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  • CLASSES

    Hepatitis Vaccines

    DEA CLASS

    Rx

    DESCRIPTION

    Intramuscular, bivalent vaccine
    Used to confer immunity in adults at risk of hepatitis A virus and hepatitis B virus
    Antibody responses to this bivalent vaccine equivalent to the use of the individual vaccines

    COMMON BRAND NAMES

    Twinrix

    HOW SUPPLIED

    Twinrix Intramuscular Inj Susp: 1mL, 720-20mcg

    DOSAGE & INDICATIONS

    For hepatitis A prophylaxis and hepatitis B prophylaxis.
    Intramuscular dosage (Twinrix)
    Adults

    1 mL IM (containing 720 ELU of inactivated hepatitis A virus and 20 mcg of hepatitis B surface antigen); repeat at 1 and 6 months after initial dose. Alternatively, 1 mL IM on day 0; give the second dose of 1 mL IM on day 7 and the third dose of 1 mL IM between days 21—30 followed by a booster dose of 1 mL IM at month 12. Prior screening for hepatitis A or B before vaccine administration is not required. One study showed the combined vaccine did not lead to more frequent or worsened ADRs in 20 initially seropositive subjects.

    Children† and Adolescents

    Dosage regimen is not yet established. An initial dose of 0.5 mL IM (containing 360 ELU of inactivated hepatitis A virus and 10 mcg of hepatitis B surface antigen); repeated at 1 and 6 months after initial dose has been used. An alternative, 2-injection schedule has been used. Initial dose is 1 mL IM (containing 720 ELU of inactivated hepatitis A virus and 20 mcg of hepatitis B surface antigen); repeat at 6 months after initial dose.

    MAXIMUM DOSAGE

    Adults

    1 mL/dose IM.

    Geriatric

    1 mL/dose IM.

    Adolescents

    Safety and efficacy have not been established; 1 mL/dose IM has been used.

    Children

    Safety and efficacy have not been established; 1 mL/dose IM has been used.

    Infants

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    No dosage adjustments are needed.

    Renal Impairment

    No dosage adjustments are needed.

    ADMINISTRATION

     
    NOTE: Health care professionals administering vaccines should take appropriate precautions to prevent allergic reactions in vaccine recipients.
     
    NOTE: According to U.S. federal laws, the health care provider must record the manufacturer, lot number, date of administration, and the name and address of the person administering the vaccine in the patient's permanent record.

    Injectable Administration

    Administer intramuscularly; do not inject intravenously or intradermally.
    Visually inspect parenteral products for particulate matter and discoloration prior to administration. After thorough agitation, the injection should appear as a slightly turbid, white suspension. Discard if it appears otherwise.

    Intramuscular Administration

    Upon storage, a fine white deposit with a clear colorless layer above may be present. The vaccine should be re-suspended before withdrawal and use.
    To re-suspend the vaccine, hold the vaccine in a closed hand and shake the syringe by tipping it upside down and back upright again vigorously for at least for at least 15 seconds. If the vaccine appears as a uniform hazy white suspension, it is ready to use. If not, tip upside down and back upright again for at least another 15 seconds and inspect again.
    Attach a sterile needle to the prefilled syringe and administer intramuscularly.[30899]
    Follow the ACIP guidelines for intramuscular injection in individuals with clotting disorders.
     
    Intramuscular (IM) injection:
    Inject into a muscle in the deltoid region; do not inject into the gluteal region as this may result in a suboptimal response.
    Use the vaccine as supplied; no dilution or reconstitution is necessary. After removal of the appropriate volume from a single-dose vial, any vaccine remaining in the vial should be discarded.
    When concomitant administration of other vaccines or immunoglobulin is required they should be given with different syringes and at different injection sites.[30899]

    STORAGE

    Twinrix:
    - Discard if product has been frozen
    - 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 administration, 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 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.
     
    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 (1:1000) injection and other agents used in the treatment of severe anaphylaxis in the event of a serious allergic reaction to the hepatitis A vaccine, inactivated; hepatitis B vaccine, recombinant.
     
    For known exposures to HAV or HBV, immune globulin for intramuscular administration (IGIM) or hepatitis B immune globulin (HBIG), respectively should be given in combination with the appropriate vaccine in accordance with the ACIP recommendations. Hepatitis A vaccine, inactivated; hepatitis B vaccine, recombinant may not prevent HAV or HBV in those with an unrecognized illness at the time of vaccination. Additionally, it may not prevent HAV or HBV if adequate antibody titers are not achieved.

