Hepatitis A Virus Vaccine Inactivated (Monograph)

Brand names: Havrix, Vaqta
Drug class: Vaccines
ATC class: J07BC02
VA class: IM100

Medically reviewed by Drugs.com on Dec 22, 2023. Written by ASHP.

Introduction

Inactivated virus vaccine.^{1 39 47 55 115 171} Hepatitis A virus vaccine inactivated contains cell culture-adapted, attenuated hepatitis A virus (HAV) and is used to stimulate active immunity to HAV infection.^{1 39 47 55 115 171} Commercially available in the US as monovalent vaccines (HepA; Havrix, Vaqta)^{1 171} and in a fixed-combination vaccine with hepatitis B vaccine (HepA-HepB; Twinrix).¹⁸⁶

Uses for Hepatitis A Virus Vaccine Inactivated

Prevention of Hepatitis A Virus (HAV) Infection

Prevention of HAV infection in adults, adolescents, and children ≥1 year of age.^{1 3 22 110 132 171 192 195 196}

Although HAV infection may be asymptomatic or relatively mild in many patients, it can result in substantial morbidity and associated health-care costs and work loss (11–22% of patients require hospitalization) and may be associated with fulminant hepatitis and hepatic failure.^{38 59 63 75 132 203} Overall HAV case-fatality rate in the US is 0.3–0.6%, but increases to about 2% in those ≥40 years of age.^{192 203} HAV is highly contagious (especially during the 2 weeks before onset of symptoms).^{4 16 21 30 32 37 42 50 57 58 85 91 92 94 97 110 120 132 203} The virus is transmitted person-to-person, principally through the fecal-oral route.^{1 4 16 21 30 32 37 42 50 57 58 85 91 92 94 97 110 120 132 171 203} HAV infection remains one of the most commonly reported vaccine-preventable diseases in travelers.^{167 192}

USPHS Advisory Committee on Immunization Practices (ACIP), AAP, and American Academy of Family Physicians (AAFP) recommend that all children be vaccinated against HAV infection at 1 year of age (i.e., 12 through 23 months of age), unless contraindicated.^{3 132 192} (See Contraindications under Cautions.)

ACIP, AAP, AAFP, American College of Obstetricians and Gynecologists (ACOG), and American College of Physicians (ACP) also recommend vaccination against HAV for all previously unvaccinated children, adolescents, and adults at high risk of exposure to HAV (see Preexposure Vaccination Against HAV Infection in High-risk Groups under Uses) and for any other unvaccinated individual desiring protection from HAV infection.^{3 132 192 195 196}

For internationally adopted children whose immune status is uncertain, vaccinations can be repeated or serologic tests performed to confirm immunity.^{60 167} For HepA vaccine, ACIP states that the simplest approach is to revaccinate according to the US recommended immunization schedule if child is ≥12 months of age.⁶⁰ (See Dosage and Administration.) Alternatively, test for serologic evidence of susceptibility to HAV.⁶⁰ (See Pre-and Postvaccination Serologic Testing under Cautions.) When a child is being adopted from a country with high or intermediate HAV endemicity, ACIP states that all previously unvaccinated individuals who anticipate close personal contact with the adoptee during the child’s initial 60 days in the US (e.g., household members, regular babysitters) should receive routine vaccination with HepA vaccine, with the first dose given as soon as adoption is planned (ideally ≥2 weeks before the child’s arrival).²⁰⁹ CDC website ([Web]) has information regarding which countries have high or intermediate levels of HAV endemicity.¹⁶⁷

HepA vaccine will not prevent hepatitis caused by other infectious agents (e.g., hepatitis B virus [HBV], hepatitis C virus [HCV], hepatitis E virus [HEV]).^{1 171}

When vaccination against both HAV and HBV infection is indicated in adults ≥18 years of age, the commercially available fixed-combination vaccine containing HepA vaccine and hepatitis B vaccine (HepA-HepB; Twinrix) can be used.^{186 192} ACIP, AAP, and AAFP state that use of a combination vaccine generally is preferred over separate injections of the equivalent component vaccines;^{3 208} considerations should include provider assessment (e.g., number of injections, vaccine availability, likelihood of improved coverage, likelihood of patient return, storage and cost considerations), patient preference, and potential for adverse effects.^{3 208} However, the HepA-HepB (Twinrix) fixed-combination vaccine should not be used for HAV postexposure prophylaxis.¹⁹⁶ (See Use of Fixed Combinations under Cautions.)

Preexposure Vaccination Against HAV Infection in High-risk Groups

Preexposure vaccination in previously unvaccinated children, adolescents, or adults who are or will be at high risk of exposure to HAV or are at high risk of developing fulminant hepatitis and hepatic failure if they become infected with HAV.^{3 132 167 192 195 196}

ACIP, AAP, AAFP, and others recommend preexposure vaccination in previously unvaccinated children ≥12 months of age who reside in states, counties, or communities where the rate of HAV infection is high and in unvaccinated travelers, unvaccinated household or sexual contacts of an individual with confirmed HAV infection, and unvaccinated individuals at risk because of their occupation or high-risk behavior.^{1 3 45 59 74 76 110 149 171 177 192 195 196}

If HepA vaccine cannot be used because it is contraindicated or unavailable and short-term protection against HAV is needed, preexposure passive immunization with IGIM is recommended.^{26 32 37 40 42 59 74 107 128 132 161 167 196}

In states, counties, or communities where the rate of HAV infection is high, ACIP recommends that existing selective preexposure HepA vaccination programs for children 2 through 18 years of age be maintained.¹⁹² In such areas, new efforts focused on routine vaccination of all children at 1 year of age should enhance, not replace, ongoing programs directed at a broader population of children.¹⁹² In areas without existing selective vaccination programs, catch-up vaccination of unvaccinated children 2 through 18 years of age may be considered.¹⁹² Such catch-up vaccination programs may be especially warranted because of rising incidence or ongoing outbreaks of HAV among children or adolescents.¹⁹²

HIV-infected individuals, especially those with chronic liver disease (including those coinfected with HBV or HCV), should be vaccinated against HAV.^{197 198} ACIP, AAP, CDC, National Institutes of Health (NIH), Infectious Diseases Society of America (IDSA), Pediatric Infectious Diseases Society, and others recommend that HAV-susceptible, HIV-infected adults, adolescents, and children receive HepA vaccine.^{197 198} Consider that the vaccine may be less immunogenic in immunocompromised individuals.^{60 159 187 192} (See Individuals with Altered Immunocompetence under Cautions.)

