ENGERIX B Hepatitis B Vaccine Recombinant
ENGERIX B Hepatitis B Vaccine Recombinant
These highlights do not include all the information needed to use injectable vaccines, including ENGERIX-B. Procedures should be in
ENGERIX-B safely and effectively. See full prescribing information for place to avoid falling injury and to restore cerebral perfusion following
ENGERIX-B. syncope. (5.2)
• Temporarily defer vaccination of in fants with a birth weight less than
ENGERIX-B [Hepatitis B Vaccine (Recombinant)] 2,000 g born to HBsAg-negative mothers. (5.3)
Suspension for Intramuscular Injection • Apnea following intramuscular vaccination has been observed in some
Initial U.S. Approval: 1989 infants born prematurely. Decisions about when to administer an
intramuscular vaccine, including ENGERIX-B, to infants born
------------------------------- INDICATIONS AND USAGE-------------------------------
prematurely should be based on consideration of the infant’s medical
ENGERIX-B is a vaccine indicated for immunization against infection caused
status, and the potential benefits and possible risks of vaccination. (5.4)
by all known subtypes of hepatitis B virus. (1)
---------------------------------- ADVERSE REACTIONS----------------------------------
-------------------------- DOSAGE AND ADMINISTRATION--------------------------
The most common solicited adverse events were injection-site soreness (22%)
For intramuscular administration. (2, 2.2)
and fatigue (14%). (6.1)
• Persons from birth through 19 years of age: A series of 3 doses (0.5 mL
each) on a 0-, 1-, 6-month schedule. (2.3) To report SUSPECTED ADVERSE REACTIONS, contact
• Persons 20 years of age and older: A series of 3 doses (1 mL each) on a Glax oSmithKline at 1-888-825-5249 or VAERS at 1-800-822-7967 or
0-, 1-, 6-month schedule. (2.3) www.vaers.hhs.gov.
• Adults on hemodialysis: A series of 4 doses (2 mL each) as a single 2-mL
dose or as two 1-mL doses on a 0-, 1-, 2-, 6-month schedule. (2.3) -----------------------------------DRUG INTERACTIONS ----------------------------------
Do not mix ENGERIX-B with any other vaccine or product in the same
------------------------ DOSAGE FORMS AND STRENGTHS ----------------------- syringe or vial. (7.1)
ENGERIX-B is a sterile suspension available in the following presentations:
-------------------------- USE IN SPECIFIC POPULATIONS--------------------------
• 0.5-mL (10 mcg) single-dose vials and prefilled syringes (3)
• 1-mL (20 mcg) single-dose vials and prefilled syringes (3) • Safety and effectiveness o f ENGERIX-B have not been established in
pregnant women and nursing mothers. ENGERIX-B should only be given
---------------------------------- CONTRAINDICATIONS ---------------------------------- to a pregnant woman if clearly needed. (8.1, 8.3)
Severe allergi c reaction (e.g., anaphylaxis) after a previous dose of any • Antibody responses are lower in persons older than 60 years of ag e than
hepatitis B-containing vaccine, or to any component of ENGERIX-B, in younger adults. (8.5)
including yeast. (4)
See 17 for PATIENT COUNSELING INFORMATION.
-------------------------- WARNINGS AND PRECAUTIONS --------------------------
Revised: 5/2016
• The tip caps of the prefilled syringes contain natural rubber latex which
may cause allergic reactions. (5.1)
1
FULL PRESCRIBING INFORMATION
2
2.3 Recommended Dose and Schedule
Persons from Birth through 19 Years
Primary immunization for infants (born of hepatitis B surface antigen [HBsAg]-negative or
HBsAg-positive mothers), children (birth through 10 years), and adolescents (aged 11 through 19
years) consists of a series of 3 doses (0.5 mL each) given on a 0-, 1-, and 6-month schedule.
Persons Aged 20 Years and Older
Primary immunization for persons aged 20 years and older consists of a series of 3 doses (1 mL
each) given on a 0-, 1-, and 6-month schedule.
