Pediarix Side Effects Center

SIDE EFFECTS

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse event 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.

A total of 23,849 doses of PEDIARIX have been administered to 8,088 infants who received one or more doses as part of the 3-dose series during 14 clinical studies. Common adverse events that occurred in ≥ 25% of subjects following any dose of PEDIARIX included local injection site reactions (pain, redness, and swelling), fever, drowsiness, irritability/fussiness, and loss of appetite. In comparative studies (including the German and US studies described below), administration of PEDIARIX was associated with higher rates of fever relative to separately administered vaccines [see WARNINGS AND PRECAUTIONS]. The prevalence of fever was highest on the day of vaccination and the day following vaccination. More than 96% of episodes of fever resolved within the 4-day period following vaccination (i.e., the period including the day of vaccination and the next 3 days).

In the largest of the 14 studies, conducted in Germany, safety data were available for 4,666 infants who received PEDIARIX administered concomitantly at separate sites with 1 of 4 Haemophilus influenzae type b (Hib) conjugate vaccines (GlaxoSmithKline [licensed in the US only for booster immunization], Wyeth Pharmaceuticals Inc. [no longer licensed in the US], Sanofi Pasteur SA [US-licensed], or Merck & Co, Inc. [US-licensed]) at 3, 4, and 5 months of age and for 768 infants in the control group that received separate US-licensed vaccines (INFANRIX, Hib conjugate vaccine [Sanofi Pasteur SA], and oral poliovirus vaccine [OPV] [Wyeth Pharmaceuticals, Inc.; no longer licensed in the US]). In this study, information on adverse events that occurred within 30 days following vaccination was collected. More than 95% of study participants were white.

In a US study, the safety of PEDIARIX administered to 673 infants was compared to the safety of separately administered INFANRIX, ENGERIX-B® [Hepatitis B Vaccine (Recombinant)], and IPV (Sanofi Pasteur SA) in 335 infants. In both groups, infants received Hib conjugate vaccine (Wyeth Pharmaceuticals Inc.; no longer licensed in the US) and 7-valent pneumococcal conjugate vaccine (Wyeth Pharmaceuticals Inc.) concomitantly at separate sites. All vaccines were administered at 2, 4, and 6 months of age. Data on solicited local reactions and general adverse events were collected by parents using standardized diary cards for consecutive days following each vaccine dose (i.e., day of vaccination and the next 3 days). Telephone follow-up was conducted 1 month and 6 months after the third vaccination to inquire about serious adverse events. At the 6-month follow-up, information also was collected on new onset of chronic illnesses. A total of 638 subjects who received PEDIARIX and 313 subjects who received INFANRIX, ENGERIX-B, and IPV completed the 6-month follow-up. Among subjects in both study groups combined, 69% were white, 18% were Hispanic, 7% were black, 3% were Oriental, and 3% were of other racial/ethnic groups.

Solicited Adverse Events

Data on solicited local reactions and general adverse events from the US safety study are presented in Table 1. This study was powered to evaluate fever > 101.3°F following dose 1. The rate of fever ≥ 100.4°F following each dose was significantly higher in the group that received PEDIARIX compared to separately administered vaccines. Other statistically significant differences between groups in rates of fever, as well as other solicited adverse events, are noted in Table 1. Medical attention (a visit to or from medical personnel) for fever within 4 days following vaccination was sought in the group who received PEDIARIX for 8 infants after the first dose (1.2%), 1 infant following the second dose (0.2%), and 5 infants following the third dose (0.8%) (Table 1). Following dose 2, medical attention for fever was sought for 2 infants (0.6%) who received separately administered vaccines (Table 1). Among infants who had a medical visit for fever within 4 days following vaccination, 9 of 14 who received PEDIARIX and 1 of 2 who received separately administered vaccines, had one or more diagnostic studies performed to evaluate the cause of fever.

