ENGERIX-B PEDIATRIC-ADOLESCENT

General Administration Information
For storage information, see the specific product information within the How Supplied section.

-Inform the parent, guardian, or responsible adult of the benefits and risks of the vaccine. Provide the Vaccine Information Statements from the manufacturer to the parent or guardian before each immunization. This action is required by the National Childhood Vaccine Injury Act of 1986.
-Record the manufacturer, lot number, administration date, and the name and address of the person administering the vaccine in the patient's permanent record. These actions are required by the National Childhood Vaccine Injury Act of 1986.
-Health care professionals administering vaccines should take appropriate precautions to prevent allergic reactions in vaccine recipients.

Route-Specific Administration

Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
-Administer as soon as possible after removal from refrigeration.
-Use as supplied; no dilution or reconstitution is necessary. The full recommended dose of the vaccine should be used.
-Hepatitis B vaccine is administered intramuscularly (preferred) or subcutaneously (only for those who are at risk). Do not administer intravenously or intradermally.
-Prior to withdrawing a dose from the vial, shake vial or pre-filled syringe thoroughly to obtain a uniform suspension.
-Hepatitis B vaccine should not be given in the same syringe nor injected at the same site as hepatitis B immune globulin; inactivation of the vaccine can occur.
-Do not mix with any other vaccine.
-A separate syringe and needle should be used for each person receiving the hepatitis B vaccine.
-Preservative-free formulations: Once the single-dose vial has been penetrated, the withdrawn vaccine should be used promptly, and the vial must be discarded.
-Storage: Store refrigerated at 2 to 8 degrees C (36 to 46 degrees F); do not freeze. Storage at room temperature for up to 72 hours may be acceptable; however, confirmation of acceptable duration of storage at room temperature directly from the manufacturer for the specific vaccine being administered is recommended.
Intramuscular Administration
-For vials, use a sterile syringe and needle to withdraw suspension from the vial. For prefilled syringes, attach a sterile needle.
-Neonates, infants, and young children: Inject into the anterolateral aspect of the mid-thigh.
-Older children and adolescents: Inject into the deltoid muscle of the upper arm. Do NOT administer in the gluteal muscle; gluteal administration has resulted in lower hepatitis B seroconversion rates.
-Injection must be accomplished with a needle long enough to ensure IM deposition of the vaccine.
-For the majority of infants younger than 1 year, a 1-inch, 22- to 25-gauge needle is sufficient to penetrate thigh muscle.
-For children 1 to 2 years, a needle at least 1 inch long is preferred for administration into the thigh; a 5/8 inch needle is sufficient for administration into the deltoid if the skin is stretched flat and the needle is inserted at a 90-degree angle.
-For pediatric patients 3 years and older, the needle size required for deltoid injection ranges from 5/8- to 1-inch.


Subcutaneous Administration
-Use subcutaneous administration ONLY in patients who are at risk of hemorrhage after intramuscular injection (e.g., hemophiliacs); patients may be at increased risk for local adverse reactions including irritation, inflammation, nodules, or skin discoloration.
-For vials, use a sterile syringe and needle to withdraw suspension from the vial. For prefilled syringes, attach a sterile needle. A 5/8-inch, 23- to 25-gauge needle is appropriate.
-Administer at a 45-degree angle into the subcutaneous tissue.
--Infants and young children: Inject into the anterolateral thigh.
-Older children and adolescents: Inject into the deltoid area.

Report all adverse reactions to the Vaccine Adverse Event Reporting System (VAERS), as well as to the manufacturer. The toll-free number for VAERS is 1-800-822-7967. Educate the responsible adult(s) to promptly report any adverse reaction after vaccine administration to a health care provider.

Most adverse reactions reported with hepatitis B vaccine, recombinant have been mild, self-limiting, and did not last for more than 48 hours. An injection site reaction (0.2% to 38.5%) may occur in patients receiving hepatitis B vaccine, recombinant and is manifested as pain (58.6% or less), tenderness (30.2% to 59.9%), soreness (22%), erythema (0.2% to 10%), swelling (0.2% to 10%), bruising (less than 1%), induration (1% to 10%), ecchymosis, warmth, or a nodule at the injection site. Injection site pruritus has been reported during postmarketing surveillance.

Fatigue and weakness are associated with hepatitis B vaccine, recombinant, reported in > 1% of injections among 147 infants and children < 10 years of age who received 5 mcg doses (n = 434 injections). Irritability (>1%) and fever >= 100 degrees F (up to 15%) were also observed in clinical trials. Fatigue has been reported in up to 14% of pediatric and adult patients who received the vaccine during clinical studies. Other systemic adverse reactions observed during these studies include chills (< 1%), malaise (>= 1%), headache (>= 1%), lymphadenopathy (< 1%), hypotension (< 1%), flushing (< 1%), diaphoresis (< 1%), achiness (< 1%), sensations of warmth (< 1%), lightheadedness (< 1%), and agitation (< 1% ). Counsel patients to report any signs or symptoms of a systemic reaction to their health care provider.

