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  • CLASSES

    Hepatitis Vaccines

    DEA CLASS

    Rx

    DESCRIPTION

    Monovalent vaccine for vaccination against hepatitis B virus infection
    Vaccinate all neonates within 24 hours of birth using Engerix-B and Recombivax HB; may use for hepatitis B prophylaxis in all ages and can be used in conjunction with hepatitis B immune globulin (HBIG) for postexposure prophylaxis; Heplisav-B is only approved in adults
    3-dose series typically required for full immunity using Engerix-B and Recombivax HB; a 2-dose series in adolescents using Recombivax HB adult formulation may be used; Heplisav-B is administered as a 2-dose series in adults

    COMMON BRAND NAMES

    Engerix-B, HEPLISAV-B, Recombivax HB

    HOW SUPPLIED

    Engerix-B/Recombivax HB Intramuscular Inj Susp: 0.5mL, 1mL, 5mcg, 10mcg, 20mcg, 40mcg
    HEPLISAV-B Intramuscular Inj Sol: 0.5mL, 20mcg
    Recombivax HB Subcutaneous Inj Susp: 0.5mL, 1mL, 5mcg, 10mcg, 40mcg

    DOSAGE & INDICATIONS

    For hepatitis B prophylaxis.
    For prophylaxis of hepatitis B using Recombivax HB.
    Intramuscular or Subcutaneous dosage (Recombivax HB)
    Adults 20 years and older

    10 mcg IM or subcutaneously at initial visit; repeat at 1 and 6 months after initial dose.[43106] Administer the second dose 1 month after the first dose, and administer the third dose at least 2 months after the second dose and at least 4 months after the first dose.[53026] Use subcutaneous administration ONLY in patients who are at risk of hemorrhage after IM injection (e.g., hemophiliacs).

    Adults younger than 20 years

    5 mcg IM or subcutaneously at initial visit. Repeat at 1 and 6 months after the initial dose.[43106] Use subcutaneous administration ONLY in patients who are at risk of hemorrhage after IM injection (e.g., hemophiliacs).

    Adult predialysis or dialysis patients

    Use dialysis formulation containing 40 mcg/mL of vaccine. Administer 40 mcg (1 mL) IM or subcutaneously at initial visit; repeat at 1 and 6 months after initial dose. For predialysis or dialysis patients, a booster dose or revaccination with 40 mcg IM or subcutaneously may be considered if the anti-HBs concentration is less than 10 milli-International Units/mL 1 to 2 months after the third dose. The ACIP recommends that the need for booster doses of vaccine be assessed by annual antibody testing. Give booster dose when antibody concentrations decline to less than 10 milli-International Units/mL.[43106] [53026] [53225] Use subcutaneous administration ONLY in patients who are at risk of hemorrhage after IM injection (e.g., hemophiliacs).

    Revaccination for Adult Vaccine Nonresponders

    Revaccination with at least 1 dose of vaccine for nonresponse after the primary series increases the proportion of those achieving seroprotection. In a study (n = 178), 47% of nonresponders developed seroprotection after 1 additional dose. Of the 86 patients without seroprotection after the first revaccination, 42% developed seroprotection after 2 additional doses. A 3-dose revaccination (n = 17) with a higher dose of 40 mcg IM or subcutaneously improved the proportion of nonresponders achieving anti-HB levels of at least 10 milli-International Units/mL in a clinical trial; single dose revaccination with a higher dose has not been demonstrated in clinical trials.

    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.[43106] [53026]

    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.[43106] [53026] 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.[62840] 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.[43106]

    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. 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.[43106] 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.[53026] [53230] 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.[62840] 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.[43106]

    Neonates born to mothers with unknown HBsAg status

    5 mcg (0.5 mL) given IM or subcutaneously.[43106] 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.[62840] In neonates weighing less than 2 kg, give the birth dose plus the standard 3-dose regimen.[53026] [53230] 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.[43106]

    For prophylaxis of hepatitis B using Engerix-B.
    Intramuscular or Subcutaneous dosage (Engerix-B)
    Adults 20 years and older

    20 mcg IM or subcutaneously at initial visit; repeat at 1 and 6 months after initial dose.[43406] Administer the second dose 1 month after the first dose, and administer the third dose at least 2 months after the second dose and at least 4 months after the first dose.[53026] Use subcutaneous administration ONLY in patients who are at risk of hemorrhage after IM injection (e.g., hemophiliacs).