Table 1: Percentage of Infants With Solicited Local Reactions or General Adverse Events Within 4 Days of Vaccinationa at 2, 4, and 6 Months of Age With PEDIARIX Administered Concomitantly With Hib Conjugate Vaccine and 7-valent Pneumococcal Conjugate Vaccine (PCV7) or With Separate Concomitant Administration of INFANRIX, ENGERIX-B, IPV, Hib Conjugate Vaccine, and PCV7 (Modified Intent To Treat Cohort)

Serious Adverse Events

Within 30 days following any dose of vaccine in the US safety study in which all subjects received concomitant Hib and pneumococcal conjugate vaccines, 7 serious adverse events were reported in 7 subjects (1% [7/673]) who received PEDIARIX (1 case each of pyrexia, gastroenteritis, and culture negative clinical sepsis and 4 cases of bronchiolitis) and 5 serious adverse events were reported in 4 subjects (1% [4/335]) who received INFANRIX, ENGERIX-B, and IPV (uteropelvic junction obstruction and testicular atrophy in one subject and 3 cases of bronchiolitis).

Deaths

In 14 clinical trials, 5 deaths were reported among 8,088 (0.06%) recipients of PEDIARIX and 1 death was reported among 2,287 (0.04%) recipients of comparator vaccines. Causes of death in the group that received PEDIARIX included 2 cases of Sudden Infant Death Syndrome (SIDS) and one case of each of the following: convulsive disorder, congenital immunodeficiency with sepsis, and neuroblastoma. One case of SIDS was reported in the comparator group. The rate of SIDS among all recipients of PEDIARIX across the 14 trials was 0.25/1,000. The rate of SIDS observed for recipients of PEDIARIX in the German safety study was 0.2/1,000 infants (reported rate of SIDS in Germany in the latter part of the 1990s was 0.7/1,000 newborns). The reported rate of SIDS in the United States from 1990 to 1994 was 1.2/1,000 live births. By chance alone, some cases of SIDS can be expected to follow receipt of pertussis-containing vaccines.

Onset of Chronic Illnesses

In the US safety study in which all subjects received concomitant Hib and pneumococcal conjugate vaccines, 21 subjects (3%) who received PEDIARIX and 14 subjects (4%) who received INFANRIX, ENGERIX-B, and IPV reported new onset of a chronic illness during the period from 1 to 6 months following the last dose of study vaccines. Among the chronic illnesses reported in the subjects who received PEDIARIX, there were 4 cases of asthma and 1 case each of diabetes mellitus and chronic neutropenia. There were 4 cases of asthma in subjects who received INFANRIX, ENGERIX-B, and IPV.

Seizures

In the German safety study over the entire study period, 6 subjects in the group that received PEDIARIX (N = 4,666) reported seizures. Two of these subjects had a febrile seizure, 1 of whom also developed afebrile seizures. The remaining 4 subjects had afebrile seizures, including 2 with infantile spasms. Two subjects reported seizures within 7 days following vaccination (1 subject had both febrile and afebrile seizures, and 1 subject had afebrile seizures), corresponding to a rate of 0.22 seizures per 1,000 doses (febrile seizures 0.07 per 1,000 doses, afebrile seizures 0.14 per 1,000 doses). No subject who received concomitant INFANRIX, Hib vaccine, and OPV (N = 768) reported seizures. In a separate German study that evaluated the safety of INFANRIX in 22,505 infants who received 66,867 doses of INFANRIX administered as a 3-dose primary series, the rate of seizures within 7 days of vaccination with INFANRIX was 13 per 1,000 doses (febrile seizures 0.0 per 1,000 doses, afebrile seizures 0.13 per 1,000 doses).

Over the entire study period in the US safety study in which all subjects received concomitant Hib and pneumococcal conjugate vaccines, 4 subjects in the group that received PEDIARIX (N = 673) reported seizures. Three of these subjects had a febrile seizure and 1 had an afebrile seizure. Over the entire study period, 2 subjects in the group that received INFANRIX, ENGERIX-B, and IPV (N = 335) reported febrile seizures. There were no afebrile seizures in this group. No subject in either study group had seizures within 7 days following vaccination.

Other Neurological Events of Interest

No cases of hypotonic-hyporesponsiveness or encephalopathy were reported in either the German or US safety studies.

