Hepatitis A Vaccine

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Injection, suspension [adult, preservative free]:

Havrix: Hepatitis A virus antigen 1440 ELISA units/mL (1 mL) [contains aluminum, neomycin (may have trace amounts); may contain natural rubber/natural latex in prefilled syringe]

VAQTA: Hepatitis A virus antigen 50 units/mL (1 mL) [contains aluminum, formaldehyde, natural rubber/natural latex in packaging]

Injection, suspension [pediatric, preservative free]:

Havrix: Hepatitis A virus antigen 720 ELISA units/0.5 mL (0.5 mL) [contains aluminum, neomycin (may have trace amounts); may contain natural rubber/natural latex in prefilled syringe]

Injection, suspension [pediatric/adolescent, preservative free]:

VAQTA: Hepatitis A virus antigen 25 units/0.5 mL (0.5 mL) [contains aluminum, formaldehyde, natural rubber/natural latex in packaging]

Pharmacology

Mechanism of Action

As an inactivated virus vaccine, hepatitis A vaccine induces active immunity against hepatitis A virus infection

Pharmacokinetics/Pharmacodynamics

Onset of Action

Protective antibodies develop in 95% of adults after the first dose and in 100% of adults after the second dose of the vaccine; ≥97% of children and adolescents will be seropositive within 1 month of the first dose and 100% will develop protective antibodies after receiving two doses. The efficacy of preventing hepatitis A disease in children living in highly infected areas is 94% to 100% (CDC 2015).

Duration of Action

Protective antibodies induced by the vaccine have been observed to persist for ≥20 years (Plumb 2017; Theeten 2015).

Use: Labeled Indications

Hepatitis A virus disease prevention:

For active immunization of persons 12 months and older against disease caused by hepatitis A virus (HAV).

The Advisory Committee on Immunization Practices (ACIP) recommends routine vaccination for:

- All children ≥12 months of age (CDC/ACIP [Fiore 2006])

- All unvaccinated adults requesting protection from HAV infection (CDC/ACIP [Fiore 2006])

- Unvaccinated persons with any of the following conditions: Men who have sex with men; injection and non-injection illicit drug users; persons who work with HAV-infected primates or with HAV in a research laboratory setting; persons with chronic liver disease; patients who receive clotting-factor concentrates (CDC/ACIP [Fiore 2006]); persons ≥6 months traveling to or working in countries with high or intermediate levels of endemic HAV infection (CDC/ACIP [Nelson 2018]); patients ≥12 months of age experiencing homelessness (CDC/ACIP [Doshani 2019])

- Unvaccinated persons who anticipate close personal contact with international adoptee from a country of intermediate to high endemicity of HAV, during their first 60 days of arrival into the United States (eg, household contacts, babysitters) (CDC/ACIP 58[36] 2009)

- Vaccination can be a component of hepatitis A outbreak response, or as postexposure prophylaxis to patients ≥12 months of age within 14 days of exposure, as determined by local public health authorities (CDC/ACIP [Fiore 2006]; CDC/ACIP [Nelson 2018])

The Canadian National Advisory Committee on Immunization (NACI) also recommends vaccination for the following (NACI 2016):

- Persons ≥6 months at risk for hepatitis A infection (eg, traveling to or from endemic countries) or severe hepatitis A (eg, underlying hepatic disease of idiopathic, metabolic, infectious or cholestatic etiology)

- Infants ≥6 months living with an individual at risk for hepatitis A infection or severe hepatitis A

- Postexposure prophylaxis:

- Healthy patients ≥6 months (vaccine is preferred over immune globulin [Ig])

- Within 14 days of exposure of susceptible adults ≥60 years of age who are household or close contacts of a case (Ig may also be given)

- Susceptible individuals with chronic liver disease (Ig should also be administered within 14 days of exposure)

- May be considered in patients who receive repeat administration of plasma-derived clotting factors

Contraindications

Immediate and/or severe allergic or hypersensitivity reaction to hepatitis A containing vaccines or any component of the formulation, including neomycin.

