Hepatitis A Vaccine Inactivated (Systemic)


VA CLASSIFICATION
Primary: IM100


Note: This monograph is specific for the inactivated whole virus vaccine derived from hepatitis A virus (HAV) and grown in human diploid cell (MRC-5) culture.

Commonly used brand name(s): Havrix; Vaqta.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Immunizing agent (active)—

Indications

General considerations
Hepatitis A virus (HAV), previously known as the infectious hepatitis virus {27}, is acquired by ingesting uncooked or undercooked seafood from polluted water, swimming in polluted water, and by person-to-person spread {06} {12} {14} {18} {28}. Food and water are the leading sources of HAV transmission because of the relative stability of the virus itself, poor sanitation in large areas of the world, and abundant HAV shedding in feces {06} {12}.

Travelers to HAV-endemic areas should avoid eating uncooked or undercooked food, especially fruits and vegetables contaminated by polluted water or human fecal fertilizer, and shellfish taken from polluted waters, and should peel fruits themselves {06} {07} {16} {18}. Travelers also should avoid drinking polluted water and the ice and drinks made from it, and should avoid swimming or bathing in polluted fresh or ocean water {06} {07}.

General improvement in hygiene, especially in water supplies and sewage disposal, in many industrialized and industrializing countries has resulted in a falling level of natural immunity to the disease {20}. This in turn has led to a substantial rise in the proportion of persons with no protective antibodies, which places them at risk for HAV infection. It has been shown that seronegative travelers and military personnel visiting regions where HAV is endemic are at higher risk of hepatitis A {17} {20}. This higher risk has also been demonstrated in seronegative health care workers and day-care center staff {20}.

In developing countries, HAV infection in children is frequent and typically mild, leading to the formation of antibodies and immunity {04}. In such areas, there is at present little need for hepatitis A vaccine {04} {27}. However, in certain industrialized countries that have a higher level of sanitation, immunity is not acquired during childhood, and hepatitis A typically occurs in adults {04} {27}. Tourism is one of the largest businesses in many developing countries where hepatitis A is endemic, and susceptible travelers are at high risk of acquiring infection {04}.

Many travel medicine experts estimate that the morbidity from HAV among international travelers is much higher than that from other vaccine-preventable infections {06} {17}. HAV infection accounts for 20 to 25% of clinically apparent acute hepatitis cases worldwide {08}. In the U.S., 20 to 30% of all documented cases of acute viral hepatitis are due to HAV {15} {19}. Therefore, travelers to areas in which there is a recognized risk of exposure to HAV should take the necessary precautions {01} {06}. Risk is greatest for travelers to countries of Africa, Asia (except Japan), parts of the Caribbean, Central and South America, eastern Europe, the Mediterranean basin, the Middle East, and Mexico {01}. For travelers to these areas of the world, risk of infection increases with duration of travel, and will be highest in those who live in or visit rural areas, travel through back country areas, or frequently eat or drink in settings of poor sanitation {07}.

