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  • CLASSES

    Hepatitis Vaccines

    DEA CLASS

    Rx

    DESCRIPTION

    Immunization against hepatitis A virus in persons at risk; products utilize inactivated whole virus propagated in MRC5 human diploid cells.

    COMMON BRAND NAMES

    Havrix, Vaqta

    HOW SUPPLIED

    Havrix/Vaqta Intramuscular Inj Susp: 0.5mL, 1mL, 25IU, 50IU, 720ELU, 1440ELU

    DOSAGE & INDICATIONS

    For hepatitis A prophylaxis.
    For primary immunization (Havrix or Vaqta).
    Intramuscular dosage
    Adults >= 19 years of age

    1 mL/dose IM followed by a 1 mL booster dose at least 6 months after the first dose. After the first dose, the ACIP recommends series completion within 18 months; the manufacturer of Havrix recommends series completion within 1 year.

    Adults 18 years of age, Adolescents, and Children

    0.5 mL/dose IM ideally given at 12—23 months of age, followed by a 0.5 mL/dose booster dose at least 6 months after the first dose. After the first dose, the ACIP recommends series completion within 18 months; the manufacturer of Havrix recommends series completion within 1 year. Catch-up vaccination may occur in patients >= 2 years, with doses separated by 6—18 months.

    For post-exposure hepatitis A prophylaxis†.
    Intramuscular dosage
    Adults > 40 years

    Immune globulin is preferred, although 1 mL/dose of the vaccine may be used if immune globulin cannot be obtained. If needed, administer the second 1 mL hepatitis A vaccine dose at a later time to complete the series. The efficacy of the vaccine for postexposure prophylaxis is unknown in patients older than 40 years. Also, more severe manifestations of hepatitis A may occur in older patients.

    Healthy Adults 19—40 years of age who have not previously received the hepatitis A vaccine and who have been exposed to HAV

    1 mL/dose as soon as possible after HAV exposure. Efficacy when administered > 2 weeks after exposure is not established. If needed, administer a booster dose at least 6 months after the first dose to complete the series. The ACIP recommends series completion within 18 months; the manufacturer of Havrix recommends series completion within 1 year. Use immune globulin for postexposure prophylaxis in immunocompromised patients, chronic liver disease patients, and anyone who cannot get the vaccine because of contraindications.

    Healthy Adults 18 years of age, Adolescents, or Children who have not previously received the hepatitis A vaccine and who have been exposed to HAV

    0.5 mL/dose as soon as possible after HAV exposure. Efficacy when administered > 2 weeks after exposure is not established. If needed, administer a booster dose at least 6 months after the first dose to complete the series. The ACIP recommends series completion within 18 months; the manufacturer of Havrix recommends series completion within 1 year. Use immune globulin for postexposure prophylaxis in immunocompromised patients, chronic liver disease patients, and anyone who cannot get the vaccine because of contraindications.

    For patients traveling to regions that have high or intermediate hepatitis A endemicity†.
    Intramuscular dosage
    Adults > 18 years

    1 mL/dose at any time before departure. For most healthy persons, adequate protection is afforded from 1 dose. A booster dose can be given at least 6 months after the first dose to complete the series. The ACIP recommends series completion within 18 months; the manufacturer of Havrix recommends series completion within 1 year. Adults > 40 years, immunosuppressed patients, or those with chronic liver disease planning to depart in <= 2 weeks should receive an initial dose of the vaccine plus immune globulin 0.02 mL/kg at a different injection site.

    Adults 18 years of age, Adolescents, and Children

    0.5 mL/dose at any time before departure. For most healthy persons, adequate protection is afforded from 1 dose. A booster dose can be given at least 6 months after the first dose to complete the series. The ACIP recommends series completion within 18 months; the manufacturer of Havrix recommends series completion within 1 year. Immunosuppressed patients or those with chronic liver disease planning to depart in <= 2 weeks should receive an initial dose of the vaccine plus immune globulin 0.02 mL/kg at a different injection site.

    MAXIMUM DOSAGE

    Adults

    Adults >= 19 years: 1 mL/dose IM.
    Adults 18 years: 0.5 mL/dose IM.

