Hepatitis A Virus Vaccine Inactivated

Class: Vaccines
ATC Class: J07BC02
VA Class: IM100
Brands: Havrix, Twinrix, Vaqta

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 () 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

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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 () 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 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

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)
IM

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)
IM

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)
IM

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

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)
IM

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)
IM

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)
IM

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)
IM

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
Adults ≥19 Years of Age (Havrix or Vaqta)
IM

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

Interactions for Hepatitis A Virus Vaccine Inactivated

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

Drug or Test

Interaction

Comments

Anti-infective agents

Concurrent use of anti-infectives generally does not affect the immune response to inactivated vaccines, including HepA vaccine or fixed-combination vaccine containing HepA vaccine and HepB vaccine (Twinrix)60

Diphtheria and tetanus toxoids and acellular pertussis vaccine adsorbed (DTaP)

May be administered concurrently with DTaP (using different syringes and different injection sites)1

Haemophilus b (Hib) vaccine

Concomitant administration of Havrix HepA vaccine with Hib polysaccharide conjugate (tetanus toxoid conjugate) vaccine (PRP-T; OmniHIB [not commercially available in the US]) and DTaP at different sites in children 15–18 months of age did not affect the immune response to Havrix or Hib vaccine;1 there was a higher incidence of some adverse effects (e.g., irritability, drowsiness, loss of appetite) in those who received Havrix concurrently with PRP-T and DTaP than in those who received Havrix alone1

May be given concurrently (using different syringes and different injection sites)1 60 132

Hepatitis B (HepB) vaccine

Simultaneous administration of monovalent HepA vaccine and monovalent HepB vaccine does not interfere with the immune response or increase the frequency of adverse effects to either vaccine104 145 146 192

A 3-dose series of the fixed-combination vaccine containing HepA vaccine and HepB vaccine (Twinrix) results in immune responses and adverse effects similar to those reported when a 2-dose series of monovalent HepA vaccine (Havrix) and a 3-dose series of monovalent HepB vaccine (Engerix-B) is given concurrently in opposite arms186

Monovalent HepA vaccine and monovalent HepB vaccine may be given simultaneously (using different syringes and different injection sites)192

Alternatively, may be given simultaneously as the fixed-combination vaccine containing HepA vaccine and HepB vaccine (Twinrix)186 192

Immune globulin (IGIM)

Anti-HAV passively acquired from IGIM may interfere with the active antibody response to HepA vaccine;35 36 58 111 125 192 although reduced titers of anti-HAV may occur in adults who receive IGIM and the vaccine concurrently, the seroconversion rate is not affected1 36 58 132 192

It has been suggested that because vaccine-induced titers generally are higher than antibody levels considered protective, the reduced immunogenicity associated with passively acquired anti-HAV may not be clinically important35 36 58 111 125 192

ACIP states that development of a protective antibody response should not be impaired if HepA vaccine is administered concurrently or at any interval before or after administration of an antibody-containing preparation60

If combined active immunization with HepA vaccine and passive immunization with IGIM is used (e.g., for postexposure prophylaxis), the first dose of vaccine should be administered simultaneously with IGIM (using different syringes and different injection sites)1 60 107 111 128 167 171 192

Immunosuppressive agents (e.g., alkylating agents, antimetabolites, corticosteroids, cytotoxic agents, radiation)

Potential for decreased antibody response to vaccines1 14 60 159 167 171 192

Vaccines generally should be administered 2 weeks prior to initiation of immunosuppressive therapy or deferred until at least 3 months after such therapy is discontinued14 60

Additional doses of HepA vaccine may be required to induce protective levels of HAV antibody1 60 171

Measles, mumps, and rubella vaccine (MMR)

Concomitant administration of HepA vaccine and MMR (at different sites) did not affect immune response to the measles, mumps, rubella, or hepA antigens171

May be given simultaneously (using different syringes and different injection sites)132 171

Pneumococcal vaccine

Pneumococcal 7-valent conjugate vaccine (PCV7; Prevnar): Concomitant administration with Havrix in children 15 months of age did not affect the immune response to either vaccine1

May be given simultaneously (using different syringes and different injection sites)1 60 132

Pneumococcal 7-valent conjugate vaccine (PCV7; Prevnar): Manufacturer states Havrix may be administered simultaneously with the fourth dose of Prevnar (using different syringes and different injection sites)1

Tests to diagnose HAV infection

Individuals who have received HepA vaccine and are being evaluated for suspected HAV infection using serologic tests that detect IgM anti-HAV may have a positive test result in the absence of infection, especially if the test is performed within 2–3 weeks after vaccine administration;172 192 only 1% of vaccinees had detectable IgM anti-HAV 1 month after vaccination172

Typhoid vaccine

Parenteral inactivated typhoid vaccine (Typhim Vi): Concomitant administration with HepA vaccine does not appear to affect the immune response or adverse reactions to either vaccine171 205

May be given simultaneously (using different syringes and different injection sites)171

Varicella vaccine

Monovalent varicella vaccine (Varivax): Concomitant administration with HepA vaccine and with MMR at different sites did not affect antibody response to HepA vaccine; immunogenicity data insufficient to date to assess response to varicella vaccine171

Yellow fever vaccine

HepA vaccine and yellow fever vaccine may be given concomitantly (using different syringes and different injection sites)171 204

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 ).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 .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.