Travelers to areas with intermediate to high levels of endemic HAV are at risk of exposure to the disease, and ACIP, CDC, WHO, and others recommend preexposure vaccination against HAV for such individuals.^{13 22 59 63 90 97 110 167 176 192 196} CDC states vaccination against HAV can be considered in individuals traveling to any destination.¹⁶⁷ CDC website ([Web]) has information regarding which countries have high or intermediate levels of HAV endemicity.¹⁶⁷ Risk of acquiring HAV while traveling varies with living conditions, length of stay, and incidence of HAV infection in the area visited.¹⁶⁷ Consider that many cases of HAV occur in travelers to developing countries with standard tourist itineraries, accommodations, and food consumption behaviors.¹⁶⁷ Ideally, the first dose of HepA vaccine should be administered as soon as travel to countries with high or intermediate HAV endemicity is considered.^{167 196} (See Preexposure Vaccination Against HAV Infection in High-risk Groups under Pediatric Patients and also Adults, in Dosage and Administration.) Alternatively, if the vaccine is contraindicated or cannot be used, passive immunization with a single dose of IGIM may provide protection for up to 3 months.^{167 196} For optimal protection in travelers at greatest risk for HAV (older adults or individuals with altered immunocompetence, chronic liver disease, or other chronic medical condition) who plan to depart in <2 weeks, a dose of IGIM should be given concomitantly with the initial dose of HepA vaccine (at a different site).¹⁶⁷ ACIP states that the fixed-combination vaccine containing HepA vaccine and HepB vaccine (HepA-HepB; Twinrix) should not be used for preexposure vaccination in travelers who will depart within 2 weeks.^{192 196} (See Use of Fixed Combinations under Cautions.)

Household and sexual contacts of individuals with confirmed HAV infection are at increased risk of exposure to HAV.^{21 192} Sexually active male adolescents and adults who have sex with men (homosexual, bisexual) should be vaccinated against HAV.^{2 110 179 192} Primary-care clinicians and those in specialty medical settings should offer the vaccine to such individuals; strategies to increase coverage (e.g., use of standing orders) should be considered.¹⁹²

Individuals who illicitly use injectable or noninjectable drugs may be at increased risk of exposure to HAV infection and should be vaccinated against HAV.^{63 74 76 97 192} Clinicians should obtain a complete history to identify individuals who might benefit from HepA vaccination (e.g., those who use illicit drugs or who are at increased risk for such drug use).¹⁹² Clinicians should consider implementing strategies to increase vaccine coverage in these patients (e.g., use of standing orders).¹⁹²

Individuals with hemophilia or other congenital bleeding disorders who are HAV-seronegative should be vaccinated against HAV.^{18 61 195} Improved donor screening, more effective viral-inactivation procedures, and/or purification or filtration procedures have reduced, but not completely eliminated, the risk of pathogen transmission from plasma-derived clotting factors.¹⁹² Therefore, recipients of blood products (e.g., whole blood, packed RBCs, plasma) and plasma-derived preparations (e.g., albumin human, antihemophilic factor [human], anti-inhibitor coagulant complex, factor IX [human], factor IX complex) may be at increased risk of HAV infection.^{18 61 64 65 66 67 68 70 100 101 102 138 165 168 169 192}

Workers handling HAV-infected nonhuman primates and workers in contact with live HAV in a research laboratory setting should be vaccinated against HAV.^{67 99 108 110 192} Routine vaccination against HAV is not currently recommended for other occupational groups in the US.¹⁹²

Individuals with chronic liver disease and those who are awaiting or have undergone liver transplantation should be vaccinated against HAV.^{132 192} Although individuals with chronic liver disease are not at increased risk of acquiring HAV infection, such individuals are at increased risk of severe consequences of HAV infection, including fatal fulminant hepatitis and hepatic failure.^{16 74 103 110 192}

Some clinicians recommend that individuals with HBV or HCV infection, autoimmune hepatitis, or primary biliary cirrhosis be vaccinated against HAV.^{132 177} ACIP states that current data do not support routine vaccination of individuals who have chronic HBV or HCV infection but do not have evidence of chronic liver disease.¹⁹²

Food handlers and restaurant employees may be vaccinated against HAV.^{84 177 192} Vaccination may be considered in restaurant employees in areas where state and local health authorities or private employers have determined that such vaccination is indicated to decrease the frequency of HAV evaluations of food handlers and decrease the need for HAV postexposure prophylaxis in restaurant patrons.^{84 177 192} Under these circumstances, a record of HepA vaccination should be provided to vaccinated food handlers, those not vaccinated should be informed of the signs and symptoms of HAV infection, and all food handlers should be instructed on food preparation practices that reduce risk of fecal contamination.¹⁹² Routine use of HepA vaccine in all food handlers is not economically feasible from a societal or food industry perspective.^{84 177 192} Occasionally, vaccination of food handlers may be considered during a community outbreak.^{110 177 192}

Incarcerated adolescents in correctional facilities located in states with existing HepA vaccination programs for adolescents should receive HepA vaccine.¹³² Because of the likelihood that adolescents in juvenile correctional systems have indications for the vaccine, other correctional facilities also should consider routine HepA vaccination of all adolescents under their care.¹³² Test those with signs or symptoms of hepatitis for acute HAV, HBV, and HCV infection.¹³² Report those with HAV to the local health department and give appropriate postexposure prophylaxis with HepA vaccine to susceptible exposed residents.¹³²

If a community-wide outbreak of HAV occurs, accelerated HepA vaccination programs should be considered.¹⁹² A decision to initiate an outbreak-control vaccination program should take into account the feasibility of rapidly vaccinating the target population of children, adolescents, or young adults, and the costs associated with such a program.¹⁹² Routine vaccination of children in affected communities should continue in order to maintain high levels of immunity and prevent future epidemics.¹⁹²

HAV outbreaks in child-care centers have decreased considerably since the implementation of routine childhood immunization against HAV and further decreases are expected.¹⁹² ACIP does not recommend routine preexposure vaccination with HepA vaccine for personnel in child-care centers.¹⁹² However, HAV postexposure prophylaxis may be indicated if HAV is reported in attendees or staff.¹⁹⁶ (See Postexposure Prophylaxis of HAV Infection under Uses.)

ACIP does not recommend routine preexposure vaccination with HepA vaccine in hospitals or schools and institutions for the developmentally disabled because the frequency of outbreaks in these institutions is not high enough to warrant such recommendations.¹⁹² Outbreaks involving student-to-student transmission in primary and secondary schools are rare in developed countries, but outbreaks have been documented;^{32 132 161 192} in developing countries, outbreaks among children in primary schools are more common.^{7 151 161} If an epidemiologic investigation indicates HAV transmission has occurred among students in a school or among patients or between patients and staff in a hospital, HAV postexposure prophylaxis should be administered to individuals who have close contact with index patients.^{107 132 192 196} (See Postexposure Prophylaxis of HAV Infection under Uses.)