Accepted

Hepatitis A (prophylaxis)—Hepatitis A vaccine inactivated is indicated for preexposure immunization against disease caused by hepatitis A virus (HAV) in persons 2 years of age or older.
—Unless otherwise contraindicated, hepatitis A vaccine inactivated is indicated in persons 2 years of age or older who are at increased risk of infection by HAV and for any person wishing to obtain immunity {31}. Examples of groups identified as being at increased risk of infection include:    • International travelers {01} {05} {12} {17} {20} {27} {29} {31}. Persons from areas of low endemicity who travel to areas of intermediate or high endemicity are at risk for acquiring hepatitis A {05}. These areas include, but are not limited to, Africa, Asia (except Japan), parts of the Caribbean, Central and South America, eastern Europe, the Mediterranean basin, the Middle East, and Mexico. Current advisories from the Centers for Disease Control and Prevention (CDC) should be consulted for information about specific locales {01} {12}. Immunization should be considered for persons traveling to areas where hepatitis A is highly endemic {01}, for travel of long duration, and for those who travel repeatedly {05}. Primary immunization with hepatitis A vaccine inactivated should be completed at least 2 weeks prior to expected exposure to HAV {01}. Travelers to Australia, Canada, Japan, New Zealand, the U.S., and western Europe do not have a significantly increased risk of hepatitis A and, therefore, vaccination is not warranted {05} {08}.
   • Military personnel identified as being at increased risk {01} {08} {23} {27} {29}. Prevention of hepatitis A in military personnel is essential {22}. This is especially important for military personnel from developed countries who are deployed in areas where hepatitis A is common, particularly during conflicts {23}. Immunization should be considered for military personnel traveling to areas of higher endemicity for hepatitis A {23}.
   • People living in or relocating to areas of higher HAV endemicity {01} {08} {31}.
   • Populations that experience cyclic hepatitis A epidemics, such as Alaskan Eskimos and Native Americans {01} {08} {31}. Hepatitis A is endemic in Native Americans; infection rates approach 100 cases per 100,000 people {16}. In Alaskan Eskimos, large HAV epidemics occur every 10 to 12 years, resulting in thousands of cases of clinical illness and a few deaths {11}. Studies have shown the effectiveness of the hepatitis A vaccine in Alaskan Eskimos {11}. Consideration should be given to vaccination of these groups of people {01}.
   • Persons engaging in high-risk sexual activity {01}, such as sexually active homosexual and bisexual males {01} {05} {08} {25} {27} {31} {32}. Extensive hepatitis A outbreaks among homosexual men have been recognized in urban areas of the U.S., England, and Australia {05} {25}. Therefore, sexually active homosexual and bisexual men should be considered for vaccination with hepatitis A vaccine {01} {05} {32}.
   • Users of illicit injectable drugs {01} {05} {08} {27} {31}. Within the past decade, hepatitis A outbreaks have been reported with increasing frequency among users of illicit injectable drugs, both in the U.S. and Europe. As these individuals may have underlying liver disease due to chronic infection with other hepatotropic viruses, they may be at higher risk for severe complications from hepatitis A {05}. Consideration should be given to vaccination of these individuals {05}.
   • Residents of a community experiencing an outbreak of hepatitis A {01} {31}.
   • Certain institutional workers, such as caretakers for the developmentally disabled {01} {29} {31}.
   • Employees of child day-care centers {01} {05} {08} {27} {29} {31}. Outbreaks have been recognized among children and employees in day-care centers, and in some instances these outbreaks may be the source of larger community epidemics {05} {24}. Outbreaks have been recognized predominantly in centers with children who are not toilet-trained, and where clinical disease occurs in staff, parents, and older siblings of day-care center children {05}. The use of immune globulin (IG) has been well documented to control outbreaks of disease in these settings. Although use of hepatitis A vaccine has not yet been studied in the day-care center setting, the available data from efficacy studies suggest that the vaccine may be able to replace IG in control of day-care center outbreaks {05}.
   • Laboratory workers who handle live HAV {01} {08}.
   • Handlers of primate animals that may be harboring HAV {01} {08} {31}. Since viral hepatitis was recognized among primates caretakers {04}, consideration should be given to vaccination of handlers of primate animals that may be harboring HAV {01}.
   • Patients with hemophilia {31} {32}. Outbreaks of HAV infection in patients with hemophilia receiving solvent detergent–treated factor concentrates have been reported primarily in Europe {32}. However, in the U.S., three cases of HAV infection were reported in the mid-1990s in patients with hemophilia who received factor VIII concentrate from a single lot from one manufacturer {32}. Available seroprevalence data in the U.S. from patients with hemophilia do not allow accurate determination of risk {32}. Nevertheless, patients with hemophilia, especially those receiving solvent detergent–treated factor concentrates, may benefit from protection against HAV infection and should be considered for immunization {32}. Preimmunization testing for anti-HAV antibody may be cost-effective because seroprevalence rates among persons with hemophilia may be higher {32}.
   • Food handlers {05} {31} {32}. Food-borne outbreaks usually are associated with contamination of uncooked food during preparation by a food handler who is infected with HAV {32}. The most effective means to prevent these outbreaks is by careful hygienic practices during food preparation {32}. Little information is available concerning seroprevalence rates of HAV antibody in food handlers compared with that in the general population {32}. Therefore, routine hepatitis A vaccination is not indicated in this population {32}. However, economic, medicolegal, and public relations implications of a food-borne HAV outbreak from a commercial establishment may indicate that use of hepatitis A vaccine inactivated should be considered in some circumstances {32}. Factors to consider in this decision include the nature of the food (e.g., materials for salads) as well as the demographic characteristics, the average duration of employment, and the number of food handlers {32}.
   • Persons with chronic liver disease {01} {05} {31} {32}, including those with alcoholic cirrhosis, chronic hepatitis B, chronic hepatitis C, autoimmune hepatitis, and primary biliary cirrhosis {01}. Since clinical hepatitis A may be more severe in persons with chronic liver disease due to hepatitis viruses or other etiologies, vaccination of these persons should be considered {05}. Although few data exist about the immunogenicity and protective efficacy of hepatitis A vaccine inactivated in persons with chronic liver disease, no reason exists to suspect that the hepatitis A vaccine inactivated would aggravate the chronic condition {32}.


