Engerix-B

CLINICAL PHARMACOLOGY

Several hepatitis viruses are known to cause a systemic infection resulting in major pathologic changes in the liver (e.g., A, B, C, D, E, and G). The estimated lifetime risk of HBV infection in the United States varies from almost 100% for the highest-risk groups to less than 20% for the population as a whole.1 Hepatitis B infection can have serious consequences including acute massive hepatic necrosis, chronic active hepatitis, and cirrhosis of the liver. Up to 90% of neonates and 6% to 10% of adults who are infected in the United States will become hepatitis B virus carriers.1 It has been estimated that 200 to 300 million people in the world today are persistently infected with hepatitis B virus.1 The Centers for Disease Control and Prevention (CDC) estimates that there are approximately 1 to 1.25 million chronic carriers of hepatitis B virus in the United States.1 Those patients who become chronic carriers can infect others and are at increased risk of developing primary hepatocellular carcinoma. Among other factors, infection with hepatitis B may be the single most important factor for development of this carcinoma.1,2

Reduced Risk of Hepatocellular Carcinoma

According to the CDC, the hepatitis B vaccine is recognized as the first anti-cancer vaccine because it can prevent primary liver cancer.3

A clear link has been demonstrated between chronic hepatitis B infection and the occurrence of hepatocellular carcinoma. In a Taiwanese study, the institution of universal childhood immunization against hepatitis B virus has been shown to decrease the incidence of hepatocellular carcinoma among children.4 In a Korean study in adult males, vaccination against hepatitis B virus has been shown to decrease the incidence of, and risk of, developing hepatocellular carcinoma in adults.5

Considering the serious consequences of infection, immunization should be considered for all persons at potential risk of exposure to the hepatitis B virus. Mothers infected with hepatitis B virus can infect their infants at, or shortly after, birth if they are carriers of the HBsAg antigen or develop an active infection during the third trimester of pregnancy. Infected infants usually become chronic carriers. Therefore, screening of pregnant women for hepatitis B is recommended.1 Because a vaccination strategy limited to high-risk individuals has failed to substantially lower the overall incidence of hepatitis B infection, the Advisory Committee on Immunization Practices (ACIP) recommends vaccination of all persons from birth to age 18.6 The Committee on Infectious Diseases of the American Academy of Pediatrics (AAP) has also endorsed universal infant immunization as part of a comprehensive strategy for the control of hepatitis B infection.7 The AAP, American Academy of Family Physicians (AAFP), and American Medical Association (AMA) also recommend routine vaccination of adolescents 11 to 12 years of age who have not been vaccinated previously.8 The AAP further recommends that providers administer hepatitis B vaccine to all previously unvaccinated adolescents.9 (See INDICATIONS AND USAGE.) There is no specific treatment for acute hepatitis B infection. However, those who develop anti-HBs antibodies after active infection are usually protected against subsequent infection. Antibody titers ≥ 10 mIU/mL against HBsAg are recognized as conferring protection against hepatitis B.1 Seroconversion is defined as antibody titers ≥ 1 mIU/mL.

Protective Efficacy

Protective efficacy with ENGERIX-B (hepatitis b vaccine recombinant) has been demonstrated in a clinical trial in neonates at high risk of hepatitis B infection.10,11 Fifty-eight neonates born of mothers who were both HBsAg and HBeAg positive were given ENGERIX-B (hepatitis b vaccine recombinant) (10 mcg at 0, 1, and 2 months) without concomitant hepatitis B immune globulin. Two infants became chronic carriers in the 12-month follow-up period after initial inoculation. Assuming an expected carrier rate of 70%, the protective efficacy rate against the chronic carrier state during the first 12 months of life was 95%.

Immunogenicity in Neonates

Immunization with 10 mcg at 0, 1, and 6 months of age produced seroconversion in 100% of infants by month 7, with a geometric mean antibody titer (GMT) of 713 mIU/mL (N = 52), and the seroprotection rate was 97%.

Clinical trials indicate that administration of hepatitis B immune globulin at birth does not alter the response to ENGERIX-B (hepatitis b vaccine recombinant) .

Immunization with 10 mcg at 0, 1, and 2 months of age produced a seroprotection rate of 96% in infants by month 4, with a GMT among seroconverters of 210 mIU/mL (N = 311); an additional dose at month 12 produced a GMT among seroconverters of 2,941 mIU/mL at month 13 (N = 126).

Immunogenicity in Pediatric Patients

In clinical trials with 242 children aged 6 months to, and including, 10 years given 10 mcg at months 0, 1, and 6, the seroprotection rate was 98% 1 to 2 months after the third dose; the GMT of seroconverters was 4,023 mIU/mL.