During clinical studies involving pediatric and adult patients, dizziness (< 10%), insomnia (< 1%), paresthesias (< 1%), otalgia (< 1%), and vertigo (< 1%) were noted in of hepatitis B vaccine, recombinant recipients. Drowsiness or somnolence was noted during clinical studies of adult patients (< 1%). During post-marketing use, tinnitus, encephalopathy, Guillain-Barre syndrome, hypoesthesia, migraine, seizures (including febrile seizures), myelitis (including transverse myelitis), peripheral neuropathy, encephalitis, Bell's palsy, neuritis, optic neuritis, muscle paralysis, paresis, and radiculopathy have been reported after use of the vaccine. Multiple sclerosis and exacerbation of multiple sclerosis have also been reported during post-marketing use, but several well-designed epidemiologic studies have not found an association with hepatitis B vaccine administration and the development of multiple sclerosis (MS). Hepatitis B vaccination does not appear to increase the risk of relapse in MS.

Approximately 60 cases of alopecia occurring after vaccination have been reported (in most cases, patients received vaccination for hepatitis B). Although some people lost all of their hair, including eyelashes, in most instances, some or all of the hair grew back. A positive rechallenge was reported in sixteen cases. This side effect is very rare following administration of hepatitis B vaccine, recombinant and has been estimated to occur in roughly 5 people a year out of about 1 billion vaccinations. Other dermatologic reactions observed during post-marketing surveillance include Stevens-Johnson syndrome, erythema multiforme, erythema nodosum, eczema, purpura, petechiae, and lichen planus-like eruption.

Rash (unspecified), pruritus, angioedema, and urticaria were each noted in < 1% of hepatitis B vaccine, recombinant adult recipients during clinical studies. Post-marketing, anaphylactoid reactions, dyspnea, bronchospasm, edema, chest discomfort, palpitations, sinus tachycardia, and symptoms consistent with a hypotensive episode have been reported within the first few hours after vaccination. An apparent hypersensitivity syndrome (serum sickness like syndrome) has been observed during post-marketing observation days to weeks after vaccination. The syndrome includes joint pain or arthritis that is usually transient, as well as fever, hives, ecchymosis, erythema multiforme, and erythema nodosum. Review the patient's immunization history for possible vaccine sensitivity and previous vaccination related adverse reactions to help determine the benefits and risks of hepatitis B vaccine receipt. If the vaccine is administered, have appropriate medical treatment and supervision available to manage possible anaphylactic reactions after vaccine administration.

Thrombocytopenia and increases in erythrocyte sedimentation rate have been reported post-marketing with the hepatitis B vaccine, recombinant. The frequency of occurrence or causal relationship to the vaccine of post-marketing events cannot be reliably determined because events are reported voluntarily from a population of uncertain size.

Syncope has been noted post-marketing with the hepatitis B vaccine, recombinant. Syncope can be accompanied by transient neurological signs such as visual disturbance, paresthesia, and tonic-clonic limb movements. Have procedures in place to avoid falling injury and to restore cerebral perfusion after syncope.

Diarrhea and anorexia within 5 days after hepatitis B vaccine, recombinant receipt were reported in > 1% of injections among 147 infants and children < 10 years of age who received 5 mcg doses (n = 434). These frequencies were similar to those in a study of adolescents that received either 5 or 10 mcg doses of the vaccine. Other adverse reactions observed during clinical studies of pediatric and adult patients include nausea (>= 1%), abdominal pain (< 1%), vomiting (< 1%), dyspepsia (< 1%), and constipation (< 1%). Elevated hepatic enzymes have been noted during post-marketing experience. Counsel patients to report any signs or symptoms of a systemic reaction to their health care provider.

Rhinitis within 5 days after hepatitis B vaccine, recombinant receipt was reported in > 1% of injections among 147 infants and children < 10 years of age who received 5 mcg doses (n = 434). This frequency was similar to that found in a study of adolescents who received either 5 or 10 mcg doses of the vaccine. Other adverse events reported within 4-5 days after administration of the vaccine in pediatric and adult patients include upper respiratory infection (>= 1%), pharyngitis (>= 1%), influenza or influenza-like symptoms (< 1%), and cough (< 1%). Herpes zoster, conjunctivitis, uveitis, keratitis, and meningitis have been noted during post-marketing experience. Counsel patients to report any signs or symptoms of a systemic reaction to their health care provider.

