Notice to Readers Licensure of Inactivated Hepatitis A Vaccine and Recommendations for Use Among International Travelers

In February 1995, Havrix(R) * , an inactivated hepatitis A vaccine distributed by SmithKline Beecham Pharmaceuticals (Philadelphia, Pennsylvania) was licensed by the Food and Drug Administration for use in persons aged greater than or equal to 2 years to prevent hepatitis A virus (HAV) infection. The vaccine is licensed in adult and pediatric formulations, with different dosages and administration schedules Table_1 and should be administered by intramuscular injection into the deltoid muscle.

Immunogenicity studies have indicated that virtually 100% of children, adolescents, and adults develop protective levels of antibody to hepatitis A virus (anti-HAV) after completing the vaccine series (1,2). Based on a controlled clinical trial, the efficacy of two doses of vaccine (360 enzyme-linked immunosorbent assay units) administered 1 month apart in preventing hepatitis A in children was estimated to be 94% (95% confidence interval=79%-99%) (3). Vaccine recipients have been followed for as long as 4 years and still have protective levels of anti-HAV. Kinetic models of antibody decline suggest that protective levels of anti-HAV could persist for at least 20 years (1,4).

Hepatitis A vaccine can be administered simultaneously with other vaccines and toxoids -- including hepatitis B, diphtheria, tetanus, oral typhoid, cholera, Japanese encephalitis, rabies, and yellow fever -- without affecting immunogenicity or increasing the frequency of adverse events (5,6). However, during simultaneous administration, the vaccines should be given at separate injection sites. When immune globulin (IG) is given concurrently with the first dose of vaccine, the proportion of persons who develop protective levels of anti-HAV is not affected, but antibody concentrations are lower. Because the final concentrations of anti-HAV are substantially higher than that considered to be protective, this reduced immunogenicity is not expected to be clinically important (7).

Vaccination of an immune person is not contraindicated and does not increase the risk for adverse effects. Prevaccination serologic testing may be indicated for adult travelers who probably have had prior 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 aged greater than 40 years and those born in areas of the world with a high endemicity of HAV infection (see recommendations). Postvaccination testing for serologic response is not indicated.

The Advisory Committee on Immunization Practices (ACIP) offers the following interim recommendations for the use of inactivated hepatitis A vaccine among international travelers.

1. All susceptible persons traveling to or working in countries with intermediate or high HAV endemicity (countries other than Australia, Canada, Japan, New Zealand, and countries in Western Europe and Scandinavia) should be vaccinated with hepatitis A vaccine or receive IG before departure. Hepatitis A vaccine at the age-appropriate dose Table_1 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 aged less than 2 years.

2. After receiving the initial dose of hepatitis A vaccine, persons are considered to be protected by 4 weeks. For long-term protection, a second dose is needed 6-12 months later. For persons who will travel to high-risk areas 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 different injection sites.

3. Persons who are allergic to a vaccine component or otherwise elect not to receive 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 greater than 5 months.

The complete ACIP recommendations for the prevention of hepatitis A will be published. Additional information about hepatitis A vaccine is available from CDC's Hepatitis Branch, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, telephone (404) 639-3048. Reported By: Advisory Committee on Immunization Practices. Div of Viral and Rickettsial Diseases, National Center for Infectious Diseases, CDC.

References

1. Clemens R, Safary A, Hepburn A, Roche C, Stanbury WJ, Andre FE. Clinical experience with an inactivated hepatitis A vaccine. J Infect Dis 1995;171(suppl 1):S44-S49.

2. Balcarek DB, Bagley MR, Pass RF, Schiff ER, Krause DS. Safety and immunogenicity of an inactivated hepatitis A vaccine in preschool children. J Infect Dis 1995;171(suppl 1):S70-S72.

3. Innis BL, Snitbhan R, Kunasol P, et al. Protection against hepatitis A by an inactivated vaccine. JAMA 1994;271:1328-34.

4. Ambrosch F, Widermann G, Andre FE, et al. Comparison of HAV antibodies induced by vaccination, passive immunization, and natural infection. In: Hollinger FB, Lemon SM, Margolis HS, eds. Viral hepatitis and liver disease. Baltimore: Williams and Wilkins, 1991:98-100.

5. Ambrosch F, Andre FE, Delem A, et al. Simultaneous vaccination against hepatitis A and B: results of a controlled study. Vaccine 1992;10(suppl 1):S142-S145.

6. Kruppenbacher J, Bienzle U, Bock HL, Clemens R. Co-administration of an inactivated hepatitis A vaccine with other travelers vaccines: interference with the immune response {Abstract}. In: Proceedings of the 34th Interscience Conference on Antimicrobial Agents and Chemotherapy. Washington, DC: American Society of Microbiologists, 1994:256.

7. Wagner G, Lavanchy D, Darioli R, et al. Simultaneous active and passive immunization against hepatitis A studied in a population of travelers. Vaccine 1993;11:1027-32.

* Use of trade names and commercial sources is for identification only and does not imply endorsement by the Public Health Service or the U.S. Department of Health and Human Services.

TABLE 1. Recommended vaccination schedule for Havris{R} *
==========================================================================
                                                  No.      Schedule
Age group (yrs)   Dose (EL.U. +)   Volume (mL)   doses    (months) &
--------------------------------------------------------------------------
  2-18                360            0.5           3      0, 1, 6-12
   >18               1440            1.0           2       0, 6-12
--------------------------------------------------------------------------
* Inactivated hepatitis A vaccine distributed by SmithKline Beecham
  Pharmaceuticals (Philadelphia, Pennsylvania). Use of trade names and
  commercial sources is for identification only and does not imply
  endorsement by the Public Health Service or the U.S. Department of
  Health and Human Services.
+ Enzyme-linked immunosorbent assay units.
& Zero months represents timing of the initial dose; subsequent numbers
  represent months after the initial dose.
==========================================================================

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