In a separate clinical trial including both children and adolescents aged 5 to 16 years, 10 mcg of ENGERIX-B (hepatitis b vaccine recombinant) was administered at 0, 1, and 6 months (N = 181) or 0, 12, and 24 months (N = 161). Immediately before the third dose of vaccine, seroprotection was achieved in 92.3% of subjects vaccinated on the 0-, 1-, and 6-month schedule and 88.8% of subjects on the 0-, 12-, and 24-month schedule (117.9 mIU/mL versus 162.1 mIU/mL, respectively, p = 0.18). One month following the third dose, seroprotection was achieved in 99.5% of children vaccinated on the 0-, 1-, and 6-month schedule compared to 98.1% of those on the 0-, 12-, and 24-month schedule. GMTs were higher (p = 0.02) for children receiving vaccine on the 0-, 1-, and 6-month schedule compared to those on the 0-, 12-, and 24-month schedule (5,687.4 mIU/mL versus 3,158.7 mIU/mL, respectively). The clinical relevance of this finding is unknown.

Immunogenicity in Adolescents

In clinical trials with healthy adolescent subjects 11 through 19 years of age, immunization with 10 mcg using a 0-, 1-, and 6-month schedule produced a seroprotection rate of 97% at month 8 (N = 119) with a GMT of 1,989 mIU/mL (N = 118, 95% confidence intervals = 1,318-3,020). Immunization with 20 mcg using a 0-, 1-, and 6-month schedule produced a seroprotection rate of 99% at month 8 (N = 122) with a GMT of 7,672 mIU/mL (N = 122, 95% confidence intervals = 5,248-10,965).

Immunogenicity in Healthy Adults and Adolescents

Clinical trials in healthy adult and adolescent subjects have shown that following a course of 3 doses of 20 mcg ENGERIX-B (hepatitis b vaccine recombinant) given according to the ACIP-recommended schedule of injections at months 0, 1, and 6, the seroprotection (antibody titers ≥ 10 mIU/mL) rate for all individuals was 79% at month 6 and 96% at month 7; the GMT for seroconverters at month 7 was 2,204 mIU/mL. On an alternate schedule (injections at months 0, 1, and 2) designed for certain populations (e.g., neonates born of hepatitis B–infected mothers, individuals who have or might have been recently exposed to the virus, and certain travelers to high-risk areas. See INDICATIONS AND USAGE), 99% of all individuals were seroprotected at month 3 and remained protected through month 12. On the alternate schedule, an additional dose at 12 months produced a GMT for seroconverters at month 13 of 9,163 mIU/mL.

Immunogenicity in Older Subjects

Among older subjects given 20 mcg at months 0, 1, and 6, the seroprotection rate 1 month after the third dose was 88%. However, as with other hepatitis B vaccines, in adults over 40 years of age, ENGERIX-B (hepatitis b vaccine recombinant) vaccine produced anti-HBs titers that were lower than those in younger adults (GMT among seroconverters 1 month after the third 20-mcg dose with a 0-, 1-, and 6-month schedule: 610 mIU/mL for individuals over 40 years of age, N = 50).

Immunogenicity in Subjects With Chronic Hepatitis C

In a clinical trial of subjects with chronic hepatitis C, 31 subjects received ENGERIX-B (hepatitis b vaccine recombinant) on the usual 0-, 1-, and 6-month schedule. All subjects responded with seroprotective titers. The GMT of anti-HBs was 1,260 mIU/mL (95% CI: 709-2,237).

Immunogenicity in Hemodialysis Patients

Hemodialysis patients given hepatitis B vaccines respond with lower titers,12 which remain at protective levels for shorter durations than in normal subjects. In a study in which patients on chronic hemodialysis (mean time on dialysis was 24 months; N = 562) received 40 mcg of the plasma-derived vaccine at months 0, 1, and 6, approximately 50% of patients achieved antibody titers ≥ 10 mIU/mL.12 Since a fourth dose of ENGERIX-B (hepatitis b vaccine recombinant) given to healthy adults at month 12 following the 0-, 1-, and 2-month schedule resulted in a substantial increase in the GMT (see above), a 4-dose regimen was studied in hemodialysis patients. In a clinical trial of adults who had been on hemodialysis for a mean of 56 months (N = 43), 67% of patients were seroprotected 2 months after the last dose of 40 mcg of ENGERIX-B (hepatitis b vaccine recombinant) (2 X 20 mcg) given on a 0-, 1-, 2-, and 6-month schedule; the GMT among seroconverters was 93 mIU/mL.

Thimerosal Free Formulation

In 3 comparative clinical trials with 1,339 adults and 587 children, the thimerosal free formulation performed as well as the preservative free formulation that contained trace amounts of thimerosal.

Interchangeability With Other Hepatitis B Vaccines

Recombinant DNA vaccines are produced in yeast by expression of a hepatitis B virus gene sequence that codes for the hepatitis B surface antigen. Like plasma-derived vaccine, the yeast-derived vaccines are protein particles visible by electron microscopy and have hepatitis B surface antigen epitopes as determined by monoclonal antibody analyses. Yeast-derived vaccines have been shown by in vitro analyses to induce antibodies (anti-HBs) which are immunologically comparable by epitope specificity and binding affinity to antibodies induced by plasma-derived vaccine.13 In cross-absorption studies, no differences were detected in the spectra of antibodies induced in man to plasma-derived or to yeast-derived hepatitis B vaccines.13