Systemic lupus erythematosus (SLE), lupus-like symptoms, vasculitis, and polyarteritis nodosa have been reported post-marketing with the hepatitis B vaccine, recombinant. The frequency of occurrence or causal relationship to the vaccine of post-marketing events cannot be reliably determined because events are reported voluntarily from a population of uncertain size.

During clinical studies in healthy adults, dysuria was reported in < 1% of hepatitis B vaccine, recombinant recipients; a conclusion regarding vaccine causality has not been provided.

During post-marketing surveillance, apnea has been reported after immunization with hepatitis b vaccine, recombinant. A casual relationship to the vaccine is not established.

During studies in healthy adults, arthralgia (including monoarticular arthralgia); myalgia; neck, extremity, shoulder, or back pain; and neck stiffness were observed in < 1% of hepatitis B vaccine, recombinant recipients. Arthritis has been observed during post-marketing experience. Counsel patients to report any signs or symptoms of a systemic reaction to their health care provider.

Prior to administration, inform the parent, guardian, or responsible adult of the benefits and risks of the vaccine, and provide the Vaccine Information Statement, accessible at the Centers for Disease Control and Prevention (CDC) website. These actions are required by the National Childhood Vaccine Injury Act of 1986. If a dose of hepatitis B vaccine, recombinant has been previously given, question the parent or guardian about previous adverse reactions that may preclude further administration. Report all adverse reactions to the Vaccine Adverse Event Reporting System (VAERS), as well as the manufacturer. The toll-free number for VAERS is 1-800-822-7967. Educate the responsible adult(s) to promptly report any adverse reaction after vaccine administration to a health care provider.

Due to the long hepatitis B incubation period, the hepatitis B vaccine, recombinant vaccine may not prevent hepatitis B infection in patients with unrecognized hepatitis B infection at the time of vaccination. Additionally, vaccination with hepatitis B, recombinant vaccine may not protect all patients.

Hepatitis B vaccine, recombinant is contraindicated in patients who have had a severe allergic reaction (e.g., anaphylaxis) temporally associated with a previous dose of this vaccine or hypersensitivity to any of its components. Use of this vaccine is contraindicated in patients with a yeast hypersensitivity; hepatitis B surface antigens (HBsAg) contained within the hepatitis B vaccine, recombinant are produced in recombinant yeast cells. Patients who develop symptoms suggestive of hypersensitivity should not receive further injections of the vaccine. Further, patients with latex hypersensitivity may not be appropriate candidates for vaccination with Recombivax HB as the syringe plunger and tip caps of prefilled syringes and the vial stopper contain dry natural latex rubber that may cause allergic reactions. Have epinephrine 1 mg/mL injection and other agents used in the treatment of severe anaphylaxis immediately available in the event of a serious allergic reaction to the vaccine.

Defer receipt of hepatitis B vaccine, recombinant for neonates who weigh < 2000 grams 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. For neonates who weigh < 2000 grams and who are born to HBsAg positive mothers or to mothers of unknown HBsAg status, administer hepatitis b vaccine, recombinant and hepatitis B immune globulin (HBIG) within 12 hours of birth. Do not count the birth dose as the first dose in the vaccine series; administer the full 3 dose standard regimen (total of 4 doses). Apnea after intramuscular vaccination has been observed in some premature neonates. Base the decision about when to administer an intramuscular vaccine to neonates born prematurely on the newborn's medical status and the potential benefits and possible risks of hepatitis B vaccine, recombinant vaccination. For example, consider 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.

The hepatitis B vaccine, recombinant is indicated for intramuscular administration and, thus, should be given cautiously to persons receiving anticoagulant therapy. Also, patients with thrombocytopenia, coagulopathy (e.g., hemophilia), other bleeding disorders, or vitamin K deficiency should be monitored closely for bleeding at the IM injection site. Steps to avoid hematoma formation are recommended.

The decision to administer or to delay vaccination with the hepatitis B vaccine, recombinant because of current or recent febrile illness depends on the severity of symptoms and on the etiology of the disease. The Advisory Committee on Immunization Practices recommends that vaccinations be delayed during the course of a moderate or severe acute febrile illness and administered after the acute phase of illness has resolved, unless the patient is at immediate risk of hepatitis B infection (e.g., neonates born to HBsAg positive mothers). Use caution when administering the vaccine to patients with severely compromised cardiopulmonary status. All vaccines can be administered to persons with minor illnesses such as diarrhea, mild upper-respiratory infection with or without low-grade fever, or other low-grade febrile illness. Persons with moderate or severe febrile illness should be vaccinated as soon as they have recovered from the acute phase of the illness.