    Adults younger than 20 years

    20 mcg IM or subcutaneously at initial visit; repeat at 1 and 2 months after initial dose. Give additional 20 mcg IM or subcutaneously at 12 months for prolonged maintenance of titers. Use subcutaneous administration ONLY in patients who are at risk of hemorrhage after IM injection (e.g., hemophiliacs).

    Adults who have been recently exposed to the virus and certain travelers to high-risk areas

    20 mcg IM or subcutaneously at initial visit; repeat at 1 and 2 months after initial dose. Give additional 20 mcg IM or subcutaneously at 12 months for prolonged maintenance of titers. Use subcutaneous administration ONLY in patients who are at risk of hemorrhage after IM injection (e.g., hemophiliacs).

    Adult hemodialysis patients

    40 mcg IM or subcutaneously at initial visit; repeat at 1, 2, and 6 months after initial dose. The ACIP recommends that the need for booster doses be assessed by antibody testing. Give booster dose (40 mcg IM or subcutaneously) if 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).

    Revaccination for Adult Vaccine Nonresponders

    Revaccination with at least 1 dose of vaccine for nonresponse after the primary series increases the proportion of those achieving seroprotection. In a study (n = 178), 47% of nonresponders developed seroprotection after 1 additional dose. Of the 86 patients without seroprotection after the first revaccination, 42% developed seroprotection after 2 additional doses. A 3-dose revaccination (n = 17) with a higher dose of 40 mcg IM or subcutaneously improved the proportion of nonresponders achieving anti-HB concentrations of at least 10 milli-International Units/mL in a clinical trial; single dose revaccination with a higher dose has not been demonstrated in clinical trials.

    Children and Adolescents 11 years and older receiving primary vaccination

    Give 3 doses 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.[43406] [53026] 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.[43406]

    Children and Adolescents 11 to 16 years for whom an extended administration schedule is acceptable based on risk of exposure to the virus

    Give a 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.

    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.

    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.[43406] [53026] 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.[62840] 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.[43406]

    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. 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.[43406] 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.[53026] [53230] 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.[62840] 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.[43406]

    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.

    For booster vaccination using Engerix-B.
    Intramuscular and Subcutaneous dosage (Engerix-B)
    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.[43406] Routine booster doses are generally 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.[53225] 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.[43406]

    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.[43406] Routine booster doses are generally 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.[53225] 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.[43406]

    For prophylaxis of hepatitis B using Heplisav-B.
    Intramuscular dosage (Heplisav-B)
    Adults

    20 mcg (0.5 mL) IM given at initial visit; repeat at 1 month after initial dose.

    MAXIMUM DOSAGE

    Adults

    20 years and older: 10 mcg/dose IM/subcutaneous for Recombivax HB; 20 mcg/dose IM/subcutaneous for Engerix-B; 20 mcg/dose IM for Heplisav-B.
    18 to 19 years: 5 mcg/dose IM/subcutaneous for Recombivax HB; 20 mcg/dose IM/subcutaneous for Engerix-B; 20 mcg/dose IM for Heplisav-B.

    Geriatric

    10 mcg/dose IM/subcutaneous for Recombivax HB; 20 mcg/dose IM/subcutaneous for Engerix-B; 20 mcg/dose IM for Heplisav-B.

    Adolescents

    16 to 17 years: 5 mcg/dose IM/subcutaneous for Recombivax HB; 20 mcg/dose IM/subcutaneous for Engerix-B.
    13 to 15 years: 5 mcg/dose IM/subcutaneous for Recombivax HB standard, 3-dose regimen or 10 mcg/dose IM/subcutaneous for Recombivax HB 2-dose regimen; 20 mcg/dose IM/subcutaneous for Engerix-B.

    Children

    11 to 12 years: 5 mcg/dose IM/subcutaneous for Recombivax HB standard, 3-dose regimen or 10 mcg/dose IM/subcutaneous for Recombivax HB 2-dose regimen; 20 mcg/dose IM/subcutaneous for Engerix-B.
    1 to 10 years: 5 mcg/dose IM/subcutaneous for Recombivax HB; 10 mcg/dose IM/subcutaneous for Engerix-B.

