Haemophilus b conjugate vaccine adverse reactions

# Adverse Reactions

## 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 with rates in the clinical trials of another vaccine, and may not reflect the rates observed in practice. There is the possibility that broad use of HIBERIX could reveal adverse reactions not observed in clinical trials.
In 7 clinical studies, 1,008 children received HIBERIX as a booster dose following primary vaccination with either HIBERIX (not approved for primary series in US, N = 530), Haemophilus b Conjugate Vaccine manufactured by Sanofi Pasteur SA (N = 235), Haemophilus b Conjugate Vaccine manufactured by Merck & Co., Inc. (N = 26), or Haemophilus b Conjugate Vaccine manufactured by Wyeth Pharmaceuticals Inc. (no longer licensed in the US, N = 217). None of the studies included a comparator group that received a booster dose with a US-licensed Haemophilus b Conjugate Vaccine. Studies were conducted in Europe, Canada, and Latin America. Across these studies, the mean age of subjects at the time of booster vaccination with HIBERIX ranged from 16 to 19 months. At the time of vaccination, 172 (17.1%) subjects were 11 to 14 months of age, 642 (63.7%) subjects were 15 to 18 months of age, and 194 (19.2%) subjects were 19 to 25 months of age. Approximately half of the subjects were male. Among subjects for whom information on race/ethnicity was available, nearly all subjects were white.
In these 7 studies, HIBERIX was administered concomitantly with non-US formulations (containing 2.5 mg 2-phenoxyethanol per dose as preservative) of one of the following US-licensed vaccines: INFANRIX (Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed) (DTaP), KINRIX (Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed andInactivated Poliovirus Vaccine) (DTaP-IPV), or PEDIARIX  (DTaP-HBV-IPV). In the studies, DTaP-IPV and DTaP-HBV-IPV were administered in dosing regimens not approved in the US. Some subjects received DTaP-HBV (GlaxoSmithKline Biologicals, not licensed in US) concomitantly with HIBERIX.
Solicited Adverse Events: In an open-label, multicenter study conducted in Germany, 371 children received a booster dose of HIBERIX administered concomitantly with DTaP-HBV-IPV. The mean age at the time of vaccination was 16 months. Subjects in this study had previously received a primary series with either HIBERIX (not approved for primary series in US, N = 92), Haemophilus b Conjugate Vaccine manufactured by Sanofi Pasteur SA (N = 96), or Haemophilus b Conjugate Vaccine manufactured by Wyeth Pharmaceuticals Inc. (no longer licensed in the US) (N = 183). All subjects previously received 3 doses of DTaP-HBV-IPV. Information on adverse events was collected by parents/guardians using standardized forms for 4 consecutive days following vaccination with HIBERIX (i.e., day of vaccination and the next 3 days). The reported frequencies of solicited local and general adverse events are presented in Table 1.

### N = all subjects for whom safety data were available
- Within 4 days of vaccination defined as day of vaccination and the next 3 days.
- In this study, 92 subjects previously received 3 doses of HIBERIX (not approved for primary immunization in the US), 96 subjects previously received 3 doses of a US-licensed Haemophilus b Conjugate Vaccine (manufactured by Sanofi Pasteur SA), and 183 subjects previously received 3 doses of a Haemophilus b Conjugate Vaccine that is no longer licensed in the US.
- In this study, DTaP-HBV-IPV was given to subjects who previously received 3 doses of DTaP-HBV-IPV. In the US, PEDIARIX is approved for use as a 3-dose primary series; use as a fourth consecutive dose is not approved in the US.
- Local reactions at the injection site for HIBERIX.
- Grade 3 redness or swelling defined as >20 mm.
- Grade 3 pain defined as causing crying when limb moved.
- Fever defined as 100.4F (38.0C) rectally or 99.5F (37.5C) axillary, oral or tympanic; Grade 3 fever defined as >103.1F (>39.5C) rectally or >102.2F (>39.0C) axillary, oral or tympanic.
- Grade 3 fussiness defined as persistent crying and could not be comforted.
- Grade 3 for these symptoms defined as preventing normal daily activity.

### Serious Adverse Events
Two of 1,008 subjects reported a serious adverse event that occurred in the 31-day period following booster immunization with HIBERIX. One subject developed bilateral pneumonia 9 days post-vaccination and one subject experienced asthenia following accidental drug ingestion 18 days post-vaccination.

## Postmarketing Experience
In addition to reports in clinical trials, worldwide voluntary reports of adverse events received for HIBERIX since market introduction (1996) of this vaccine are listed below. This list includes serious events and/or events which have a plausible causal connection to HIBERIX. Because these events are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to vaccination.
====General Disorders and Administration Site Conditions
Extensive swelling of the vaccinated limb, injection site induration.

### Immune System Disorders
Allergic reactions (including anaphylactic and anaphylactoid reactions), angioedema.

### Nervous System Disorders
Convulsions (with or without fever), hypotonic-hyporesponsive episode, somnolence, syncope orvasovagal responses to injection.

### Respiratory, Thoracic, and Mediastinal Disorders
Apnea.

### Skin and Subcutaneous Tissue Disorders
Rash,urticaria.