Generic Name: hepatitis A adult vaccine

Brand Names: Havrix, Vaqta

Uses

Prevention of Hepatitis A Virus (HAV) Infection

Prevention of HAV infection in adults, adolescents, and children ≥1 year of age.

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. Overall HAV case-fatality rate in the US is 0.3–0.6%, but increases to about 2% in those ≥40 years of age. HAV is highly contagious (especially during the 2 weeks before onset of symptoms). The virus is transmitted person-to-person, principally through the fecal-oral route. HAV infection remains one of the most commonly reported vaccine-preventable diseases in travelers.

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., 12–23 months of age), unless contraindicated. (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.

For internationally adopted children whose immune status is uncertain, vaccinations can be repeated or serologic tests performed to confirm immunity. 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. (See Dosage and Administration.) Alternatively, test for serologic evidence of susceptibility to HAV. (See Pre-and Postvaccination Serologic Testing under Cautions.)

HepA vaccine will not prevent hepatitis caused by HBV, hepatitis C virus (HCV), hepatitis E virus (HEV), or other viruses known to infect the liver.

When vaccination against both HAV and HBV infection is indicated in adults ≥19 years of age, the commercially available fixed-combination bivalent vaccine containing HepA vaccine and hepatitis B vaccine (HepA-HepB; Twinrix^®) can be used.

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.

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.

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.

In states, counties, or communities where the rate of HAV infection is high, ACIP recommends that existing selective preexposure HepA vaccination programs for children 2–18 years of age be maintained. 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. In areas without existing selective vaccination programs, catch-up vaccination of unvaccinated children 2–18 years of age may be considered. Such catch-up vaccination programs may be especially warranted because of rising incidence or ongoing outbreaks of HAV among children or adolescents.

HIV-infected individuals, especially those with chronic liver disease (including those coinfected with HBV or HCV), should be vaccinated against HAV. The fact that the vaccine may be less immunogenic in immunocompromised individuals should be considered. (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. This includes individuals who will be traveling to or working in any region outside the US, Canada, Australia, New Zealand, Japan, and developed countries in Europe. Because the risk for travelers to developed areas of the Caribbean is unclear, travelers to Caribbean areas where questionable sanitation is anticipated should be considered at high risk of exposure and should be vaccinated. Ideally, the first vaccine dose should be administered as soon as travel is considered. (See Preexposure Vaccination Against HAV Infection in High-risk Groups under Pediatric Patients and also Adults, in Dosage and Administration.) 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. The fixed-combination bivalent 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. (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. Sexually active male adolescents and adults who have sex with men (homosexual, bisexual) should be vaccinated against HAV. 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.

Individuals who illicitly use injectable or noninjectable drugs may be at increased risk of exposure to HAV infection and should be vaccinated against HAV. 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). Clinicians should consider implementing strategies to increase vaccine coverage in these patients (e.g., use of standing orders).

Individuals with hemophilia or other congenital bleeding disorders who are HAV-seronegative should be vaccinated against HAV. 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. 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.

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

Individuals with chronic liver disease and those who are awaiting or have undergone liver transplantation should be vaccinated against HAV. 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.

Some clinicians recommend that individuals with HBV or HCV infection, autoimmune hepatitis, or primary biliary cirrhosis be vaccinated against HAV. 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.

Food handlers and restaurant employees may be vaccinated against HAV. 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. 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. Routine use of HepA vaccine in all food handlers is not economically feasible from a societal or food industry perspective. Occasionally, vaccination of food handlers may be considered during a community outbreak.

If a community-wide outbreak of HAV occurs, accelerated HepA vaccination programs should be considered. 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. Routine vaccination of children in affected communities should continue in order to maintain high levels of immunity and prevent future epidemics.

HAV outbreaks in child-care centers have decreased considerably since the implementation of routine childhood immunization against HAV and further decreases are expected. ACIP does not recommend routine preexposure vaccination with HepA vaccine for personnel in child-care centers. However, HAV postexposure prophylaxis may be indicated if HAV is reported in attendees or staff. (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. Outbreaks involving student-to-student transmission in primary and secondary schools are rare in developed countries, but outbreaks have been documented; in developing countries, outbreaks among children in primary schools are more common. 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. (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. 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. 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. (See Postexposure Prophylaxis of HAV Infection under Uses.) The usefulness of HepA vaccine in controlling outbreaks in health-care settings has not been investigated.