Adults on Hemodialysis
Primary immunization consists of a series of 4 doses (2-mL each) given as a single 2-mL dose or
two 1-mL doses on a 0-, 1-, 2-, and 6-month schedule. In hemodialysis patients, antibody
response is lower than in healthy persons and protection may persist only as long as antibody
levels remain above 10 mIU/mL. Therefore, the need for booster doses should be assessed by
annual antibody testing. A 2-mL booster dose (as a single 2-mL dose or two 1-mL doses) should
be given when antibody levels decline below 10 mIU/mL.1 [See Clinical Studies (14.2).]
3
2.4 Alternate Dosing Schedules
There are alternate dosing and administration schedules which may be used for specific
populations (e.g., neonates born of hepatitis B–infected mothers, persons who have or might
have been recently exposed to the virus, and travelers to high-risk areas) (Table 2). For some of
these alternate schedules, an additional dose at 12 months is recommended for prolonged
maintenance of protective titers.
4
insert for HBIG. ENGERIX-B can be given on either dosing schedule (0, 1, and 6 months or 0,
1, 2, and 12 months).
4 CONTRAINDICATIONS
Severe allergic reaction (e.g., anaphylaxis) after a previous dose of any hepatitis B-containing
vaccine, or to any component of ENGERIX-B, including yeast, is a contraindication to
administration of ENGERIX-B [see Description (11)].
5
born prematurely should be based on consideration of the infant’s medical status, and the
potential benefits and possible risks of vaccination. For ENGERIX-B, this assessment should
include consideration of the mother’s hepatitis B antigen status and the high probability of
maternal transmission of hepatitis B virus to infants born of mothers who are HBsAg positive if
vaccination is delayed.
5.5 Preventing and Managing Allergic Vaccine Reactions
Prior to immunization, the healthcare provider should review the immunization history for
possible vaccine sensitivity and previous vaccination-related adverse reactions to allow an
assessment of benefits and risks. Epinephrine and other appropriate agents used for the control of
immediate allergic reactions must be immediately available should an acute anaphylactic
reaction occur. [See Contraindications (4).]
5.6 Moderate or Severe Acute Illness
To avoid diagnostic confusion between manifestations of an acute illness and possible vaccine
adverse effects, vaccination with ENGERIX-B should be postponed in persons with moderate or
severe acute febrile illness unless they are at immediate risk of hepatitis B infection (e.g., infants
born of HBsAg-positive mothers).
5.7 Altered Immunocompetence
Immunocompromised persons may have a diminished immune response to ENGERIX-B,
including individuals receiving immunosuppressant therapy.
5.8 Multiple Sclerosis
Results from 2 clinical studies indicate that there is no association between hepatitis B
vaccination and the development of multiple sclerosis,3 and that vaccination with hepatitis B
vaccine does not appear to increase the short-term risk of relapse in multiple sclerosis.4
5.9 Limitations of Vaccine Effectiveness
Hepatitis B has a long incubation period. ENGERIX-B may not prevent hepatitis B infection in
individuals who had an unrecognized hepatitis B infection at the time of vaccine administration.
Additionally, it may not prevent infection in individuals who do not achieve protective antibody
titers.
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates
observed in the clinical trials of a vaccine cannot be directly compared with rates in the clinical
trials of another vaccine and may not reflect the rates observed in practice.
The most common solicited adverse events were injection site soreness (22%) and fatigue (14%).
6
In 36 clinical studies, a total of 13,495 doses of ENGERIX-B were administered to 5,071 healthy
adults and children who were initially seronegative for hepatitis B markers, and healthy
neonates. All subjects were monitored for 4 days post-administration. Frequency of adverse
events tended to decrease with successive doses of ENGERIX-B.
Using a symptom checklist, the most frequently reported adverse events were injection site
soreness (22%) and fatigue (14%). Other events are listed below. Parent or guardian completed
forms for children and neonates. Neonatal checklist did not include headache, fatigue, or
dizziness.