Unaccepted
Hepatitis A vaccine inactivated will not give protection from hepatitis caused by infectious agents other than HAV {01}.


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Source—
    Hepatitis A vaccine inactivated is a sterile suspension for intramuscular injection {01}. The vaccine is a whole virus vaccine derived from hepatitis A virus (HAV), grown in human diploid cell (MRC-5) culture, and inactivated with formalin {01} {02} {26}. The vaccine contains HAV antigen adsorbed onto aluminum provided as aluminum hydroxide {01} {02} {26}.


Protective effect

Clinical studies in animals {19} and humans have shown that hepatitis A vaccine inactivated is safe and highly immunogenic {20} {21}. Immunogenicity studies have shown that 70 to 90% of persons develop antibodies to HAV (anti-HAV) following a single dose, and nearly 100% of persons develop antibodies following two doses of vaccine {05}. The presence of anti-HAV confers protection against hepatitis A infection {01}. However, the lowest titer needed to confer protection has not been determined {01}. Antibody levels obtained after a single dose of vaccine are often higher than those obtained after a single dose of IG, and substantial levels of anti-HAV neutralizing antibody are present in the majority of recipients of a complete immunization series {05}. One immunogenicity study has suggested that simultaneous administration of large doses of immune globulin (IG) with the first vaccine dose may lower the active antibody response {05}. However, the lowering of antibody titer levels does not appear great enough to have an impact on the protective effect of the vaccine {05}.


Time to protective effect

After receiving the initial dose of hepatitis A vaccine, persons are considered protected in 4 weeks. For long-term protection, a second dose is needed 6 to 12 months later {10}. For persons who will travel to high-risk areas in < 4 weeks after the initial vaccine dose, IG (0.02 mL per kg of body weight) should be administered simultaneously with the first dose of vaccine but at different injection sites {10}.


Duration of protective effect

The duration of protection after vaccination is unknown. However, antibody decay studies suggest that measurable antibody will persist for many years {05}. Continued observation of immunized persons will be required to determine the need for later booster doses of vaccine {05}.


Precautions to Consider

Pregnancy/Reproduction

Pregnancy—
Adequate and well-controlled studies have not been done in humans {01}. However, hepatitis A vaccine inactivated, if indicated, should be given to pregnant women {32}. Although data on the safety of hepatitis A vaccine inactivated for the developing fetus are not available, no risk would be expected because the vaccine contains inactivated, purified viral proteins {32}. In contrast, infection with the hepatitis A virus (HAV) in a pregnant woman can result in severe disease in the mother {32}.

Studies have not been done in animals {01}.

FDA Pregnancy Category C {01} {03}.

Breast-feeding

It is not known whether hepatitis A vaccine inactivated is distributed into breast milk. However, problems in humans have not been documented {01} {03}.

Pediatrics

Children have the highest age-specific incidence of hepatitis A and are likely to play a role in its spread {26}. Hepatitis A vaccine inactivated is well tolerated and highly immunogenic and effective in children 2 years of age and older {01} {03} {18}. In a double-blind, controlled study in the U.S. involving 1037 children, aged 2 to 16 years, who were randomly assigned to receive either one intramuscular injection of inactivated hepatitis A vaccine or placebo, 25 cases of clinical hepatitis A occurred in the control group while none were noted in the vaccinated group, establishing a protective efficacy of 100% {08} {24}. A similar study performed in Thailand showed similar results {08}. Safety and efficacy of hepatitis A vaccine inactivated in infants and children younger than 2 years of age have not been established, and use is not recommended {01} {03}.


