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Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a vaccine cannot be directly compared to rates in the clinical trials of another vaccine, and may not reflect the rates observed in practice. As with any vaccine, there is the possibility that broad use of HAVRIX (hepatitis a vaccine, inactivated) could reveal adverse reactions not observed in clinical trials.

The safety of HAVRIX (hepatitis a vaccine, inactivated) has been evaluated in clinical trials involving approximately 32,500 individuals receiving doses ranging from 360 EL.U. to 1440 EL.U.

The frequency of solicited adverse events tended to decrease with successive doses of HAVRIX (hepatitis a vaccine, inactivated) .

Of solicited adverse events in clinical trials, the most frequently reported by volunteers was injection-site soreness (56% of adults and 21% of children); however, 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 events occurring during clinical trials are listed below.

Incidence 1% to 10% of Injections:Metabolism and nutrition disorders: Anorexia.

Gastrointestinal disorders: Nausea.

General disorders and administration site conditions: Fatigue, fever ( > 37.5°C), injection site induration, injection site redness, injection site swelling, malaise.

Incidence < 1% of Injections: Infections and infestations: Pharyngitis, upper respiratory tract infections.

Blood and lymphatic system disorders: Lymphadenopathy.

Psychiatric disorders: Insomnia.

Nervous system disorders: Dysgeusia, hypertonia.

Eye disorders: Photophobia.

Ear and labyrinth disorders: Vertigo.

Gastrointestinal disorders: Abdominal pain, diarrhea, vomiting.

Skin and subcutaneous tissue disorders: Pruritus, rash, urticaria.

Musculoskeletal and connective tissue disorders: Arthralgia, myalgia.

General disorders and administration site conditions: Injection site hematoma.

Investigations:Creatine phosphokinase increased.

Outbreak Setting and a Field Efficacy Trial: Safety data were obtained from 2 additional sources in which large populations were vaccinated. In an outbreak setting in which 4,930 individuals were immunized with a single dose of either 720 EL.U. or 1440 EL.U. of HAVRIX (hepatitis a vaccine, inactivated) , no serious adverse events due to vaccination were reported. Overall, less than 10% of vaccinees reported solicited general adverse events following the vaccine. The most common solicited local adverse reaction was pain at the injection site, reported in 22.3% of subjects at 24 hours and decreasing to 2.4% by 72 hours.

In a field efficacy trial, 19,037 children received the 360 EL.U. dose of HAVRIX (hepatitis a vaccine, inactivated) . The most commonly reported adverse events following administration of HAVRIX (hepatitis a vaccine, inactivated) were injection-site pain (9.5%) and tenderness (8.1%), which were reported following first doses of HAVRIX (hepatitis a vaccine, inactivated) . Other adverse events were infrequent and comparable to the control vaccine ENGERIX-B® [Hepatitis B Vaccine (Recombinant)]. Additionally, no serious adverse events due to the vaccine were reported. The large trial further allowed for analysis of rare adverse events, including hospitalization and death. No significant differences were found between the cohorts.

HAVRIX (hepatitis a vaccine, inactivated) 720 EL.U./0.5 mL at 11 Months of Age and Older: In a multicenter study, parents/guardians recorded local and general symptoms on diary cards for 4 days (Days 0 to 3) after vaccination [see Clinical Studies]. In the 3 groups of children who received HAVRIX (hepatitis a vaccine, inactivated) alone, safety data were available for 723 children who received 1,396 documented doses of HAVRIX (hepatitis a vaccine, inactivated) . Additional safety data were available for 181 children who received HAVRIX (hepatitis a vaccine, inactivated) coadministered with INFANRIX® (Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed) (DTaP) and Haemophilus influenzae type b (Hib) conjugate vaccine (tetanus toxoid conjugate) (PRP-T) (Sanofi Pasteur SA).

The frequencies of solicited local and general events following receipt of HAVRIX (hepatitis a vaccine, inactivated) were monitored during the 4-day observation period. The following ranges of solicited adverse event rates were observed among 3 groups of children that received their first dose of HAVRIX (hepatitis a vaccine, inactivated) alone at between 11 and 25 months of age: Injection site pain in 15-21% of subjects, redness in 16-21% of subjects, swelling in 8% of subjects, irritability in 24-36% of subjects, loss of appetite in 16-19% of subjects, drowsiness in 15-17% of subjects and fever > 39.5° C in ≤ 2% of subjects. Following the booster dose of HAVRIX (hepatitis a vaccine, inactivated) , among local reactions: Pain was reported in 16-21% of subjects, redness in 17-22%, swelling in 8-10% of subjects. Following the booster dose of HAVRIX (hepatitis a vaccine, inactivated) , among general events, irritability was reported in 19-29% of subjects, loss of appetite in 14-18% of subjects, drowsiness in 13-16% of subjects and fever > 39.5° C in ≤ 1% of subjects.

Drowsiness and loss of appetite occurred at statistically significantly higher rates in subjects 15 to 18 months of age who received Hib conjugate vaccine (PRP-T) (Sanofi Pasteur SA) and INFANRIX concomitantly with HAVRIX (hepatitis a vaccine, inactivated) as compared to subjects 15 to 18 months of age who received Hib conjugate vaccine (PRP-T) and INFANRIX (drowsiness 34% and 22% and loss of appetite 29% and 19%, respectively). With the exception of fever ( > 39.5° C), the solicited general symptoms occurred at statistically significantly higher rates in subjects 15 to 18 months of age who received Hib conjugate vaccine (PRP-T) and INFANRIX concomitantly with HAVRIX (hepatitis a vaccine, inactivated) as compared to subjects 15 to 18 months of age who received HAVRIX (hepatitis a vaccine, inactivated) alone (irritability 46% and 30%, drowsiness 34% and 17%, and loss of appetite 29% and 17%, respectively).