Hepatitis A Virus Vaccine Inactivated

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injectable suspension, for IM use

25 units (of viral antigen) per 0.5 mL

Vaqta Pediatric/Adolescent

Merck

50 units (of viral antigen) per mL

Vaqta Adult

Merck

720 ELISA units (of viral antigen) per 0.5 mL

Havrix Pediatric

GlaxoSmithKline

1440 ELISA units (of viral antigen) per mL

Havrix Adult

GlaxoSmithKline

Hepatitis A Inactivated and Hepatitis B (Recombinant) Vaccine (HepA-HepB)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injectable suspension, for IM use

Hepatitis A Virus Vaccine Inactivated 720 ELISA units (of viral antigen) and Hepatitis B Vaccine (Recombinant) 20 mcg (of hepatitis B surface antigen) per mL

Twinrix

GlaxoSmithKline

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Havrix 1440ELU/ML Suspension (GLAXO SMITH KLINE): 1/$74.99 or 3/$209.98

Vaqta 50UNIT/ML Suspension (MERCK SHARP &amp; DOHME): 1/$76.71 or 3/$211.98

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions January 1, 2010. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. GlaxoSmithKline. Havrix (hepatitis A vaccine) prescribing information. Research Triangle Park, NC; 2009 Oct.

2. Krause DS. SmithKline Beecham Pharmaceuticals, Philadelphia, PA; Personal communication.

3. Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention, American Academy of Pediatrics, and American Academy of Family Physicians. Recommended immunization schedules for persons aged 0 through 18 years—United States, 2010; 59.

4. Stapleton JT. Host immune response to hepatitis A virus. J Infect Dis. 1995; 171(Suppl 1):S9-14. [PubMed 7876654]

6. Lemon SM. Type A viral hepatitis: new developments in an old disease. N Engl J Med. 1985; 313:1059-67. [IDIS 206157] [PubMed 2413356]

7. Innis BL, Snitbhan R, Kunasol P et al. Protection against hepatitis A by an inactivated vaccine. JAMA. 1994; 271:1328-34. [IDIS 329029] [PubMed 8158817]

8. Clemens R, Safary A, Hepburn A et al. Clinical experience with inactivated hepatitis A vaccine. J Infect Dis. 1995; 171(Suppl 1):S44-9. [IDIS 343520] [PubMed 7876648]

9. Westblom TU, Gudipati S, DeRousse C et al. Safety and immunogenicity of an inactivated hepatitis A vaccine: effect of dose and vaccination schedule. J Infect Dis. 1994; 169:996-1001. [IDIS 329293] [PubMed 8169430]

10. Balcarek KB, Bagley RM, Pass RF et al. Safety and immunogenicity of an inactivated hepatitis A vaccine in preschool children. J Infect Dis. 1995; 171(Suppl 1):S70-2. [IDIS 343524] [PubMed 7876652]

11. Tong MT, Co RL, Bellak C. Hepatitis A vaccination. West J Med. 1993; 158:602-5. [IDIS 316166] [PubMed 8393253]

12. Sandman L, Davidson M, Krugman S. Inactivated hepatitis A vaccine: a safety and immunogenicity study in health professionals. J Infect Dis. 1995; 171(Suppl 1):S50-2. [IDIS 343521] [PubMed 7876649]

13. DeFraites RF, Feighner BH, Binn LN et al. Immunization of US soldiers with a two-dose primary series of inactivated hepatitis A vaccine: early immune response, persistence of antibody, and response to a third dose at 1 year. J Infect Dis. 1995; 171(Suppl 1): S61-9.

14. . Recommendations of the Advisory Committee on Immunization Practices (ACIP): use of vaccines and immune globulins for persons with altered immunocompetence. MMWR Recomm Rep. 1993; 42:1-18.

15. André FE. Approaches to a vaccine against hepatitis A: development and manufacture of an inactivated vaccine. J Infect Dis. 1995; 171(Suppl 1):S33-9.

16. Hadler SC. Global impact of hepatitis A virus infection changing patterns. In: Hollinger FB, Lemon SM, Margolis H, eds. Viral hepatitis and liver disease. Baltimore: Williams & Wilkins; 1991:14-20.

17. Sjogren MH, Tanno H, Fay O et al. Hepatitis A virus in stool during clinical relapse. Ann Intern Med. 1987; 106:221-6. [PubMed 3026213]

18. Medical and Scientific Advisory Council (MASAC), National Hemophilia Foundation. MASAC recommendations for hepatitis A and B immunization of individuals with bleeding disorders (November 2001). MASAC recommendation #128. From National Hemophilia Foundation website ().

19. Decker RH, Kosakowski SM, Vanderbilt AS et al. Diagnosis of acute hepatitis A by HAVAB-M, a direct radioimmunoassay for IgM anti-HAV. Am J Clin Path. 1981; 76:140-7. [PubMed 6267929]

20. Chiriaco P, Gaudalupi C, Armigliato M et al. Polyphasic course of hepatitis type A in children. J Infect Dis. 1986; 153:378-9. [PubMed 3080536]

21. Everhart JE, ed. Digestive diseases in the United States: epidemiology and impact. 1994 May:128-33. (NIH publication No. 94-1447.)

22. Steffen R, Kane MA, Shapiro CN et al. Epidemiology and prevention of hepatitis A in travelers. JAMA. 1994; 272:885-9. [IDIS 335279] [PubMed 8078167]

23. André FE, Hepburn A, D’Hondt E. Inactivated candidate vaccines for hepatitis A. Prog Med Virol. 1990; 37:72-95. [PubMed 2173850]

24. Hadler SC, Erben JJ, Francis DP et al. Risk factors for hepatitis A in day-care centers. J Infect Dis. 1982; 145:255-61. [PubMed 7054328]

25. Mosley JW. Hepatitis types B and non-B: epidemiologic background. JAMA. 1975; 233:967-9. [PubMed 168417]

26. Woodson RD, Clinton JJ. Hepatitis prophylaxis abroad: effectiveness of immune serum globulin in protecting Peace Corps volunteers. JAMA. 1969; 209:1053-8. [PubMed 4183968]

27. Krugman S, Giles JP. Viral hepatitis: new light on an old disease. JAMA. 1970; 212:1019-29. [PubMed 4191502]

28. Mackowiak PA, Caraway CT, Portnoy BL. Oyster-associated hepatitis: lessons from the Louisiana experience. Am J Epidemiol. 1976; 103:181-91. [PubMed 1251833]

29. Dienstag JL, Routenberg JA, Purcell RH et al. Foodhandler-associated outbreak of hepatitis type A: an immune electron microscopic study. Ann Intern Med. 1975; 83:647-50. [PubMed 173217]

30. Tassopoulos NC, Papaevangelou GJ, Ticehurst JR et al. Fecal excretion of Greek strains of hepatitis A virus in patients with hepatitis A and in experimentally infected chimpanzees. J Infect Dis. 1986; 154:231-7. [PubMed 3014009]

31. Shapiro CN, Shaw FE, Mandel EJ et al. Epidemiology of hepatitis A in the United States. In: Hollinger FB, Lemon SM, Margolis H, eds. Viral hepatitis and liver disease. Baltimore: Williams & Wilkins; 1991:71-6.