    Geriatric

    1 mL/dose IM.

    Adolescents

    0.5 mL/dose IM.

    Children

    0.5 mL/dose IM.

    Infants

    Use not recommended.

    Neonates

    Use not recommended.

    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

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

    ADMINISTRATION

     
    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.
    Inform the patient, parent, guardian, or responsible adult of the benefits and risks of the vaccine. Provide the Vaccine Information Statements from the manufacturer to the recipient or guardian before each immunization. The action is required by the National Childhood Vaccine Injury Act of 1986. As of July 1, 2006, health care providers who administer any hepatitis A vaccine to a child or adult must provide copies of the vaccine information statement developed by the Centers for Disease Control and Prevention.
    Health care professionals administering vaccines should take appropriate precautions to prevent allergic reactions in vaccine recipients. 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.
    If a prior hepatitis A vaccine dose has been given, question the parent, guardian, or patient about any symptoms or signs of an adverse reaction after the previous dose. Complete a Vaccine Adverse Event Reporting System (VAERS) report form if adverse events have been identified. The reporting of events is required by the National Childhood Vaccine Injury Act of 1986. The toll-free number for VAERS is 1—800—822—7967. Also, report an adverse event to the manufacturer of the specific agent administered. Depending on the adverse reaction, a subsequent dose may be contraindicated.

    Injectable Administration

    Inactivated hepatitis A vaccine is administered intramuscularly; do not inject intravenously, intradermally, or subcutaneously.
    Visually inspect parenteral products for particulate matter and discoloration prior to administration. After agitation, the injection should appear as an opaque, white, homogenous suspension. Discard if it appears otherwise.

    Intramuscular Administration

    Preparation:
    The vaccine should be used as supplied; no dilution or reconstitution is necessary. 
    Shake vigorously just prior to administration. With through agitation, Harvix is a homogenous, turbid white suspension, and Vaqta is a slightly opaque, white suspension. If the vaccine cannot be resuspended or the appearance is not as described, discard it.
    Do not mix with any other vaccine or immune globulin.
    Storage of unopened vials:
    Manufacturer recommendations: Store refrigerated at 2—8 degrees C (36 to 46 degrees F); do not freeze.
    Off-label storage information: According to a 2007 published article, storage of Havrix (GlaxoSmithKline) at room temperature for up to 72 hours is acceptable, and Vaqta (Merck) can be stored at 37 degrees C (98.6 degrees F) for up to 12 months. Other sources suggest that Havrix (GlaxoSmithKline) may maintain stability for up to 3 weeks at 37 degrees C. NOTE: Because changes in vaccine formulation can affect stability and effectiveness, confirmation of acceptable duration of storage at room temperature directly from the manufacturer for the specific vaccine being administered is recommended.
     
    Intramuscular (IM) injection:
    A separate syringe and needle should be used for each person receiving hepatitis A vaccine, inactivated.
    Aspirate prior to injection to avoid injection into a blood vessel. Inject into the deltoid muscle of the upper arm. Do not inject into the gluteal region as this may result in a suboptimal response.
    When concomitant administration of other vaccines or immunoglobulin is required, they should be given with different syringes and at different injection sites.

    STORAGE

    Havrix:
    - Discard if product has been frozen
    - Do not freeze
    - Refrigerate (between 36 and 46 degrees F)
    Vaqta:
    - 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, 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 A vaccine, inactivated 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.

    Latex hypersensitivity, neomycin hypersensitivity

    Hepatitis A vaccine, inactivated 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 neomycin hypersensitivity; the vaccines contain a residual amount of neomycin from the manufacturing process. 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 the vaccine as the syringe plunger and tip caps of prefilled syringes and the vial stopper of Vaqta contain dry natural latex rubber that may cause allergic reactions; the plunger and tip caps of Havrix may also contain dry natural latex rubber. The vial stopper of Havrix does not contain latex. Epinephrine (1:1000) injection and other agents used in the treatment of severe anaphylaxis should be immediately available in the event of a serious allergic reaction to the vaccine.