ACIP and Hospital Infection Control Practices Advisory Committee (HICPAC) state that routine preexposure vaccination with HepA vaccine or routine use of HAV postexposure prophylaxis in health-care personnel providing care to patients with HAV infection is not indicated.^{178 192} Instead, hygienic practices should be emphasized and health-care personnel should be made aware of the risk of exposure to HAV and precautions regarding direct contact with potentially infective materials.^{178 192} In documented outbreaks of HAV infection, HAV postexposure prophylaxis may be indicated in health-care workers and others who have close contact with the infected individuals.¹⁷⁸ (See Postexposure Prophylaxis of HAV Infection under Uses.) The usefulness of HepA vaccine in controlling outbreaks in health-care settings has not been investigated.¹⁷⁸

Postexposure Prophylaxis of HAV Infection

Postexposure prophylaxis of HAV^{† [off-label]} in susceptible individuals with recent (within 2 weeks) exposure to HAV.^{132 178 179 192 196}

The choice of active immunization with HepA vaccine and/or passive immunization with IGIM for postexposure prophylaxis should take into account the magnitude of risk associated with the exposure and characteristics of the patient that may be associated with more severe manifestations of HAV (e.g., older age, chronic liver disease).^{132 178 179 192 196}

Although IGIM was traditionally the recommended regimen for HAV postexposure prophylaxis since it is 80–90% effective if administered within 2 weeks of exposure,¹⁹⁶ there is some evidence that monovalent HepA vaccine administered within 2 weeks of exposure may be as effective as IGIM in healthy individuals 1–40 years of age.^{196 199} The vaccine also offers certain advantages over IGIM (e.g., induces active immunity and longer protection, more readily available, easier to administer, greater patient acceptance).^{196 199}

For HAV postexposure prophylaxis in healthy individuals 12 months to 40 years of age, ACIP prefers use of monovalent HepA vaccine.¹⁹⁶ In adults >40 years of age, ACIP prefers use of IGIM since data not available to date regarding efficacy of the vaccine for postexposure prophylaxis in this age group and these individuals are at risk of more severe manifestations of HAV; the vaccine can be used if IGIM cannot be obtained.¹⁹⁶ IGIM should be used for HAV postexposure prophylaxis in children <12 months of age, immunocompromised individuals, individuals with chronic liver disease, and whenever the vaccine is contraindicated.¹⁹⁶

In those individuals in whom IGIM is preferred for HAV postexposure prophylaxis, a dose of HepA vaccine should be given simultaneously (using different syringes and different injection sites) if the vaccine is indicated for other reasons (e.g., catch-up vaccination, preexposure vaccination in high-risk groups) and is not contraindicated.¹⁹⁶ If a dose of HepA vaccine is used with or without IGIM for HAV postexposure prophylaxis, a second (booster) dose of the vaccine should be administered according to the usually recommended schedule to ensure long-term protection.^{192 196} (See Dosage under Dosage and Administration.)

Monovalent HepA vaccine (Havrix, Vaqta) should be used when active immunization is indicated for HAV postexposure prophylaxis.¹⁹⁶ Data not available to date regarding efficacy of the fixed-combination vaccine containing HepA vaccine and HepB vaccine (HepA-HepB; Twinrix) for postexposure prophylaxis.¹⁹⁶ (See Use of Fixed Combinations under Cautions.)

If HAV postexposure prophylaxis is indicated, administer as soon as possible (within 2 weeks of exposure).^{192 196} Data not available regarding efficacy of HAV postexposure prophylaxis administered >2 weeks after exposure.¹⁹⁶

HAV postexposure prophylaxis is indicated in all previously unvaccinated individuals who have had household or sexual contact (within the last 2 weeks) with an individual with serologically confirmed HAV.¹⁹⁶ Also consider HAV postexposure prophylaxis for individuals exposed (within the last 2 weeks) through other types of ongoing, close personal contact (e.g., regular babysitting).¹⁹⁶

Contacts who have shared illicit drugs (within the last 2 weeks) with an individual with serologically confirmed HAV should receive HAV postexposure prophylaxis.¹⁹⁶

Administer HAV postexposure prophylaxis to all previously unvaccinated staff and attendees of child-care centers or homes if ≥1 case of HAV is recognized in children or employees or if HAV is recognized in ≥2 households of center attendees (within the last 2 weeks).¹⁹⁶ In centers that do not provide care to children who wear diapers, HAV postexposure prophylaxis is indicated only in classroom contacts of the index patient.¹⁹⁶ If an outbreak occurs (i.e., HAV in ≥3 families), HAV postexposure prophylaxis should also be considered for members of households that have diapered children attending the center.¹⁹⁶

If HAV is diagnosed in a food handler, ACIP recommends HAV postexposure prophylaxis (within 2 weeks) for other food handlers at the same establishment.¹⁹⁶ Because common-source transmission to patrons is unlikely, HAV postexposure prophylaxis is not usually indicated for restaurant patrons, but may be considered if the food handler directly handled uncooked or cooked food and had diarrhea or poor hygienic practices and if patrons can be identified and treated within 2 weeks of exposure.¹⁹⁶ Settings where repeated HAV exposure might have occurred (e.g., institutional cafeterias) warrant stronger consideration of postexposure prophylaxis for patrons.¹⁹⁶

When an individual with HAV is admitted to a hospital, health-care personnel do not need to receive routine HAV postexposure prophylaxis; careful hygienic practices should be emphasized in such situations.¹⁹⁶

If an epidemiologic investigation indicates that HAV transmission has occurred among students in a school or among hospital patients and/or hospital staff, ACIP recommends HAV postexposure prophylaxis in individuals who have close contact with index patients.¹⁹⁶

Routine HAV postexposure prophylaxis is not indicated when a single HAV case occurs in an elementary or secondary school or an office or other work setting and the source case is outside the school or work setting.¹⁹⁶

HAV postexposure prophylaxis is not usually indicated after a common-source HAV outbreak if cases have begun to occur because the 2-week period when such prophylaxis is known to be effective will have been exceeded.¹⁹⁶

Related/similar drugs

Havrix, Twinrix, hepatitis a adult vaccine, Vaqta

Hepatitis A Virus Vaccine Inactivated Dosage and Administration

Administration

IM Injection

Administer monovalent HepA vaccine (Havrix, Vaqta) by IM injection.^{1 171}

Administer fixed-combination vaccine containing HepA vaccine and HepB vaccine (HepA-HepB; Twinrix) by IM injection.¹⁸⁶

Do not administer IV, intradermally, or sub-Q.^{1 171}

Shake vaccine well immediately prior to administration to provide a uniform, slightly turbid, white, suspension.^{1 171 186 200} Discard vaccine if there are cracks in the vial or syringe or if it contains particulates, appears discolored, or cannot be resuspended with thorough agitation.^{1 171 200}

Do not dilute.^{1 186} Do not mix with any other vaccine or solution.^{1 60 171 186}