32. Kendall BJ, Cooksley WGE. Prophylactic treatment regimens for the prevention of hepatitis A: current concepts. Drugs. 1991; 41:883-8. [PubMed 1715265]

33. Ambrosch F, Wiedermann G, André FE et al. Comparison of HAV antibodies induced by vaccination, passive immunization, and natural infection. In: Hollinger FB, Lemon SM, Margolis H, eds. Viral hepatitis and liver disease. Baltimore: Williams & Wilkins; 1991:98-100.

34. Centers for Disease Control and Prevention. Vaccine adverse event reporting system—United States. MMWR Morb Mortal Wkly Rep. 1990; 39:730-3. [IDIS 273928] [PubMed 2120567]

35. Leentvaar-Kuijpers A, Coutinho RA, Brulein V et al. Simultaneous passive and active immunization against hepatitis A. Vaccine. 1992; 10(Suppl 1):S138-41. [PubMed 1335646]

36. Green MS, Cohen D, Lerman Y et al. Depression of the immune response to an inactivated hepatitis A virus vaccine administered concomitantly with immune globulin. J Infect Dis. 1993; 168:740-3. [IDIS 320050] [PubMed 8394864]

37. Hollinger FB, Glombicki AP. Hepatitis A virus. In: Mandell GL, Douglas RG Jr, Bennett JE, eds. Principles and practices of infectious diseases. 3rd ed. Churchill Livingstone: New York; 1990:1383-99.

38. Lemon SM. Inactivated hepatitis A vaccines. JAMA. 1994; 271:1363-4. [IDIS 329030] [PubMed 8158824]

39. Peetermans J. Production, quality control and characterization of an inactivated hepatitis A vaccine. Vaccine. 1992; 10(Suppl 1):S99-101. [PubMed 1335671]

40. Werzberger A, Mensch B, Kuter B et al. A controlled trial of a formalin-inactivated hepatitis A vaccine in healthy children. N Engl J Med. 1992; 327:453-7. [IDIS 300159] [PubMed 1320740]

41. Bancroft WH. Hepatitis A vaccine. N Engl J Med. 1992; 327:488-90. [IDIS 300161] [PubMed 1320741]

42. Hollinger FB, Ticehurst J. Hepatitis A virus. In: Hollinger FB, Robinson WS, Purcell RH et al, eds. Viral hepatitis: biological and clinical features, specific diagnosis, and prophylaxis. New York; 1990:1-37.

43. Midthun K, Ellerbeck E, Gershman K et al. Safety and immunogenicity of a live attenuated hepatitis A virus vaccine in seronegative volunteers. J Infect Dis. 1991; 163:735-9. [IDIS 279849] [PubMed 1849160]

44. Mao JS, Dong DX, Zhang HY et al. Primary study of attenuated live hepatitis A vaccine (H2 strain) in humans. J Infect Dis. 1989; 159:621-4. [IDIS 253814] [PubMed 2538518]

45. Larson L. First U.S. hepatitis A vaccine released. AAP News. 1995; 11:1,17.

46. Wiedermann G, Ambrosch F, André FE et al. Persistence of vaccine-induced antibody to hepatitis A virus. Vaccine. 1992; 10(Suppl 1):S129-31.

47. Just M, Berger R. Reactogenicity and immunogenicity of inactivated hepatitis A vaccines. Vaccine. 1992; 10(Suppl 1):S110-3.

48. André FE, D’Hondt E, Delem A et al. Clinical assessment of the safety and efficacy of an inactivated hepatitis A vaccine: rationale and summary of findings. Vaccine. 1992; 10(Suppl 1):S160-8.

49. Victor J, Knudsen JD, Nielsen LP et al. Hepatitis A vaccine. A new convenient single-dose schedule with booster when long-term immunization is warranted. Vaccine. 1994; 12:1327-9. [PubMed 7856299]

50. Nalin D, Brown L, Kuter B et al. Inactivated hepatitis A vaccine in childhood: implications for disease control. Vaccine. 1993; 11(Suppl 1):15-7.

51. Wiedermann G, Ambrosch F, Kollaritsch H et al. Safety and immunogenicity of an inactivated hepatitis A candidate vaccine in healthy adult volunteers. Vaccine. 1990; 8:581-4. [PubMed 1965077]

52. Newcomer W, Rivin B, Reid R et al. Immunogenicity, safety and tolerability of varying doses and regimens of inactivated hepatitis A virus vaccine in Navajo children. Pediatr Infect Dis J. 1994; 13:640-2. [IDIS 332323] [PubMed 7970954]

53. Block SL, Hedrick JA, Tyler RD et al. Safety, tolerability and immunogenicity of a formalin-inactivated hepatitis A vaccine (VAFTA) in rural Kentucky children. Pediatr Infect Dis J. 1993; 12:976-80. [PubMed 8108223]

54. Hoffman M. Hepatitis A vaccine shows promise. Science. 1991; 254:1581-2. [IDIS 288902] [PubMed 1749931]

55. Lewis JA, Armstrong ME, Larson VM et al. Use of a live, attenuated hepatitis A vaccine to prepare a highly purified, formalin-inactivated hepatitis A vaccine. In: Hollinger FB, Lemon SM, Margolis H, eds. Viral hepatitis and liver disease. Baltimore: Williams & Wilkins; 1991:94-7.