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

    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 because bleeding can occur at the IM injection site. The vaccine should be given only if the potential benefits clearly outweigh the risk of administration. If the decision is made to administer the vaccine in such persons, the vaccine should be given with caution. Steps should be taken to avoid the risk of bleeding and hematoma formation following intramuscular administration.

    Fever, infection

    The decision to administer or to delay vaccination with the hepatitis A vaccine, inactivated 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 A infection. 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.

    Agammaglobulinemia, human immunodeficiency virus (HIV) infection, hypogammaglobulinemia, immunosuppression, neoplastic disease, radiation therapy, severe combined immunodeficiency (SCID)

    Patients with immunosuppression may respond to hepatitis A vaccine, inactivated with lower antibody titers than non-immunosuppressed patients. 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 (< 2 weeks) corticosteroid therapy or intra-articular, bursal, or tendon injections with corticosteroids should not be immunosuppressive. Patients vaccinated with hepatitis A vaccine, inactivated 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. Lower antibody titers are particularly a concern in patients with human immunodeficiency virus (HIV) infection, as the CD4 count at the time of vaccination has been associated with reduced development of anti-HAV IgG antibodies; however, data suggest that patients will respond to vaccination after immunologic reconstitution with highly active antiretroviral therapy. In a study, response to vaccination was directly related to the CD4 cell count at vaccination: the higher the CD4 cell count, the higher the likelihood of detectable anti-HAV IgG. Patients with a CD4 cell count less than 200 cells/mm3 were 16 times more likely to be nonresponders, and a CD4 cell count of 200—500 cells/mm3 was associated with a 2.5 increased risk of non-response. The relationship between the CD4 count and vaccination response was independent of the nadir CD4 cell count and viral load. According to the guidelines for the prevention and treatment of opportunistic infections in HIV-infected adolescents and adults, assess the IgG antibody response to the hepatitis A vaccine, inactivated one month after vaccination, and revaccinate nonresponders.

    Pregnancy

    The hepatitis A vaccine, inactivated is classified in FDA pregnancy risk category C. According to the Advisory Committee on Immunization Practices (ACIP), administration of inactivated virus vaccines to pregnant women have 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 of the vaccine to pregnant women only if clearly needed.

    Breast-feeding

    Data are limited regarding use of the hepatitis A vaccine, inactivated 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 vaccines pose no risk to breast-feeding mothers or their infants. 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.
     

    Intravenous administration, subcutaneous administration

    Hepatitis A vaccine, inactivated is only indicated for intramuscular administration; do not give via intravenous administration, subcutaneous administration, or intradermal administration. Incorrect administration may result in inadequate immunity.

    Hepatic disease

    Patients with chronic hepatic disease may have a lower antibody response to hepatitis A vaccine, inactivated. During immunogenicity studies in adults, subjects with various forms of chronic hepatic disease had lower geometric mean antibody titers 1 month following dose 1 of the vaccine (ranging from 478 milli-international units/ml for chronic hepatitis C patients to 1245 milli-international units/ml in healthy patients). One month after a booster dose given 6 months after dose 1, seroconversion rates were similar among groups. The relationship between these data and the duration of protective immunity is unknown.

    ADVERSE REACTIONS

    Severe

    seizures / Delayed / 0-1.0
    Guillain-Barre syndrome / Delayed / Incidence not known
    aluminum toxicity / Delayed / Incidence not known
    myelitis / Delayed / Incidence not known
    anaphylactic shock / Rapid / Incidence not known
    vasculitis / Delayed / Incidence not known
    angioedema / Rapid / Incidence not known
    serum sickness / Delayed / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    erythema multiforme / Delayed / Incidence not known

    Moderate

    erythema / Early / 21.2-21.2
    constipation / Delayed / 0-10.0
    lymphadenopathy / Delayed / 0-1.0
    hypertonia / Delayed / 0-1.0
    photophobia / Early / 0-1.0
    wheezing / Rapid / 0-1.0
    peripheral neuropathy / Delayed / Incidence not known
    encephalopathy / Delayed / Incidence not known
    dyspnea / Early / Incidence not known
    thrombocytopenia / Delayed / Incidence not known

