July 5, 2015

Engerix-B




CLINICAL PHARMACOLOGY

Mechanism Of Action

Infection with hepatitis B virus can have serious consequences including acute massive hepatic necrosis and chronic active hepatitis. Chronically infected persons are at increased risk for cirrhosis and hepatocellular carcinoma.

Antibody concentrations ≥ 10 mIU/mL against HBsAg are recognized as conferring protection against hepatitis B virus infection.1 Seroconversion is defined as antibody titers ≥ 1 mIU/mL.

Clinical Studies

Efficacy In Neonates

Protective efficacy with ENGERIX-B has been demonstrated in a clinical trial in neonates at high risk of hepatitis B infection.6,7 Fifty-eight neonates born of mothers who were both HBsAg-positive and hepatitis B “e” antigen (HBeAg)-positive were given ENGERIX-B (10 mcg/0.5 mL) at 0, 1, and 2 months, without concomitant hepatitis B immune globulin (HBIG). 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%.

Efficacy And Immunogenicity In Specific Populations

Homosexual Men

ENGERIX-B (20 mcg/1 mL) given at 0, 1, and 6 months was evaluated in homosexual men 16 to 59 years of age. Four of 244 subjects became infected with hepatitis B during the period prior to completion of the 3-dose immunization schedule. No additional subjects became infected during the 18-month follow-up period after completion of the immunization course.

Adults with Chronic Hepatitis C

In a clinical trial of 67 adults 25 to 67 years of age with chronic hepatitis C, ENGERIX-B (20 mcg/1 mL) was given at 0, 1, and 6 months. Of the subjects assessed at month 7 (N = 31), 100% responded with seroprotective titers. The geometric mean antibody titer (GMT) was 1,260 mIU/mL (95% Confidence Interval [CI]: 709, 2,237).

Adults on Hemodialysis

Hemodialysis patients given hepatitis B vaccines respond with lower titers, which remain at protective levels for shorter durations than in normal subjects. In a clinical trial of 56 adults who had been on hemodialysis for a mean period of 56 months, ENGERIX-B (40 mcg/2 mL given as two 1-mL doses) was given at 0, 1, 2, and 6 months. Two months after the fourth dose, 67% (29/43) of patients had seroprotective antibody levels ( ≥ 10 mIU/mL) and the GMT among seroconverters was 93 mIU/mL.

Immunogenicity In Neonates

In clinical studies, neonates were given ENGERIX-B (10 mcg/0.5 mL) at 0, 1, and 6 months or at 0, 1, and 2 months of age. The immune response to vaccination was evaluated in sera obtained one month after the third dose of ENGERIX-B.

Among infants administered ENGERIX-B at 0, 1, and 6 months, 100% of evaluable subjects (N = 52) seroconverted by month 7. The GMT was 713 mIU/mL. Of these, 97% had seroprotective levels ( ≥ 10 mIU/mL).

Among infants enrolled (N = 381) to receive ENGERIX-B at 0, 1, and 2 months of age, 96% had seroprotective levels ( ≥ 10 mIU/mL) by month 4. The GMT among seroconverters (N = 311) (antibody titer ≥ 1 mIU/mL) was 210 mIU/mL. A subset of these children received a fourth dose of ENGERIX-B at 12 months of age. One month following this dose, seroconverters (N = 126) had a GMT of 2,941 mIU/mL.

Immunogenicity In Children And Adults

Persons 6 Months Through 10 Years of Age

In clinical trials, children (N = 242) 6 months through 10 years of age were given ENGERIX-B (10 mcg/0.5 mL) at 0, 1, and 6 months. One to 2 months after the third dose, the seroprotection rate was 98% and the GMT of seroconverters was 4,023 mIU/mL.

Persons 5 Through 16 Years of Age

In a separate clinical trial including both children and adolescents 5 through 16 years of age, ENGERIX-B (10 mcg/0.5 mL) 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 (GMT: 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).

Persons 11 Through 19 Years of Age

In clinical trials with healthy adolescent subjects 11 through 19 years of age, ENGERIX-B (10 mcg/0.5 mL) given at 0, 1, and 6 months produced a seroprotection rate of 97% at month 8 (N = 119) with a GMT of 1,989 mIU/mL (N = 118, 95% CI: 1,318, 3,020). Immunization with ENGERIX-B (20 mcg/1 mL) at 0, 1, and 6 months produced a seroprotection rate of 99% at month 8 (N = 122) with a GMT of 7,672 mIU/mL (N = 122, 95% CI: 5,248, 10,965).

Persons 16 Through 65 Years of Age

Clinical trials in healthy adult and adolescent subjects (16 through 65 years of age) have shown that following a course of 3 doses of ENGERIX-B (20 mcg/1 mL) given at 0, 1, and 6 months, the seroprotection (antibody titers ≥ 10 mIU/mL) rate for all individuals was 79% at month 6 (5 months after second dose) and 96% at month 7 (1 month after third dose); the GMT for seroconverters was 2,204 mIU/mL at month 7 (N = 110).

An alternate 3-dose schedule (20 mcg/1 mL given at 0, 1, and 2 months) designed for certain populations (e.g., individuals who have or might have been recently exposed to the virus and travelers to high-risk areas) was also evaluated. At month 3 (1 month after third dose), 99% of all individuals were seroprotected and remained protected through month 12. On the alternate schedule, a fourth dose of ENGERIX-B (20 mcg/1 mL) at 12 months produced a GMT of 9,163 mIU/mL at month 13 (1 month after fourth dose) (N = 373).

Persons 40 Years of Age and Older

Among subjects 40 years of age and older given ENGERIX-B (20 mcg/1 mL) at 0, 1, and 6 months, the seroprotection rate 1 month after the third dose was 88% and the GMT for seroconverters was 610 mIU/mL (N = 50). In adults older than 40 years of age, ENGERIX-B produced anti-HBsAg antibody titers that were lower than those in younger adults.

Interchangeability With Other Hepatitis B Vaccines

A controlled study (N = 48) demonstrated that completion of a course of immunization with 1 dose of ENGERIX-B (20 mcg/1 mL) at month 6 following 2 doses of RECOMBIVAX HB® (10 mcg) at months 0 and 1 produced a similar GMT (4,077 mIU/mL) to immunization with 3 doses of RECOMBIVAX HB (10 mcg) at months 0, 1, and 6 (GMT: 2,654 mIU/mL). Thus, ENGERIX-B can be used to complete a vaccination course initiated with RECOMBIVAX HB.8

REFERENCES

6. André FE, 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.

7. 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.

8. 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: 9/2/2014
This monograph has been modified to include the generic and brand name in many instances.

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