To ensure delivery into muscle, IM injections should be made at a 90° angle to the skin⁶⁰ using a needle length appropriate for the individual’s age and body mass, thickness of adipose tissue and muscle at the injection site, and injection technique.^{60 206 207} Consider anatomic variability, especially in the deltoid; use clinical judgment to avoid inadvertent underpenetration or overpenetration of muscle.^{206 207}

For adults, administer IM into the deltoid muscle.^{1 60} For children 1–2 years of age, IM injections should preferably be administered into the anterolateral thigh;^{1 60} deltoid muscle is an alternative if muscle mass is adequate.⁶⁰ For children and adolescents 3–18 years of age, deltoid muscle is preferred,^{1 60} although anterolateral thigh is an alternative.⁶⁰

Generally do not administer vaccines into buttock muscle in children because of potential for injection-associated injury to sciatic nerve.⁶⁰ In addition, studies in adults indicate suboptimal immunologic response may occur if HepA vaccine is injected into gluteal muscle.^{1 60}

Although some experts state that aspiration (i.e., pulling back on the syringe plunger after needle insertion and before injection) can be performed to ensure that a blood vessel has not been entered, ACIP and AAP state this procedure is not required because large blood vessels are not present at recommended IM injection sites.^{60 132}

Since syncope may occur following vaccination, observe vaccinees for approximately 15 minutes after the dose.⁶⁰ Syncope occurs most frequently in adolescents and young adults.⁶⁰ If syncope occurs, observe patient until symptoms resolve.⁶⁰

May be given simultaneously with IGIM (using different syringes and different injection sites) when passive immunization is considered necessary in addition to active immunization with the vaccine (e.g., in travelers who will depart within 2 weeks).^{1 60 132 171 192 196} (See Interactions.)

May be given simultaneously with other age-appropriate vaccines during the same health-care visit (using different syringes and different injection sites).^{60 132 192} (See Interactions.)

When multiple vaccines are administered during a single health-care visit, each vaccine should be given with a different syringe and at different injection sites.⁶⁰ Separate injection sites by at least 1 inch (if anatomically feasible) to allow appropriate attribution of any local adverse effects that may occur.⁶⁰ If multiple vaccines must be given into a single limb, the deltoid may be used in older children and adults, but the thigh is preferred in younger children.⁶⁰

Dosage

Dose and dosing schedule vary according to the individual’s age and specific vaccine administered.^{1 171 186} Follow dosage recommendations for the specific preparation used.¹⁹²

Whenever possible, the HepA monovalent vaccine used for the initial dose should be used for subsequent doses in the same individual.¹⁹² However, ACIP and AAP state that the currently available monovalent formulations may be considered interchangeable.^{60 132 192}

For both monovalent vaccines, the minimum interval between the first and second dose is 6 months.^{1 3 171 192} Dosage for the second (booster) dose should be based on the individual’s age at the time the second dose is given.²⁰³ Although only limited data are available regarding the immune response to delayed administration of the second dose,¹⁹² some experts state it is not necessary to repeat the first dose if the interval between the first and second dose extends beyond 18 months.²⁰³

When vaccination against both HAV and HBV infection is indicated in adults ≥18 years of age, the commercially available fixed-combination vaccine containing HepA vaccine and HepB vaccine (HepA-HepB; Twinrix) can be used.^{186 192}

Pediatric Patients

Prevention of Hepatitis A Virus (HAV) Infection

Children and Adolescents 12 Months through 18 Years of Age (Havrix)

Primary immunization consists of 2 doses given 6–12 months apart.^{1 3 192}

Give initial dose of 720 units.^{1 132 192} Give second (booster) dose of 720 units at 6–12 months after initial dose.^{1 192}

ACIP, AAP, and AAFP recommend that the initial dose be given routinely to all children at 1 year of age (i.e., 12 through 23 months of age) and that the second dose be given at least 6 months after the initial dose.³

Children not fully vaccinated by 2 years of age can be vaccinated at subsequent health-care visits.³ ACIP recommends that catch-up vaccination be considered for children 2 through 18 years of age in areas without existing selective preexposure HepA vaccination programs.¹⁹²

If a different HepA vaccine (e.g., Vaqta) was used for the initial dose, a booster dose of Havrix may be given 6–18 months after the initial dose of the other vaccine.¹⁹² However, whenever possible, the formulation chosen for the initial dose should be used for the booster dose in the same individual.¹⁹²

Duration of immunity and need for subsequent doses after the initial dose and additional (booster) dose not fully determined.^{1 2 6 7 23 33 41 46 49 74 76 77 84 145 149 150 155 192} (See Duration of Immunity under Cautions.) Subsequent booster doses not recommended.¹⁹²

Children and Adolescents 12 Months through 18 Years of Age (Vaqta)

Primary immunization consists of 2 doses given 6–18 months apart.^{3 171 192} Use pediatric/adolescent formulation containing 25 units/0.5 mL.¹⁷¹

Give initial dose of 25 units.^{132 171 192} Give second (booster) dose of 25 units 6–18 months after initial dose.¹⁷¹

ACIP, AAP, and AAFP recommend that the initial dose be given routinely to all children at 1 year of age (i.e., 12 through 23 months of age) and that the second dose be given at least 6 months after the initial dose.³

Children not fully vaccinated by 2 years of age can be vaccinated at subsequent health-care visits.³ ACIP recommends that catch-up vaccination be considered for children 2 through 18 years of age in areas without existing selective preexposure HepA vaccination programs.¹⁹²

If a different HepA vaccine (e.g., Havrix) was used for the initial dose, a booster dose of Vaqta may be given 6–12 months after the initial dose of the other vaccine.^{171 192} However, whenever possible, the formulation chosen for the initial dose should be used for the booster dose in the same individual.¹⁹²

Duration of protection and need for subsequent doses after the initial dose and second (booster) dose not fully determined.^{2 6 7 23 33 41 46 49 74 76 77 84 145 149 150 155 171 192} (See Duration of Immunity under Cautions.) Subsequent booster doses not recommended.¹⁹²

Preexposure Vaccination Against HAV Infection in High-risk Groups

Children and Adolescents 12 Months through 18 Years of Age (Havrix or Vaqta)

Primary immunization with the usually recommended age-appropriate initial and second (booster) doses before an expected exposure to HAV ensures the highest level of protection.^{1 148 158 171 192 196} (See Prevention of Hepatitis A Virus (HAV) Infection under Dosage and Administration.) Those who have received at least 1 dose given 1 month prior to an exposure probably will be protected.^{167 192 196}

For individuals who plan to travel or work in areas with intermediate to high levels of endemic HAV (see Preexposure Vaccination Against HAV Infection in High-risk Groups under Uses), give first vaccine dose as soon as travel is considered.^{167 196} For most healthy children, a single dose will provide adequate protection regardless of the scheduled departure date.^{167 196} To ensure protection in immunocompromised individuals or those with chronic liver disease or other chronic medical conditions who plan to depart within 2 weeks, give initial vaccine dose and simultaneously (using a different syringe and different injection site) give a single dose of IGIM (0.02 mL/kg).^{167 196}

Postexposure Prophylaxis of HAV Infection† [off-label]

Children and Adolescents 12 Months through 18 Years of Age (Havrix or Vaqta)

Give an age-appropriate dose of vaccine alone or in conjunction with a dose of IGIM (0.02 mL/kg) as soon as possible.¹⁹⁶ Efficacy of HAV postexposure prophylaxis not established if given >2 weeks after exposure.¹⁹⁶ (See Postexposure Prophylaxis of HAV Infection under Uses.)