Incidence 1% to 10% of Injections
Nervous System Disorders: Dizziness, headache.
General Disorders and Administration Site Conditions: Fever (>37.5°C), injection site
erythema, injection site induration, injection site swelling.
Incidence <1% of Injections
Infections and Infestations: Upper respiratory tract illnesses.
Blood and Lymphatic System Disorders: Lymphadenopathy.
Metabolism and Nutrition Disorders: Anorexia.
Psychiatric Disorders: Agitation, insomnia.
Nervous System Disorders: Somnolence, tingling.
Vascular Disorders: Flushing, hypotension.
Gastrointestinal Disorders: Abdominal pain/cramps, constipation, diarrhea, nausea, vomiting.
Skin and Subcutaneous Tissue Disorders: Erythema, petechiae, pruritus, rash, sweating,
urticaria.
Musculoskeletal and Connective Tissue Disorders: Arthralgia, back pain, myalgia,
pain/stiffness in arm, shoulder, or neck.
General Disorders and Administration Site Conditions: Chills, influenza-like symptoms,
injection site ecchymosis, injection site pain, injection site pruritus, irritability, malaise,
weakness.
In a clinical trial, 416 adults with type 2 diabetes and 258 control subjects without type 2
diabetes who were seronegative for hepatitis B markers received at least 1 dose of ENGERIX-B.
Subjects were monitored for solicited adverse events for 4 days following each vaccination. The
most frequently reported solicited adverse events in the entire study population were injection
site pain (reported in 39% of diabetic subjects and 45% of control subjects) and fatigue (reported
in 29% of diabetic subjects and 27% of control subjects). Serious adverse events were monitored
7
through 30 days following the last vaccination. Serious adverse events (SAEs) occurred in 3.8%
of diabetic subjects and 1.6% of controls. No SAEs were deemed related to ENGERIX-B.
6.2 Postmarketing Experience
In addition to reports in clinical trials, worldwide voluntary reports of adverse events received
for ENGERIX-B since market introduction (1990) are listed below. This list includes SAEs or
events that have a suspected causal connection to components of ENGERIX-B.
Because these events are reported voluntarily from a population of unknown size, it is not always
possible to reliably estimate their frequency or establish a causal relationship to the vaccine.
Infections and Infestations
Herpes zoster, meningitis.
Blood and Lymphatic System Disorders
Thrombocytopenia.
Immune System Disorders
Allergic reaction, anaphylactoid reaction, anaphylaxis. An apparent hypersensitivity syndrome
(serum sickness-like) of delayed onset has been reported days to weeks after vaccination,
including: arthralgia/arthritis (usually transient), fever, and dermatologic reactions such as
urticaria, erythema multiforme, ecchymoses, and erythema nodosum.
Nervous System Disorders
Encephalitis; encephalopathy; migraine; multiple sclerosis; neuritis; neuropathy including
hypoesthesia, paresthesia, Guillain-Barré syndrome and Bell’s palsy; optic neuritis; paralysis;
paresis; seizures; syncope; transverse myelitis.
Eye Disorders
Conjunctivitis, keratitis, visual disturbances.
Ear and Labyrinth Disorders
Earache, tinnitus, vertigo.
Cardiac Disorders
Palpitations, tachycardia.
Vascular Disorders
Vasculitis.
Respiratory, Thoracic, and Mediastinal Disorders
Apnea, bronchospasm including asthma-like symptoms.
8
Gastrointestinal Disorders
Dyspepsia.
Skin and Subcutaneous Tissue Disorders
Alopecia, angioedema, eczema, erythema multiforme including Stevens-Johnson syndrome,
erythema nodosum, lichen planus, purpura.
Musculoskeletal and Connective Tissue Disorders
Arthritis, muscular weakness.
General Disorders and Administration Site Conditions
Injection site reaction.
Investigations
Abnormal liver function tests.