    Mild

    injection site reaction / Rapid / 18.2-67.0
    irritability / Delayed / 2.8-33.3
    drowsiness / Early / 20.8-22.3
    headache / Early / 0-16.1
    fever / Early / 1.0-12.4
    fatigue / Early / 1.0-10.0
    malaise / Early / 1.0-10.0
    vomiting / Early / 0-10.0
    anorexia / Delayed / 1.0-10.0
    nausea / Early / 1.0-10.0
    insomnia / Early / 0-10.0
    myalgia / Early / 0-5.0
    diarrhea / Early / 0-4.6
    chills / Rapid / 0-1.3
    abdominal pain / Early / 0-1.2
    arthralgia / Delayed / 0-1.0
    dysgeusia / Early / 0-1.0
    vertigo / Early / 0-1.0
    pruritus / Rapid / 0-1.0
    ocular irritation / Rapid / 0-1.0
    urticaria / Rapid / 0-1.0
    rash (unspecified) / Early / 0-1.0
    paresthesias / Delayed / Incidence not known
    hypoesthesia / Delayed / Incidence not known
    dizziness / Early / Incidence not known
    ocular pruritus / Rapid / Incidence not known
    syncope / Early / Incidence not known

    DRUG INTERACTIONS

    There are no drug interactions associated with Hepatitis A Vaccine, Inactivated products.

    PREGNANCY AND LACTATION

    Pregnancy

    The hepatitis A vaccine, inactivated is classified in FDA pregnancy risk category C. According to the Advisory Committee on Immunization Practices (ACIP), administration of inactivated virus vaccines to pregnant women have 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 of the vaccine to pregnant women only if clearly needed.

    Data are limited regarding use of the hepatitis A vaccine, inactivated 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 vaccines pose no risk to breast-feeding mothers or their infants. 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

    Injection of hepatitis A vaccine produces antibodies that confer protection against hepatitis A infection. Stimulation of specific antibodies takes place without producing any disease symptoms. During the course of natural infection with the hepatitis A virus, the initial antibody response is predominantly of the IgM class. This response lasts for several months, but during convalescence antibodies of the IgG class become dominant. Patients with anti-HAV of the IgG class are immune to reinfection. The IgG antibodies remain detectable indefinitely. Two years after immunization with hepatitis A vaccine IgG levels remained relatively high in the serum of immunized patients. The duration of protection from a course of hepatitis A vaccine is as yet unknown. Long term follow-up studies will determine the necessity for booster doses of HAV.

    PHARMACOKINETICS

    Both hepatitis A vaccine products (e.g., Havrix, VAQTA) are administered by intramuscular injection.
     
    Rapid seroconversion from a single-dose can provide protection against hepatitis A for at least 12 months. Increasing the dose of viral antigen directly affects the speed at which seroconversion occurs. However, a primary response to the vaccine can be expected 8—10 days after administration. To maintain the highest antibody titers a booster dose is recommended between 6 and 18 months after the initial dose. The response to this booster dose is vigorous and increases the protection time against hepatitis A. Some investigators have postulated a minimum level of protective antibody concentration at 10 milliunits/mL. However, a concentration of 20 milliunits/mL of anti-HAV antibodies was recognized as the definition of seroconversion in clinical trials. Clinical data reveal Havrix induced an immune response in 97% of those immunized after a single dose of 720 EL.U. After a second dose, there was a 100% seroconversion rate. The lowest antibody titer needed to confer protection is unknown. Although the total duration of protection is also unknown, 100% of children at least 2 years of age and adolescents had anti-HAV antibody titers of at least 10 milliunits/mL for at least 10 years after 2 doses of VAQTA separated by 6 months. The geometric mean titers ranged from 505 milliunits/mL to 819 milliunits/mL. Among adults who got 2 doses of VAQTA separated by 6 months, the hepatitis A antibody response persisted at least 6 years; more than 99% of adults had anti-HAV antibody titers of at least 10 milliunits/mL, and the geometric mean titers ranged from 605 milliunits/mL to 1734 milliunits/mL.