In previously unvaccinated individuals, give primary immunization with the usually recommended age-appropriate initial and second (booster) doses of the vaccine.^{1 107 111 128 171 192} (See Prevention of Hepatitis A Virus (HAV) Infection under Dosage and Administration.) The first vaccine dose can be administered simultaneously with IGIM (using different syringes and different injection sites).^{1 107 111 128 171 192}

Individuals who have received at least 1 vaccine dose at least 1 month prior to the current HAV exposure do not need to receive postexposure prophylaxis with IGIM.^{179 192}

Adults

Prevention of Hepatitis A Virus (HAV) Infection

Adults ≥19 Years of Age (Havrix)

Primary immunization consists of 2 doses given 6–12 months apart.^{1 192}

Give initial dose of 1440 units.^{1 171 192} Give second (booster) dose of 1440 units 6–12 months after initial dose.^{1 192}

If a different HepA vaccine (e.g., Vaqta) was used for the initial dose, a booster dose of Havrix may be given 6–12 months after the initial dose of the other vaccine.¹⁹² However, whenever possible, the formulation chosen for the initial dose should be used for the booster dose in the same individual.^{132 192}

Duration of protection and need for subsequent doses after the initial dose and second (booster) dose not fully determined.^{1 2 6 7 23 33 41 46 49 74 76 77 84 145 149 150 155 171 192} (See Duration of Immunity under Cautions.) Subsequent booster doses not recommended.¹⁹²

Adults ≥19 Years of Age (Vaqta)

Primary immunization consists of 2 doses given 6–18 months apart.^{171 192} Use adult formulation containing 50 units per mL.¹⁷¹

Give initial dose of 50 units.^{171 192} Give second (booster) dose of 50 units 6–18 months after initial dose.¹⁷¹

If a different HepA vaccine (e.g., Havrix) was used for the initial dose, a booster dose of Vaqta may be given 6–12 months after the initial dose of the other vaccine.^{171 192} However, whenever possible, the formulation chosen for the initial dose should be used for subsequent doses in the same individual.¹⁹²

Duration of protection and need for subsequent doses after the initial primary dose and second (booster) dose not fully determined.^{2 6 7 23 33 41 46 49 74 76 77 84 145 149 150 155 192} (See Duration of Immunity under Cautions.) Subsequent booster doses not recommended.¹⁹²

Adults ≥18 Years of Age (HepA-HepB; Twinrix)

Primary immunization consists of a series of 3 doses.¹⁸⁶ Each 1-mL dose contains at least 720 units of HAV antigen and 20 mcg of hepatitis B surface antigen (HBsAg).¹⁸⁶

For primary immunization in most patients, give initial dose on a selected date and give second and third doses at 1 and 6 months, respectively, after initial dose.¹⁸⁶

Alternatively, if an accelerated dosing schedule is needed, give initial dose on a selected date and give second and third doses at 7 and 21–30 days, respectively, after initial dose; also give a fourth (booster) dose at 12 months after initial dose.¹⁸⁶

Duration of immunity and need for subsequent doses after the recommended vaccine series not fully determined.¹⁸⁶ (See Duration of Immunity under Cautions.) Booster dose is indicated if an accelerated dosing schedule is used, but booster doses not recommended following the usually recommended 3-dose regimen.¹⁸⁶

Preexposure Vaccination Against HAV Infection in High-risk Groups

Adults≥19 Years of Age (Havrix or Vaqta)

Primary immunization with the usually recommended initial and second (booster) doses before an expected exposure to HAV ensures the highest level of protection.^{1 148 158 171 192 196} (See Prevention of Hepatitis A Virus (HAV) Infection under Dosage and Administration.) Those who have received at least 1 dose given 1 month prior to an exposure probably will be protected.^{167 192 196}

For individuals who plan to travel or work in areas with intermediate to high levels of endemic HAV (see Preexposure Vaccination Against HAV Infection in High-risk Groups under Uses), give first vaccine dose as soon as travel is considered.^{167 196} For most healthy adults ≤40 years of age, a single vaccine dose will provide adequate protection regardless of the scheduled departure date.^{167 196} To ensure protection in adults >40 years of age, immunocompromised individuals, or those with chronic liver disease or other chronic medical conditions who plan to depart within 2 weeks, give initial vaccine dose and simultaneously (using a different syringe and different injection site) give a single dose of IGIM (0.02 mL/kg).^{167 196}

Postexposure Prophylaxis of HAV Infection† [off-label]

Adults ≥19 Years of Age (Havrix or Vaqta)

Adults ≤40 years of age: Give an age-appropriate dose of vaccine alone or in conjunction with IGIM (0.02 mL/kg) as soon as possible.¹⁹⁶ Efficacy of HAV postexposure prophylaxis not established if given >2 weeks after exposure.¹⁹⁶ (See Postexposure Prophylaxis of HAV Infection under Uses.)

Adults >40 years of age: An age-appropriate dose of vaccine can be given, but individuals in this age group should receive IGIM for postexposure prophylaxis.¹⁹⁶

In previously unvaccinated individuals, give primary immunization with the usually recommended age-appropriate initial and second (booster) doses of the vaccine.^{1 107 111 128 171 192} (See Prevention of Hepatitis A Virus (HAV) Infection under Dosage and Administration.) The first vaccine dose can be administered simultaneously with IGIM (using different syringes and different injection sites).^{1 107 111 128 171 192}

Individuals who have received at least 1 vaccine dose at least 1 month prior to the current HAV exposure do not need to receive postexposure prophylaxis with IGIM.^{179 192}

Special Populations

Hepatic Impairment

No specific dosage recommendations.^{1 171}

Renal Impairment

No specific dosage recommendations.^{1 171}

Geriatric Patients

No specific dosage recommendations.^{1 171}

Cautions for Hepatitis A Virus Vaccine Inactivated

Contraindications

Monovalent HepA Vaccine (Havrix, Vaqta)

• Previous severe or allergic reaction (e.g., anaphylaxis) to any HepA vaccine.^{1 60 171}

• Hypersensitivity to any ingredient in the formulation, including neomycin.^{1 60 171}

Fixed-combination Vaccine Containing HepA Vaccine and HepB Vaccine (HepA-HepB; Twinrix)

• Hypersensitivity to any ingredient in the formulation, including the HepA vaccine component (Havrix), the HepB vaccine component (Engerix-B), yeast, or neomycin.¹⁸⁶

• Previous hypersensitivity reaction to Twinrix or monovalent HepA or HepB vaccines.¹⁸⁶

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

Although risk of sensitivity reactions appears to be low,⁷ anaphylaxis and anaphylactoid manifestations have been reported rarely.^{1 2 192} Bronchoconstriction,¹⁷¹ asthma,¹⁷¹ wheezing,¹⁷¹ and serum sickness-like syndrome¹ also reported rarely.