Dosage and Administration

Dosing: Adult

Immunization: Note: Although it is preferred to use the vaccines according to their approved labeling, Havrix and VAQTA are considered to be interchangeable for booster doses (CDC/ACIP [Fiore 2006]).

Primary immunization: Note: When used for primary immunization, the vaccine should be given at least 2 weeks prior to expected hepatitis A virus (HAV) exposure. When used prior to an international adoption, the vaccination series should begin when adoption is being planned, but ideally ≥2 weeks prior to expected arrival of adoptee (CDC 58[36] 2009).

Manufacturer’s labeling:

Avaxim [Canadian product]: IM: 160 units (0.5 mL) with a booster dose of 160 units (0.5 mL) to be given 6 to 36 months following primary immunization

Havrix: IM: 1,440 ELISA units (1 mL) with a booster dose of 1,440 ELISA units (1 mL) to be given 6 to 12 months following primary immunization.

VAQTA: IM: 50 units (1 mL) with a booster dose of 50 units (1 mL) to be given 6 to 18 months after primary immunization (6 to 12 months if initial dose was with Havrix).

Postexposure prophylaxis (off-label use): Adults without immunity: IM: Administer a single dose as soon as possible following recent exposure to HAV (within 14 days); for long-term protection, complete vaccine series with a second dose ≥6 months after initial dose (CDC/ACIP [Nelson 2018]).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Consult CDC/ACIP annual immunization schedules or National Advisory Committee on Immunization (NACI) guidelines (Canada) for additional information including specific detailed recommendations for catch-up scenarios and/or care of patients with high-risk conditions. According to ACIP, doses administered ≤4 days before minimum interval or age are considered valid; however, local or state mandates may supersede this timeframe (ACIP [Kroger 2017]).

Primary immunization: Note: When used for primary immunization, the vaccine should be given at least 2 weeks prior to expected hepatitis A virus (HAV) exposure. When used prior to an international adoption, the vaccination series should begin when adoption is being planned, but at least ≥2 weeks prior to expected arrival of adoptee (CDC 58[36] 2009).

ACIP recommendations (CDC/ACIP [Fiore 2006]): Havrix, VAQTA: Note: Although it is preferred to use the vaccines according to their approved labeling, Havrix and VAQTA are considered to be interchangeable for booster doses (CDC/ACIP [Fiore 2006]).

Children 12 to 23 months: IM: 0.5 mL per dose for a total of two doses. The series should be initiated at 12 to 23 months of age; the two doses should be separated by 6 to 18 months.

Children ≥2 years and Adolescents (unvaccinated) if immunity against hepatitis A virus infection is desired: IM: 0.5 mL per dose for a total of two doses separated by 6 to 18 months.

Note: Havrix doses should be separated by 6 to 12 months; VAQTA doses should be separated by 6 to 18 months. If VAQTA is used as booster dose following primary Havrix, the VAQTA dose should be administered at 6 to 12 months post-dose immunization.

Canadian labeling: Note: Review product labeling carefully; although dose volume is the same, products differ by concentration and appropriate ages; use extra precaution to ensure accuracy.

Avaxim-Pediatric [Canadian product]: Children and Adolescents ≤15 years: IM: 0.5 mL with a booster dose of 0.5 mL to be administered ideally 6 to 36 months following primary immunization but can be administered up to 7 years following primary vaccination series. Note: The need for an additional booster dose has not been determined; anti-HAV antibodies have been observed up to 14 to 15 years following primary series with Avaxim-Pediatric in healthy subjects.

Avaxim [Canadian product]: Children ≥12 years and Adolescents: IM: 0.5 mL with a booster dose of 0.5 mL to be administered 6 to 36 months following primary immunization.

Catch-up immunization: CDC (ACIP) recommendations (CDC/ACIP [Fiore 2006]): Note: Do not restart the series. If doses have been given, begin the following schedule at the applicable dose number. Children ≥2 years and Adolescents if immunity against HAV infection is desired: IM: 0.5 mL per dose for a total of two doses separated by at least 6 months.