    Infants

    5 mcg/dose IM/subcutaneous for Recombivax HB; 10 mcg/dose IM/subcutaneous for Engerix-B.

    Neonates

    5 mcg/dose IM/subcutaneous for Recombivax HB; 10 mcg/dose IM/subcutaneous for Engerix-B.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    In adult predialysis and dialysis patients, a special formulation containing 40 mcg/mL of vaccine should be administered. For all other patients with renal impairment, it appears that no dosage adjustments are needed.
     
    Intermittent hemodialysis
    A dialysis formulation containing 40 mcg/mL of vaccine should be used. See dosage for specific regimens.
     
    Continuous hemodialysis
    A dialysis formulation containing 40 mcg/mL of vaccine should be used. See dosage for specific regimens.
     
    Peritoneal dialysis
    A dialysis formulation containing 40 mcg/mL of vaccine should be used. See dosage for specific regimens.

    ADMINISTRATION

     
    Inform the patient or 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.[52653]
    Health care professionals administering vaccines should take appropriate precautions to prevent allergic reactions in vaccine recipients.

    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; administer Heplisav-B intramuscularly only) 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.[43106] [43406] [62619]

    Intramuscular Administration

    For vials, use a sterile syringe and needle to withdraw suspension from the vial. For prefilled syringes, attach a sterile needle.
    Adults, adolescents, and older children: 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.
    Neonates, infants, and young children: Inject into the anterolateral aspect of the mid-thigh.[43106] [43406]
    Injection must be accomplished with a needle long enough to ensure IM deposition of the vaccine.
    For adults, the needle size required for deltoid injection ranges from 5/8- to 1 1/2-inches, depending on patient size.
    For pediatric patients 3 years and older, the needle size required for deltoid injection ranges from 5/8- to 1-inch.
    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 the majority of infants younger than 1 year, a 1-inch, 22- to 25-gauge needle is sufficient to penetrate thigh muscle.[43236]

    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.
    Adults, adolescents, and older children: Inject into the deltoid area.
    Infants and young children: Inject into the anterolateral thigh.[43106] [43236] [43406]

    STORAGE

    Engerix-B:
    - Discard if product has been frozen
    - Do not freeze
    - Refrigerate (between 36 and 46 degrees F)
    HEPLISAV-B:
    - Discard if product has been frozen
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not freeze
    - Store between 35 to 46 degrees F
    Recombivax HB:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not freeze
    - Store between 36 to 46 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Prior to the administration of hepatitis B vaccine, health care personnel should inform the patient, parent, guardian, or responsible adult of the vaccine's benefits and risks. This should include the provision of the hepatitis B vaccine information statement from the manufacturer. The responsible adult should report any adverse reaction following vaccine administration to the health care provider. The US Department of Health and Human Services has established a Vaccine Adverse Event Reporting System (VAERS) to accept all reports of suspected adverse events after the administration of any vaccine. This includes, but is not limited to, the reporting of events required by the National Childhood Vaccine Injury Act of 1986. The toll-free number for VAERS is (800) 822—7967.
     
    Results from 2 clinical studies indicate that there is no association between hepatitis B vaccination and the development of multiple sclerosis, and vaccination with hepatitis B vaccine does not appear to increase the short-term risk of relapse in multiple sclerosis.
     
    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.

    Yeast hypersensitivity

    Hepatitis B vaccine, recombinant is contraindicated for use by persons with known yeast hypersensitivity or hypersensitivity to any component of the vaccine and in patients with a severe allergic reaction such as anaphylaxis after a previous dose of any hepatitis B-containing vaccine. Anaphylaxis has been reported with the use of the hepatitis B vaccine, recombinant. Review the patient's immunization history for possible vaccine sensitivity and previous vaccination-related adverse reactions to allow an assessment of benefits and risks before administering the vaccine. As with any biologic product, the prescriber or health care professional should take precautions to prevent allergic reactions. The health care professional should have immediate availability of epinephrine (1 mg/mL) injection and other agents used in the treatment of severe anaphylaxis in the event of a serious allergic reaction to the vaccine.

    Neonates, premature neonates

    Defer receipt of Engerix-B 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 infants who weigh < 2000 grams and who are born to HBsAg-positive mothers or to mothers of unknown HBsAg status, administer Engerix-B 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.