Take all known precautions to prevent adverse reactions, including a review of the patient’s history with respect to possible hypersensitivity to the vaccine or similar vaccines.¹⁸⁶

Epinephrine and other appropriate agents should be readily available in case anaphylaxis or an anaphylactoid reaction occurs.^{1 60 171 186} If a hypersensitivity reaction occurs, immediately institute appropriate therapy as indicated.^{60 171 186}

Do not administer additional vaccine doses to individuals who had a hypersensitivity reaction to a previous dose.^{1 60 171}

Neomycin Allergy

Havrix and Twinrix contains trace amounts of neomycin sulfate.^{1 186} Manufacturers state these vaccines contraindicated in individuals hypersensitive to neomycin.^{1 186}

Neomycin allergy usually results in delayed-type (cell-mediated) hypersensitivity reactions manifested as contact dermatitis.^{60 132} ACIP and AAP state that vaccines containing trace amounts of neomycin should not be used in individuals with a history of anaphylactic reaction to neomycin, but use of such vaccines may be considered in those with a history of delayed-type neomycin hypersensitivity if benefits of vaccination outweigh risks.^{60 132}

Latex Sensitivity

Some packaging components (e.g., needle cover, syringe plunger) of the single-dose prefilled syringes of Havrix¹ and some packaging components (e.g., vial stopper, syringe plunger) of Vaqta¹⁷¹ contain dry natural latex.

Some individuals may be hypersensitive to natural latex proteins.^{60 189 190 191} Take appropriate precautions if these preparations are administered to individuals with a history of latex sensitivity.^{60 189 190 191}

General Precautions

Limitations of Vaccine Effectiveness

May not protect all vaccine recipients against HAV infection.^{1 171}

Individuals who have received at least 1 dose of vaccine given 1 month prior to HAV exposure probably will be protected.^{167 192} Use of both an initial and second (booster) dose given ≥6 months later ensures the highest level of protection.^{1 148 158 171 192}

Consider possibility that unrecognized HAV infection may be present in some individuals at the time of vaccination (infection has an incubation period of 15–50 days) and that the vaccine may not prevent infection in such individuals.^{1 171}

May not prevent infection in individuals who do not achieve protective antibody titers; the minimum titer needed to confer HAV immunity has not been established.^{1 171} (See Actions.)

Monovalent HepA vaccine (Havrix or Vaqta) provides protection only against HAV.^{1 171 192} Fixed-combination vaccine containing HepA virus vaccine and HepB vaccine (HepA-HepB; Twinrix) provides protection only against HAV and HBV.^{186 192} These vaccines do not provide protection against other infectious agents (e.g., HCV, HEV).^{1 171 186 192}

Travelers to areas with intermediate to high levels of endemic HAV who are >40 years of age, immunocompromised, or have chronic liver disease or other chronic medical conditions who receive preexposure vaccination with a dose of monovalent HepA vaccine given within 2 weeks of departure should also receive passive immunization with a dose of IGIM to ensure optimal protection.¹⁹⁶

ACIP states that the fixed-combination vaccine containing HepA vaccine and HepB vaccine (HepA-HepB; Twinrix) should not be used for preexposure vaccination in travelers who will depart within 2 weeks and should not be used for postexposure prophylaxis against HAV.¹⁹⁶ (See Use of Fixed Combinations under Cautions.)

Duration of Immunity

Duration of protection and need for subsequent doses after the initial dose and second (booster) dose of HepA vaccine not fully determined.^{1 2 6 7 23 33 41 46 49 74 76 77 84 132 145 149 150 155 167 171 192}

HepA vaccine has only been available in the US since 1995–1996.^{192 203} Data to date indicate that vaccine-induced antibodies are detectable for at least 5–12 years,^{33 132 167 192} but decline over time.^{62 192} It has been estimated that protective levels of anti-HAV may persist for ≥20–25 years after vaccination.^{2 62 132 167 192 203} Additional study is necessary before recommendations can be made regarding the need, if any, for additional booster doses of the vaccine.^{171 192}

Individuals with Altered Immunocompetence

May be administered to individuals immunosuppressed as the result of disease or immunosuppressive therapy.^{60 159 167 192} Consider possibility that the immune response to the vaccine and efficacy may be reduced in these individuals.^{1 14 60 132 159 167 171 192}

Recommendations regarding use in HIV-infected adults, adolescents, and children are the same as those for individuals who are not infected with HIV.^{197 198} Because HIV-infected individuals with chronic liver disease (including those coinfected with HBV or HCV) are at risk of fulminant hepatic failure if they acquire HAV, ACIP, AAP, CDC, NIH, IDSA, Pediatric Infectious Diseases Society, and others recommend that such individuals receive HepA vaccine.^{197 198} Response to the vaccine may be reduced in those with CD4⁺ T-cell counts <200 cells/mm³; some experts suggest delaying vaccination until patient is receiving antiretroviral therapy and CD4⁺ T-cell count is >200 cells/mm³.¹⁹⁷ Assess antibody response 1 month after vaccination; revaccinate nonresponders.¹⁹⁷

Concomitant Illness

A decision to administer or delay vaccination in an individual with a current or recent febrile illness depends on the severity of symptoms and etiology of the illness.⁶⁰

Some manufacturers state the vaccine may be given to individuals with acute infection or febrile illness if withholding the vaccine poses greater risk to the patient.¹⁷¹

ACIP states that minor acute illness, such as mild diarrhea or mild upper respiratory tract infection (with or without fever) generally does not preclude vaccination, but vaccination should be deferred in individuals with moderate or severe acute illness (with or without fever).⁶⁰

Individuals with Bleeding Disorders

Because bleeding may occur following IM administration in individuals with thrombocytopenia or a bleeding disorder (e.g., hemophilia) or in those receiving anticoagulant therapy, use caution in such individuals.^{18 60 169 171 186}

ACIP states that vaccines may be given IM to individuals who have bleeding disorders or are receiving anticoagulant therapy if a clinician familiar with the patient’s bleeding risk determines that the preparation can be administered with reasonable safety.⁶⁰ In these cases, use a fine needle (23 gauge) to administer the vaccine and apply firm pressure to the injection site (without rubbing) for ≥2 minutes.^{18 60} If patient is receiving antihemophilia therapy, administer the IM vaccine shortly after a scheduled dose of such therapy.^{18 60}