    Neomycin hypersensitivity, yeast hypersensitivity

    Hepatitis A vaccine, inactivated; hepatitis B vaccine, recombinant (Twinrix) is contraindicated in patients with a previous or known hypersensitivity to any component of the combination or individual vaccines including patients with yeast hypersensitivity or neomycin hypersensitivity. Anaphylaxis and anaphylactoid reactions have been reported after routine use of Twinrix.

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

    Do not give hepatitis A vaccine, inactivated; hepatitis B vaccine, recombinant via intravenous administration or intradermal administration. Patients with thrombocytopenia, vitamin K deficiency, a coagulopathy (e.g., hemophilia) or receiving anticoagulant therapy should be monitored closely when given hepatitis A vaccine, inactivated; hepatitis B vaccine because bleeding can occur at the IM injection site.

    Cardiac disease, fever, infection

    Any serious active infection including a fever is reason for delaying use of the hepatitis A vaccine, inactivated; hepatitis B vaccine, recombinant except when in the opinion of the prescriber, withholding the vaccination entails a greater risk. Caution and appropriate care should be exercised in administering the vaccine to individuals with severe 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 A vaccine, inactivated; 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, repeat doses may be required.

    Children, infants, neonates

    In the US, the safety and effectiveness of hepatitis A vaccine, inactivated; hepatitis B vaccine (Twinrix), recombinant in neonates, infants, and children < 18 years have not been established.

    Geriatric

    Adequate numbers of geriatric subjects (> 65 years of age) were not included in clinical trials to determine if geriatric populations will respond differently to hepatitis A vaccine, inactivated; hepatitis B vaccine, recombinant. The response to hepatitis B immunization is known to decline in vaccinees over age 40.

    Pregnancy

    No adequate and well controlled studies have been conducted with hepatitis A vaccine, inactivated; hepatitis B vaccine, recombinant during pregnancy. A pregnancy exposure registry of 245 women who received hepatitis A vaccine, inactivated; 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. Additionally, 45 pregnant women who were inadvertently administrated hepatitis A vaccine, inactivated; hepatitis B vaccine, recombinant in pre- and post-licensure clinical studies had no increased rates of miscarriage or major birth defects. According to the Advisory Committee on Immunization Practices (ACIP), administration of inactivated or 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. The manufacturer recommends administration to pregnant women only if clearly indicated.[30899] [43236]

    Breast-feeding

    Data are limited regarding use of the hepatitis A vaccine, inactivated; hepatitis B vaccine, recombinant during breast feeding and its' excretion in human milk is unknown. The manufacturer recommends caution when administering to nursing mothers; however, according to the Advisory Committee on Immunization Practices (ACIP), inactivated and recombinant vaccines pose no risk to breast-feeding mothers or their infant. Additionally, breast-feeding does not adversely affect immunization; limited data suggest breast-feeding may enhance the immune response to certain vaccine antigens. 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

    The hepatitis A vaccine, inactivated; hepatitis B vaccine, recombinant (Twinrix) is available in vials and 2 types of prefilled syringes. One type of prefilled syringe has a tip cap that may contain natural rubber latex. The other type has a tip cap and a rubber plunger that contain dry natural latex rubber. The vial stopper does not contain latex. Use of a prefilled syringe in someone with latex hypersensitivity may be unadvisable.

    Laboratory test interference

    Laboratory test interference may occur between the hepatitis A vaccine, inactivated; 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.[30899]

    ADVERSE REACTIONS

    Severe

    erythema nodosum / Delayed / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    erythema multiforme / Delayed / Incidence not known
    serum sickness / Delayed / Incidence not known
    vasculitis / Delayed / Incidence not known
    anaphylactic shock / Rapid / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    angioedema / Rapid / Incidence not known
    bronchospasm / Rapid / Incidence not known
    myelitis / Delayed / Incidence not known
    Guillain-Barre syndrome / Delayed / Incidence not known
    optic neuritis / Delayed / Incidence not known
    aluminum toxicity / Delayed / Incidence not known
    seizures / Delayed / Incidence not known

    Moderate

    erythema / Early / 8.0-11.0
    migraine / Early / 0-1.0
    lymphadenopathy / Delayed / Incidence not known
    dyspnea / Early / Incidence not known
    photophobia / Early / Incidence not known
    encephalopathy / Delayed / Incidence not known
    peripheral neuropathy / Delayed / Incidence not known
    neuritis / Delayed / Incidence not known
    hypertonia / Delayed / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    constipation / Delayed / Incidence not known