Geriatrics


No information is available on the relationship of age to the effects of hepatitis A vaccine inactivated in geriatric patients.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

Immunosuppressive agents or
Radiation therapy    (because normal defense mechanisms are suppressed, the patient's antibody response to hepatitis A vaccine inactivated may be decreased {01})



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With physiology/laboratory test values
Alanine aminotransferase (ALT [SGPT]) and
Alkaline phosphatase and
Aspartate aminotransferase (AST [SGOT])    (serum values may be increased {03} {13})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problem exists
» Hypersensitivity to hepatitis A vaccine inactivated    (there have been rare reports of anaphylaxis/anaphylactoid reactions following the use of hepatitis A vaccine inactivated in some countries {01}; therefore, persons experiencing hypersensitivity reactions after a dose of hepatitis A vaccine inactivated should not receive further doses of the vaccine {01}.)




Side/Adverse Effects

Note: Cases of convulsions, dizziness, encephalopathy, Guillain-Barré syndrome, multiple sclerosis, myelitis, neuropathy, and paresthesia have been reported following administration of hepatitis A vaccine inactivated {01}. However, no causal relationship has been established {01}.
Angioedema, dyspnea, erythema multiforme, hepatitis, hyperhidrosis, jaundice, lymphadenopathy, and syncope have been reported since market introduction of the vaccine, but the relationship to the vaccine is unclear {01}.

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence rare
    
Anaphylactic reaction {01}(difficulty in breathing or swallowing; hives; itching, especially of soles or palms; reddening of skin, especially around ears; swelling of eyes, face, or inside of nose; unusual tiredness or weakness, sudden and severe)



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Soreness at injection site {01}{02}{22}{24}—incidence 21 to 56%{32}

Note: Local reactions are common but generally mild {32}. Although rare, since market introduction of the vaccine, localized edema has also been reported following administration of the vaccine. {01}


Incidence less frequent
    
Anorexia (lack of appetite){01}{22}{24}
    
fever ³ 37.7 °C (100 °F) {01}
    
headache {01}{13}{21}{22}
    
malaise {09}{22}(general feeling of discomfort or illness)
    
nausea {09}
    
tenderness or warmth at injection site {01}{09}

Incidence rare
    
Arthralgia, arthritis, or myalgia {01}{22}(aches or pain in joints or muscles)
    
diarrhea or stomach cramps or pain
    
lymphadenopathy (swelling of glands in armpits or neck)
    
pruritus (itching)
    
urticaria (welts)
    
vomiting {01}





Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Hepatitis A Vaccine Inactivated (Systemic) .

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Hypersensitivity to hepatitis A vaccine inactivated





Use in children—Use is not recommended in infants and children younger than 2 years of age


Proper use of this medication

» Proper dosing


Side/adverse effects
Signs of potential side effects, especially anaphylactic reaction


General Dosing Information
Appropriate precautions should be taken prior to vaccine injection to prevent allergic or other unwanted reactions. Precautions should include a review of the patient's history regarding possible sensitivity and the ready availability of epinephrine 1:1000 and other appropriate agents used for control of immediate allergic reactions {03}.

Hepatitis A vaccine inactivated is administered by intramuscular injection. It should not be injected intravenously, intradermally, or subcutaneously {01} {03}.

The deltoid muscle (outer aspect of the upper arm) is the recommended site for the immunization of adults and older children {01} {03}. The vaccine should not be administered in the gluteal region since administration at this site may result in suboptimal response {01}.