    Anticoagulant therapy, coagulopathy, hemophilia, intravenous administration, subcutaneous administration, thrombocytopenia, vitamin K deficiency

    Do not give hepatitis B vaccine via intradermal administration or intravenous administration. Patients with thrombocytopenia, vitamin K deficiency, a coagulopathy (e.g., hemophilia) or receiving anticoagulant therapy should be monitored closely when given hepatitis B vaccine, recombinant because bleeding can occur at the IM injection site. In some of these patients, the vaccine may be administered via subcutaneous administration. However, the risk of local reactions may be greater with subcutaneous administration of aluminum adsorbed vaccines. Subcutaneous dosing may also result in lower GMTs.

    Cardiac disease, fever, infection

    In general, postpone hepatitis B vaccine administration to a patient with a moderate or severe acute infection or illness unless they are at immediate risk of hepatitis B infection such as neonates born to HBsAg-positive mothers. Any serious active infection including an illness with a fever is a reason for delaying use of the hepatitis B vaccine, recombinant except when in the opinion of the prescriber, withholding the vaccination entails a greater risk. Postponing the vaccine receipt can help avoid diagnostic confusion between manifestations of an acute illness and possible vaccine adverse effects. Use caution and appropriate care when administering the vaccine to individuals with severely compromised cardiopulmonary status such as some patients with cardiac disease or to others in whom a febrile or systemic reaction could pose a significant risk.

    Chemotherapy, human immunodeficiency virus (HIV) infection, immunosuppression

    Patients with immunosuppression may respond to hepatitis B vaccine, recombinant with lower antibody titers than non-immunosuppressed patients. This is particularly a concern in patients receiving chemotherapy or in patients with human immunodeficiency virus (HIV) infection. Since a second infection in HIV-positive patients further weakens their immune system, it is still preferable to administer the vaccine. The seroconversion (SC) rate to hepatitis A vaccine is higher than the seroprotection (SP) rate to hepatitis B in these patients. Following vaccination with hepatitis A vaccine, inactivated the SC rates ranged between 77%—88% for HIV-positive individuals and was 100% for HIV-negative individuals. Following vaccination with hepatitis B vaccine, recombinant the seroprotection rates ranged between 24%—46% in HIV-positive individuals and was 93% in HIV-negative individuals. If a primary immunization course fails to confer immunity, additional doses of hepatitis B vaccine, recombinant may be required. Deferral of vaccination for at least 3 months after immunosuppressive therapy may also be considered.

    Dialysis, renal disease, renal failure

    Patients with renal disease or renal failure requiring hemodialysis may require larger doses to achieve adequate serum antibody titers (see Dosage). Hepatitis B vaccine products containing 10 mcg/ml of HBsAg should be avoided in these patients because of the inconvenience of large-volume IM administration as well as the potential problems associated with exceeding the recommended amount of aluminum hydroxide per dose of vaccine. 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 children.

    Pregnancy

    No adequate and well controlled studies have been conducted with hepatitis B vaccine, recombinant during pregnancy. In pre- and post-licensure clinical studies, 58 pregnant women who were inadvertently administrated hepatitis B vaccine, recombinant had rates of miscarriage and major birth defects that were consistent with estimated background rates. A pregnancy exposure registry of 245 women who received hepatitis A vaccine, inactivated; hepatitis B vaccine, recombinant (a bivalent vaccine containing the same hepatitis B surface antigen component and quantity as used in the hepatitis B vaccine, recombinant) during pregnancy or within 28 days prior to conception found that the rates of miscarriage and major birth defects were consistent with estimated background rates. Reproductive and developmental toxicity studies performed in rats given doses of Heplisav-B 0.3 mL revealed no vaccine-related fetal malformations or variations. Animal reproduction studies have not been conducted with Engerix-B or Recombivax HB. According to the Advisory Committee on Immunization Practices (ACIP), administration of recombinant virus vaccines to pregnant women has not resulted in adverse effects in the fetus. The ACIP recommends vaccination during pregnancy when the likelihood of disease exposure is high, potential infection would cause harm to mother or fetus, and when the vaccine is unlikely to cause harm.[43106] [43406] [43236] [62619] A pregnancy exposure registry is available for women exposed to Heplisav-B during pregnancy. Patients are encouraged to register by calling 1-844-443-7734.[62619]

    Breast-feeding

    Data are limited regarding use of the hepatitis B vaccine, recombinant during breast feeding and its' excretion in human milk is unknown. According to the Advisory Committee on Immunization Practices (ACIP), recombinant vaccines pose no risk to breast-feeding mothers or their infants. The manufacturer recommends caution when administering to nursing mothers. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.