56. Long-an R, Dun-zhi W, Qian-you D et al. Safety and immunogenicity of live attenuated hepatitis A virus vaccine (H2 strain) in humans. Chin Med J. 1993; 106: 604-7.

57. Lemon SM. Hepatitis A virus: clinical course and serology. Paper presented at American Association for the Study of Liver Diseases annual meeting. Chicago: 1994 Nov 12.

58. McMahon BJ. Prevention of hepatitis A. Paper presented at American Association for the Study of Liver Diseases annual meeting. Chicago: 1994 Nov 12.

59. World Health Organization. International travel and health: vaccination requirements and health advice. Geneva: World Health Organization; 1995:63,64,84.

60. Kroger AT, Atkinson WL, Marcuse EK et al. General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2006; 55:1-48. [PubMed 17136024]

61. Medical and Scientific Advisory Council (MASAC), National Hemophilia Foundation. MASAC recommendations concerning the treatment of hemophilia and other bleeding disorders (revised March 2003). MASAC recommendation #141. From National Hemophilia Foundation website ().

62. Van Damme P, Thoelen S, Cramm M et al. Inactivated hepatitis A vaccine: reactogenicity, immunogenicity, and long-term antibody persistence. J Med Virol. 1994; 44:446-51. [PubMed 7897379]

63. Lemon SM, Shapiro CN. The value of immunization against hepatitis A. Infect Agents Dis. 1994; 1:38-49.

64. Mannucci PM. Outbreak of hepatitis A among Italian patients with haemophilia. Lancet. 1992; 339:819. [PubMed 1347851]

65. Peerlinck K, Vermylen J. Acute hepatitis A in patients with haemophilia A. Lancet. 1993; 341:179. [PubMed 8093776]

66. Gerritzen A, Schneweis KE, Brackmann H-H et al. Acute hepatitis A in haemophiliacs. Lancet. 1992; 340:1231-2. [IDIS 305120] [PubMed 1359305]

67. Normann A, Graff J, Gerritzen A et al. Detection of hepatitis A virus RNA in commercially available factor VIII preparation. Lancet. 1992; 340:1232. [IDIS 305121] [PubMed 1359306]

68. Giacoia GP, Kasprisin DO. Transfusion-acquired hepatitis A. South Med J. 1989; 82:1357-60. [IDIS 261013] [PubMed 2683125]

69. Santagostino E, Gringeri A, Rocino A et al. Patterns of immunogenicity of an inactivated hepatitis A vaccine in anti-HIV positive and negative hemophilic patients. Thromb Haemost. 1994; 72:508-10. [IDIS 337578] [PubMed 7878624]

70. Robinson SM, Schwinn H, Smith A. Clotting factors and hepatitis A. Lancet. 1992; 340:1465. [IDIS 307252] [PubMed 1360575]

73. Henning KJ, Bell E, Braun J et al. A community-wide outbreak of hepatitis A: risk factors for infection among homosexual and bisexual men. Am J Med. 1995; 99:132-6. [PubMed 7625417]

74. Van Damme P, Kane M. Report on the hepatitis A meeting in Marlow. Viral Hepatitis. 1995; 3:3-14.

75. van Doorslaer E, Tormans G, van Damme P et al. Cost effectiveness of alternative hepatitis A immunisation strategies. PharmacoEconomics. 1995; 8:5-8. [PubMed 10155602]

76. Severo CA, Fagnani F, Lafuma A. Cost effectiveness of hepatitis A prevention in France. PharmacoEconomics. 1995; 8:46-61. [PubMed 10155601]

77. Margolis HS, Shapiro CN. Who should receive hepatitis A vaccine? Considerations for the development of an immunization strategy. Vaccine. 1992; 10(Suppl1):S85-7.

78. Nalin DR, Kuter BJ, Brown L et al. Worldwide experience with the CR326F-derived inactivated hepatitis A virus vaccine in pediatric and adult populations: an overview. J Hepatol. 1993; 18(Suppl 2):S51-5.

79. Kane MA. Prospects for the introduction of hepatitis A vaccine into public health use. Prog Med Virol. 1990; 37:96-100. [PubMed 2173851]

80. Margolis HS, Alter MJ. Will hepatitis A become a vaccine-preventable disease? Ann Intern Med. 1995; 122:464-5.

81. Corey L, Holmes KK. Sexual transmission of hepatitis A in homosexual men: incidence and mechanism. N Engl J Med. 1980; 302:435-8. [PubMed 6243391]

82. Rajan E, Albloushi S, O’Farrell B et al. Two year old hepatitis A vaccine (Havrix) retains its immunogenicity. Gastroenterology. 1995; 108:A899.

83. Hadler SC, Webster HM, Erben JJ et al. Hepatitis A in day-care centers. N Engl J Med. 1980; 302:1222-7. [PubMed 6245363]

84. Hollinger FB, Eickhoff T, Gershon A et al. Discussion: who should receive hepatitis A vaccine? A strategy for controlling hepatitis A in the United States. J Infect Dis. 1995; 171(Suppl 1):S73-7. [PubMed 7876653]

85. Melnick JL. History and epidemiology of hepatitis A virus. J Infect Dis. 1995; 171(Suppl 1):S2-8. [PubMed 7876643]

86. Tong MJ, El-Farra NS, Grew MI. Clinical manifestations of hepatitis A: recent experience in a community teaching hospital. J Infect Dis. 1995; 171(Suppl 1):S15-8. [PubMed 7876641]

87. Horng Y-C, Chang M-H, Lee C-Y et al. Safety and immunogenicity of hepatitis A vaccine in healthy children. Pediatr Infect Dis J. 1993; 12:359-62. [PubMed 8392163]

88. Shaw FE Jr, Shapiro CN, Welty TK et al. Hepatitis transmission among the Sioux Indians of South Dakota. Am J Public Health. 1990; 80:1091-4. [PubMed 2166446]

89. Poole CJM, Shakespeare AT. Should sewage workers and carers for people with learning disabilities be vaccinated for hepatitis A? Br Med J. 1993; 306:1102.