Patients with significant immunosuppression may not have an adequate antibody response to hepatitis B vaccine, recombinant. Immunosuppressed persons may include patients with human immunodeficiency virus (HIV) infection; severe combined immunodeficiency (SCID); hypogammaglobulinemia; agammaglobulinemia; altered immune states due to generalized neoplastic disease; or an immune system compromised by radiation therapy or drug therapy (e.g., chemotherapy or corticosteroid therapy with greater than physiologic doses). Short-term (less than 2 weeks) corticosteroid therapy or intra-articular, bursal, or tendon injections with corticosteroids should not be immunosuppressive. Patients vaccinated with hepatitis B vaccine, recombinant within 2 weeks before starting immunosuppressive therapy or while receiving immunosuppressive therapy should be considered unvaccinated and should be revaccinated at least 3 months after therapy is discontinued if immune competence has been restored. The guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV recommend vaccinating patients with a CD4 count less than 200 cells/mm3 if they have ongoing risks for hepatitis B. For HIV patients without risk factors, waiting to vaccinate until CD4 count is 200 cells/mm3 or higher is an option. Assess the antibody response (anti-HBs) to the vaccine 1 to 2 months after completing the series. If a primary immunization course fails to confer immunity, repeat doses may be required.

Patients with renal disease or renal failure requiring dialysis may require larger doses of hepatitis B vaccine, recombinant to achieve adequate serum antibody titers. A formulation containing 40 mcg/mL of antigen is available for use in dialysis patients, but has not been tested for safety in the pediatric population and should be avoided in pediatric patients.

The hepatitis B vaccine, recombinant is indicated for intramuscular administration; do not give via intravenous administration or intradermal administration. Incorrect administration may result in inadequate immunity. The vaccine may be administered subcutaneously; however, subcutaneous administration has been associated with lower antibody response and an increased incidence of local adverse reactions. Administer the vaccine subcutaneously only in patients at high risk of hemorrhage from intramuscular injection (e.g., hemophiliacs).

Laboratory test interference may occur between the hepatitis B vaccine, recombinant and hepatitis B surface antigen (HBsAg) in blood samples. HBsAg has been transiently detected in blood samples after vaccination. Serum HBsAg may not have diagnostic value within 28 days after receipt of a hepatitis B vaccine.

Description: Hepatitis B vaccine, recombinant is a monovalent viral vaccine derived from hepatitis B surface antigen (HBsAg) produced by yeast cells (Saccharomyces cerevisiae). The vaccine is indicated for hepatitis B prophylaxis in pediatric patients of all ages and can be used in conjunction with hepatitis B immune globulin (HBIG) for postexposure prophylaxis. Hepatitis B vaccine, alone or combined with HBIG, has reduced the risk of perinatal transmission of hepatitis B to infants of mothers who are HBsAg positive and hepatitis B e antigen (HBeAg) positive. Recombinant hepatitis B vaccine is approved for use in pediatric patients as young as neonates; ideally immunization should begin at birth.

General Dosing Information
-Immunization with hepatitis B vaccine, recombinant is recommended for all neonates, infants, children, and adolescents.
-Use monovalent hepatitis B vaccine rather than combination vaccines in patients younger than 6 weeks; a total of 4 doses of hepatitis B vaccines is recommended if a combination vaccine is used after a birth dose.
-Different brands of hepatitis B vaccines are interchangeable with the exception of the 2-dose hepatitis B vaccination series for adolescents 11 to 15 years of age; only Recombivax HB should be used in this schedule.
-Interruption of the recommended schedule with a delay between doses should not interfere with the final immunity achieved with the hepatitis B vaccine. There is no need to start the primary series over again, regardless of the time between doses.
-Routine booster doses are not recommended as the duration of protective effect is unknown; however, revaccination may be recommended for the following populations: infants born to hepatitis B virus surface antigen (HBsAg)-positive mothers, hemodialysis patients, and other immunocompromised patients. In hemodialysis patients, the Advisory Committee on Immunization Practices (ACIP) recommends annual antibody testing and revaccination when HBsAg antibody concentrations decline to less than 10 milli-International Units/mL.

