ENGERIX-B: Package Insert and Label Information

ENGERIX-B- hepatitis b virus subtype adw2 hbsag surface protein antigen injection, suspension
GlaxoSmithKline Biologicals SA

1 INDICATIONS AND USAGE

ENGERIX-B is indicated for immunization against infection caused by all known subtypes of hepatitis B virus.

2 DOSAGE AND ADMINISTRATION

For intramuscular administration. See Section 2.2 for subcutaneous administration in persons at risk of hemorrhage.

2.1 Preparation for Administration

Shake well before use. With thorough agitation, ENGERIX-B is a homogeneous, turbid white suspension. Do not administer if it appears otherwise. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. If either of these conditions exists, the vaccine should not be administered.

For the prefilled syringes, attach a sterile needle and administer intramuscularly.

For the vials, use a sterile needle and sterile syringe to withdraw the vaccine dose and administer intramuscularly. Changing needles between drawing vaccine from a vial and injecting it into a recipient is not necessary unless the needle has been damaged or contaminated. Use a separate sterile needle and syringe for each individual.

2.2 Administration

ENGERIX-B should be administered by intramuscular injection. The preferred administration site is the anterolateral aspect of the thigh for infants younger than 1 year and the deltoid muscle in older children (whose deltoid is large enough for an intramuscular injection) and adults. ENGERIX-B should not be administered in the gluteal region; such injections may result in suboptimal response.

ENGERIX-B may be administered subcutaneously to persons at risk of hemorrhage (e.g., hemophiliacs). However, hepatitis B vaccines administered subcutaneously are known to result in a lower antibody response. Additionally, when other aluminum-adsorbed vaccines have been administered subcutaneously, an increased incidence of local reactions including subcutaneous nodules has been observed. Therefore, subcutaneous administration should be used only in persons who are at risk of hemorrhage with intramuscular injections.

Do not administer this product intravenously or intradermally.

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).]

Table 1. Recommended Dosage and Administration Schedules

Group

Dosea

Schedules

Infants born of:

HBsAg-negative mothers

0.5 mL

0, 1, 6 months

HBsAg-positive mothersb

0.5 mL

0, 1, 6 months

Children:

Birth through 10 years

0.5 mL

0, 1, 6 months

Adolescents:

Aged 11 through 19 years

0.5 mL

0, 1, 6 months

Adults:

Aged 20 years and older

1 mL

0, 1, 6 months

Adults on hemodialysis

2 mLc

0, 1, 2, 6 months

HBsAg = Hepatitis B surface antigen.

a 0.5 mL (10 mcg); 1 mL (20 mcg).

b Infants born to HBsAg-positive mothers should receive vaccine and hepatitis B immune globulin (HBIG) within 12 hours after birth [see Dosage and Administration (2.6)].

c Given as a single 2-mL dose or as two 1-mL doses.

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.

Table 2. Alternate Dosage and Administration Schedules

Group

Dosea

Schedules

Infants born of:

HBsAg-positive mothersb

0.5 mL

0, 1, 2, 12 months

Children:

Birth through 10 years

0.5 mL

0, 1, 2, 12 months

Aged 5 through 10 years

0.5 mL

0, 12, 24 monthsc

Adolescents:

Aged 11 through 16 years

0.5 mL

0, 12, 24 monthsc

Aged 11 through 19 years

1 mL

0, 1, 6 months

Aged 11 through 19 years

1 mL

0, 1, 2, 12 months

Adults:

Aged 20 years and older

1 mL

0, 1, 2, 12 months

HBsAg = Hepatitis B surface antigen.

a 0.5 mL (10 mcg); 1 mL (20 mcg).

b Infants born to HBsAg-positive mothers should receive vaccine and hepatitis B immune globulin (HBIG) within 12 hours after birth [see Dosage and Administration (2.6)].

c For children and adolescents for whom an extended administration schedule is acceptable based on risk of exposure.

2.5 Booster Vaccinations

Whenever administration of a booster dose is appropriate, the dose of ENGERIX-B is 0.5 mL for children aged 10 years and younger and 1 mL for persons aged 11 years and older. Studies have demonstrated a substantial increase in antibody titers after booster vaccination with ENGERIX-B. See Section 2.3 for information on booster vaccination for adults on hemodialysis.

2.6 Known or Presumed Exposure to Hepatitis B Virus

Persons with known or presumed exposure to the hepatitis B virus (e.g., neonates born of infected mothers, persons who experienced percutaneous or permucosal exposure to the virus) should be given hepatitis B immune globulin (HBIG) in addition to ENGERIX-B in accordance with Advisory Committee on Immunization Practices recommendations and with the package insert for HBIG. ENGERIX-B can be given on either dosing schedule (0, 1, and 6 months or 0, 1, 2, and 12 months).

3 DOSAGE FORMS AND STRENGTHS

ENGERIX-B is a sterile suspension available in the following presentations:

0.5-mL (10 mcg) prefilled TIP-LOK syringes
1-mL (20 mcg) single-dose vials and prefilled TIP-LOK syringes

[See Description (11), How Supplied/Storage and Handling (16).]

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 WARNINGS AND PRECAUTIONS

5.1 Latex

The tip caps of the prefilled syringes contain natural rubber latex which may cause allergic reactions.

5.2 Syncope

Syncope (fainting) can occur in association with administration of injectable vaccines, including ENGERIX-B. Syncope can be accompanied by transient neurological signs such as visual disturbance, paresthesia, and tonic-clonic limb movements. Procedures should be in place to avoid falling injury and to restore cerebral perfusion following syncope.

5.3 Infants Weighing Less than 2,000 g at Birth

Hepatitis B vaccine should be deferred for infants with a birth weight <2,000 g if the mother is documented to be HBsAg negative at the time of the infant’s birth. Vaccination can commence at chronological age 1 month or hospital discharge. Infants born weighing <2,000 g to HBsAg-positive mothers should receive vaccine and HBIG within 12 hours after birth. Infants born weighing <2,000 g to mothers of unknown HBsAg status should receive vaccine and HBIG within 12 hours after birth if the mother’s HBsAg status cannot be determined within the first 12 hours of life. The birth dose in infants born weighing <2,000 g should not be counted as the first dose in the vaccine series and it should be followed with a full 3-dose standard regimen (total of 4 doses).2 [See Dosage and Administration (2).]

5.4 Apnea in Premature Infants

Apnea following intramuscular vaccination has been observed in some infants born prematurely. Decisions about when to administer an intramuscular vaccine, including ENGERIX-B, to infants 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 reactions were injection site soreness (22%) and fatigue (14%).

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 reactions tended to decrease with successive doses of ENGERIX-B.

Using a symptom checklist, the most frequently reported adverse reactions were injection site soreness (22%) and fatigue (14%). Other reactions 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 reactions for 4 days following each vaccination. The most frequently reported solicited adverse reactions 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 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.

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