Twinrix—A New Vaccine for Hepatitis A and B

By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD

The FDA recently approved a vaccine that provides dual protection against hepatitis A and B. Marketed as Twinrix by GlaxoSmithKline Pharmaceuticals, the vaccine combines inactivated hepatitis A vaccine with hepatitis B recombinant vaccine, the antigenic components in Havrix and Engerix B, respectively. The combination reduces the number of injections needed to immunize patients to both viruses from 5 to 3. An exact release date is expected soon.

Indications

Twinrix is indicated for the active immunization of adults (18 years of age or older) against disease caused by hepatitis A virus and infections by all known subtypes of hepatitis B virus.1

Dosage

The primary immunization for adults is 1 mL given intramuscularly in 3 doses at 0, 1, and 6 months. The injection should be given in the deltoid region, not in the gluteal region. Administration in the gluteal region may result in a suboptimal response.1 Each 1 mL dose of Twinrix contains 720 ELISA units (EL.U) of inactivated hepatitis A virus and 20 mcg of recombinant hepatitis B surface antigen (HbsAg).

Potential Advantages

The combined vaccine offers more convenience and potentially better compliance. Twinrix requires 3 injections and 3 sites compared to 5 injections and 5 injection sites (2 for hepatitis A and 3 for hepatitis B).

Potential Disadvantages

Safety and effectiveness of Twinrix have not been established in pediatric patients. The effectiveness in patients age 65 years and older has also not been established.1

Comments

The immunogenicity and safety of Twinrix has been demonstrated in more than 1500 subjects. After the completion of the 3-dose regimen, seroconversion was detected in more than 98% of subjects against both hepatitis A and B.1,2 In a comparative trial, Twinrix was at least as effective as Havrix and Engerix-B administered separately.1 The antibody titers achieved with Twinrix were actually higher than that achieved with Havrix. This may be attributed to a difference in dosing. Twinrix is given as 3 doses of 720 EL.U at 0, 1, and 6 months while Havrix is given as 2 doses of 1440 EL.U at 0 and 6 months.

The most frequent reported side effects are local soreness and headache or fatigue. These were similar to that reported with Havrix or Engerix-B.1

Clinical Implications

Hepatitis B is a viral infection with serious consequences including acute hepatic necrosis, chronic active hepatitis, and cirrhosis of the liver. Chronic hepatitis B infection has been linked to hepatocellular carcinoma. The main modes of transmission are parenteral drug abuse, unprotected sex, visits to high-prevalence countries, exposure to infected body fluids, and high-risk occupations or settings. The CDC estimates that there are 1-1.25 million chronic carriers of hepatitis B in the United States. These persons can infect others in the community. Currently, vaccination is routine in children. This strategy will not only protect persons from infection but reduce disease incidence by reducing transmission.

Hepatitis A is one of the most frequently reported vaccine preventable diseases and is considered a major public health problem.3 The main mode of transmission is fecal-oral. Contaminated food or water or infected food handlers are a major source of transmission. Unlike hepatitis B, there is no routine childhood vaccination for hepatitis A. Twinrix offers a vaccine for adults who have not been vaccinated with either hepatitis A or B, and is recommended for those at risk of exposure to these viruses. These include travelers to endemic areas (who often are immunized against hepatitis A but rarely against hepatitis B), those with chronic liver disease, high-risk workers (laboratory, sanitation workers, medical personnel), employees of day-care centers, correctional facilities, persons with at-risk behavior (homosexuals, parenteral drug users), military personnel, persons with clotting-factor disease (eg, hemophiliacs), and those in close contact with individuals with hepatitis A.

Twinrix provides a convenient vaccine for the immunization against preventable diseases caused by hepatitis A and B in adults. The duration of protection is at least 4 years.1

References

1. Twinrix Product Labeling. GlaxoSmithKline Pharmaceuticals. May 2001.

2. Thoelen S, et al. Vaccine. 1999;17:1657-1662.

3. CDC. MMWR Morb Mortal Wkly Rep. 1999;48 (no. RR-12):18-29.