Postexposure Prophylaxis of HAV Infection

Postexposure prophylaxis of HAV† in susceptible individuals with recent (within 2 weeks) exposure to HAV.

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).

Although IGIM was traditionally the recommended regimen for HAV postexposure prophylaxis since it is 80–90% effective if administered within 2 weeks of exposure, 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. 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).

For HAV postexposure prophylaxis in healthy individuals 12 months to 40 years of age, ACIP prefers use of monovalent HepA vaccine. 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. 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.

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. 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. (See Dosage under Dosage and Administration.)

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

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

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. 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).

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

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). 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. 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.

If HAV is diagnosed in a food handler, ACIP recommends HAV postexposure prophylaxis (within 2 weeks) for other food handlers at the same establishment. 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. Settings where repeated HAV exposure might have occurred (e.g., institutional cafeterias) warrant stronger consideration of postexposure prophylaxis for patrons.

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.

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.

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.

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.

Dosage and Administration

Administration

IM Injection

Administer monovalent HepA vaccine (Havrix^®, Vaqta^®) by IM injection.

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

Do not administer IV, intradermally, or sub-Q.

Shake vaccine well immediately prior to administration to provide a uniform, slightly turbid, white, suspension. Discard vaccine if it contains particulates, appears discolored, or cannot be resuspended with thorough agitation.

Do not dilute. Do not mix with any other vaccine or solution.

Depending on patient age, administer IM into the deltoid muscle or anterolateral thigh. To ensure delivery into muscle, IM injections should be made at a 90° angle to the skin using a needle length appropriate for the individual's age and body mass.

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

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

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.

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). (See Interactions.)

May be given simultaneously with other age-appropriate vaccines during the same health-care visit (using different syringes and different injection sites). (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. Separate injection sites by at least 1 inch (if anatomically feasible) to allow appropriate attribution of any local adverse effects that may occur. 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.

Dosage

Dose and dosing schedule vary according to the individual’s age and specific vaccine administered. Follow dosage recommendations for the specific preparation used.

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

For both monovalent vaccines, the minimum interval between the first and second dose is 6 months. Dosage for the second (booster) dose should be based on the individual's age at the time the second dose is given. Although only limited data are available regarding the immune response to delayed administration of the second dose, 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.

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

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.

Give initial dose of 720 units. Give second (booster) dose of 720 units at 6–12 months after initial dose.

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

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

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. However, whenever possible, the formulation chosen for the initial dose should be used for the booster dose in the same individual.

Duration of immunity and need for subsequent doses after the initial dose and additional (booster) dose not fully determined. (See Duration of Immunity under Cautions.) Subsequent booster doses not currently recommended.

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

IM

Primary immunization consists of 2 doses given 6–18 months apart. Use pediatric/adolescent formulation containing 25 units/0.5 mL.

Give initial dose of 25 units. Give second (booster) dose of 25 units 6–18 months after initial dose.

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

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

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. However, whenever possible, the formulation chosen for the initial dose should be used for the booster dose in the same individual.

Duration of protection and need for subsequent doses after the initial dose and second (booster) dose not fully determined. (See Duration of Immunity under Cautions.) Subsequent booster doses not currently recommended.

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. (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.

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. For most healthy children, a single dose will provide adequate protection regardless of the scheduled departure date. 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).

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. Efficacy of HAV postexposure prophylaxis not established if given >2 weeks after exposure. (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. (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).†

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.†

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.

Given initial dose of 1440 units. Give second (booster) dose of 1440 units 6–12 months after initial dose.

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. However, whenever possible, the formulation chosen for the initial dose should be used for the booster dose in the same individual.

Duration of protection and need for subsequent doses after the initial dose and second (booster) dose not fully determined. (See Duration of Immunity under Cautions.) Subsequent booster doses not currently recommended.

Adults ≥19 Years of Age (Vaqta^®)

IM

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

Give initial dose of 50 units. Give second (booster) dose of 50 units 6–18 months after initial dose.

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. However, whenever possible, the formulation chosen for the initial dose should be used for subsequent doses in the same individual.

Duration of protection and need for subsequent doses after the initial primary dose and second (booster) dose not fully determined. (See Duration of Immunity under Cautions.) Subsequent booster doses not currently recommended.

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

IM

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

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.

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.

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

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. (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.

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. For most healthy adults ≤40 years of age, a single vaccine dose will provide adequate protection regardless of the scheduled departure date. 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).