Preexposure prophylaxis: Infants 6 to 11 months of age: IM: 0.5 mL once, administer as soon as travel is considered. Note: Dose does not count toward primary immunization series; at 12 months of age, the full 2-dose primary immunization hepatitis A schedule should be initiated (see Primary Immunization) (CDC/ACIP [Nelson 2018]).

Postexposure prophylaxis: Children and Adolescents without immunity: IM: 0.5 mL as soon as possible following recent exposure to HAV (during last 2 weeks); immunocompromised individuals or those with chronic liver disease should also receive immune globulin. A second vaccine dose is not necessary for postexposure prophylaxis but should be considered in 6 months following initial dose to complete the hepatitis A vaccine series to ensure long-term immunity (CDC/ACIP [Nelson 2018]).

Administration

For IM administration. The deltoid muscle is the preferred site for injection. Do not administer to the gluteal region; may decrease efficacy. Do not administer intravenously, intradermally, or subcutaneously. Shake well prior to use; discard if the suspension is discolored or does not appear homogenous after shaking, or if there are cracks in the vial or syringe. Do not dilute. Do not mix with other vaccines or injections; separate needles and syringes should be used for each injection (ACIP [Kroger 2017]). To prevent syncope related injuries, patients should be vaccinated while seated or lying down (ACIP [Kroger 2017]). US law requires that the date of administration, the vaccine manufacturer, lot number of vaccine, and the administering person's name, title, and address be entered into the patient's permanent medical record.

For patients at risk of hemorrhage following intramuscular injection, the vaccine should be administered intramuscularly if, in the opinion of the physician familiar with the patient's bleeding risk, the vaccine can be administered by this route with reasonable safety. If the patient receives antihemophilia or other similar therapy, intramuscular vaccination can be scheduled shortly after such therapy is administered. A fine needle (23 gauge or smaller) can be used for the vaccination and firm pressure applied to the site (without rubbing) for at least 2 minutes. The patient should be instructed concerning the risk of hematoma from the injection. Patients on anticoagulant therapy should be considered to have the same bleeding risks and treated as those with clotting factor disorders (ACIP [Kroger 2017]).

Storage

Store refrigerated between 2°C and 8°C (36°F and 46°F). Do not freeze; discard if the product has been frozen. Extended storage information at room temperature may be available; contact product manufacturer to obtain current recommendations.

VAQTA: Canadian labeling suggests that the vaccine may be used if cumulative exposure to temperatures of 0°C to 2˚C (32°F to 36°F) or 8°C to 25˚C (46°F to 77°F) is ≤72 hours.

Drug Interactions

Fingolimod: May diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting fingolimod. If vaccinated during fingolimod therapy, revaccinate 2 to 3 months after fingolimod discontinuation. Consider therapy modification

Immunosuppressants: May diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Exceptions: Cytarabine (Liposomal). Consider therapy modification

Siponimod: May diminish the therapeutic effect of Vaccines (Inactivated). Management: Avoid administration of vaccines (inactivated) during treatment with siponimod and for 1 month after discontinuation due to potential decreased vaccine efficacy. Consider therapy modification

Venetoclax: May diminish the therapeutic effect of Vaccines (Inactivated). Monitor therapy

Adverse Reactions

All serious adverse reactions must be reported to the US Department of Health and Human Services (DHHS) Vaccine Adverse Event Reporting System (VAERS) at 1-800-822-7967 or online at https://vaers.hhs.gov/. In Canada, adverse reactions may be reported to local provincial/territorial health agencies or to the Vaccine Safety Section at Public Health Agency of Canada (1-866-844-0018).

Frequency dependent upon age, product used, and concomitant vaccine administration. In general, headache and injection site reactions were less common in younger children.

