• General Information
• Evaluating Unlicensed Schedules
• Acceptable Ages
• Acceptable Dosing Intervals
• Mixed Schedules
• Mixed Schedules that Include Doses of Twinrix Junior
• Resources

General Information

Twinrix® is a combined hepatitis A and hepatitis B vaccine recently approved by the Food and Drug Administration for persons >18 years. Primary immunization consists of three doses, given on a 0-, 1-, and 6- month schedule, the same schedule as that used for single-antigen hepatitis B vaccine. This means that a person can be fully vaccinated against both hepatitis A and hepatitis B with three injections compared to the five shots needed to complete the series using the single-antigen formulations. Minimum time to complete the hepatitis A and hepatitis B series is the same (see table).

Twinrix is indicated for immunization of persons 18 years of age or older against hepatitis A and hepatitis B. Any person in this age group having an indication for both hepatitis A and hepatitis B vaccination can be administered Twinrix, including patients with chronic liver disease, users of illicit injectable drugs, men who have sex with men, and persons with clotting factor disorders who receive therapeutic blood products. For international travel, hepatitis A vaccine is recommended for travelers to areas of high or intermediate hepatitis A endemicity; hepatitis B vaccine is recommended for travelers to areas of high or intermediate hepatitis B endemicity who plan to stay for 6 months and have frequent close contact with the local population.

Evaluating Unlicensed Schedules

The information below may be helpful to immunization program personnel and clinicians in determining if patients who have received mixed schedules that include Twinrix need further vaccinations to complete the series. In general, it is best to start and finish a series with the same vaccine formulation, using the licensed dosage and schedule. The information below is not intended to serve as a set of alternate schedules for the vaccines.

Acceptable Ages

In the United States, Twinrix is not licensed for persons <18 years old. However, if doses of the U.S. licensed formulation of Twinrix have been inadvertently given to pediatric patients, they may be counted towards completion of the series. A pediatric formulation (Twinrix Junior®) is licensed in other parts of the world, including Canada and Europe. Acceptable complete series for children who have already received dose(s) of Twinrix Junior are described below.

Acceptable Dosing Intervals

For all of the vaccines in question, the intervals between the first dose and the last dose are critical to eliciting long term protection. Therefore, regardless of the vaccine used, the interval between first dose of hepatitis A antigen and the last dose must be at least 6 months, and the interval between first and last dose of hepatitis B antigen must be at least 4 months.

1. The interval between 1st Twinrix dose and 3rd Twinrix dose should be at least 6 months.

2. The interval between 1st Twinrix dose and 2nd Twinrix dose should be at least 1 month.

3. The interval between 2nd Twinrix dose and 3rd Twinrix dose should be at least 2 months.

4. Recommended intervals for single-antigen vaccines, when used in combination series that include Twinrix, must still be observed.

Mixed Schedules

The hepatitis A component in Twinrix is formulated with a different dosage and schedule than the single-antigen formulation (see table). The following guidelines are written with the assumption that for any one individual, the impact of having a decreased amount of antigen in one shot of the series (e.g., 720 EL.U. and 1,440 EL.U. of hepatitis A antigen) is probably not large. However, it is important to recognize that this has not been studied directly. Seroconversion rates (percent of persons who develop a protective level of antibody) are very high even after a single-dose of 720 EL.U. of hepatitis A vaccine, but long term protection may be related to the peak concentration of antibody generated by vaccination. The effect on peak antibody concentrations of a 720 EL.U. dose given with a 1,440 EL.U. dose as part of a two-dose series, compared to two 1,440 EL.U. doses, is unknown. The appropriate single-antigen vaccine dosage (pediatric or adult) in a series is determined by the age at the time of each dose.

Acceptable Mixed Schedules for Persons >18 Years Old

Combination vaccine followed by single-antigen vaccine(s):

• Following one dose of Twinrix: One or two doses of adult hepatitis A vaccine and two doses of adult hepatitis B vaccine, at appropriate intervals.

• Following two doses of Twinrix: One dose of adult hepatitis A vaccine and one dose of adult hepatitis B vaccine, at appropriate intervals.

