Recombivax

CLINICAL PHARMACOLOGY

Hepatitis B virus is one of several hepatitis viruses that cause a systemic infection, with a major pathology in the liver. These include hepatitis A virus, hepatitis D virus, and hepatitis C and E viruses, previously referred to as non-A, non-B hepatitis viruses.

Hepatitis B virus is an important cause of viral hepatitis. There is no specific treatment for this disease. The incubation period for hepatitis B is relatively long; six weeks to six months may elapse between exposure and the onset of clinical symptoms. The prognosis following infection with hepatitis B virus is variable and dependent on at least three factors: (1) Age - Infants and younger children usually experience milder initial disease than older persons;1 (2) Dose of virus - The higher the dose, the more likely acute icteric hepatitis B will result;1 and, (3) Severity of associated underlying disease - Underlying malignancy or pre-existing hepatic disease predisposes to increased morbidity and mortality.1

Persistence of viral infection (the chronic hepatitis B virus carrier state) occurs in 5-10% of persons following acute hepatitis B, and occurs more frequently after initial anicteric hepatitis B than after initial icteric disease. Consequently, carriers of hepatitis B surface antigen (HBsAg) frequently give no history of having had recognized acute hepatitis. The Centers for Disease Control and Prevention (CDC) estimates that there are more than 300 million chronic carriers worldwide and 1.25 million chronic carriers of hepatitis B virus in the USA.29,30 Chronic carriers represent the largest human reservoir of hepatitis B virus.

Serious complications and sequelae of hepatitis B virus infection include massive hepatic necrosis, cirrhosis of the liver and chronic active hepatitis. More than one million people worldwide die each year of hepatitis B-associated acute and chronic liver disease.33 In the United States, hepatitis B-virus-related acute and chronic liver disease causes approximately 4-5000 deaths annually.29,30

Reduced Risk of Hepatocellular Carcinoma

Hepatocellular carcinoma is another serious complication of hepatitis B virus infection. Studies have demonstrated the link between chronic hepatitis B infection and hepatocellular carcinoma; 80% of primary liver cancers are caused by hepatitis B virus infection. The CDC has recognized hepatitis B vaccine as the first anti-cancer vaccine because it can prevent primary liver cancer.34

There is also evidence that several diseases other than hepatitis have been associated with hepatitis B virus infection through an immunologic mechanism involving antigen-antibody complexes. Such diseases include a syndrome with rash, urticaria, and arthralgia resembling serum sickness; periarteritis nodosa; membranous glomerulonephritis; and infantile papular acrodermatitis.3,4

Although the vehicles for transmission of the virus are often blood and blood products, viral antigen has also been found in tears, saliva, breast milk, urine, semen and vaginal secretions. Hepatitis B virus is capable of surviving at least a month29 on environmental surfaces exposed to body fluids containing hepatitis B virus. Infection may occur when hepatitis B virus, transmitted by infected body fluids, is implanted via mucous surfaces or percutaneously introduced through accidental or deliberate breaks in the skin.

Transmission of hepatitis B virus infection is often associated with close interpersonal contact with an infected individual and with crowded living conditions. In such circumstances, transmission by inoculation via routes other than overt percutaneous ones may be quite common.1 Perinatal transmission of hepatitis B infection from infected mother to child, at or shortly after birth, can occur if the mother is a hepatitis B surface antigen (HBsAg) carrier or if the mother has an acute hepatitis B infection in the third trimester. Infection in infancy by the hepatitis B virus usually leads to the chronic carrier state. Without prophylaxis, infants born to women whose sera are positive for both the hepatitis B surface antigen and the e antigen have an 85-90% likelihood of being infected and becoming a chronic carrier.5,6 Wellcontrolled studies have shown that administration of three 0.5 mL doses of Hepatitis B Immune Globulin (Human) - HBIG starting at birth is 75% effective in preventing establishment of the chronic carrier state in these infants during the first year of life.6 However, the protective effect of HBIG is transient.

