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  • CLASSES

    Hepatitis Vaccines

    DEA CLASS

    Rx

    DESCRIPTION

    Intramuscular vaccine
    Used for protection against hepatitis A
    Ideally, immunization should occur between 12 to 23 months of age

    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.
    Intramuscular dosage
    Adults 19 years and older

    1 mL IM followed by a 1 mL booster dose at least 6 months after the first dose. Complete the Havrix series 6 to 12 months apart or Vaqta series 6 to 18 months apart.

    Adults 18 years

    0.5 mL IM followed by a 0.5 mL booster dose at least 6 months after the first dose. Complete the Havrix series 6 to 12 months apart or Vaqta series 6 to 18 months apart. Catch-up vaccination may occur in patients 2 years and older, with doses separated by 6 to 18 months.

    Children and Adolescents

    0.5 mL IM ideally given at 12 to 23 months of age followed by a 0.5 mL booster dose at least 6 months after the first dose. Complete the Havrix series 6 to 12 months apart or Vaqta series 6 to 18 months apart. Catch-up vaccination may occur in patients 2 years and older, with doses separated by 6 to 18 months.

    For postexposure hepatitis A prophylaxis†.
    Intramuscular dosage
    Adults older than 19 years who have not previously received the hepatitis A vaccine

    1 mL IM as soon as possible after exposure. Efficacy when administered more than 2 weeks after exposure is not established. A second dose is not necessary for postexposure prophylaxis; however, a 1 mL booster dose can be administered at least 6 months after the first dose to complete the series. Complete the Havrix series 6 to 12 months apart or Vaqta series 6 to 18 months apart.[31413] [40356] [53026] [65007]

    Adults 18 years of age who have not previously received the hepatitis A vaccine

    0.5 mL IM as soon as possible after exposure. Efficacy when administered more than 2 weeks after exposure is not established. A second dose is not necessary for postexposure prophylaxis; however, a 0.5 mL booster dose can be administered at least 6 months after the first dose to complete the series. Complete the Havrix series 6 to 12 months apart or Vaqta series 6 to 18 months apart.[31413] [40356] [53026] [65007]

    Children and Adolescents who have not previously received the hepatitis A vaccine

    0.5 mL IM as soon as possible after exposure. Efficacy when administered more than 2 weeks after exposure is not established. A second dose is not necessary for postexposure prophylaxis; however, a 0.5 mL booster dose can be administered at least 6 months after the first dose to complete the series. Complete the Havrix series 6 to 12 months apart or Vaqta series 6 to 18 months apart.[31413] [40356] [53026] [65007]

    For patients traveling to regions that have high or intermediate hepatitis A endemicity†.
    Intramuscular dosage
    Adults 19 years and older

    1 mL IM at any time before departure; ideally, administer as soon as travel is considered.[65007] Administer a 1 mL booster at least 6 months after the first dose to complete the series. Complete the Havrix series 6 to 12 months apart or Vaqta series 6 to 18 months apart.[31413] [40356] [53026] [65007]

    Adults 18 years

    0.5 mL IM at any time before departure; ideally, administer as soon as travel is considered.[65007] Administer a 0.5 mL booster at least 6 months after the first dose to complete the series. Complete the Havrix series 6 to 12 months apart or Vaqta series 6 to 18 months apart.[31413] [40356] [53026] [65007]

    Children and Adolescents

    0.5 mL IM at any time before departure; ideally, administer as soon as travel is considered.[65007] Administer a 0.5 mL booster at least 6 months after the first dose to complete the series. Complete the Havrix series 6 to 12 months apart or Vaqta series 6 to 18 months apart.[31413] [40356] [53026] [65007]

    Infants 6 to 11 months

    0.5 mL IM before departure; revaccinate with 2 doses, separated by 6 to 18 months, between 12 to 23 months of age.[53026]

    MAXIMUM DOSAGE

    Adults

    Adults 19 years and older: 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

    Infants 6 to 11 months: 0.5 mL/dose IM is recommended by ACIP for international travel; not FDA-approved.
    Infants 5 months and younger: Safety and efficacy have not been established.

    Neonates

    Safety and efficacy have not been established.

    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 (less than 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 count at vaccination: the higher the CD4 count, the higher the likelihood of detectable anti-HAV IgG. Patients with a CD4 count less than 200 cells/mm3 were 16 times more likely to be nonresponders, and a CD4 cell count of 200 to 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. 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 A. 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 (total or anti-HAV IgG) to the hepatitis A vaccine, inactivated 1 to 2 months after completing the series. If negative, revaccinate, preferably after the CD4 count is 200 cells/mm3 or higher.

    Pregnancy

    No adequate and well-controlled studies have been conducted with the hepatitis A vaccine, inactivated during pregnancy. In pre- and post-licensure clinical studies and post-approval reports, pregnant women who were administered hepatitis A vaccine, inactivated had rates of miscarriage and major birth defects that were consistent with estimated background rates.[31413] [40356] According to the Advisory Committee on Immunization Practices (ACIP), administration of inactivated 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.[43236]

    Breast-feeding

    There is no information regarding the presence of hepatitis A vaccine, inactivated in human milk, its effects on the breast-fed infant, or its effects on milk production.[31413] [40356] According to the Advisory Committee on Immunization Practices (ACIP), inactivated vaccines pose no risk to breast-feeding mothers or their infants. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for hepatitis A vaccine, inactivated and any potential adverse effects on the breast-fed child from hepatitis A vaccine, inactivated or the underlying maternal condition.[43236] 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
    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
    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 / 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 / Early / 0-1.0
    paresthesias / Delayed / Incidence not known
    dizziness / Early / Incidence not known
    hypoesthesia / Delayed / Incidence not known
    ocular pruritus / Rapid / Incidence not known
    syncope / Early / Incidence not known

    DRUG INTERACTIONS

    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.
    Ofatumumab: (Major) Administer all needed non-live vaccines according to immunization guidelines at least 2 weeks before initiation of ofatumumab. Ofatumumab may interfere with the effectiveness of inactivated vaccines due to its actions, which cause B-cell depletion.
    Satralizumab: (Major) Administer all non-live vaccines according to immunization guidelines at least 2 weeks before initiation of satralizumab.
    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 the hepatitis A vaccine, inactivated during pregnancy. In pre- and post-licensure clinical studies and post-approval reports, pregnant women who were administered hepatitis A vaccine, inactivated had rates of miscarriage and major birth defects that were consistent with estimated background rates.[31413] [40356] According to the Advisory Committee on Immunization Practices (ACIP), administration of inactivated 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.[43236]

    There is no information regarding the presence of hepatitis A vaccine, inactivated in human milk, its effects on the breast-fed infant, or its effects on milk production.[31413] [40356] According to the Advisory Committee on Immunization Practices (ACIP), inactivated vaccines pose no risk to breast-feeding mothers or their infants. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for hepatitis A vaccine, inactivated and any potential adverse effects on the breast-fed child from hepatitis A vaccine, inactivated or the underlying maternal condition.[43236] 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

    Hepatitis A vaccine, inactivated is administered intramuscularly. 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 to 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.[24197] 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.[24196] 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 1,734 milliunits/mL.