90. Wolfe MS. Hepatitis A and the American traveler. J Infect Dis. 1995; 171(Suppl 1):S29-32. [PubMed 7876645]

91. Centers for Disease Control and Prevention. Foodborne hepatitis A—Missouri, Wisconsin, and Alaska, 1990-1992. MMWR Morb Mortal Wkly Rep. 1993; 42:526-9. [PubMed 8321179]

92. Koff RS. Seroepidemiology of hepatitis A in the United States. J Infect Dis. 1995; 171(Suppl 1):S19-23.

93. Francis DP, Hadler SC, Prendergast TJ et al. Occurrence of hepatitis A, B, and non-A/non-B in the United States: CDC Sentinel County Hepatitis Study 1. Am J Med. 1984; 76:69-74. [PubMed 6419605]

94. Dienstag JL, Szmuness W, Stevens CE et al. Hepatitis A virus infection: new insights from seroepidemiologic studies. J Infect Dis. 1978; 137:328-40. [PubMed 204711]

95. Steffen R. Hepatitis A in travelers: the European experience. J Infect Dis. 1995; 171(Suppl 1):S24-8. [PubMed 7876644]

96. Rosenblum LS, Villarino ME, Nainan OV et al. Hepatitis A outbreak in a neonatal intensive care unit: risk factors for transmission and evidence of prolonged viral excretion among preterm infants. J Infect Dis. 1991; 164:476-82. [PubMed 1651359]

97. Shapiro CN, Coleman PJ, McQuillan GM et al. Epidemiology of hepatitis A: seroepidemiology and risk groups in the USA. Vaccine. 1992; 10(Suppl 1):S59-62. [PubMed 1476001]

98. Cohen JI, Feinstone S, Purcell RH. Hepatitis A virus infection in a chimpanzee: duration of viremia and detection of virus in saliva and throat swabs. J Infect Dis. 1989; 160:887-90. [PubMed 2572653]

99. Dienstag JL, Davenport FM, McCollum RW et al. Nonhuman primate-associated viral hepatitis type A. JAMA. 1976; 236:462-4. [PubMed 180303]

100. Shouval D, Gerlich WH for the Working Group on Hepatitis A and Clotting Factors. Clotting factors and hepatitis A. Lancet. 1992; 340:1465-6.

101. Temperley IJ, Cotter KP, Walsh TJ. Clotting factors and hepatitis A. Lancet. 1992; 340:1466. [IDIS 307254] [PubMed 1360577]

102. Mah MW, Royce RA, Rathouz PJ et al. Prevalence of hepatitis A antibodies in hemophiliacs: preliminary results from the Southeastern Delta Hepatitis Study. Vox Sang. 1994; 67(Suppl 1):21-2. [PubMed 8091730]

103. Akriviadis EA, Redeker AG. Fulminant hepatitis A in intravenous drug users with chronic liver disease. Ann Intern Med. 1989; 110:838-9. [PubMed 2712463]

104. Ambrosch F, André FE, Delem A et al. Simultaneous vaccination against hepatitis A and B: results of a controlled study. Vaccine. 1992; 10(Suppl 1):S142-5.

106. Feinstone SM, Kapikian AZ, Purcell RH. Hepatitis A: detection by immune electron microscopy of a virus-like antigen associated with acute illness. Science. 1973; 182:1026-8. [PubMed 4356028]

107. Winokur PL, Stapleton JT. Immunoglobulin prophylaxis for hepatitis A. Clin Infect Dis. 1992; 14:580-6. [IDIS 292073] [PubMed 1554845]

108. Hinthorn DR, Foster MT Jr, Bruce HL et al. An outbreak of chimpanzee associated hepatitis. J Occupation Med. 1974; 16:388-91.

109. Lemon SM. Immunologic approaches to assessing the response to inactivated hepatitis A vaccine. J Hepatol. 1993; 18(Suppl 2):S15-9. [PubMed 8182266]

110. Gardner P, Eickhoff T, Poland GA et al. Adult immunizations. Ann Intern Med. 1996; 12:35-40.

111. Wagner G, Lavanchy D, Darioli R et al. Simultaneous active and passive immunization against hepatitis A studied in a population of travellers. Vaccine. 1993; 11:1027-32. [PubMed 8212822]

112. McMahon BJ, Williams J, Bulkow L et al. Immunogenicity of an inactivated hepatitis A vaccine in Alaska native children and native and non-native adults. J Infect Dis. 1995; 171:676-9. [IDIS 346019] [PubMed 7876615]

113. D’Hondt E. Possible approaches to develop vaccines against hepatitis A. Vaccine. 1992; 10(Suppl 1):S48-52.

114. Shaw FE Jr, Sudman JH, Smith SM et al. A community-wide epidemic of hepatitis A in Ohio. Am J Epidemiol. 1986; 123:1057-65. [PubMed 3706276]

115. Armstrong ME, Giesa PA, Davide JP et al. Development of the formalin-inactivated hepatitis A vaccine, VAQTA™ from the live attenuated virus strain CR326F. J Hepatol. 1993; 18(Suppl 2):S20-6. [PubMed 8182268]

116. Robertson BH, D’Hondt EH, Spelbring J et al. Effect of postexposure vaccination in a chimpanzee model of hepatitis A virus infection. J Med Virol. 1994; 43:249-51. [PubMed 7931186]

118. Lemon SM, Binn LN. Serum neutralizing antibody response to hepatitis A virus. J Infect Dis. 1983; 148:1033-9. [PubMed 6317766]

119. Kashiwagi S, Hayashi J, Ikematsu H et al. Prevalence of immunologic markers of hepatitis A and B infection in hospital personnel in Miyazaki Prefecture, Japan. Am J Epidemiol. 1985; 122:960-9. [PubMed 4061446]

120. Battegay M, Gust ID, Feinstone SM. Hepatitis A virus. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and practice of infectious diseases. 4th ed. New York: Churchill Livingstone; 1995:1636-56.