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. Efficacy of HAV postexposure prophylaxis not established if given >2 weeks after exposure. (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.†

In previously unvaccinated individuals, give primary immunization with the usually recommended age-appropriate initial and second (booster) doses of the vaccine. (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).†

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.†

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

No specific dosage recommendations.

Geriatric Patients

No specific dosage recommendations.

Cautions

Contraindications

Monovalent HepA Vaccine (Havrix^®, Vaqta^®)
• Hypersensitivity to any ingredient in the formulation, including neomycin.
• Previous hypersensitivity reaction to any HepA vaccine.

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

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

Although risk of sensitivity reactions appears to be low, anaphylaxis and anaphylactoid manifestations have been reported rarely. Bronchoconstriction, asthma, and wheezing 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.

Epinephrine and other appropriate agents should be readily available in case anaphylaxis or an anaphylactoid reaction occurs. If a hypersensitivity reaction occurs, immediately institute appropriate therapy as indicated.

Do not administer additional vaccine doses to individuals who had hypersensitivity reactions to a previous dose.

Neomycin Allergy

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

Neomycin allergy usually results in delayed-type (cell-mediated) hypersensitivity reactions manifested as contact dermatitis. 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.

Latex Sensitivity

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

Some individuals may be hypersensitive to natural latex proteins. Take appropriate precautions if these preparations are administered to individuals with a history of latex sensitivity.

General Precautions

Limitations of Vaccine Effectiveness

May not protect all vaccine recipients against HAV infection.

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

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.

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. (See Actions.)

Monovalent HepA vaccine (Havrix^® or Vaqta^®) provides protection only against HAV. Fixed-combination bivalent vaccine containing HepA virus vaccine and HepB vaccine (HepA-HepB; Twinrix^®) provides protection only against HAV and HBV. These vaccines do not provide protection against other hepatitis viruses (e.g., HCV, HEV).

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.

The fixed-combination bivalent 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. (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.

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

Individuals with Altered Immunocompetence

May be administered to individuals immunosuppressed as the result of disease or immunosuppressive therapy. Consider possibility that the immune response to the vaccine and efficacy may be reduced in these individuals.

Recommendations regarding use in HIV-infected individuals are the same as those for individuals who are not infected with HIV. 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, CDC, NIH, and IDSA recommend that such individuals receive 2 doses of HepA vaccine. The vaccine should preferably be administered before CD4⁺ T-cell counts decline to <200 cells/mm³ since the immunologic response will be better.

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.

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.

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).

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.

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. 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. If patient is receiving antihemophilia therapy, administer the IM vaccine shortly after a scheduled dose of such therapy.

Advise individual and/or their family about the risk of hematoma from IM injections.

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. Natural HAV infection produces lifelong immunity and high rates of HAV seropositivity are present in some populations for whom HepA vaccination is recommended. However, vaccination of an individual with preexisting immunity is not associated with any unusual risk.

Prevaccination serologic testing is not indicated before routine or catch-up vaccination of children or most adolescents.

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.

If prevaccination testing is indicated, commercially available tests that measure total anti-HAV (i.e., both IgG and IgM anti-HAV) are used. A positive result indicates the individual is immune as the result of past infection or vaccination.

Routine screening of contacts for preexisting HAV immunity prior to administration of HAV postexposure prophylaxis is not recommended. 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.

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. However, the National Hemophilia Foundation’s Medical and Scientific Advisory Council (MASAC) strongly recommends such testing following HepA vaccination in adults and children with hemophilia.

Use of Fixed Combinations

Fixed-combination bivalent vaccine containing HepA vaccine and HepB vaccine (HepA-HepB; Twinrix^®) should not be used for preexposure vaccination of travelers who will depart within 2 weeks after receipt of the vaccine; the bivalent vaccine contains less HAV antigen and may be less immunogenic than the monovalent vaccine.

Fixed-combination bivalent vaccine containing HepA vaccine and HepB vaccine (HepA-HepB; Twinrix^®) should not be used for HAV postexposure prophylaxis; the bivalent vaccine contains less HAV antigen and may be less immunogenic than the monovalent vaccine.

Improper Storage and Handling

Improper storage or handling of vaccines may result in loss of vaccine potency and reduced immune response in vaccinees.

Do not administer HepA vaccine that has been mishandled or has not been stored at the recommended temperature (2–8°C). (See Storage under Stability.)

Inspect all vaccines upon delivery and monitor during storage to ensure that the appropriate temperature is maintained.

Specific Populations

Pregnancy

Havrix^® or Vaqta^®: Category C.