Vaccination of an immune person is not contraindicated and does not increase the risk of adverse effects. Prevaccination serologic testing may be indicated for adult travelers who probably have had prior hepatitis A virus (HAV) infection, if the cost of testing is less than the cost of vaccination and if testing will not interfere with completion of the vaccine series. Such persons may include those older than 40 years of age and those born in areas of the world having a high endemicity of HAV infection. Postvaccination testing for serologic response is not indicated {05} {10}.
The Advisory Committee on Immunization Practices (ACIP) offers the following recommendations for the use of inactivated hepatitis A vaccine among international travelers:

   • All susceptible persons traveling to or working in countries with intermediate or high HAV endemicity (countries other than Australia, Canada, Japan, New Zealand, the U.S., and countries in Scandinavia and western Europe) should be vaccinated or receive immune globulin (IG) before departure. Hepatitis A vaccine at the age-appropriate dose is preferred for persons who plan to travel repeatedly to, or reside for long periods in, these high-risk areas. IG is recommended for travelers younger than 2 years of age {10}.
   • After receiving the initial dose of hepatitis A vaccine, persons are considered protected in 4 weeks. For long-term protection, a second dose is needed 6 to 12 months later. For persons who will travel to high-risk areas in less than 4 weeks after the initial vaccine dose, IG (0.02 mL per kg of body weight) should be administered simultaneously with the first dose of vaccine but at a different injection site {10}.
   • Persons who are allergic to a vaccine component or otherwise elect not to receive the vaccine should receive a single dose of IG (0.02 mL per kg of body weight), which provides effective protection against hepatitis A for up to 3 months. IG should be administered at 0.06 mL per kg of body weight and must be repeated if travel is longer than 5 months {10}.
Hepatitis A vaccine inactivated can be administered simultaneously with other vaccines and toxoids, including cholera, diphtheria, hepatitis B, Japanese encephalitis, rabies, tetanus, oral typhoid, and yellow fever, without affecting immunogenicity or increasing the frequency of adverse effects {10} {20} {22}. However, during simultaneous administration, the vaccines should be given at separate injection sites {10}. Hepatitis A and hepatitis B vaccines induce a similar immune response when given either separately or concomitantly {20}.

When IG is given concurrently with the first dose of vaccine, the proportion of persons who develop protective levels of anti-HAV antibody is not affected, but antibody concentrations are lower. Because the final concentrations of anti-HAV antibody are substantially higher than those considered to be protective, this reduced immunogenicity is not expected to be clinically important {10}.

Hepatitis A vaccine inactivated should replace IG for use in preexposure prophylaxis against HAV {33}. On the other hand, hepatitis A vaccine inactivated has little to offer after a person has been exposed to HAV, because the need for protection is immediate and exposure is almost always limited to a brief period {33}. Thus, when hepatitis A is recognized in a patient, close family member, or household contact, IG should be given for prophylaxis, optimally within two weeks after exposure {33}.

Hepatitis A vaccine inactivated does not enhance disease progression in human immunodeficiency virus (HIV)–infected persons and can be administered safely to persons who are HIV-positive {20}.

For treatment of adverse effects
Recommended treatment consists of the following:
   • For mild hypersensitivity reaction—Administering antihistamines, and, if necessary, corticosteroids {34}. In mild anaphylaxis, antihistamines or subcutaneous epinephrine may be all that is necessary if the condition is progressing slowly and is not life-threatening, regardless of the organ or system affected {34}. Under these circumstances the risks associated with intravenous epinephrine administration outweigh the benefits {34}.
   • For severe hypersensitivity or anaphylactic reaction—Administering epinephrine. Antihistamines or corticosteroids may also be administered as required {34}. Epinephrine is the treatment of choice for severe hypersensitivity or anaphylactic reaction {34}. If the patient's condition is not stable, epinephrine should be infused {34}. Norepinephrine may be preferable if there is no bronchospasm {34}. For bronchospasm, epinephrine should be given with corticosteroids {34}. Other bronchodilators, such as intravenous aminophylline or albuterol by nebulization, also should be considered {34}.

Note: All cases of suspected or confirmed side/adverse effects following the administration of hepatitis A vaccine inactivated should be reported to the U.S. Department of Health and Human Services' Vaccine Adverse Events Reporting System (VAERS) at 1–800–822–7967.



Parenteral Dosage Forms

HEPATITIS A VACCINE INACTIVATED INJECTION

Usual adult dose
Hepatitis A (prophylaxis)
Intramuscular, a single dose of 1440 enzyme linked immunosorbent assay (ELISA) Units ( Havrix {01} {02} {31}) or 50 Units ( Vaqta {03} {31}).


Note: A booster dose is recommended six months after the first dose of ( Vaqta {03} {31}), or six to twelve months after the first dose of ( Havrix {01} {02} {31}).