Advise individual and/or their family about the risk of hematoma from IM injections.^{18 60 171}

Pre- and Postvaccination Serologic Testing

Prevaccination testing for susceptibility to HAV is not usually indicated unless such testing would be less costly than unnecessarily vaccinating an individual who is already immune.^{140 145 149 167 192 203} Natural HAV infection produces lifelong immunity and high rates of HAV seropositivity are present in some populations for whom HepA vaccination is recommended.^{192 203} However, vaccination of an individual with preexisting immunity is not associated with any unusual risk.^{167 192 203}

Prevaccination serologic testing is not indicated before routine or catch-up vaccination of children or most adolescents.^{132 192 203}

Prevaccination serologic testing can be considered for adults who were born in or resided for extensive periods in geographic areas with intermediate or high levels of endemic HAV (e.g., Central and South America, Africa, Asia), older adolescents and adults in populations or groups with a high prevalence of infection (e.g., Native Americans, Alaska Natives, Hispanics), adults >40 years of age, adult men who have sex with men, and adults who illicitly use injectable or noninjectable drugs.^{140 141 142 144 167 192 203}

If prevaccination testing is indicated, commercially available tests that measure total anti-HAV (i.e., both IgG and IgM anti-HAV) are used.^{7 9 11 23 37 42 57 76 84 87 140 141 142 192 203} A positive result indicates the individual is immune as the result of past infection or vaccination.²⁰³

Routine screening of contacts for preexisting HAV immunity prior to administration of HAV postexposure prophylaxis is not recommended.^{107 132 192} However, because HAV infection cannot be diagnosed reliably by clinical presentation alone, serologic confirmation of HAV in the index case is recommended before HAV postexposure prophylaxis in contacts.^{42 86 132 192}

Postvaccination serologic testing to confirm HAV immunity is not necessary in most individuals because of the high rate of vaccine response among adults and children.^{109 142 145 167 192 203} When HepA vaccine is used in HIV-infected individuals, some experts recommend assessing antibody response 1 month after vaccination and revaccinating nonresponders.¹⁹⁷ The National Hemophilia Foundation’s Medical and Scientific Advisory Council (MASAC) strongly recommends such testing following HepA vaccination in adults and children with hemophilia.¹⁸

Use of Fixed Combinations

Whenever the fixed-combination vaccine containing HepA vaccine and HepB vaccine (HepA-HepB; Twinrix) is used, consider the contraindications and precautions associated with both antigens.¹⁸⁶

Although an accelerated dosing schedule of the fixed-combination vaccine containing HepA vaccine and HepB vaccine (HepA-HepB; Twinrix) can be used when necessary (e.g., for travelers), a booster dose is necessary 1 year later.^{167 186} (See Adults ≥18 Years of Age (HepA-HepB; Twinrix) under Dosage.) The ACIP states that HepA-HepB (Twinrix) should not be used for preexposure vaccination of travelers who will depart within 2 weeks after receipt of the vaccine;¹⁹⁶ the vaccine contains less HAV antigen and data are not available regarding efficacy in this situation.^{192 196}

Fixed-combination vaccine containing HepA vaccine and HepB vaccine (HepA-HepB; Twinrix) should not be used for HAV postexposure prophylaxis;¹⁹⁶ the vaccine contains less HAV antigen and data are not available regarding efficacy in this situation.^{192 196}

Improper Storage and Handling

Improper storage or handling of vaccines may result in loss of vaccine potency and reduced immune response in vaccinees.^{60 200}

Inspect all vaccines upon delivery and monitor during storage to ensure that the appropriate temperature is maintained.^{60 200}

Do not administer HepA vaccine that has been mishandled or has not been stored at the recommended temperature.^{60 200} (See Storage under Stability.) If there are concerns about mishandling, contact the manufacturer or state or local health departments for guidance on whether the vaccine is usable.²⁰⁰

Specific Populations

Pregnancy

Havrix or Vaqta: Category C.^{1 171}

Twinrix: Category C.¹⁸⁶ Pregnancy registry at 888-452-9622.¹⁸⁶ Clinicians or vaccinees should report any exposure to the vaccine that occurs during pregnancy.¹⁸⁶

Manufacturers state HepA vaccine may be used during pregnancy if clearly needed.^{1 171}

Because HepA vaccine is an inactivated vaccine, the theoretical risk to the fetus is expected to be low,^{60 167} ACIP, AAP, AAFP, ACOG, and ACP state the vaccine may be used in pregnant women when indicated for preexposure vaccination in high-risk groups (including travelers) or for postexposure prophylaxis.^{195 201}

If only short-term protection against HAV infection is needed during pregnancy, consider passive immunization with IGIM as an alternative to active immunization with HepA vaccine.^{107 128 132 192}

Lactation

Use with caution in nursing women.^{1 60 171 186}

Because inactivated vaccines do not multiply within the body, they should not pose any unusual problems for lactating women or their infants.^{60 167}

Pediatric Use

Havrix or Vaqta: Safety and efficacy not established in children <12 months of age.^{1 171} In young infants, passively acquired maternal anti-HAV antibody may interfere with the active immune response to HepA vaccine.^{188 192} Passively acquired antibody declines to undetectable levels in most infants by 1 year of age, and the vaccine is highly immunogenic in children who begin the vaccine series after 1 year of age (regardless of maternal anti-HAV status).¹⁹²

Twinrix: Safety and efficacy not established in children <18 years of age.¹⁸⁶

Geriatric Use

Havrix : Clinical studies did not include sufficient numbers of patients ≥65 years of age to determine whether geriatric patients respond differently from younger patients; other clinical experience has not revealed evidence of age-related differences.¹

Vaqta: Clinical studies and postmarketing safety studies included individuals ≥65 years of age.¹⁷¹ No overall differences in immunogenicity or safety were observed between geriatric and younger patients and there has been no evidence of age-related differences, but the possibility that some older patients may exhibit increased sensitivity to the vaccine cannot be ruled out.¹⁷¹

Twinrix: Clinical studies did not include sufficient numbers of individuals ≥65 years of age to determine whether geriatric individuals respond differently than younger adults.¹⁸⁶

Hepatic Impairment

Individuals with chronic liver disease may have lower antibody responses to HepA vaccine than healthy individuals.¹ (See Actions.)