Twinrix^®: Category C. Pregnancy registry at 888-825-5249. Clinicians or vaccinees should report any exposure to the vaccine that occurs during pregnancy.

Because HepA vaccine is an inactivated vaccine, the theoretical risk to the fetus is expected to be low. 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.

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.

Lactation

Use with caution in nursing women.

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

Pediatric Use

Havrix^® or Vaqta^®: Safety and efficacy not established in children <12 months of age. In young infants, passively acquired maternal anti-HAV antibody may interfere with the active immune response to HepA vaccine. 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).

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

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.

Vaqta^®: Clinical studies and postmarketing safety studies included individuals ≥65 years of age. 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.

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

Common Adverse Effects

Havrix^® and Vaqta^®: Injection site reactions (soreness, tenderness, pain, erythema, warmth, induration), headache, GI effects (nausea, vomiting, diarrhea, anorexia), irritability, fatigue/asthenia, fever, rash.

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

Interactions

Other Vaccines

Although specific studies may not be available evaluating concurrent administration with each antigen, simultaneous administration with other age-appropriate vaccines, including live virus vaccines, toxoids, or inactivated or recombinant vaccines, during the same health-care visit is not expected to affect immunologic responses or adverse reactions to any of the preparations. 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. However, each vaccine should be administered using a different syringe and different injection site.

Specific Drugs and Laboratory Tests

Stability

Storage

Parenteral

Injectable Suspension, for IM Use

Havrix^® and Vaqta^®: 2–8°C. Do not freeze; if freezing occurs, discard vaccine.

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

Havrix^®, Vaqta^®, and Twinrix^® do not contain thimerosal or any other preservatives.

Actions

• HepA vaccine is a noninfectious, sterile suspension of cell culture-adapted, attenuated HAV. The vaccine virus is propagated in human MRC-5 diploid fibroblasts, purified, inactivated with formalin, and adsorbed onto an aluminum adjuvant.
• HepA vaccine is commercially available as monovalent vaccine (Havrix^®, Vaqta^®) and as a fixed-combination bivalent vaccine containing both HAV and HBV antigens (HepA-HepB; Twinrix^®).
• Havrix^® and Vaqta^® contain different HAV antigens, but are considered to have equivalent immunogenicity when administered in recommended dosages. Twinrix^® contains the same HAV antigen as Havrix^® (but in a lower concentration) and the same HBV antigen as Engerix-B^® HepB vaccine.
• HepA vaccine stimulates active immunity to HAV infection by inducing production of HAV-specific IgG and IgM antibodies (anti-HAV).
• HepA vaccine is highly immunogenic in most adults, adolescents, and children ≥1 year of age. 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. 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.
• 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.
• Although vaccine-induced anti-HAV levels are lower than those induced by natural infection, protection against HAV is virtually complete in those who develop anti-HAV after immunization.
• 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. HAV also can be spread by infected food handlers, sewage-contaminated drinking water, raw or undercooked shellfish (e.g., clams, mussels, oysters) from contaminated waters, uncooked contaminated foods (e.g. fruits, vegetables), poor hygienic conditions during travel to certain areas of the world, closed living conditions (e.g., among institutionalized children and adults), health-care settings, and parenteral transmission (e.g., transfusions of blood or plasma-derived preparations from HAV-infected individuals, sharing needles with infected individuals).
• Natural HAV infection results in lifelong immunity. Because of HepA vaccination programs, the rate of HAV infection has declined sharply in the US during the last decade, especially among children. 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).
• The minimum titer of anti-HAV conferring protection against HAV has not been established. 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.

Advice to Patients

• Provide copy of manufacturer's patient information to the patient and/or patient's parent or guardian. 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 http://www.cdc.gov/vaccines/pubs/vis/default.htm).
• Advise patient and/or patient's parent or guardian of the risks and benefits of vaccination with HepA vaccine.

• Importance of receiving both the initial dose and second (booster) dose to ensure the highest level of protection against HAV.
• Importance of informing clinicians if any adverse reactions (e.g., hypersensitivity reactions) occur. Clinicians or individuals can report any adverse reactions that occur following vaccination to Vaccine Adverse Event Reporting System (VAERS) at 800-822-7967 or http://www.vaers.hhs.gov/.
• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.
• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

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

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 09/2009. For the most current and up-to-date pricing information, please visit www.drugstore.com. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

AHFS Drug Information. © Copyright, 1959-2009, Selected Revisions June 2008. 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.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.