121. Hughes PJ, Saadeh IK, Cox JPDT et al. Probable post-hepatitis A vaccination encephalopathy. Lancet. 1993; 342:302.

122. Mao JS, Dong DX, Zhang SY et al. Further studies of attenuated live hepatitis A vaccine (H2 strain) in humans. In: Hollinger FB, Lemon SM, Margolis H, eds. Viral hepatitis and liver disease. Proceedings of the 1990 International Symposium on Viral Hepatitis and Liver Disease: contemporary issues and future prospects. Baltimore: Williams & Wilkins; 1991:110-1.

123. Steininger P, Bader T. Declining prevalence of immunity to hepatitis A virus. Gastroenterology. 1995; 108:A1176.

125. Anon. Hepatitis A vaccine. Med Lett Drugs Ther. 1995; 37:51-2. [PubMed 7760768]

126. Centers for Disease Control and Prevention. Hepatitis A among homosexual men—United States, Canada, and Australia. MMWR Morb Mortal Wkly Rep. 1992; 41:155-64. [PubMed 1741008]

127. Meyboom RHB, Fucik H, Edwards IR. Thrombocytopenia reported in association with hepatitis B and A vaccines. Lancet. 1995; 345:1638. [IDIS 349059] [PubMed 7632294]

128. Gerety RJ, Smallwood LA, Finlayson JS et al. Standardization of the antibody to hepatitis A virus (anti-HAV) content of immunoglobulin. Dev Biol Standard. 1983; 54:411-6.

129. Centers for Disease Control and Prevention. Case definitions for public health surveillance. MMWR Recomm Rep. 1990; 39(RR-13):17.

130. Halliwell T, Jones M, Diment J et al. A new enhanced luminescence immunoassay for the detection of IgM anti-HAV. In: Hollinger FB, Lemon SM, Margolis H, eds. Viral hepatitis and liver disease. Proceedings of the 1990 International Symposium on Viral Hepatitis and Liver Disease: contemporary issues and future prospects. Baltimore: Williams & Wilkins; 1991:82-5.

131. Nainan OV, Brinton MA, Margolis HS. Identification of amino acids located in the antibody binding sites of human hepatitis A virus. Virology. 1992; 191:984-7. [PubMed 1280386]

132. American Academy of Pediatrics. 2006 Red Book: Report of the Committee on Infectious Diseases. 27th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2006.

133. Niu MT, Polish LB, Robertson BH et al. Multistate outbreak of hepatitis A associated with frozen strawberries. J Infect Dis. 1992; 166:518-24. [PubMed 1323618]

134. Ramsay CN, Upton PA. Hepatitis A and frozen raspberries. Lancet. 1989; I:43-4.

135. Rosenblum LS, Mirkin IR, Allen DT et al. A multifocal outbreak of hepatitis A traced to commercially distributed lettuce. Am J Public Health. 1990; 80:1075-80. [PubMed 2382744]

136. Desenclos JCA, Klontz KC, Wilder MH et al. A multistate outbreak of hepatitis A caused by the consumption of raw oysters. Am J Public Health. 1991; 81:1268-72. [PubMed 1928524]

137. Bloch AB, Stramer SL, Smith JD et al. Recovery of hepatitis A virus from a water supply responsible for a common source outbreak of hepatitis A. Am J Public Health. 1990; 80:428-30. [PubMed 2156462]

138. Mannucci PM, Gdovin S, Gringeri A et al. Transmission of hepatitis A to patients with hemophilia by Factor VIII concentrates treated with organic solvent and detergent to inactivate viruses. Ann Intern Med. 1994; 120:1-7. [IDIS 323062] [PubMed 7504424]

139. Shapiro CN. Transmission of hepatitis viruses. Ann Intern Med. 1994; 120:82-4. [PubMed 8250462]

140. Bryan JP, Nelson M. Testing for antibody to hepatitis A to decrease the cost of hepatitis A prophylaxis with immune globulin or hepatitis A vaccines. Arch Intern Med. 1994; 154:663-8. [IDIS 327146] [PubMed 8129500]

141. Turner PC, Eglin RE, Woodward CG et al. Screening before hepatitis A vaccination. Lancet. 1992; 340:1160. [IDIS 305016] [PubMed 1359229]

142. Krah DL, Amin RD, Nalin DR et al. A simple antigen-reduction assay for the measurement of neutralizing antibodies to hepatitis A virus. J Infect Dis. 1991; 163: 634-7. [PubMed 1847404]

143. Poovorawan Y, Tieamboonlers A, Chumdermpadetsuk S et al. Control of a hepatitis A outbreak by active immunization of high-risk susceptible subjects. J Infect Dis. 1994; 169:228-9. [IDIS 324771] [PubMed 8277191]

144. Bulkow LR, Wainwright RB, McMahon BJ et al. Secular trends in hepatitis A virus infection among Alaska natives. J Infect Dis. 1993; 168:1017-20. [PubMed 8376812]

145. Hoke CH Jr, Egan JE, Sjogren MH et al. Administration of hepatitis A vaccine to a military population by needle and jet injector and with hepatitis B vaccine. J Infect Dis. 1995; 171(Suppl 1):S53-60. [IDIS 343522] [PubMed 7876650]