Additionally, patients immunized approximately 3 years previously with plasma-derived vaccine and whose antibody titers were < 100 mIU/mL (GMT: 35 mIU/mL; range: 9-94) were given a 20-mcg dose of ENGERIX-B (hepatitis b vaccine recombinant) . All patients, including 2 who had not responded to the plasma-derived vaccine, showed a response to ENGERIX-B (hepatitis b vaccine recombinant) (GMT: 5,069 mIU/mL; range: 624-15,019). There have been no clinical studies in which a 3-dose vaccine series was initiated with a plasma-derived hepatitis B vaccine and completed with ENGERIX-B (hepatitis b vaccine recombinant) , or vice versa. However, because the in vitro and in vivo studies described above indicate the comparability of the antibody produced in response to plasma-derived vaccine and ENGERIX-B (hepatitis b vaccine recombinant) , it should be possible to interchange the use of ENGERIX-B and plasma-derived vaccines (but see CONTRAINDICATIONS).

A controlled study (N = 48) demonstrated that completion of a course of immunization with 1 dose of ENGERIX-B (hepatitis b vaccine recombinant) (20 mcg, month 6) following 2 doses of RECOMBIVAX HB®* (10 mcg, months 0 and 1) produced a similar GMT (4,077 mIU/mL) to immunization with 3 doses of RECOMBIVAX HB (10 mcg, months 0, 1, and 6; 2,654 mIU/mL). Thus, ENGERIX-B (hepatitis b vaccine recombinant) can be used to complete a vaccination course initiated with RECOMBIVAX HB.14

Other Clinical Studies

In 1 study, 4 of 244 (1.6%) adults (homosexual men) at high risk of contracting hepatitis B virus became infected during the period prior to completion of 3 doses of ENGERIX-B (hepatitis b vaccine recombinant) (20 mcg at 0, 1, and 6 months).15 No additional patients became infected during the 18-month follow-up period after completion of the immunization course.

REFERENCES

1. Centers for Disease Control and Prevention. Hepatitis B. In: Atkinson W, Wolfe C, Humiston S, Nelson R, eds. Epidemiology and prevention of vaccine-preventable diseases. 6th ed. Atlanta, GA: Public Health Foundation; 2000:207-229.

2. Beasley RP, Hwang L-Y, Stevens CE, et al. Efficacy of hepatitis B immune globulin for prevention of perinatal transmission of hepatitis B virus carrier state: Final report of a randomized double-blind, placebo-controlled trial. Hepatology 1983;3(2):135-141.

3. Centers for Disease Control and Prevention. New vaccine information materials for hepatitis B, haemophilus influenzae type B (Hib), and varicella (chickenpox) vaccines, and revised vaccine information materials for measles, mumps, rubella (MMR) vaccines. Federal Register February 23, 1999;64(35):9044-9045.

4. Chang M-H, Chen C-J, Lai M-S, et al. Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children. N Engl J Med 1997;336(26):1855-1859.

5. Lee M-S, Kim D-H, Kim H, et al. Hepatitis B vaccination and reduced risk of primary liver cancer among male adults: A cohort study in Korea. Int J Epidemiol 1998;27(2):316-319.

6. Centers for Disease Control and Prevention. Effectiveness of a Seventh Grade school entry vaccination requirement - Statewide and Orange County, Florida, 1997-1998. MMWR 1998;47(34):711-715.

7. American Academy of Pediatrics. Universal hepatitis B immunization. Pediatrics 1992;89(4):795-800.

8. Centers for Disease Control and Prevention. Immunization of adolescents: Recommendations of the Advisory Committee on Immunization Practices, the American Academy of Pediatrics, the American Academy of Family Physicians, and the American Medical Association. MMWR 1996;45(RR-13):1-16.

9. American Academy of Pediatrics. Immunization of adolescents: Recommendations of the Advisory Committee on Immunization Practices, the American Academy of Pediatrics, the American Academy of Family Physicians, and the American Medical Association. Pediatrics 1997;99(3):479-488.

10. André FE and Safary A. Clinical experience with a yeast-derived hepatitis B vaccine. In: Zuckerman AJ, ed. Viral hepatitis and liver disease. New York, NY: Alan R Liss, Inc.; 1988:1025-1030.

11. Poovorawan Y, Sanpavat S, Pongpunlert W, et al. Protective efficacy of a recombinant DNA hepatitis B vaccine in neonates of HBe antigen-positive mothers. JAMA 1989;261(22):3278-3281.

12. Stevens CE, Alter HJ, Taylor PE, et al. Hepatitis B vaccine in patients receiving hemodialysis. N Engl J Med 1984;311(8):496-501.

13. Hauser P, Voet P, Simoen E, et al. Immunological properties of recombinant HBsAg produced in yeast. Postgrad Med J 1987;63(Suppl 2):83-91.

14. Bush LM, Moonsammy GI, Boscia JA. Evaluation of initiating a hepatitis B vaccination schedule with one vaccine and completing it with another. Vaccine 1991;9(11):807-809.

Last reviewed on RxList: 10/29/2009
This monograph has been modified to include the generic and brand name in many instances.

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