Hepatitis B is endemic throughout the world and is a serious medical problem in population groups at increased risk. Because vaccination limited to high-risk individuals has failed to substantially lower the overall incidence of hepatitis B infection, both the Advisory Committee on Immunization Practices (ACIP) and the Committee on Infectious Diseases of the American Academy of Pediatrics (AAP) have also endorsed universal infant immunization as part of a comprehensive strategy for the control of hepatitis B infection.7,8 In addition, the ACIP also recommends hepatitis B vaccination for all infants and children born after November 21, 1991 and catch-up vaccination of children at high risk of infection (children < 11 years of age in households of Pacific Islander ethnicity or of first generation immigrants/refugees from countries with an intermediate or high endemicity of infection).30 These advisory groups further Hepatitis B Vaccine (Recombinant) 7994332 recommend broad-based vaccination of adolescents. The ACIP recommends that all individuals not previously vaccinated with hepatitis B vaccine be vaccinated at 11-12 years of age with the ageappropriate dose of vaccine and that the vaccination schedule take into account the feasibility of delivering three doses of vaccine to this age group. In addition, older unvaccinated adolescents with identified risk factors for hepatitis B virus infection should also be vaccinated.30 Similarly, the AAP recommends that universal immunization of all adolescents should be implemented when resources permit with emphasis on those individuals in high-risk settings.8 A National Institutes of Health Consensus Development Conference Panel on the management of hepatitis C recommends the immunization of all hepatitis C virus (HCV) positive individuals with hepatitis B vaccine.35 (Refer to INDICATIONS AND USAGE.)

Numerous epidemiological studies have shown that persons who develop anti-HBs following active infection with the hepatitis B virus are protected against the disease on re-exposure to the virus.9

Clinical studies have shown that RECOMBIVAX (hepatitis b vaccine (recombinant)) HB when injected into the deltoid muscle induced protective levels of antibody in 96% of 1213 healthy adults who received the recommended 3-dose regimen. Antibody responses varied with age; a protective level of antibody was induced in 98% of 787 young adults 20-29 years of age, 94% of 249 adults 30-39 years of age and in 89% of 177 adults ≥ 40 years of age.10 Studies with hepatitis B vaccine derived from plasma have shown that a lower response rate (81%) to vaccine may be obtained if the vaccine is administered as a buttock injection.11Seroconversion rates and geometric mean antibody titers were measured 1 to 2 months after the third dose. Multiple clinical studies have defined a protective antibody (anti-HBs) level as 1) 10 or more sample ratio units (SRU) as determined by radioimmunoassay or 2) a positive result as determined by enzyme immunoassay.2 Note: 10 SRU is comparable to 10 mIU/mL of antibody.12,13,14,15

RECOMBIVAX (hepatitis b vaccine (recombinant)) HB was shown to be highly immunogenic in clinical studies involving infants, children, and adolescents. Three 5 mcg doses of vaccine induced a protective level of antibody in 100% of 92 infants, 99% of 129 children, and in 99% of 112 adolescents10 (see DOSAGE AND ADMINISTRATION).

The protective efficacy of three 5 mcg doses of RECOMBIVAX (hepatitis b vaccine (recombinant)) HB has been demonstrated in neonates born of mothers positive for both HBsAg and HBeAg (a core-associated antigenic complex which correlates with high infectivity). In a clinical study of infants who received one dose of HBIG at birth followed by the recommended three-dose regimen of RECOMBIVAX (hepatitis b vaccine (recombinant)) HB, chronic infection had not occurred in 96% of 130 infants after nine months of follow-up.16 The estimated efficacy in prevention of chronic hepatitis B infection was 95% as compared to the infection rate in untreated historical controls.17 Significantly fewer neonates became chronically infected when given one dose of HBIG at birth followed by the recommended three-dose regimen of RECOMBIVAX (hepatitis b vaccine (recombinant)) HB when compared to historical controls who received only a single dose of HBIG.6 Testing for HBsAg and anti-HBs is recommended at 12-15 months of age. If HBsAg is not detectable, and anti-HBs is present, the child has been protected.

As demonstrated in the above study, HBIG, when administered simultaneously with RECOMBIVAX (hepatitis b vaccine (recombinant)) HB at separate body sites, did not interfere with the induction of protective antibodies against hepatitis B virus elicited by the vaccine.