>10%:

Central nervous system: Drowsiness, headache, irritability

Gastrointestinal: Decreased appetite

Local: Erythema at injection site, injection site reaction (soreness, warmth), pain at injection site, swelling at injection site, tenderness at injection site

Neuromuscular & skeletal: Weakness

Miscellaneous: Fever (≥100.4°F [1-5 days postvaccination], >98.6°F [1-14 days postvaccination])

1% to 10%:

Central nervous system: Chills, fatigue, insomnia, malaise

Dermatologic: Skin rash

Endocrine & metabolic: Menstrual disease

Gastrointestinal: Abdominal pain, anorexia, constipation, diarrhea, gastroenteritis, nausea, vomiting

Local: Bruising at injection site, induration at injection site

Neuromuscular & skeletal: Arm pain, back pain, myalgia, stiffness

Ophthalmic: Conjunctivitis

Otic: Otitis media

Respiratory: Asthma, cough, nasal congestion, nasopharyngitis, pharyngitis, rhinitis, rhinorrhea, upper respiratory tract infection

Miscellaneous: Excessive crying, fever ≥102°F (1-5 days postvaccination)

<1%, postmarketing, and/or case reports: Anaphylaxis, angioedema, arthralgia, ataxia (cerebellar), bronchiolitis, bronchoconstriction, croup, dehydration, dermatitis, dizziness, dysgeusia, dyspnea, encephalitis, erythema multiforme, eye irritation, flu-like symptoms, Guillain-Barre syndrome, hematoma at injection site, hepatitis, hyperhidrosis, hypersensitivity reaction, hypertonia, hypoesthesia, increased creatine kinase, increased serum transaminases (transient), injection site reaction (nodule), insomnia, jaundice, lymphadenopathy, multiple sclerosis, myelitis, neuropathy, otitis, paresthesia, photophobia, pneumonia, pruritus, rash at injection site, respiratory congestion, seizure, serum sickness-like reaction, syncope, thrombocytopenia, urticaria, vasculitis, vertigo, viral exanthem, wheezing

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylactoid/hypersensitivity reactions: Immediate treatment (including epinephrine 1 mg/mL) for anaphylactoid and/or hypersensitivity reactions should be available during vaccine use (ACIP [Kroger 2017]).
• Syncope: Syncope has been reported with use of injectable vaccines and may result in serious secondary injury (eg, skull fracture, cerebral hemorrhage); typically reported in adolescents and young adults and within 15 minutes after vaccination. Procedures should be in place to avoid injuries from falling and to restore cerebral perfusion if syncope occurs (ACIP [Kroger 2017]).

Disease-related concerns:

• Acute illness: The decision to administer or delay vaccination because of current or recent febrile illness depends on the severity of symptoms and the etiology of the disease. Defer administration in patients with moderate or severe acute illness (with or without fever); vaccination should not be delayed for patients with mild acute illness (with or without fever) (ACIP [Kroger 2017]).
• Bleeding disorders: Use with caution in patients with bleeding disorders (including thrombocytopenia); bleeding/hematoma may occur from IM administration; if the patient receives antihemophilia or other similar therapy, IM injection can be scheduled shortly after such therapy is administered (ACIP [Kroger 2017]). Canadian product labeling suggests that subcutaneous administration may be considered in exceptional circumstances (eg, patients with thrombocytopenia or at risk for hemorrhage); however, this may convey a higher risk for local reactions (eg, injection site nodule). In healthy adults, seroconversion following an initial subcutaneous dose of VAQTA was slower than that historically observed following intramuscular administration (Linglöf 2001).
• Hepatic impairment: Recommended for patients with chronic liver disease; however, these patients may have decreased antibody response.

Special populations:

• Altered immunocompetence: Consider deferring immunization during periods of severe immunosuppression (eg, patients receiving chemo/radiation therapy or other immunosuppressive therapy [including high-dose corticosteroids]); may have a reduced response to vaccination. An exception when administration should not be delayed may include use of the hepatitis A vaccine for preexposure prophylaxis prior to international travel to certain areas (CDC/ACIP [Nelson 2018]). In general, household and close contacts of persons with altered immunocompetence may receive all age-appropriate vaccines. Inactivated vaccines should be administered ≥2 weeks prior to planned immunosuppression when feasible; inactivated vaccines administered during chemotherapy should be readministered after immune competence is regained (ACIP [Kroger 2017]; IDSA [Rubin 2014]).