146. Flehmig B, Heinricy U, Pfisterer M. Simultaneous vaccination for hepatitis A and B. J Infect Dis. 1990; 161:865-8. [IDIS 304873] [PubMed 2157770]

147. Brewer MA, Edwards KM, Decker MD. Who should receive hepatitis A vaccine? Pediatr Infect Dis J. 1995; 14:258-60.

148. Lonergan G. Hepatitis A vaccine: which dose is best? JAMA. 1995; 273:999. Letter.

149. Anon. Hepatitis A: a vaccine at last. Lancet. 1992; 339:1198-9. [PubMed 1349941]

150. Sjogren MH. The success of hepatitis A vaccine. Gastroenterology. 1993; 104:1214-6. [IDIS 313686] [PubMed 8385043]

151. Lee S-D, Lo K-J, Chan C-Y et al. Immunogenicity of inactivated hepatitis A vaccine in children. Gastroenterology. 1993; 104:1129-32. [IDIS 313681] [PubMed 8462802]

152. Scheifele DW, Bjornson GJ. Evaluation of inactivated hepatitis A vaccine in Canadians 40 years of age or more. CMAJ. 1993; 148:551-5. [IDIS 310345] [PubMed 8431816]

153. Delem A, Safary A, De Namur F et al. Characterization of the immune response of volunteers vaccinated with a killed vaccine against hepatitis A. Vaccine. 1993; 11: 479-84. [PubMed 8385844]

154. Jilg W, Bittner R, Bock HL et al. Vaccination against hepatitis A: comparison of different short-term immunization schedules. Vaccine. 1992; 10(Suppl 1):S126-8.

155. Tilzey AJ, Palmer SJ, Barrow S et al. Clinical trial with inactivated hepatitis A vaccine and recommendations for its use. BMJ. 1992; 304:1272-6. [IDIS 296802] [PubMed 1318765]

156. Sjogren MH, Hoke CH, Binn LN et al. Immunogenicity of an inactivated hepatitis A vaccine. Ann Intern Med. 1991; 114:470-1. [IDIS 278981] [PubMed 1994794]

157. Westblom TU, Gudipati S, DeRousse C et al. Safety and immunogenicity of an inactivated hepatitis A vaccine. Clin Res. 1991; 39:727A.

158. Lonergan G. Hepatitis A vaccine: which dose is best? JAMA. 1995; 273:999. Reply.

159. Hess G, Clemens R, Bienzle U et al. Immunogenicity and safety of an inactivated hepatitis A vaccine in anti-HIV positive and negative homosexual men. J Med Virol. 1995; 46:40-2. [PubMed 7623005]

160. Goilav C, Zuckerman J, Lafrenz M et al. Immunogenicity and safety of a new inactivated hepatitis A vaccine in a comparative study. J Med Virol. 1995; 46:287-92. [PubMed 7561805]

161. Reviewers’ comments (personal observations).

162. SmithKline Beecham, Philadelphia, PA: Personal communication.

163. Wiedermann G, Ambrosch F. Immunogenicity of an inactivated hepatitis A vaccine after exposure at 37°C for 1 week. Vaccine. 1994; 12:401-2. [PubMed 8023546]

164. Glikson M, Galun E, Oren R et al. Relapsing hepatitis A: review of 14 cases and literature survey. Medicine (Baltimore). 1992; 71:14-23. [IDIS 290537] [PubMed 1312659]

165. Lemon SM. The natural history of hepatitis A: the potential for transmission by transfusion of blood or blood products. Vox Sang. 1994; 67(Suppl 4):19-23. [PubMed 7831865]

166. Anon. Discussion [The natural history of hepatitis A: the potential for transmission by transfusion of blood or blood products]. Vox Sang. 1994; 67(Suppl 4):24-6. [PubMed 8091731]

167. Centers for Disease Control and Prevention. Health information for international travel, 2010. Atlanta, GA: US Department of Health and Human Services. Updates available from CDC website ().

168. Bachorik L (US Food and Drug Administration). Factor VIII and Factor IX products associated with hepatitis A transmission. Rockville, MD; 1996 Jan 16. Press release No. T96-5.

169. Centers for Disease Control and Prevention. Hepatitis A among persons with hemophilia who received clotting factor concentrate—United States, September–December 1995. MMWR Morb Mortal Wkly Rep. 1996; 45:29-32. [IDIS 359576] [PubMed 8531917]

170. Bell PB (Hepatitis Branch, US Centers for Disease Control and Prevention, Atlanta, GA): Personal communication.

171. Merck & Company. Vaqta (hepatitis A vaccine inactivated) prescribing information. Whitehouse Station, NJ; 2007 Dec.

172. Centers for Disease Control and Prevention. Prevention of hepatitis A through active or passive immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 1999; 48(RR-12):1-37.

173. Espig D. Merck & Company Inc, West Point, PA; personal communication.

174. Bock HL, Kruppenbacher JP, Bienzle U et al. Does the concurrent administration of an inactivated hepatitis A vaccine influence the immune response to other travelers vaccines? J Travel Med. 2000; 7:74-8.

175. Anon. Hepatitis A associated with consumption of frozen strawberries, Michigan, March 1997. MMWR Morb Mortal Wkly Rep. 1997; 46:288,295. [PubMed 9121422]

176. Anon. Advice for travelers. Med Lett Treat Guid. 2006; 4:25-34.

177. Gershon AA, Gardner P, Peter G et al. Guidelines from the Infectious Diseases Society of America: quality standards for immunization. Clin Infect Dis. 1997; 25:782-6. [IDIS 395784] [PubMed 9356789]

178. Centers for Disease Control and Prevention. Immunization of health-care workers: recommendations of the Advisory Committee on Immunization Practices (ACIP) and the Hospital Infection Control Practices Advisory Committee (HICPAC). MMWR Recomm Rep. 1997; 46(RR 18):27.

