Canadian Immunization Guide
Seventh Edition - 2006

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Part 4
Active Immunizing Agents

Hepatitis Vaccines Combined

Epidemiology Preparations approved for use in Canada Efficacy and immunogenicity Recommended usage Schedule and dosage Route of administration Booster doses and re-immunization

Serologic testing Storage requirements Simultaneous administration with other vaccines Adverse reactions Contraindications and precautions Selected references

There are vaccine formulations for adults and children that protect against both hepatitis A and hepatitis B. The reader should consult the chapters on the monovalent hepatitis A and B vaccines for more information on epidemiology, efficacy and immunogenicity, recommended usage, pre- and post-immunization serologic testing and adverse reactions.

Since the publication of the 2002 Canadian Immunization Guide, the key change is the addition of a new table on schedule and dosage.

Epidemiology

Please refer to the Hepatitis A Vaccine chapter and the Hepatitis B Vaccine chapter for more information.

Preparations approved for use in Canada

This chapter will deal only with vaccines that are currently marketed in Canada.

• Twinrix^® (hepatitis A and hepatitis B vaccine), GlaxoSmithKline Inc. Bivalent vaccine for individuals 19 years and over
• Twinrix^® Junior (hepatitis A and hepatitis B vaccine), GlaxoSmithKline Inc. Reduced dose format for individuals aged 1 to 18 years

Each Twinrix^® dose contains 20 µg of purified hepatitis B surface antigen (HBsAg) protein and 720 ELISA units of inactivated hepatitis A viral antigen (HM 175 strain) in 1 mL. Twinrix^® Junior contains 10 µg of purified HBsAg and 360 ELISA units of inactivated hepatitis A antigen in 0.5 mL. These vaccines are made from the same bulk vaccines as are used in the monovalent formulations.

For a list of all approved products in Canada, please refer to Table 1 in the General Considerations chapter.

Efficacy and immunogenicity

There is no reduction and possibly even an increase in seroprotection rates and geometric mean titres (GMT) achieved by the combined vaccine compared with the monovalent vaccines for both hepatitis A and B components.

Recommended usage

Combined or bivalent hepatitis vaccine is the preferred vaccine for people with indications for immunization against both hepatitis A and hepatitis B:

• Travellers to certain areas of Africa, Asia and the Americas where both hepatitis A and hepatitis B are endemic
• Persons engaging in illicit drug use
• Men who have sex with men (MSM)
• Hemophiliacs receiving plasma-derived replacement clotting factors
• Populations and communities in which both hepatitis A and hepatitis B are endemic
• People who have previously received hepatitis A vaccine and hepatitis B vaccine, and who require additional doses of both
• People with clinically significant chronic liver disease, including persons infected with hepatitis C virus

There are also situations in which different indications may apply for the two vaccine components. Under these circumstances, bivalent vaccine is an efficient way to protect against both diseases. Examples include:

• Children who are scheduled to receive hepatitis B vaccine routinely in a universal program and who also have an indication for hepatitis A vaccine
• Inmates of correctional facilities who have not already received hepatitis B vaccine and who are in a facility with uncontrolled transmission of hepatitis A

The combined vaccine is also used in some countries for efficient universal immunization against hepatitis A and B of pre-adolescents in school-based programs. This vaccine should be used for any person who wishes to decrease his or her risk of acquiring hepatitis A and B.

Schedule and dosage

As is the case for the monovalent hepatitis A and B vaccines, a large number of different schedules and dosages, both approved and unapproved, have been tested and are being used. The reader should consult the monovalent hepatitis B vaccine chapter for a discussion of the interpretation of this vaccine's immunogenicity and effectiveness.

There are a number of approved schedules for Twinrix^® formulations in Canada. For individuals 19 years and over, the regular schedule is 0, 1 and 6 months. There is also a rapid schedule of 0, 7 and 21 days, followed by a fourth dose at 1 year. The dose of Twinrix^® is 1.0 mL. For individuals from 1-18 years, the regular schedule of Twinrix^® Junior is 0, 1 and 6 months. The dose of Twinrix^® Junior is 0.5 mL. There is an alternative schedule for children 1-15 years of age consisting of two doses of Twinrix^® given at 0, and 6-12 months. A dose of Twinrix^® is 1.0 mL.

Clinical trials have shown that other schedules and dosages provide good seroprotection rates and GMT. A 0, 6 month schedule with Twinrix Junior^® in Canadian schoolchildren (8-10 years) has been tested with good results (100% seroprotection rate for hepatitis A, 96.5% seroprotection rate for hepatitis B with very high GMTs).

Injection drug users have a reduced immune response but need a rapid protection. Some provinces use a rapid schedule combining a double dose of Twinrix^® at 0 and 12 months with the hepatitis B dosage for immunocompromised people at days 7 and 21.

Table 5. Schedule and Dosage for Combined Hepatitis A and B Vaccine

Route of administration

Combined hepatitis vaccines should be given intramuscularly.

Booster doses and re-immunization

Booster doses are not needed for individuals who have completed a course of Twinrix^® or Twinrix^® Junior or their equivalent in the form of monovalent hepatitis vaccines.

Serologic testing

The same pre- and post-immunization indications as those for the monovalent vaccines apply.

Storage requirements

Twinrix^® and Twinrix^® Junior should be stored at a temperature between +2º C and +8º C and should not be frozen.

Simultaneous administration with other vaccines

Twinrix^® Junior has been administered at the age of 2 years with DTaP-IPV-Hib or MMR without interference. Although it has not been tested in clinical trials, it is assumed that it can be given at the same time as other vaccines.

Adverse reactions

Serious adverse events are rare following immunization and, in most cases, data are insufficient to determine a causal association.

There is no increase in adverse events when combined vaccine is compared with the monovalent vaccines. When the adult dose is given to children in the two-dose schedule, there is also no increase in adverse events compared with those occurring after the children's dosage.

Contraindications and precautions

The only contraindication to bivalent hepatitis vaccines is previous anaphylaxis demonstrated to any component of the bivalent vaccine.

Selected references

Duval B, Gîlca V, Boulianne N et al. Immunogenicity of two paediatric doses of monovalent hepatitis B or combined hepatitis A and B vaccine in 8-10-year-old children. Vaccine 2005;23(31):4082-87.

Navas E, Salleras L, Gisbert R et al. Efficiency of the incorporation of the hepatitis A vaccine as a combined A+B vaccine to the hepatitis B vaccination programme of preadolescents in schools. Vaccine 2005;23(17-18): 2185-89.

Product Monograph. Twinrix^®:combined hepatitis A and hepatitis B vaccine. GlaxoSmithKline Inc., 2004.

Roberton D, Marshall H, Nolan TM et al. Reactogenicity and immunogenicity profile of a two-dose combined hepatitis A and B vaccine in 1-11-year-old children. Vaccine 2005(43);23:5099-105.

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