    Latex hypersensitivity

    Recombivax HB may be inappropriate for use by patients with latex hypersensitivity, as the vial stopper and the syringe plunger stopper and tip cap contain dry natural latex rubber that may cause allergic reactions. Also, the Engerix-B prefilled syringes may be inappropriate for use by patients with latex hypersensitivity. Engerix-B is available in 2 types of prefilled syringes: one type has a tip cap that may contain natural rubber latex, and the other type has a tip cap and a rubber plunger that contain dry natural latex rubber. Use of these syringes may cause allergic reactions in latex sensitive individuals. The vial stopper of Engerix-B does not contain latex.

    Laboratory test interference

    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.[43406]

    ADVERSE REACTIONS

    Severe

    angioedema / Rapid / 0-1.0
    erythema multiforme / Delayed / Incidence not known
    erythema nodosum / Delayed / Incidence not known
    serum sickness / Delayed / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    vasculitis / Delayed / Incidence not known
    optic neuritis / Delayed / Incidence not known
    seizures / Delayed / Incidence not known
    Guillain-Barre syndrome / Delayed / Incidence not known
    myelitis / Delayed / Incidence not known
    anaphylactic shock / Rapid / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    myocardial infarction / Delayed / Incidence not known

    Moderate

    erythema / Early / 0.2-10.0
    hypotension / Rapid / 0-1.0
    lymphadenopathy / Delayed / 0-1.0
    constipation / Delayed / 0-1.0
    neuritis / Delayed / Incidence not known
    migraine / Early / Incidence not known
    encephalopathy / Delayed / Incidence not known
    peripheral neuropathy / Delayed / Incidence not known
    dyspnea / Early / Incidence not known
    thrombocytopenia / Delayed / Incidence not known

    Mild

    injection site reaction / Rapid / 0.2-38.5
    fatigue / Early / 10.0-17.4
    headache / Early / 1.0-16.9
    fever / Early / 0.6-10.0
    dizziness / Early / 0-10.0
    myalgia / Early / 0-9.6
    malaise / Early / 1.0-9.2
    flushing / Rapid / 0-1.0
    back pain / Delayed / 0-1.0
    chills / Rapid / 0-1.0
    agitation / Early / 0-1.0
    petechiae / Delayed / 0-1.0
    arthralgia / Delayed / 0-1.0
    vertigo / Early / 0-1.0
    paresthesias / Delayed / 0-1.0
    insomnia / Early / 0-1.0
    rash / Early / 0-1.0
    urticaria / Rapid / 0-1.0
    pruritus / Rapid / 0-1.0
    alopecia / Delayed / 0-1.0
    vomiting / Early / 0-1.0
    anorexia / Delayed / 0-1.0
    dyspepsia / Early / 0-1.0
    abdominal pain / Early / 0-1.0
    irritability / Delayed / 1.0
    weakness / Early / 1.0
    nausea / Early / 1.0
    diarrhea / Early / 1.0
    ecchymosis / Delayed / Incidence not known
    tinnitus / Delayed / Incidence not known
    hypoesthesia / Delayed / Incidence not known
    lichen planus-like eruption / Delayed / Incidence not known
    purpura / Delayed / Incidence not known
    syncope / Early / Incidence not known

