:541-550.

3. Horowitz B: Investigations into the application of tri(n-butyl)phosphate/detergent mixtures to blood derivatives. Morgenthaler J (ed): Virus Inactivation in Plasma Products, Curr Stud Hematol Blood Transfus 1989; 56:83-96.

4. Burnouf T: Value of virus filtration as method for improving the safety of plasma products. Vox Sang 1996; 70:235-236.

5. Unpublished data on file, Viral Validation Study Reports, Biotest Pharmaceuticals.

6. Grady GF, and Lee VA: Hepatitis B immune globulin - prevention of hepatitis from accidental exposure among medical personnel. N Engl J Med 1975; 293:1067-1070.

7. Seeff LB, et al.: Type B hepatitis after needle-stick exposure: Prevention with hepatitis B immune globulin. Ann Int Med 1978; 88:285-293.

8. Krugman S, and Giles JP: Viral hepatitis, type B (MS-2-strain). Further observations on natural history and prevention. N Engl J Med 1973; 288:755-760.

9. Hoofnagle JH, et al.: Passive - active immunity from hepatitis B immune globulin. Ann Int Med 1979; 91:813-818.

10. Beasley RP, et al.: Efficacy of hepatitis B immune globulin for prevention of perinatal transmission of the hepatitis B virus carrier state: Final report of a randomized doubleblind, placebo - controlled trial. Hepatology 1983; 3:135-141.

11. Szmuness W, et al.: Passive active immunisation against hepatitis B: Immunogenicity studies in adult Americans. Lancet 1981; 1:575-577.

12. Centers for Disease Control: Recommendations for protection against viral hepatitis. Recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR 1985; 34(22):313-335.

13. Shiraki Y, et al.: Hepatitis B surface antigen and chronic hepatitis in infants born to asymptomatic carrier mothers. Am J Dis Child 1977; 131:644-647.

14. Beasley RP, et al.: The e antigen and vertical transmission of hepatitis B surface antigen. Am J Epidemiol 1977; 105:94-98.

15.Wong VCW, et al.: Prevention of the HBsAg carrier state in newborn infants of mothers who are chronic carriers of HBsAg and HBeAg by administration of hepatitis B vaccine and hepatitis B immunoglobulin: Double-blind randomized placebo-controlled study. Lancet 1984; 1:921-926.

16. Poovorawan Y, et al.: Long term hepatitis B vaccine in infants born to hepatitis B e antigen positive mothers. Archives of Diseases in Childhood 1997; 77:F47-F51.

17. Stevens CE, et al.: Perinatal Hepatitis B virus transmission in the United States: Prevention by passive-active immunization. JAMA 1985; 253:1740-1745.

18. Jhaveri R, et al.: High titer multiple dose therapy with HBIG in newborn infants of HBsAg positive mothers. J Pediatr 1980; 97:305-308.

19. Centers for Disease Control: Hepatitis B virus: A comprehensive strategy for eliminating transmission in the United States through universal childhood vaccination. Recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR 1991; 40(13):1-25.

20. Data on file, Biotest Pharmaceuticals.

21. Scheiermann N, Kuwert EK: Uptake and elimination of hepatitis B immunoglobulins after intramuscular application in man. Develop Biol Standard 1983; 54:347.

22. Centers for Disease Control: General recommendations on immunization. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 1994; 43:1-38.

23. Ellis EF, Henney CS: Adverse reactions following administration of human gamma globulin. J Allerg 1969; 43:45-54.

Manufactured by: Biotest Pharmaceuticals Corporation Boca Raton, FL 33487 U.S. License No. 1792 April 2008

Hepatitis B Immune Globulin (Human)

Nabi-HB

Solvent/Detergent Treated and Filtered

Store at 2-8 C (36-46 F)

Do not freeze. RX Only.

For intramuscular Administration only.