Common Adverse Effects

Havrix and Vaqta: Injection site reactions (soreness, tenderness, pain, erythema, warmth, induration),^{1 2 7 8 9 11 13 23 35 36 110 112 120 151 152 155 156 157 171 192} headache,^{1 2 7 8 10 12 13 35 36 110 120 152 155 192} GI effects (nausea, vomiting, diarrhea, anorexia),^{1 2 145 151 152 171} irritability,^{1 171} fatigue/asthenia,^{112 120 151 155 157 171} fever,¹⁹² rash.^{171 192}

Twinrix: Adverse effects similar to those reported when monovalent HepA vaccine and monovalent HepB vaccine are administered alone or concurrently at different sites.¹⁸⁶

Drug Interactions

Other Vaccines

Although specific studies may not be available evaluating concurrent administration with each antigen, simultaneous administration with other age-appropriate vaccines, including live virus vaccines, toxoids, or inactivated or recombinant vaccines, during the same health-care visit is not expected to affect immunologic responses or adverse reactions to any of the preparations.^{60 132 192} Immunization with HepA vaccine can be integrated with immunization against diphtheria, tetanus, pertussis, Haemophilus influenzae type b (Hib), hepatitis B, influenza, measles, mumps, rubella, meningococcal disease, pneumococcal disease, poliomyelitis, and varicella.^{3 132 192} However, each vaccine should be administered using a different syringe and different injection site.^{1 132 171}

Specific Drugs and Laboratory Tests

Stability

Storage

Parenteral

Injectable Suspension, for IM Use

Havrix and Vaqta: 2–8°C.^{1 60 171 200} Do not freeze;^{1 60 171 200} if freezing occurs, discard vaccine.¹

Twinrix: 2–8°C.¹⁸⁶ Do not freeze;¹⁸⁶ if freezing occurs, discard vaccine.¹⁸⁶

Havrix, Vaqta, and Twinrix do not contain thimerosal or any other preservatives.^{1 171 186}

Actions

• HepA vaccine is a noninfectious, sterile suspension of cell culture-adapted, attenuated HAV.^{1 171 192} The vaccine virus is propagated in human MRC-5 diploid fibroblasts, purified, inactivated with formalin, and adsorbed onto an aluminum adjuvant.^{1 171 192}

• HepA vaccine is commercially available as monovalent vaccine (Havrix, Vaqta)^{1 171} and as a fixed-combination vaccine containing both HAV and HBV antigens (HepA-HepB; Twinrix).¹⁸⁶

• Havrix and Vaqta contain different HAV antigens,^{1 171 192} but are considered to have equivalent immunogenicity when administered in recommended dosages.^{60 132 192} Twinrix contains the same HAV antigen as Havrix (but in a lower concentration) and the same HBV antigen as Engerix-B HepB vaccine.^{186 192}

• HepA vaccine stimulates active immunity to HAV infection by inducing production of HAV-specific IgG and IgM antibodies (anti-HAV).^{1 6 7 8 9 10 11 13 23 32 47 155 171 192 203}

• HepA vaccine is highly immunogenic in most adults, adolescents, and children ≥1 year of age.^{1 7 8 9 10 11 12 33 35 36 47 48 49 62 112 150 151 152 153 154 155 156 157 171 192 203} Anti-HAV is detectable in most individuals within 2 weeks after a single dose of monovalent HepA vaccine; protection may not be complete until 4 weeks after the dose.¹⁹² At least 94% of adults, adolescents, and children develop protective antibody within 4 weeks after a single dose; almost 100% seroconvert after 2 vaccine doses.^{192 203}

• A reduced immune response to HepA vaccine and lower antibody titers may occur in immunocompromised individuals (e.g., HIV-infected individuals), individuals with chronic liver disease, and liver or kidney transplant recipients.^{1 14 60 132 159 167 171 187 192}

• In a study in adults with chronic liver disease (chronic HBV, chronic HCV, alcoholic cirrhosis, autoimmune hepatitis, chronic hepatitis/cryptogenic cirrhosis, hemochromatosis primary biliary cirrhosis, primary sclerosing cholangitis), seroconversion rates after first dose of HepA vaccine were lower than those in healthy adults;¹ however, seroconversion rates 1 month after the second (booster) dose were similar in both groups.¹

• Although vaccine-induced anti-HAV levels are lower than those induced by natural infection,¹⁹² protection against HAV is virtually complete in those who develop anti-HAV after immunization.^{4 7 8 9 10 11 12 13 22 32 33 47 48 49 62 63 192}

• The principal mode of transmission of HAV is enteric (i.e., through fecal contamination and oral ingestion), most commonly from person to person, particularly from children to adults.^{4 6 16 21 32 37 42 50 59 85 91 92 94 97 120 132 167 171 192 203} HAV also can be spread by infected food handlers,^{6 16 29 192} sewage-contaminated drinking water,¹³⁷ raw or undercooked shellfish (e.g., clams, mussels, oysters) from contaminated waters,^{16 28 91 136} uncooked contaminated foods (e.g. fruits, vegetables),^{167 192} poor hygienic conditions during travel to certain areas of the world,^{16 22 26 27 90 167 192} closed living conditions (e.g., among institutionalized children and adults),²⁵ health-care settings,¹⁹² and parenteral transmission (e.g., transfusions of blood or plasma-derived preparations from HAV-infected individuals, sharing needles with infected individuals).^{1 16 21 27 32 42 63 92 94 97 138 139 165 166 171 192}

• Natural HAV infection results in lifelong immunity.²⁰³ Because of HepA vaccination programs, the rate of HAV infection has declined sharply in the US during the last decade, especially among children.^{192 203} However, an increasingly larger proportion of older Americans are susceptible to the disease (i.e., at an age when the risk of fulminant hepatitis is increased).^{9 31 38 57 75 92 192}

• The minimum titer of anti-HAV conferring protection against HAV has not been established.^{1 2 33 107 128 192} ACIP states that any level of anti-HAV detected by commercially available assays can be considered protective; however, individuals who are anti-HAV negative may still have protective levels of anti-HAV depending on the lower limits of detection of the assay.^{109 192}

Advice to Patients

• Provide copy of manufacturer’s patient information to the patient and/or patient’s parent or guardian.^{1 171 186} Prior to administration of each vaccine dose, also provide a copy of the appropriate CDC Vaccine Information Statement (VIS) to the patient or patient’s legal representative as required by the National Childhood Vaccine Injury Act (VISs are available at [Web]).^{192 202}

• Advise patient and/or patient’s parent or guardian of the risks and benefits of vaccination with HepA vaccine.^{1 171 186}

• Importance of receiving both the initial dose and second (booster) dose to ensure the highest level of protection against HAV.^{1 171 192}

• Importance of informing clinicians if any adverse reactions (e.g., hypersensitivity reactions) occur.^{1 171 186} Clinicians or individuals can report any adverse reactions that occur following vaccination to Vaccine Adverse Event Reporting System (VAERS) at 800-822-7967 or [Web].^{1 171}

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.^{1 171 186}

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{1 171 186}

• Importance of informing patients of other important precautionary information.^{1 171 186} (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Medical Disclaimer