    DRUG INTERACTIONS

    Hepatitis B Immune Globulin, HBIG: (Minor) Administration of hepatitis B virus vaccines (e.g., hepatitis B vaccine, recombinant) at the same site or in the same syringe as hepatitis B immune globulin, HBIG can result in neutralization. Hepatitis B Immune Globulin (human) may be administered at the same time (but at a different site) or up to one month preceding hepatitis B vaccination without impairing the active immune response to hepatitis B vaccine.
    Ocrelizumab: (Moderate) Administer all non-live vaccines at least 2 weeks before ocrelizumab initiation, whenever possible. Ocrelizumab may interfere with the effectiveness of non-live virus vaccines. Attenuated antibody responses to tetanus toxoid-containing vaccine, pneumococcal polysaccharide and pneumococcal conjugate vaccines, and seasonal influenza vaccine were observed in patients exposed to ocrelizumab at the time of vaccination during an open-label study. Infants born to mothers exposed to ocrelizumab during pregnancy may receive non-live vaccines as indicated before B-cell recovery; however, consider assessing the immune response to the vaccine. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.
    Siponimod: (Moderate) Administer all non-live vaccines at least 4 weeks before siponimod initiation, whenever possible. Vaccines may be less effective if given during siponimod treatment and for 1 month after discontinuation of siponimod treatment.

    PREGNANCY AND LACTATION

    Pregnancy

    No adequate and well controlled studies have been conducted with hepatitis B vaccine, recombinant during pregnancy. In pre- and post-licensure clinical studies, 58 pregnant women who were inadvertently administrated hepatitis B vaccine, recombinant had rates of miscarriage and major birth defects that were consistent with estimated background rates. A pregnancy exposure registry of 245 women who received hepatitis A vaccine, inactivated; hepatitis B vaccine, recombinant (a bivalent vaccine containing the same hepatitis B surface antigen component and quantity as used in the hepatitis B vaccine, recombinant) during pregnancy or within 28 days prior to conception found that the rates of miscarriage and major birth defects were consistent with estimated background rates. Reproductive and developmental toxicity studies performed in rats given doses of Heplisav-B 0.3 mL revealed no vaccine-related fetal malformations or variations. Animal reproduction studies have not been conducted with Engerix-B or Recombivax HB. According to the Advisory Committee on Immunization Practices (ACIP), administration of recombinant virus vaccines to pregnant women has not resulted in adverse effects in the fetus. The ACIP recommends vaccination during pregnancy when the likelihood of disease exposure is high, potential infection would cause harm to mother or fetus, and when the vaccine is unlikely to cause harm.[43106] [43406] [43236] [62619] A pregnancy exposure registry is available for women exposed to Heplisav-B during pregnancy. Patients are encouraged to register by calling 1-844-443-7734.[62619]

    Data are limited regarding use of the hepatitis B vaccine, recombinant during breast feeding and its' excretion in human milk is unknown. According to the Advisory Committee on Immunization Practices (ACIP), recombinant vaccines pose no risk to breast-feeding mothers or their infants. The manufacturer recommends caution when administering to nursing mothers. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Many epidemiological studies indicate that patients who develop anti-hepatitis B surface antigen antibodies (anti-HBs) following infection with hepatitis B are immune to the virus upon reexposure. Active immunization with hepatitis B vaccine stimulates the immune system to produce anti-HBs without exposing the patient to the risks of active infection. Infection with hepatitis D can occur only with concurrent hepatitis B infection, so vaccination with recombinant hepatitis B vaccine provides protection against hepatitis D as well.
     
    The recombinant hepatitis B vaccine is produced by injecting Saccharomyces cerevisiae (yeast) with a plasmid that codes for the adw subtype of HBsAg. The genetically altered yeast produce significant quantities of HBsAg, which are released by cell disruption, collected, and purified. The particulate matter present in the hepatitis B vaccine, recombinant contains large amounts of protein derived from HBsAg against which an immune response occurs, resulting in the formation of anti-HBs. Extensive study of the recombinant-stimulated antibodies reveals that they are remarkably similar to naturally occurring anti-HBs in variety, biochemistry, potency, and protective efficacy.

    PHARMACOKINETICS

    Engerix-B and Recombivax HB are intended for intramuscular administration, although both can be given subcutaneously in patients where IM injections are contraindicated. Heplisav-B is administered intramuscularly. The pharmacokinetics of hepatitis B vaccine recombinant are not well understood. The exact distribution of the recombinant hepatitis B vaccines is not clear, and it is not known if HBsAg crosses the placenta or is excreted in human milk. Similarly, the metabolism and elimination of these vaccines are not well characterized.

    Intramuscular Route

    Studies evaluating plasma-derived hepatitis B vaccine reveal that anti-HBs appear in the serum 2 weeks after IM administration, peak within 6 months, and can remain detectable for 3 to 7 years. The minimum anti-HBs titer needed to provide protection against active viral infection is 10 milliunits/mL.