7 DRUG INTERACTIONS
7.1 Concomitant Administration with Vaccines and Immune Globulin
ENGERIX-B may be administered concomitantly with immune globulin.
When concomitant administration of other vaccines or immune globulin is required, they should
be given with different syringes and at different injection sites. Do not mix ENGERIX-B with
any other vaccine or product in the same syringe or vial.
7.2 Interference with Laboratory Tests
Hepatitis B surface antigen (HBsAg) derived from hepatitis B vaccines has been transiently
detected in blood samples following vaccination. Serum HBsAg detection may not have
diagnostic value within 28 days after receipt of a hepatitis B vaccine, including ENGERIX-B.
9
8.3 Nursing Mothers
It is not known whether ENGERIX-B is excreted in human milk. Because many drugs are
excreted in human milk, caution should be exercised when ENGERIX-B is administered to a
nursing woman.
8.4 Pediatric Use
Safety and effectiveness of ENGERIX-B have been established in all pediatric age-groups.
Maternally transferred antibodies do not interfere with the active immune response to the
vaccine. [See Adverse Reactions (6), Clinical Studies (14.1, 14.3, 14.4).]
The timing of the first dose in infants weighing less than 2,000 g at birth depends on the HBsAg
status of the mother. [See Warnings and Precautions (5.3).]
8.5 Geriatric Use
Clinical studies of ENGERIX-B used for licensure did not include sufficient numbers of subjects
aged 65 years and older to determine whether they respond differently from younger subjects.
However, in later studies it has been shown that a diminished antibody response and
seroprotective levels can be expected in persons older than 60 years.5 [See Clinical Studies
(14.2).]
11 DESCRIPTION
ENGERIX-B [Hepatitis B Vaccine (Recombinant)] is a sterile suspension of noninfectious
hepatitis B virus surface antigen (HBsAg) for intramuscular administration. It contains purified
surface antigen of the virus obtained by culturing genetically engineered Saccharomyces
cerevisiae cells, which carry the surface antigen gene of the hepatitis B virus. The HBsAg
expressed in the cells is purified by several physicochemical steps and formulated as a
suspension of the antigen adsorbed on aluminum hydroxide. The procedures used to manufacture
ENGERIX-B result in a product that contains no more than 5% yeast protein.
Each 0.5-mL pediatric/adolescent dose contains 10 mcg of HBsAg adsorbed on 0.25 mg
aluminum as aluminum hydroxide.
Each 1-mL adult dose contains 20 mcg of HBsAg adsorbed on 0.5 mg aluminum as aluminum
hydroxide.
ENGERIX-B contains the following excipients: Sodium chloride (9 mg/mL) and phosphate
buffers (disodium phosphate dihydrate, 0.98 mg/mL; sodium dihydrogen phosphate dihydrate,
0.71 mg/mL).
ENGERIX-B is available in vials and prefilled syringes. The tip caps of the prefilled syringes
contain natural rubber latex; the plungers are not made with natural rubber latex. The vial
stoppers are not made with natural rubber latex.
ENGERIX-B is formulated without preservatives.
10
12 CLINICAL PHARMACOLOGY
12.1 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.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
ENGERIX-B has not been evaluated for carcinogenic or mutagenic potential, or for impairment
of fertility.
14 CLINICAL STUDIES
14.1 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%.
14.2 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
aged 16 to 59 years. 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 aged 25 to 67 years 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).
11
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.
Adults with Type 2 Diabetes Mellitus
In a descriptive study, 674 adult subjects with type 2 diabetes (diagnosed within the preceding 5
years) or without type 2 diabetes were enrolled and stratified by age and body mass index (BMI).
The per-protocol immunogenicity cohort included 378 diabetic subjects and 189 matched control
subjects who received ENGERIX-B (20 mcg/1 mL) at 0, 1, and 6 months. Among these subjects,
the mean age was 54 years (range: 20 to 82 years); mean BMI was 32 kg/m2 (range: 17 to 64
kg/m2); 51% were male; 88% were white, 3% were American Indian or Alaskan Native, 3%
were black, 2% were Asian, 4% were other racial groups; 2% were Hispanic or Latino.