Single-antigen vaccine(s) followed by combination vaccine:

• Following one dose each of adult single-antigen hepatitis A and hepatitis B vaccines: Two doses of combination vaccine or one dose of combination vaccine followed by one dose of adult single-antigen hepatitis B vaccine, at appropriate intervals.

• Following two doses each of adult single-antigen hepatitis A and hepatitis B vaccines (at appropriate intervals): One dose of adult hepatitis B vaccine, or one dose of Twinrix (although this gives an extra dose of hepatitis A vaccine).

See above section for acceptable dosing intervals.

Acceptable Mixed Schedules for Persons Who Are 18 Years Old

Combination vaccine followed by single-antigen vaccines:

• Following one dose of combination vaccine: One dose of pediatric single-antigen hepatitis A vaccine and one dose of pediatric single-antigen hepatitis B vaccine, followed by one dose of pediatric single-antigen hepatitis B vaccine, at appropriate intervals.

• Following two doses of combination vaccine: Twinrix contains the pediatric dose of hepatitis A antigen, so an 18-year-old who receives two Twinrix doses 6 months apart is fully immunized for hepatitis A (if both given when he/she was 18), and can finish the hepatitis B vaccine series with one more shot of single-antigen hepatitis B vaccine, pediatric or adult, depending on if he/she has turned 20 already.

Single-antigen pediatric vaccines followed by combination vaccine:

• Following one dose each of pediatric single-antigen hepatitis A and hepatitis B vaccines: Two doses of Twinrix spaced appropriately (this gives an extra dose of hepatitis A vaccine). Or, one dose of Twinrix followed by one dose of pediatric single-antigen hepatitis B vaccine, at appropriate intervals.

See above section for acceptable dosing intervals.

Mixed Schedules that Include Dose(s) of Twinrix Junior

Twinrix Junior is not licensed in the United States, as of September 30, 2001. Twinrix Junior is a combined hepatitis A and hepatitis B vaccine used in several other countries for persons <18 years. Primary immunization consists of three doses, given on a 0-, 1-, and 6- month schedule, the same schedule as that used for single-antigen hepatitis B vaccine. Twinrix Junior contains 360 EL.U. of hepatitis A antigen and 10 micrograms of hepatitis B antigen. Twinrix Junior is formulated with a different dosage and schedule than the single-antigen pediatric hepatitis A vaccine. The issues about a decreased amount of antigen in 1 dose in mixed schedules that include Twinrix (see Mixed Schedules above) also apply for Twinrix Junior.

Twinrix Junior can count towards the hepatitis B series for persons who are <19 years old, because the combination vaccine contains the same dosage of hepatitis B antigen as the pediatric Engerix B. If Twinrix Junior is given to a person >19 years old, it does not count toward any series. The guidelines below provide information that may be helpful to immunization program personnel and clinicians in determining if patients who have received mixed schedules that include Twinrix Junior need further vaccinations to complete the series.

Acceptable Mixed Schedules for Persons <18 Years Old

Combination vaccine Twinrix Junior followed by single-antigen vaccine(s):

• Following one dose of Twinrix Junior: One or two doses of pediatric hepatitis A vaccine and two doses of pediatric hepatitis B vaccine, at appropriate intervals.

• Following two doses of Twinrix Junior: One dose of pediatric hepatitis A vaccine and one dose of pediatric hepatitis B vaccine, at appropriate intervals.

Acceptable Mixed Schedules for Persons Who Are 18 Years Old

Combination vaccine Twinrix Junior followed by single-antigen vaccine(s):

• Following one dose of Twinrix Junior: One or two doses of pediatric hepatitis A vaccine and two doses of pediatric hepatitis B vaccine, at appropriate intervals.

• Following two doses of Twinrix Junior: One dose of pediatric hepatitis A vaccine and one dose of pediatric hepatitis B vaccine, at appropriate intervals.

Combination vaccine Twinrix Junior followed by Twinrix (adult):

• Following one dose of Twinrix Junior: Two doses of Twinrix, at appropriate intervals.

• Following two doses of Twinrix Junior: One dose of Twinrix.

Resources

1. Vaccine Information Statements (VIS), CDC National Immunization Program

2. Notice to Readers: FDA Approval for a Combined Hepatitis A and Hepatitis B Vaccine, MMWR, September 21, 2001/50(37);806-7.