Usual pediatric dose
Hepatitis A (prophylaxis)
Children 2 to 18 years of age—Intramuscular, a single dose of 720 enzyme linked immunosorbent assay (ELISA) Units {30} {31} or two doses of 360 enzyme linked immunosorbent assay (ELISA) Units given one month apart ( Havrix—U.S. and Canada {01} {02} {31}).

Children 2 to 17 years of age—Intramuscular, a single dose of 25 Units ( Vaqta—U.S. {03} {31}).

Children younger than 2 years of age—Use is not recommended.


Note: A booster dose is recommended six months after the first dose of ( Vaqta—U.S. {03} {31}), or six to twelve months after the first dose of ( Havrix—U.S. and Canada {01} {02} {31}).


Strength(s) usually available
U.S.—


1440 enzyme linked immunosorbent assay (ELISA) units viral antigen, adsorbed on 0.5 mg of aluminum hydroxide in each 1-mL adult dose (Rx) [Havrix (formalin approximately 0.1 mg)]{01}{02}


360 enzyme linked immunosorbent assay (ELISA) units viral antigen, adsorbed on 0.25 mg of aluminum hydroxide in each 0.5-mL pediatric dose (Rx) [Havrix (formalin approximately 0.05 mg)]{01}{02}


720 enzyme linked immunosorbent assay (ELISA) units viral antigen, adsorbed on 0.25 mg of aluminum hydroxide in each 0.5-mL pediatric dose (Rx) [Havrix (formalin approximately 0.05 mg)]{30}


50 units viral antigen, adsorbed on 0.45 mg of aluminum hydroxide in each 1-mL adult dose (Rx) [Vaqta (formaldehyde approximately 0.8 mcg)]{03}


25 units viral antigen, adsorbed on 0.225 mg of aluminum hydroxide in each 0.5-mL pediatric dose (Rx) [Vaqta (formaldehyde approximately 0.4 mcg)]{03}

Canada—


1440 enzyme linked immunosorbent assay (ELISA) units viral antigen, adsorbed on 0.5 mg of aluminum hydroxide in each 1-mL adult dose (Rx) [Havrix (formalin approximately 0.1 mg)]{01}{02}


360 enzyme linked immunosorbent assay (ELISA) units viral antigen, adsorbed on 0.25 mg of aluminum hydroxide in each 0.5-mL pediatric dose (Rx) [Havrix (formalin approximately 0.05 mg)]{01}{02}


50 units viral antigen, adsorbed on 0.45 mg of aluminum hydroxide in each 1-mL adult dose (Rx) [Vaqta (formaldehyde approximately 0.8 mcg)]{35}


25 units viral antigen, adsorbed on 0.225 mg of aluminum hydroxide in each 0.5-mL pediatric dose (Rx) [Vaqta (formaldehyde approximately 0.4 mcg)]{35}

Packaging and storage:
Store between 2 and 8 ºC (36 and 46 ºF), unless otherwise specified by the manufacturer. Protect from freezing {01} {02} {03}.

Preparation of dosage form:
The vaccine should be used as supplied, and should not be diluted {01} {02} {03}. The vial should be shaken well immediately before withdrawal of the dose {01} {02} {03}. In addition, thorough agitation at the time of administration is necessary to maintain suspension of the vaccine. After agitation, the vaccine is a slightly opaque, white suspension {01} {02} {03}. The vaccine should be discarded if the suspension does not appear homogenous {01} {02} {03}.

Stability:
Storage below the recommended temperature may reduce potency {01} {02} {03}. Freezing destroys potency, and the vaccine should be discarded if freezing occurs {01} {02} {03}.

Auxiliary labeling:
   • Do not freeze; discard if freezing occurs {01} {02} {03}.
   • Shake well {01} {02} {03}.