Concurrent drug therapy issues:

• Anticoagulant therapy: Use with caution in patients receiving anticoagulant therapy; bleeding/hematoma may occur from IM administration (ACIP [Kroger 2017]).
• Vaccines: In order to maximize vaccination rates, the ACIP recommends simultaneous administration (ie, >1 vaccine on the same day at different anatomic sites) of all age-appropriate vaccines (live or inactivated) for which a person is eligible at a single clinic visit, unless contraindications exist. The use of combination vaccines is generally preferred over separate injections, taking into consideration provider assessment, patient preference, and adverse events. When using combination vaccines, the minimum age for administration is the oldest minimum age for any individual component; the minimum interval between dosing is the greatest minimum interval between any individual components. The ACIP prefers each dose of a specific vaccine in a series come from the same manufacturer when possible (ACIP [Kroger 2017]).

Dosage form specific issues:

• Latex: Packaging may contain natural latex rubber.
• Neomycin: Some products may contain neomycin.

Other warnings/precautions:

• Antipyretics: Antipyretics have not been shown to prevent febrile seizures; antipyretics may be used to treat fever or discomfort following vaccination (ACIP [Kroger 2017]). One study reported that routine prophylactic administration of acetaminophen prior to vaccination to prevent fever decreased the immune response of some vaccines; the clinical significance of this reduction in immune response has not been established (Prymula 2009).
• Appropriate use: Use of this vaccine for specific medical and/or other indications (eg, immunocompromising conditions, hepatic or kidney disease, diabetes) is also addressed in the annual ACIP Recommended Immunization Schedules (refer to CDC schedule for detailed information). Specific recommendations for vaccination in immunocompromised patients with asplenia, cancer, HIV infection, cerebrospinal fluid leaks, cochlear implants, hematopoietic stem cell transplant (prior to or after), sickle cell disease, solid organ transplant (prior to or after), or those receiving immunosuppressive therapy for chronic conditions as well as contacts of immunocompromised patients are available from the IDSA (Rubin 2014).
• Effective immunity: Vaccination may not result in effective immunity in all patients. Response depends upon multiple factors (eg, type of vaccine, age of patient) and is improved by administering the vaccine at the recommended dose, route, and interval. Vaccines may not be effective if administered during periods of altered immune competence (ACIP [Kroger 2017]). Due to the long incubation period for hepatitis A (15 to 50 days), unrecognized hepatitis A infection may be present; immunization may not prevent infection in these patients.

Monitoring Parameters

Liver function tests; monitor for anaphylaxis and syncope for 15 minutes following administration (ACIP [Kroger 2017]). If seizure-like activity associated with syncope occurs, maintain patient in supine or Trendelenburg position to reestablish adequate cerebral perfusion.

Pregnancy

Pregnancy Considerations

The safety of vaccination during pregnancy has not been determined; however, the theoretical risk to the infant is expected to be low (CDC/ACIP [Fiore 2006]). Based on limited data, an increased risk for miscarriage or major birth defects has not been observed following maternal vaccination during the first or second trimester. Inactivated vaccines have not been shown to cause increased risks to the fetus (ACIP [Kroger 2017]). Refer to current immunization schedule for vaccinating pregnant females.

Patient Education

What is this drug used for?

• It is used to prevent hepatitis A infection.

Frequently reported side effects of this drug

• Headache
• Loss of strength and energy
• Nausea
• Injection site pain, redness, swelling, or irritation
• Irritability (children)
• Fatigue (children)
• Lack of appetite

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Burning or numbness feeling
• Abnormal movements
• Severe dizziness
• Passing out
• High fever
• Vision changes
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.