For hepatitis B prophylaxis:
Intramuscular or Subcutaneous dosage (Recombivax HB):
Neonates born to HBsAg-negative mothers: 5 mcg (0.5 mL) given IM or subcutaneously within 24 hours of birth. ACIP recommends repeat doses ideally at 1 and 6 months after initial dose; the final dose (3rd or 4th dose) should be administered no earlier than age 24 weeks. A minimum interval of 4 weeks is needed between doses 1 and 2, and a minimum interval of 8 weeks is needed between doses 2 and 3. If the neonate weighs less than 2 kg at birth, delay the initial vaccination until 1 month of age or hospital discharge (whichever is earlier and even if weight is still less than 2 kg). Use subcutaneous administration ONLY in patients who are at risk of hemorrhage after IM injection (e.g., hemophiliacs); patients may be at increased risk for local adverse reactions including subcutaneous nodules.
Neonates born to HBsAg-positive mothers: 5 mcg (0.5 mL) given IM or subcutaneously. Administer the vaccine within 12 hours of birth with hepatitis B immune globulin (HBIG). In neonates weighing less than 2 kg at birth, give the birth dose plus the standard 3-dose regimen. Test for HBsAg and antibody to HBsAg at age 9 through 12 months, preferably at the next well-child visit, or 1 to 2 months after completion of the hepatitis B series if the series was delayed. Revaccinate HBsAg-negative infants with anti-HBs less than 10 milli-International Units/mL with a single dose of hepatitis B vaccine; serologic testing should follow 1 to 2 months later. Infants whose anti-HBs remains less than 10 milli-International Units/mL should receive 2 additional doses of hepatitis B vaccine to complete the second series, followed by serologic testing 1 to 2 months after the final dose. Use subcutaneous administration ONLY in patients who are at risk of hemorrhage after IM injection (e.g., hemophiliacs); patients may be at increased risk for local adverse reactions including subcutaneous nodules.
Neonates born to mothers with unknown HBsAg status: 5 mcg (0.5 mL) given IM or subcutaneously. Administer the vaccine within 12 hours of birth. Give hepatitis B immune globulin (HBIG) concomitantly for neonates weighing less than 2 kg; give HBIG to infants weighing at least 2 kg only with positive maternal HBsAg test result (within age 1 week) or if evidence is suggestive of maternal HBV infection (e.g., presence of HBV DNA, HBeAg-positive, or mother known to be chronically infected with HBV). In neonates whom it is not possible to determine the mother's HBsAg status (e.g., when a neonate is surrendered confidentially), complete the vaccine series according to a recommended schedule for infants born to HBsAg-positive mothers with the final dose in the series administered after 24 weeks. Test for HBsAg and antibody to HBsAg at age 9 through 12 months; revaccinate if necessary. In neonates weighing less than 2 kg, give the birth dose plus the standard 3-dose regimen. Use subcutaneous administration ONLY in patients who are at risk of hemorrhage after IM injection (e.g., hemophiliacs); patients may be at increased risk for local adverse reactions including subcutaneous nodules.
Infants and Children 1 month to 10 years: 5 mcg (0.5 mL) given IM or subcutaneously at initial visit. Repeat dose ideally at 1 and 6 months after initial dose; the final dose (3rd or 4th dose) should be administered no earlier than age 24 weeks. A minimum interval of 4 weeks is needed between doses 1 and 2, and a minimum interval of 8 weeks is needed between doses 2 and 3. In infants and children born to HBsAg-positive mothers, test for HBsAg and antibody to HBsAg at age 9 through 12 months or 1 to 2 months after completion of the hepatitis B series if the series was delayed. Revaccinate HBsAg-negative infants with anti-HBs less than 10 milli-International Units/mL with a single dose of hepatitis B vaccine; serologic testing should follow 1 to 2 months later. Infants whose anti-HBs remains less than 10 milli-International Units/mL should receive 2 additional doses of hepatitis B vaccine to complete the second series, followed by serologic testing 1 to 2 months after the final dose. Use subcutaneous administration ONLY in patients who are at risk of hemorrhage after IM injection (e.g., hemophiliacs); patients may be at increased risk for local adverse reactions including subcutaneous nodules.
Children and Adolescents 11 years and older: 5 mcg (0.5 mL) given IM or subcutaneously at initial visit. Repeat dose ideally at 1 and 6 months after initial dose; a minimum interval of 4 weeks is needed between doses 1 and 2, and a minimum interval of 8 weeks is needed between doses 2 and 3. For pediatric patients between 11 and 15 years of age, an alternative regimen using the Recombivax HB Adult Formulation is 10 mcg (1 mL) given IM or subcutaneously for 2 doses, given 4 to 6 months apart. Use subcutaneous administration ONLY in patients who are at risk of hemorrhage after IM injection (e.g., hemophiliacs); patients may be at increased risk for local adverse reactions including subcutaneous nodules.
Intramuscular or Subcutaneous dosage (Engerix-B):
Neonates born to HBsAg-negative mothers: 10 mcg (0.5 mL) given IM or subcutaneously within 24 hours of birth. ACIP recommends repeat doses ideally at 1 and 6 months after initial dose; the final dose (3rd or 4th dose) should be administered no earlier than age 24 weeks. A minimum interval of 4 weeks is needed between doses 1 and 2, and a minimum interval of 8 weeks is needed between doses 2 and 3. If the neonate weighs less than 2 kg at birth, delay the initial vaccination until 1 month of age or hospital discharge (whichever is earlier and even if weight is still less than 2 kg). Use subcutaneous administration ONLY in patients who are at risk of hemorrhage after IM injection (e.g., hemophiliacs); patients may be at increased risk for local adverse reactions including subcutaneous nodules.
Neonates born to HBsAg-positive mothers: 10 mcg (0.5 mL) given IM or subcutaneously. Administer the vaccine within 12 hours of birth with hepatitis B immune globulin (HBIG). In neonates weighing less than 2 kg at birth, give the birth dose plus the standard 3-dose regimen. Test for HBsAg and antibody to HBsAg at age 9 through 12 months, preferably at the next well-child visit, or 1 to 2 months after completion of the hepatitis B series if the series was delayed. Revaccinate HBsAg-negative infants with anti-HBs less than 10 milli-International Units/mL with a single dose of hepatitis B vaccine; serologic testing should follow 1 to 2 months later. Infants whose anti-HBs remains less than 10 milli-International Units/mL should receive 2 additional doses of hepatitis B vaccine to complete the second series, followed by serologic testing 1 to 2 months after the final dose. Use subcutaneous administration ONLY in patients who are at risk of hemorrhage after IM injection (e.g., hemophiliacs); patients may be at increased risk for local adverse reactions including subcutaneous nodules.