Revised: 07/31/1998



References
  1. Havrix package insert (SmithKline Beecham—US), Rev 6/97, Rec 10/97.
  1. Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 31st ed. Canadian Pharmaceutical Association; 1996. p. 604-5.
  1. VAQTA package insert (Merck—US), Rev 3/96, Rec 5/96.
  1. Melinick JL. History and epidemiology of hepatitis A virus. J Infect Dis 1995; 171(Suppl 1): S2-S8.
  1. Memorandum from a WHO meeting: Public health control of hepatitis A. Bull World Health Organ 1995; 73(1): 15-20.
  1. Wolfe MS. Hepatitis A and the American traveler. J Infect Dis 1995; 171(Suppl 1): S29-S32.
  1. Centers for Disease Control. Health information for international travel 1995. Washington, D.C.: Government Printing Office, 1995: 112-5.
  1. Strader DB, Seeff LB. New hepatitis A vaccines and their role in prevention. Drugs 1996; 51(3): 359-66.
  1. Lo YC, Lee SS, Wong KH, et al. Inactivated hepatitis A vaccine in healthy Chinese adults. J Intern Med 1996; 239: 173-6.
  1. Centers for Disease Control. Recommendations of the Advisory Committee on Immunization Practices (ACIP): licensure of inactivated hepatitis A vaccine and recommendations for use among international travelers. MMWR Morb Mortal Wkly Rep 1995; 44(29): 559-60.
  1. 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.
  1. Steffen R, Kane MA, Shapiro CN, et al. Epidemiology and prevention of hepatitis A in travelers. JAMA 1994; 272(11): 885-9.
  1. Innis BL, Snitbhan R, Kunasol P, et al. Protection against hepatitis A by an inactivated vaccine. JAMA 1994; 271(17): 1328-34.
  1. Stapleton JT. Host immune response to hepatitis A virus. J Infect Dis 1995; 171(Suppl 1): S9-S14.
  1. 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-S18.
  1. Koff RS. Seroepidemiology of hepatitis A in the United States. J Infect Dis 1995; 171(Suppl 1): S19-S23.
  1. Steffen R. Hepatitis A in travelers: the European experience. J Infect Dis 1995; 171(Suppl 1): S24-S28.
  1. Andre FE. Approaches to a vaccine against hepatitis A: development and manufacture of an inactivated vaccine. J Infect Dis 1995; 171(Suppl 1): S33-S39.
  1. D'Hondt E, Purcell RH, Emerson SU, et al. Efficacy of an inactivated hepatitis A vaccine in pre- and postexposure conditions in marmosets. J Infect Dis 1995; 171(Suppl 1): S40-S43.
  1. Clemens R, Safary A, Hepburn A, et al. Clinical experience with an inactivated hepatitis A vaccine. J Infect Dis 1995; 171(Suppl 1): S44-S49.
  1. 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-S52.
  1. Hoke CH, 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-S60.
  1. DeFraites RF, Feighner BH, Binn LN. Immunization of U.S. 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-S69.
  1. Balcarek KB, Bagley MR, Pass RF, et al. Safety and immunogenicity of an inactivated hepatitis A vaccine in preschool children. J Infect Dis 1995; 171(Suppl 1): S70-S72.
  1. 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.
  1. Marwick C. Changes ahead in childhood immunization: Vaqta for hepatitis A. JAMA 1996; 275(8): 582.
  1. Hirschman SZ. Current therapeutic approaches to viral hepatitis. Clin Infect Dis 1995; 20: 741-6.
  1. Bianco C. Hepatitis testing. Immun Invest 1995; 24(1&2): 155-61.
  1. Laufer DS, Hurni W, Watson B, et al. Saliva and serum as diagnostic media for antibody to hepatitis A virus in adults and in individuals who have received an inactivated hepatitis A vaccine. Clin Infect Dis 1995; 20: 869-71.
  1. Reviewer comment, 12/96.
  1. Centers for Disease Control. Recommendations of the Advisory Committee on Immunization Practices (ACIP): prevention of hepatitis A through active or passive immunization. MMWR Morb Mortal Wkly Rep 1996; 45(15): 1-30.
  1. American Academy of Pediatrics. Hepatitis A. In: Peter G, editor. 1997 Red Book: report of the Committee on Infectious Diseases. 24th ed. Elk Grove Village, IL: American Academy of Pediatrics; 1997. p. 237-46.
  1. Wood AJJ, Lemon SM, Thomas DL. Vaccines to prevent viral hepatitis. N Engl J Med 1997; 336(3): 196-204.
  1. Fisher M. Treatment of acute anaphylaxis. BMJ 1995; 311: 731-3.
  1. Reviewer comment, 05/98.
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