179. , Workowski KA, Berman SM. Sexually transmitted diseases treatment guidelines, 2006. MMWR Recomm Rep. 2006; 55:1-94. [PubMed 16888612]

180. Niu MT, Salive M, Krueger C et al. Two-year review of hepatitis A vaccine safety: data from the Vaccine Adverse Event Reporting System (VAERS). Clin Infect Dis. 1998; 26:1475-6. [IDIS 409174] [PubMed 9636890]

182. Stark K, Gunther M, Neuhaus R et al. Immunogenicity and safety of hepatitis A vaccine in liver and renal transplant recipients. J Infect Dis. 1999; 180:2014-7. [IDIS 440660] [PubMed 10558960]

183. Piazza M, Safary A, Vegnente A et al. Safety and immunogenicity of hepatitis A vaccine in infants: a candidate for inclusion in the childhood vaccination programme. Vaccine. 1999; 17:585-8. [PubMed 10075165]

184. Van Herck K, Van Damme P, Thoelen S. A high potency inactivated hepatitis A vaccine: long-term follow-up. Proceedings of 6th Conference of the International Society of Travel Medicine. Montreal, Quebec, Canada 1999. Abstract.

185. Sagliocca L, Amoroso P, Stroffolini T et al. Efficacy of hepatitis A vaccine in prevention of secondary hepatitis A infection: a randomized trial. Lancet. 1999; 353:1136-9. [IDIS 423809] [PubMed 10209977]

186. GlaxoSmithKline. Twinrix (hepatitis A inactivated and hepatitis B [recombinant] vaccine) prescribing information. Research Triangle Park, NC; 2009 May.

187. Kemper CA, Haubrich R, Frank I et al. Safety and immunogenicity of hepatitis A vaccine in human immunodeficiency virus-infected patients: a double-blind, randomized, placebo-controlled trial. J Infect Dis. 2003; 187:1327-31. [IDIS 522706] [PubMed 12696015]

188. Fiore AE, Shapiro CN, Sabin K et al. Hepatitis A vaccination of infants: effect of maternal antibody status on antibody persistence and response to booster dose. Pediatr Infect Dis. 2003; 22:354-9.

189. Food and Drug Administration. Amended economic impact analysis of final rule requiring use of labeling on natural rubber containing devices. 21 CFR Part 801. Final rule. (Docket No. 96N-0119) Fed Regist. 1998; 63:50660-704.

190. Food and Drug Administration. Latex-containing devices; user labeling. 21 CFR Part 801. Proposed rule. (Docket No. 96N-0119) Fed Regist. 1996; 61:32617-21.

191. Food and Drug Administration. Natural rubber-containing medical devices; user labeling. 21 CFR Part 801. Final rule. (Docket No. 96N-0119) Fed Regist. 1997; 62:51021-30.

192. Centers for Disease Control and Prevention. Prevention of hepatitis A through active or passive immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2006; 55(RR-7):1-23.

195. Centers for Disease Control and Prevention. Recommended adult immunization schedule—United States, 2010. MMWR Morb Mortal Wkly Rep. 2010; 59:.

196. . Update: Prevention of hepatitis A after exposure to hepatitis A virus and in international travelers. Updated recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2007; 56:1080-4. [PubMed 17947967]

197. Kaplan JE, Benson C, Holmes KH et al. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep. 2009; 58:1-207; quiz CE1-4.

198. Mofenson LM, Brady MT, Danner SP et al. Guidelines for the Prevention and Treatment of Opportunistic Infections among HIV-exposed and HIV-infected children: recommendations from CDC, the National Institutes of Health, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American Academy of Pediatrics. MMWR Recomm Rep. 2009; 58:1-166. [PubMed 19730409]

199. Victor JC, Monto AS, Surdina TY et al. Hepatitis A vaccine versus immune globulin for postexposure prophylaxis. N Engl J Med. 2007; 357:1685-94. [PubMed 17947390]

200. Centers for Disease Control and Prevention. Vaccine management: recommendations for storage and handling of selected biologicals. 2007 Nov. From CDC website (http://www.cdc.gov/vaccines/pubs/vac-mgt-book.htm).

201. American College of Obstetricians and Gynecologists. Immunization during pregnancy. Committee Opinion No. 282. Obstet Gynecol. 2003; 101:207-12. [PubMed 12517674]

202. Centers for Disease Control and Prevention. Hepatitis A vaccine information statement. 2006 Mar 21. From CDC website. ().

203. Centers for Disease Control and Prevention. Epidemiology and prevention of vaccine-preventable diseases. 10th ed. Washington DC: Public Health Foundation; 2007.

204. Centers for Disease Control and Prevention. Yellow fever vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2002; 51(RR-17):1-11.

205. Jong EC, Kaplan KM, Eves KA et al. An open randomized study of inactivated hepatitis A vaccine administered concomitantly with typhoid fever and yellow fever vaccines. J Travel Med. 2002; 9:66-70. [PubMed 12044272]

206. Lippert WC, Wall EJ. Optimal intramuscular needle-penetration depth. Pediatrics. 2008; 122:e556-63. [PubMed 18694903]

207. Groswasser J, Kahn A, Bouche B et al. Needle length and injection technique for efficient intramuscular vaccine delivery in infants and children evaluated through an ultrasonographic determination of subcutaneous and muscle layer thickness. Pediatrics. 1997; 100:400-3. [PubMed 9282716]

208. Centers for Disease Control and Prevention. ACIP provisional recommendations for the use of combination vaccines. August 28, 2009. From CDC website ().

209. Centers for Disease Control and Prevention (CDC), Advisory Committee on Immunization Practices. Updated recommendations from the Advisory Committee on Immunization Practices (ACIP) for use of hepatitis A vaccine in close contacts of newly arriving international adoptees. MMWR Morb Mortal Wkly Rep. 2009; 58:1006-7. [PubMed 19763077]

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