Neonates born to mothers with unknown HBsAg status: 10 mcg (0.5 mL) given IM or subcutaneously. Administer the vaccine within 12 hours of birth. Give HBIG concomitantly for neonates weighing less than 2 kg; give HBIG to infants weighing at least 2 kg only with positive maternal HBsAg test result (within age 1 week) or if evidence is suggestive of maternal HBV infection (e.g., presence of HBV DNA, HBeAg-positive, or mother known to be chronically infected with HBV). In neonates whom it is not possible to determine the mother's HBsAg status (e.g., when a neonate is surrendered confidentially), complete the vaccine series according to a recommended schedule for infants born to HBsAg-positive mothers with the final dose in the series administered after 24 weeks. Test for HBsAg and antibody to HBsAg at age 9 through 12 months; revaccinate if necessary. In neonates weighing less than 2 kg born to mothers with unknown HBsAg status, give the birth dose plus the standard 3-dose regimen. Use subcutaneous administration ONLY in patients who are at risk of hemorrhage after IM injection (e.g., hemophiliacs); patients may be at increased risk for local adverse reactions including subcutaneous nodules.
Infants and Children 1 month to 4 years: 10 mcg (0.5 mL) given IM or subcutaneously at initial visit. ACIP recommends repeat doses ideally at 1 and 6 months after initial dose; the final dose (3rd or 4th dose) should be administered no earlier than age 24 weeks. A minimum interval of 4 weeks is needed between doses 1 and 2, and a minimum interval of 8 weeks is needed between doses 2 and 3. In infants and children born to HBsAg-positive mothers, an alternative schedule of doses at 0, 1, 2, and 12 months may be used; the fourth dose is given at 12 months to prolong maintenance titers. In these infants and children, test for HBsAg and antibody to HBsAg at age 9 through 12 months, preferably at the next well-child visit, or 1 to 2 months after completion of the hepatitis B series if the series was delayed. Revaccinate HBsAg-negative infants with anti-HBs less than 10 milli-International Units/mL with a single dose of hepatitis B vaccine; serologic testing should follow 1 to 2 months later. Infants whose anti-HBs remains less than 10 milli-International Units/mL should receive 2 additional doses of hepatitis B vaccine to complete the second series, followed by serologic testing 1 to 2 months after the final dose. Use subcutaneous administration ONLY in patients who are at risk of hemorrhage after IM injection (e.g., hemophiliacs); patients may be at increased risk for local adverse reactions including subcutaneous nodules.
Children 5 to 10 years receiving primary vaccination: 10 mcg (0.5 mL) given IM or subcutaneously. Give 3 doses. ACIP recommends the second and third doses ideally at 1 and 6 months after initial dose. A minimum interval of 4 weeks is needed between doses 1 and 2, and a minimum interval of 8 weeks is needed between doses 2 and 3. If prolonged duration of protective titers is desired, doses may be given at 0, 1, 2, and 12 months. Use subcutaneous administration ONLY in patients who are at risk of hemorrhage after IM injection (e.g., hemophiliacs); patients may be at increased risk for local adverse reactions including subcutaneous nodules.
Children 5 to 10 years for whom an extended administration schedule is acceptable based on risk of exposure to the virus: 10 mcg (0.5 mL) given IM or subcutaneously. Give 3 doses with the second and third dose given 12 and 24 months after the first, respectively. Use subcutaneous administration ONLY in patients who are at risk of hemorrhage after IM injection (e.g., hemophiliacs); patients may be at increased risk for local adverse reactions including subcutaneous nodules.
Children and Adolescents 11 years and older receiving primary vaccination: Give 3-dose series of 10 mcg (0.5 mL) IM or subcutaneously. ACIP recommends the second and third doses ideally at 1 and 6 months after initial dose. A minimum interval of 4 weeks is needed between doses 1 and 2, and a minimum interval of 8 weeks is needed between doses 2 and 3. Alternatively, a higher dose of 20 mcg (1 mL) may also be given at 0, 1, and 6 months. If prolonged duration of protective titers is desired, the higher dose of 20 mcg (1 mL) may be given at 0, 1, 2, and 12 months. Use subcutaneous administration ONLY in patients who are at risk of hemorrhage after IM injection (e.g., hemophiliacs); patients may be at increased risk for local adverse reactions including subcutaneous nodules.
Children and Adolescents 11 to 16 years for whom an extended administration schedule is acceptable based on risk of exposure to the virus: Give 3-dose series of 10 mcg (0.5 mL) IM or subcutaneously, with the second and third dose given 12 and 24 months after the first, respectively. Use subcutaneous administration ONLY in patients who are at risk of hemorrhage after IM injection (e.g., hemophiliacs); patients may be at increased risk for local adverse reactions including subcutaneous nodules.
-for booster vaccination using Engerix-B:
Intramuscular and Subcutaneous dosage (Engerix-B):
Children 1 to 10 years: 10 mcg (0.5 mL) given IM or subcutaneously, whenever administration of a booster dose is appropriate. Studies have demonstrated a substantial increase in antibody titers after booster vaccination with Engerix-B. Routine booster doses are not recommended as the duration of protective effect is unknown. In hemodialysis patients, ACIP recommends annual antibody testing and revaccination when HBsAg antibody concentrations decline to less than 10 milli-International Units/mL. Use subcutaneous administration ONLY in patients who are at risk of hemorrhage after IM injection (e.g., hemophiliacs); patients may be at increased risk for local adverse reactions including subcutaneous nodules.
Children and Adolescents 11 years and older: 20 mcg (1 mL) given IM or subcutaneously, whenever administration of a booster dose is appropriate. Studies have demonstrated a substantial increase in antibody titers after booster vaccination with Engerix-B. Routine booster doses are not recommended as the duration of protective effect is unknown. In hemodialysis patients, ACIP recommends annual antibody testing and revaccination when HBsAg antibody concentrations decline to less than 10 milli-International Units/mL. Use subcutaneous administration ONLY in patients who are at risk of hemorrhage after IM injection (e.g., hemophiliacs); patients may be at increased risk for local adverse reactions including subcutaneous nodules.