For adolescents (11 through 15 years of age), the immunogenicity of a two-dose regimen (10 mcg at 0 and 4-6 months) was compared with that of the standard three-dose regimen (5 mcg at 0, 1, and 6 months) in an open, randomized, multicenter study. The proportion of adolescents receiving the two-dose regimen who developed a protective level of antibody one month after the last dose (99% of 255 subjects) appears similar to that among adolescents who received the three-dose regimen (98% of 121 subjects). After adolescents (11 through 15 years of age) received the first 10-mcg dose of the two-dose regimen, the proportion who developed a protective level of antibody was approximately 72%.10

In one published study, the seroprotection rates in individuals with chronic HCV infection given the standard regimen of RECOMBIVAX (hepatitis b vaccine (recombinant)) HB was approximately 70%.36 In a second published study of intravenous drug users given an accelerated schedule of RECOMBIVAX (hepatitis b vaccine (recombinant)) HB, infection with HCV did not affect the response to RECOMBIVAX (hepatitis b vaccine (recombinant)) HB.37

As with other hepatitis B vaccines, the duration of the protective effect of RECOMBIVAX (hepatitis b vaccine (recombinant)) HB in healthy vaccinees is unknown at present, and the need for booster doses is not yet defined. However, long-term follow-up (5 to 9 years) of approximately 3000 high-risk vaccinees (infants of carrier mothers, male homosexuals, Alaskan Natives) who developed an anti-HBs titer of ≥ 10 mIU/mL when given a similar plasma-derived vaccine at intervals of 0, 1, and 6 months showed that no subjects developed clinically apparent hepatitis B infection and that 5 subjects developed antigenemia, even though up to half of the subjects failed to maintain a titer at this level.18-21 Persistence of vaccine-induced immunologic memory among healthy vaccinees who responded to a primary course of plasma-derived or recombinant hepatitis B vaccine has been demonstrated by an anamnestic antibody response to a booster dose of RECOMBIVAX (hepatitis b vaccine (recombinant)) HB given 5-12 years later.22

Predialysis and Dialysis Patients

Predialysis and dialysis adult patients respond less well to hepatitis B vaccines than do healthy individuals; however, vaccination of adult patients early in the course of their renal disease produces higher seroconversion rates than vaccination after dialysis has been initiated.30 In addition, the responses to these vaccines may be lower if the vaccine is administered as a buttock injection. When 40 mcg of Hepatitis B Vaccine (Recombinant), was administered in the deltoid muscle, 89% of 28 participants developed anti-HBs with 86% achieving levels Ý10 mIU/mL. However, when the same dosage of this vaccine was administered inappropriately either in the buttock or a combination of buttock and deltoid, 62% of 47 participants developed anti-HBs with 55% achieving levels of ≥ 10 mIU/mL.10

A booster dose or revaccination with RECOMBIVAX (hepatitis b vaccine (recombinant)) HB Dialysis Formulation may be considered in predialysis/dialysis patients if the anti-HBs level is less than 10 mIU/mL.23

Reports in the literature describe a more virulent form of hepatitis B associated with superinfections or coinfections by delta virus, an incomplete RNA virus. Delta virus can only infect and cause illness in persons infected with hepatitis B virus since the delta agent requires a coat of HBsAg in order to become infectious. Therefore, persons immune to hepatitis B virus infection should also be immune to delta virus infection.2

Interchangeability of Plasma-Derived and Recombinant Hepatitis B Vaccines

Although there have been no clinical studies in which a three-dose vaccine series was initiated with HEPTAVAX-B* (Hepatitis B Vaccine) and completed with RECOMBIVAX (hepatitis b vaccine (recombinant)) HB, or vice versa, extensive in vitroand in vivo studies have demonstrated that these two vaccines are immunologically comparable.22,24-28

REFERENCES

1. Robinson, W.S.: Hepatitis B Virus and the Delta Virus, in “Principles and Practice of Infectious Diseases,” G.L. Mandell; R.G. Douglas; J.E. Bennett (eds), vol. 2, New York, John Wiley & Sons, 1002-1029, 1985.

2. Recommendation of the Immunization Practices Advisory Committee (ACIP): Protection Against Viral Hepatitis, MMWR 39(RR-2): 5-22, Feb. 9, 1990.

3. Balistreri, W.F.: Viral Hepatitis, Unique Aspects of Infection During Childhood, Consultant 24(4): 131-153 passim, April 1984.

4. Robinson, W.S.: Hepatitis B Virus and Hepatitis Delta Virus, in “Principles and Practice of Infectious Diseases,” G.L. Mandell, R.G. Douglas, and J.E. Bennett (eds), Churchill Livingstone, 1204-1231, 1990.