    Mild

    injection site reaction / Rapid / 0-41.0
    headache / Early / 13.0-22.0
    fatigue / Early / 11.0-14.0
    diarrhea / Early / 4.0-6.0
    fever / Early / 2.0-4.0
    nausea / Early / 2.0-4.0
    flushing / Rapid / 0-1.0
    back pain / Delayed / 0-1.0
    myalgia / Early / 0-1.0
    irritability / Delayed / 0-1.0
    arthralgia / Delayed / 0-1.0
    rash / Early / 0-1.0
    urticaria / Rapid / 0-1.0
    alopecia / Delayed / 0-1.0
    paresthesias / Delayed / 0-1.0
    insomnia / Early / 0-1.0
    weakness / Early / 0-1.0
    vertigo / Early / 0-1.0
    dizziness / Early / 0-1.0
    syncope / Early / 0-1.0
    anorexia / Delayed / 0-1.0
    abdominal pain / Early / 0-1.0
    vomiting / Early / 0-1.0
    malaise / Early / Incidence not known
    chills / Rapid / Incidence not known
    ecchymosis / Delayed / Incidence not known
    tinnitus / Delayed / Incidence not known
    hypoesthesia / Delayed / Incidence not known
    purpura / Delayed / Incidence not known
    dysgeusia / 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.

    PREGNANCY AND LACTATION

    Pregnancy

    No adequate and well controlled studies have been conducted with hepatitis A vaccine, inactivated; hepatitis B vaccine, recombinant during pregnancy. A pregnancy exposure registry of 245 women who received hepatitis A vaccine, inactivated; 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. Additionally, 45 pregnant women who were inadvertently administrated hepatitis A vaccine, inactivated; hepatitis B vaccine, recombinant in pre- and post-licensure clinical studies had no increased rates of miscarriage or major birth defects. According to the Advisory Committee on Immunization Practices (ACIP), administration of inactivated or 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. The manufacturer recommends administration to pregnant women only if clearly indicated.[30899] [43236]

    Data are limited regarding use of the hepatitis A vaccine, inactivated; hepatitis B vaccine, recombinant during breast feeding and its' excretion in human milk is unknown. The manufacturer recommends caution when administering to nursing mothers; however, according to the Advisory Committee on Immunization Practices (ACIP), inactivated and recombinant vaccines pose no risk to breast-feeding mothers or their infant. Additionally, breast-feeding does not adversely affect immunization; limited data suggest breast-feeding may enhance the immune response to certain vaccine antigens. 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

    Active immunization with hepatitis A and B vaccine stimulates the immune system to produce antibodies 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 hepatitis A vaccine, inactivated; hepatitis B vaccine, recombinant provides protection against hepatitis D as well.
     
    Hepatitis A vaccine, inactivated; hepatitis B vaccine, recombinant contains inactivated hepatitis A virus (HAV, strain HM175) that is propagated in MRC5 cells and combined with purified hepatitis B surface antigen (HBsAg). The purified HBsAg is obtained by culturing genetically engineered Saccharomyces cerevisiae cells, which carry the surface antigen gene of the hepatitis B virus. Natural infection with either HAV or HBV that results in adequate antibody titers provides lifelong immunity. Routine booster doses of hepatitis A and hepatitis B vaccine are not currently recommended by the ACIP, except for the use of hepatitis B vaccine boosters in hemodialysis patients.

    PHARMACOKINETICS

    Hepatitis A vaccine, inactivated; hepatitis B vaccine, recombinant is administered by intramuscular injection only.
     
    The distribution, metabolism, and elimination of these vaccines are not well characterized. Anti-HAV antibody titers >= 33 milliunits/mL are considered consistent with seroconversion; anti-HBs antibodies >= 1 milliunits/mL indicate seroconversion and titers >= 10 milliunits/mL are considered protective. Antibodies to both HAV and HBV persisted in adults for at least 4 years after the 3-dose series of hepatitis A vaccine, inactivated; hepatitis B vaccine, recombinant. In this study, immunogenicity was positive in > 95% of subjects at month two. Follow-up determined that after 4 years, 100% of evaluated subjects were positive for anti-HAV and 95.3% were protected against hepatitis B. A decline in antibody titers did occur, but titers were similar to those seen with the corresponding monovalent vaccines. The seroprotection rate for hepatitis B at month 13 after 4 doses of Hepatitis A vaccine, inactivated; hepatitis B vaccine, recombinant given on days 0, 7, 21—30, and month 12 was 96.4% (92.7—98.5). In contrast, the seroprotection rate for hepatitis B after separate vaccinations with monovalent hepatitis A vaccine at 0 and 12 months and hepatitis B vaccine at 0, 1, 2, and 12 months was 93.4% (89—96.4). The seroconversion rate for hepatitis A at month 13 was 100% (98.1—100) for both groups.