The overall seroprotection rates (1 month after the third dose) were 75% (95% CI: 71, 80) in
patients with diabetes and 82% (95% CI: 76, 87) in control subjects. The seroprotection rates in
those with diabetes aged 20 to 39 years, 40 to 49 years, 50 to 59 years, and at least 60 years were
89%, 81%, 83%, and 58%, respectively. The seroprotection rates in those without diabetes in
these same age-groups were 100%, 86%, 82%, and 70%, respectively. Subjects with diabetes and
a BMI of at least 30 kg/m2 had a seroprotection rate of 72% compared with 80% in diabetic
subjects with lower BMIs. In control subjects, seroprotection rates were 82% in those with a
BMI of at least 30 kg/m2 and 83% in those with lower BMIs.
14.3 Immunogenicity in Neonates
In clinical studies, neonates were given ENGERIX-B (10 mcg/0.5 mL) at age 0, 1, and 6 months
or at age 0, 1, and 2 months. The immune response to vaccination was evaluated in sera obtained
1 month after the third dose of ENGERIX-B.
Among infants administered ENGERIX-B at age 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 age 0, 1, and 2 months, 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 age 12 months. One month following this dose, seroconverters (n = 126) had
a GMT of 2,941 mIU/mL.
12
14.4 Immunogenicity in Children and Adults
Persons Aged 6 Months through 10 Years
In clinical trials, children (N = 242) aged 6 months through 10 years 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 Aged 5 through 16 Years
In a separate clinical trial including both children and adolescents aged 5 through 16 years,
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: 118 mIU/mL versus 162 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 with 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 with those on the 0-, 12-, and 24-month schedule
(5,687 mIU/mL versus 3,159 mIU/mL, respectively).
Persons Aged 11 through 19 Years
In clinical trials with healthy adolescent subjects aged 11 through 19 years, 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 Aged 16 through 65 Years
Clinical trials in healthy adult and adolescent subjects (aged 16 through 65 years) 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).
13
Persons Aged 40 Years and Older
Among subjects aged 40 years 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 aged older than 40 years, ENGERIX-B
produced anti-HBsAg antibody titers that were lower than those in younger adults.
14.5 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
[Hepatitis B Vaccine (Recombinant)] (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
15 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. Centers for Disease Control and Prevention. A Comprehensive Immunization Strategy to
Eliminate Transmission of Hepatitis B Virus Infection in the United States.
Recommendations of the Advisory Committee on Immunization Practices (ACIP). Part 1:
Immunization of Infants, Children, and Adolescents, MMWR. 2005;54(RR-16):1-23.
3. Ascherio A, Zhang SM, Hernán MA, et al. Hepatitis B vaccination and the risk of multiple
sclerosis. N Engl J Med. 2001;344(5):327-332.
4. Confavreux C, Suissa S, Saddier P, et al. Vaccination and the risk of relapse in multiple
sclerosis. N Engl J Med. 2001-344(5):319-326.
5. Centers for Disease Control and Prevention. A Comprehensive Immunization Strategy to
Eliminate Transmission of Hepatitis B Virus Infection in the United States.
Recommendations of the Advisory Committee on Immunization Practices (ACIP). Part 2:
Immunization of Adults, MMWR. 2006;55(RR-16):1-25.
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.
14
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.
ENGERIX-B and TIP-LOK are registered trademarks of the GSK group of companies. The other
brand listed is a trademark of the respective owner and is not a trademark of the GSK group of
companies. The maker of this brand is not affiliated with and does not endorse the GSK group of
companies or its products.
15
Manufactured by GlaxoSmithKline Biologicals
Rixensart, Belgium, US License No. 1617
Distributed by GlaxoSmithKline
Research Triangle Park, NC 27709
©2016 the GSK group of companies. All rights reserved.
ENG:56PI
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