5. Stevens, C.E.; Toy, P.T.; Tong, M.J.; Taylor, P.E.; Vyas, G.N.; Nair, P.V.; Gudavalli, M.; Krugman, S.: Perinatal Hepatitis B Virus Transmission in the United States, JAMA 253(12): 1740-1745, 1985.

6. Beasley, R.P.; Hwang, L.; Stevens, C.E.; Lin, C.; Hsieh, F.; Wang, K.; Sun, T.; Szmuness, W.: Efficacy of Hepatitis B Immune Globulin for Prevention of Perinatal Transmission of the Hepatitis B Virus Carrier State: Final Report of a Randomized Double- Blind, Placebo-Controlled Trial, Hepatology 3: 135-141, 1983.

7. Recommendations of the Immunization Practices Advisory Committee (ACIP): Hepatitis B Virus: A Comprehensive Strategy for Eliminating Transmission in the United States Through Universal Childhood Vaccination, MMWR 40(RR-13): 1-25, November 22, 1991.

8. Universal Hepatitis B Immunization, Committee on Infectious Diseases, Pediatrics89(4): 795-800, 1992.

9. Melnick, J.L.: Historical Aspects of Hepatitis B Vaccine, in “Hepatitis B Vaccine INSERM Symposium No. 18,” P. Maupas and P. Guesry (eds), Elsevier/North-Holland Biomedical Press, 23-31, 1981.

10. Data on file at Merck Research Laboratories.

11. Centers for Disease Control: Suboptimal Response to Hepatitis B Vaccine Given by Injection into the Buttock. MMWR 34(8): 105-113, March 1, 1985.

12. Hadler, S.C., et al.: Long-term Immunogenicity and Efficacy of Hepatitis B Vaccine in Homosexual Men, NEJM 315: 209-214, 1986.

13. Szmuness, W.; Stevens, C.E.; Horley, H.J., et al.: Hepatitis B Vaccine. Demonstration of Efficacy in a Controlled Clinical Trial in a High-risk Population in the United States. NEJM 303: 833-841, 1980.

14. Francis, D.P.; Hadler, S.C.; Thompson, S.E., et al.: The Prevention of Hepatitis B with Vaccine. Report of the Centers for Disease Control Multi-center Efficacy Trial among Homosexual Men. Ann. Int. Med. 97: 362-366, 1982.

15. Szmuness, W.; Stevens, C.E.; Horley, H.J., et al.: Hepatitis B Vaccine in Medical Staff of Hemodialysis Units. Efficacy and Subtype Cross-protection, NEJM 307: 1481-1486, 1982.

16. Stevens, C.E.; Taylor, P.E.; Tong, M.J., et al.: Prevention of Perinatal Hepatitis B Virus Infection with Hepatitis B Immune Globulin and Hepatitis B Vaccine, in Zuckerman, A.J. (ed.), “Viral Hepatitis and Liver Diseases”, Alan R. Liss, 982-983, 1988.

17. Stevens, C.E.; Taylor, P.E.; Tong, M.J., et al.: Yeast-Recombinant Hepatitis B Vaccine, Efficacy with Hepatitis B Immune Globulin in Prevention of Perinatal Hepatitis B Virus Transmission, JAMA 257(19): 2612-2616, 1987.

18. Wainwright, R.B.; McMahon, B.J.; Bulkow, L.R., et al.: Duration of Immunogenicity and Efficacy of Hepatitis B Vaccine in a Yupik Eskimo Population, Preliminary Results of an 8-Year Study, in “Viral Hepatitis and Liver Disease,” F.B. Hollinger, S.M. Lemon, and H. Margolis (eds), Williams & Wilkins, 762-766, 1990.

19. Hadler, S.C.; Coleman, P.J.; O'Malley, P., et al.: Evaluation of Long-Term Protection by Hepatitis B Vaccine for Seven to Nine Years in Homosexual Men, in “Viral Hepatitis and Liver Disease,” F.B. Hollinger, S.M. Lemon, and H. Margolis (eds), Williams & Wilkins, 766-768, 1990.

20. Tong, M.J.; Stevens, C.E.; Taylor, P.E., et al.: Prevention of Hepatitis B Infection in Infants Born to HBeAg Positive HbsAg Carrier Mothers in the United States, in “An Update, 1989, Progress in Hepatitis B Immunization,” P. Coursaget and M.J. Tong (eds), Colloque INSERM/John Libbey Eurotext Ltd., Vol. 194, 339-345, 1990.

