Hepatitis A virus has a relatively long incubation period (15 to 50 days). HAVRIX may not prevent hepatitis A infection in individuals who have an unrecognized hepatitis A infection at the time of vaccination. Additionally, vaccination with HAVRIX may not protect all individuals.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a vaccine cannot be directly compared with rates in the clinical trials of another vaccine and may not reflect the rates observed in practice.

The safety of HAVRIX has been evaluated in 61 clinical trials involving approximately 37,000 individuals receiving doses of 360 EL.U. (n = 21,928 in 3- or 4-dose schedule), 720 EL.U. (n = 12,274 in 2- or 3-dose schedule), or 1440 EL.U. (n = 2,782 in 2- or 3-dose schedule).

Of solicited adverse reactions in clinical trials of adults, who received HAVRIX 1440 EL.U., and children (aged 2 years and older), who received either HAVRIX 360 EL.U. or 720 EL.U., the most frequently reported was injection-site soreness (56% of adults and 21% of children); less than 0.5% of soreness was reported as severe. Headache was reported by 14% of adults and less than 9% of children. Other solicited and unsolicited reactions occurring during clinical trials are listed below.

General Disorders and Administration Site Conditions: Fatigue; fever >99.5°F (37.5°C); induration, redness, and swelling of the injection site; malaise.

Incidence <1% of Injections

Infections and Infestations: Pharyngitis, upper respiratory tract infections.

General Disorders and Administration Site Conditions: Injection site hematoma.

Investigations: Creatine phosphokinase increased.

Coadministration Studies of HAVRIX in Children Aged 11 to 25 Months

In 4 studies, 3,152 children aged 11 to 25 months received at least 1 dose of HAVRIX 720 EL.U. administered alone or concomitantly with other routine childhood vaccinations [see Clinical Studies (14.2, 14.5)]. The studies included HAV 210 (N = 1,084), HAV 232 (N = 394), HAV 220 (N = 433), and HAV 231 (N = 1,241).

In the largest of these studies (HAV 231) conducted in the U.S., 1,241 children aged 15 months were randomized to receive: Group 1) HAVRIX alone; Group 2) HAVRIX concomitantly with measles, mumps, and rubella (MMR) vaccine (manufactured by Merck and Co.) and varicella vaccine (manufactured by Merck and Co.); or Group 3) MMR and varicella vaccines. Subjects in Group 3 who received MMR and varicella vaccines received the first dose of HAVRIX 42 days later. A second dose of HAVRIX was administered to all subjects 6 to 9 months after the first dose of HAVRIX. Solicited local adverse reactions and general events were recorded by parents/guardians on diary cards for 4 days (Days 0 to 3) after vaccination. Unsolicited adverse events were recorded on the diary card for 31 days after vaccination. Telephone follow-up was conducted 6 months after the last vaccination to inquire about serious adverse events, new onset chronic illnesses, and medically significant events. A total of 1,035 children completed the 6-month follow-up. Among subjects in all groups combined, 53% were male; 69% of subjects were White, 16% were Hispanic, 9% were Black, and 6% were other racial/ethnic groups.

Percentages of subjects with solicited local adverse reactions and general adverse reactions following HAVRIX administered alone (Group 1) or concomitantly with MMR and varicella vaccines (Group 2) are presented in Table 1. The solicited adverse reactions from the 3 additional coadministration studies conducted with HAVRIX were comparable to those from Study HAV 231.

Serious Adverse Events in Children Aged 11 to 25 Months: Among these 4 studies, 0.9% (29/3,152) of subjects reported a serious adverse event within the 31-day period following vaccination with HAVRIX. Among subjects administered HAVRIX alone 1.0% (13/1,332) reported a serious adverse event. Among subjects who received HAVRIX concomitantly with other childhood vaccines, 0.9% (8/909) reported a serious adverse event. In these 4 studies, there were 4 reports of seizure within 31 days post-vaccination: these occurred 2, 9, and 27 days following the first dose of HAVRIX administered alone and 12 days following the second dose of HAVRIX. In 1 subject who received INFANRIX (Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed) and Hib conjugate vaccine followed by HAVRIX 6 weeks later, bronchial hyperreactivity and respiratory distress were reported on the day of administration of HAVRIX alone.