Therapeutic Drug Monitoring:
Postvaccination monitoring for infants and children born to HBsAg-positive mothers:
-Both antigen (HBsAg) and antibody (anti-HBs) testing should be performed after completion of the vaccine series, usually between ages 9-18 months. Do not test before age 9 months to avoid detection of anti-HBs from any previous hepatitis B immune globulin administration.
-HBsAg negative infants with anti-HBs < 10 milli-international units/ml should be revaccinated with a second 3-dose series and retested 1-2 months after the final vaccine dose.
-HBsAg negative infants with anti-HBs >= 10 milli-international units/ml are considered protected and do not need further medical management.
-Infants or children who are HBsAg positive should receive appropriate care.

Maximum Dosage Limits:
-Neonates
5 mcg/dose IM/SC for Recombivax HB; 10 mcg/dose IM/SC for Engerix-B.
-Infants
5 mcg/dose IM/SC for Recombivax HB; 10 mcg/dose IM/SC for Engerix-B.
-Children
< 11 years: 5 mcg/dose IM/SC for Recombivax HB; 10 mcg/dose IM/SC for Engerix-B.
>= 11 years: 5 mcg/dose IM/SC for Recombivax HB standard, 3-dose regimen or 10 mcg/dose IM/SC for Recombivax HB 2-dose regimen; 20 mcg/dose IM/SC for Engerix-B.
-Adolescents
<= 15 years: 5 mcg/dose IM/SC for Recombivax HB standard, 3-dose regimen or 10 mcg/dose IM/SC for Recombivax HB 2-dose regimen; 20 mcg/dose IM/SC for Engerix-B.
> 15 years: 5 mcg/dose IM/SC for Recombivax HB; 20 mcg/dose IM/SC for Engerix-B.

Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed. However, consult current immunization schedules for recommended vaccines for use in young dialysis patients; the ACIP states that all routine vaccinations are likely effective in patients with chronic renal disease.

*non-FDA-approved indication

Monograph content under development

Mechanism of Action: Hepatitis B vaccine, recombinant confers immunity against the virus that causes hepatitis B.

Immunization with hepatitis B vaccine stimulates the immune system to produce anti-hepatitis B surface antigen antibodies without exposing the patient to the risks of active infection. An antibody concentration of at least 10 milli-international units/ml is considered protective. Infection with hepatitis D can occur only with concurrent hepatitis B infection; therefore, vaccination with recombinant hepatitis B vaccine provides protection against hepatitis D as well.

Pharmacokinetics: Hepatitis B vaccine, recombinant is administered intramuscularly. The vaccine may be administered subcutaneously in patients at risk of hemorrhage from IM injection. In some individuals, immune response to the vaccine may not be sufficient to provide protection against hepatitis B infections. The distrubution, metabolism, and excretion of the vaccine have not been well defined.


-Special Populations
Pediatrics
Neonates and Infants < 6 months
In neonates and infants given hepatitis B vaccine, recombinant (Engerix) (10 mcg/dose) at 0, 1, and 6 months of age (n = 52) or at 0, 1, and 2 months of age (n = 381), sera was obtained 1 month following the third dose. At 7 months, 97% of infants given the vaccine at 0, 1, and 6 months of age developed seroprotective hepatitis b virus surface antigen (HBsAg) antibody concentrations (>= 10 milli-international units/ml). At 4 months, 96% of infants given the vaccine at 0, 1, and 2 months of age developed seroprotective HBsAg antibody concentrations.. Additionally, 100% of infants given the 3-dose Recombivax series had protective antibody concentrations. In neonates born to HBsAg and HBeAg positive mothers, efficacy in the prevention of hepatitis B infection after 3 doses of Recombivax and HBIG was 95% as compared to historical controls who only received HBIG.

Infants > 6 months, Children, and Adolescents
In infants and children who received hepatitis B vaccine, recombinant (Engerix) (10 mcg/dose) at 0, 1, and 6 months, the seroprotective rate 1-2 months after the third dose was 98%. The geometric mean titer of seroconverters was 4023 milli-international units/ml. Similar rates of protection were found in adolescents. In infants and children, 100% and 99% experienced a protective level of antibodies after the 3-dose Recombivax series. The immunogenicity of the 2 dose regimen (10 mcg at 0 and 4-6 months) of hepatitis B vaccine, recombinant (Recombivax) was compared to the standard 3 dose regimen (5 mcg at 0, 1, and 6 months) in an open-label, randomized clinical study. One month after the last dose in each series, 99% of 255 adolescents who received the 2 dose regimen developed protective HBsAg antibody concentrations compared to 98% of 121 adolescents who received the 3 dose regimen. After receipt of the first 10 mcg dose, 72% of recipients developed protective HBsAg antibody concentrations.

Alternative Dosing Strategies
In a clinical trial involving children > 5 years and adolescents immunized with 10 mcg doses of hepatitis B vaccine, recombinant (Engerix) at 0, 1, and 6 months (n = 181) or 1, 12, and 24 months (n = 161), seroprotection occurred 1 month after the third dose in 99.5% and 98.1% of recipients in each group, respectively. Geometric mean titers were higher (p = 0.02) in children who received the vaccine on the 0, 1, 6 month schedule (5687.4 milli-international units/ml vs. 3158.7 milli-international units/ml.

Booster Vaccination
The immune response to a booster dose of the vaccine was evaluated among children 5-7 years and adolescents 10-15 years who completed the primary series and got the first vaccine dose within 7 days of birth. Among the children, 70 got Engerix-B and 96 got Recombivax HB; most adolescents (132 of 138) got Recombivax HB. Four weeks after a booster dose, an anamnestic response was obtained in 99% of the 166 children and in 88% of the 138 adolescents. An anamnestic response was defined as a HBsAg antibody concentration of at least 10 milli-international units/ml for patients with a baseline concentration below 10 milli-international units/ml and at least a 4-fold increase in the concentration for patients with a baseline concentration above 10 milli-international units/ml. Only 29% of the children and 14% of the adolescents had HBsAg antibody concentrations of at least 10 milli-international units/ml before booster dose receipt. However, 95-100% of the 116 children with a baseline HBsAg antibody concentration < 10 milli-international units/ml had an anamnestic response whereas only 77-81% of the 118 adolescents with a baseline HBsAg antibody concentration < 10 milli-international units/ml had an anamnestic response; all of the children and adolescents with a baseline HBsAg antibody concentration of at least 10 milli-international units/ml had an anamnestic response.