21. Hwang, L-Y.; Lee, C-Y.; and Beasley, R.P.: Five-Year Follow-up of HBV Vaccination with Plasma-derived Vaccine in Neonates: Evaluation of Immunogenicity and Efficacy Against Perinatal Transmission, in “Viral Hepatitis and Liver Disease,” F.B. Hollinger, S.M. Lemon, and H. Margolis (eds), Williams & Wilkins, 759-761, 1990.

22. West, D.J.; Calandra, G.B.: Vaccine Induced Immunologic Memory for Hepatitis B Surface Antigen; Implications for Policy on Booster Vaccination, Vaccine, 14(11): 1019-1027, 1996.

23. Recommendations of the Immunization Practices Advisory Committee (ACIP): Update on Hepatitis B Prevention, MMWR 36(23): 353-366, June 19, 1987.

24. Emini, E.A.; Ellis, R.W.; Miller, W.J.; McAleer, W.J.; Scolnick, E.M. and Gerety, R.J.: Production and Immunological Analysis of Recombinant Hepatitis B Vaccine, J. Infection, 13(Sup. A): 3-9, 1986.

25. Brown, S.E.; Stanley, C.; Howard, C.R.; Zuckerman, A.J.; Steward, M.W.: Antibody Responses to Recombinant and Plasma- derived Hepatitis B Vaccines, Brit. Med. J., 292: 159-161, 1986.

26. Yamamoto, S.; Kuroki, T.; Kurai, K.; Iino, S.: Comparison of Results for Phase I Studies with Recombinant and Plasma-derived Hepatitis B Vaccines, and Controlled Study Comparing Intramuscular and Subcutaneous Injections of Recombinant Hepatitis B Vaccine, J. Infection, 13(Sup. A): 53-60, 1986.

27. Jilg, W.; Schmidt, M.; Zoulek, G.; Lorbeer, B.; Wilske, B.; Deinhardt, F.: Clinical Evaluation of a Recombinant Hepatitis B Vaccine, Lancet, 1174-1175, Nov. 24, 1984.

28. Schalm, S.W.; Heytink, R.A.; Kruining, H.; Bakker-Bendik, M.: Immunogenicity of Recombinant Yeast Hepatitis-B Vaccine, Neth. J. Med. 29: 28, 1986.

29. Centers for Disease Control: Epidemiology and Prevention of Vaccine-preventative Diseases, W. Atkinson, L. Furphy, J. Gantt, M. Mayfield, G. Phyne (eds), chapter 9.

30. Recommendations of the Advisory Committee on Immunization Practices (ACIP): Hepatitis B Virus Infection: A Comprehensive Strategy to Eliminate Transmission in the United States, 1996 update, MMWR (draft January 13, 1996).

34. Centers for Disease Control and Prevention, Federal Register, February 23, 1999, 64(35): 9044-9045.

35. National Institutes of Health, National Institutes of Health Consensus Development Conference Panel Statement: Management of Hepatitis C, Hepatology, 26(Suppl. 1): 2S-10S, 1997.

36. Wiedmann, M.; Liebert, U.G.; Oesen, U.; Porst, H.; Wiese, M.; Schroeder, S.; Halm, U.; Mossner, J.; Berr, F.: Decreased Immunogenicity of Recombinant Hepatitis B Vaccine in Chronic Hepatitis C, Hepatology, 31: 230-234, 2000.

37. Minniti, F.; Baldo, V.; Trivello, R.; Bricolo, R.; Di Furia, L.; Renzulli, G.; Chiaramonte, M.: Response to HBV vaccine in Relation to anti-HCV and anti-HBc Positivity: a Study in Intravenous Drug Addicts, Vaccine, 17: 3083-3085, 1999.

Last reviewed on RxList: 9/2/2008
This monograph has been modified to include the generic and brand name in many instances.

A A A

Recombivax - User Reviews

Recombivax User Reviews

Now you can gain knowledge and insight about a drug treatment with Patient Discussions.

Here is a collection of user reviews for the medication Recombivax sorted by most helpful. Patient Discussions FAQs

Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


Women's Health

Find out what women really need.