A febrile seizure was reported in an 18-month-old subject 2 days after receiving the first dose of HAVRIX (hepatitis a vaccine, inactivated) . Other serious adverse events reported during the course of this study included a single case each of hepatitis 5 months post dose 1, insulin-dependent diabetes 4 months post dose 1, and Kawasaki's disease 3½ months post dose 1. The association of these events with vaccination is unknown.

In a US multicenter study, children 15 months of age (range 14 to 16 months) received either HAVRIX (hepatitis a vaccine, inactivated) coadministered with a US-licensed pneumococcal 7-valent conjugate vaccine (Wyeth Pharmaceuticals Inc.) followed by a second dose of HAVRIX (hepatitis a vaccine, inactivated) 6 to 9 months later; HAVRIX (hepatitis a vaccine, inactivated) administered alone followed by a second dose of HAVRIX (hepatitis a vaccine, inactivated) 6 to 9 months later; or pneumococcal 7-valent conjugate vaccine administered alone followed by a first dose of HAVRIX (hepatitis a vaccine, inactivated) one month later and a second dose of HAVRIX 6 to 9 months after the first[see Clinical Studies]. Parents/guardians recorded local and general symptoms on diary cards for 4 days (Days 0 to 3) after vaccination.

Solicited local adverse events were reported as follows among children who received the first dose HAVRIX (hepatitis a vaccine, inactivated) coadministered with pneumococcal 7-valent conjugate vaccine: Pain was reported in 36% of subjects, redness in 41% of subjects, and swelling in 29% of subjects. The reported rates of these local adverse events were similar to those reported in children who received the first dose of pneumococcal 7-valent conjugate vaccine alone (44%, 46%, and 27%, respectively). Among children who received the first dose of HAVRIX (hepatitis a vaccine, inactivated) alone, pain was reported in 28% of subjects, redness in 22% of subjects, and swelling in 7% of subjects.

Solicited general adverse events were reported as follows among children who received the first dose HAVRIX (hepatitis a vaccine, inactivated) coadministered with pneumococcal 7-valent conjugate vaccine: Irritability was reported in 35% of subjects, drowsiness in 26% of subjects, loss of appetite in 25% of subjects, and fever in 14% of subjects. The reported rates of these general adverse events were similar to those reported in children who received the first dose of pneumococcal 7-valent conjugate vaccine alone (41%, 32%, 25%, and 16%, respectively). Among children who received the first dose of HAVRIX (hepatitis a vaccine, inactivated) alone, irritability was reported in 35% of subjects, drowsiness in 29% of subjects, loss of appetite in 26% of subjects, and fever in 9% of subjects.

Postmarketing Experience

In addition to reports in clinical trials, worldwide voluntary reports of adverse events received for HAVRIX (hepatitis a vaccine, inactivated) since market introduction of this vaccine are listed below. This list includes serious adverse events or events which have a suspected causal connection to components of HAVRIX (hepatitis a vaccine, inactivated) or other vaccines or drugs. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to the vaccine.

Blood and lymphatic system disorders: Thrombocytopenia.

Immune system disorders: Anaphylactic reaction, anaphylactoid reaction.

Nervous system disorders: Convulsion, dizziness, encephalopathy, Guillain-Barré syndrome, multiple sclerosis, myelitis, neuropathy, paresthesia, somnolence, syncope.

Respiratory, thoracic, and mediastinal disorders: Dyspnea.

Hepatobiliary disorders: Hepatitis, jaundice.

Skin and subcutaneous tissue disorders: Angioedema, erythema multiforme, hyperhidrosis.

Congenital, familial and genetic disorders: Congenital anomaly.

General disorders and administration site conditions: Local swelling.

Concomitant Administration With Vaccines and Immune Globulin (IG)

HAVRIX (hepatitis a vaccine, inactivated) may be given concurrently with Haemophilus influenzae type b (Hib) conjugate vaccine (tetanus toxoid conjugate) (PRP-T) (Sanofi Pasteur SA) in children 15 to 18 months of age [see ADVERSE REACTIONS and Clinical Studies].

HAVRIX (hepatitis a vaccine, inactivated) may be given concurrently with the fourth dose of pneumococcal 7-valent conjugate vaccine (Wyeth Pharmaceuticals Inc.) in children 15 months of age (range 14 to 16 months) [see ADVERSE REACTIONS and Clinical Studies].

The safety of HAVRIX (hepatitis a vaccine, inactivated) given concomitantly with INFANRIX has been evaluated [see ADVERSE REACTIONS]. Insufficient data are available to assess the immune response of a fourth dose of DTaP vaccine when administered with HAVRIX (hepatitis a vaccine, inactivated) .

HAVRIX (hepatitis a vaccine, inactivated) may be administered concomitantly with IG.

When concomitant administration of other vaccines or IG is required, they should be given with different syringes and at different injection sites. Do not mix HAVRIX (hepatitis a vaccine, inactivated) with any other vaccine or product in the same syringe or vial.

Immunosuppressive Therapies

Immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs, and corticosteroids (used in greater than physiologic doses), may reduce the immune response to HAVRIX (hepatitis a vaccine, inactivated) .

Last reviewed on RxList: 10/20/2008
This monograph has been modified to include the generic and brand name in many instances.