Safety of PEDIARIX After a Previous Dose of Hepatitis B Vaccine

Limited data are available on the safety of administering PEDIARIX after a previous dose of hepatitis B vaccine. In 2 separate studies, 160 Moldovan infants and 96 US infants, respectively, received 3 doses of PEDIARIX following 1 previous dose of hepatitis B vaccine. Neither study was designed to detect significant differences in rates of adverse events associated with PEDIARIX administered after a previous dose of hepatitis B vaccine compared to PEDIARIX administered without a previous dose of hepatitis B vaccine.

Postmarketing Safety Surveillance Study

In a safety surveillance study conducted at a health maintenance organization in the US, infants who received one or more doses of PEDIARIX from approximately mid-2003 through mid-2005 were compared to age-, gender-, and area-matched historical controls who received one or more doses of separately administered US-licensed DTaP vaccine from 2002 through approximately mid-2003. Only infants who received 7-valent pneumococcal conjugate vaccine (Wyeth Pharmaceuticals Inc.) concomitantly with PEDIARIX or DTaP vaccine were included in the cohorts. Other US-licensed vaccines were administered according to routine practices at the study sites, but concomitant administration with PEDIARIX or DTaP was not a criterion for inclusion in the cohorts. A birth dose of hepatitis B vaccine had been administered routinely to infants in the historical DTaP control cohort, but not to infants who received PEDIARIX. For each of Doses 1-3, a random sample of 40,000 infants who received PEDIARIX was compared to the historical DTaP control cohort for the incidence of seizures (with or without fever) during the 8-day period following vaccination. For each dose, random samples of 7,500 infants in each cohort were also compared for the incidence of medically-attended fever (fever ≥ 100.4°F that resulted in hospitalization, an emergency department visit, or an outpatient visit) during the 4- day period following vaccination. Possible seizures and medical visits plausibly related to fever were identified by searching automated inpatient and outpatient data files. Medical record reviews of identified events were conducted to verify the occurrence of seizures or medically- attended fever. The incidence of verified seizures and medically-attended fever from this study are presented in Table 2.

Table 2:  Percentage of Infants With Seizures (With or Without Fever) Within 8 Days of Vaccination and Medically-Attended Fever Within 4 Days of Vaccination With PEDIARIX Compared With Historical Controls

Postmarketing Spontaneous Reports For PEDIARIX

In addition to reports in clinical trials, worldwide voluntary reports of adverse events received for PEDIARIX 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 PEDIARIX. 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 vaccine exposure.

Cardiac Disorders: Cyanosis.

Gastrointestinal Disorders: Diarrhea, vomiting.

General Disorders and Administration Site Conditions: Fatigue, injection site cellulitis, injection site induration, injection site itching, injection site nodule/lump, injection site reaction, injection site vesicles, injection site warmth, limb pain, limb swelling.

Immune System Disorders: Anaphylactic reaction, anaphylactoid reaction, hypersensitivity.

Infections and Infestations: Upper respiratory tract infection.

Investigations: Abnormal liver function tests.

Nervous System Disorders: Bulging fontanelle, depressed level of consciousness, encephalitis, hypotonia, hypotonic-hyporesponsive episode, lethargy, somnolence, syncope.

Psychiatric Disorders: Crying, insomnia, nervousness, restlessness, screaming, unusual crying.

Respiratory, Thoracic, and Mediastinal Disorders: Apnea, cough, dyspnea.

Skin and Subcutaneous Tissue Disorders: Angioedema, erythema, rash, urticaria.

Vascular Disorders: Pallor, petechiae.

Postmarketing Spontaneous Reports For INFANRIX And/Or ENGERIX-B

Worldwide voluntary reports of adverse events received for INFANRIX and/or ENGERIX-B in children younger than 7 years of age but not already reported for PEDIARIX are listed below. This list includes serious adverse events or events which have a suspected causal connection to components of INFANRIX and/or ENGERIX-B. 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 vaccine exposure.

Blood and Lymphatic System Disorders: Idiopathic thrombocytopenic purpura^a,b, lymphadenopathy^a, thrombocytopenia^a,b.

Gastrointestinal Disorders: Abdominal pain^b, intussusception^a,b, nausea^b.

General Disorders and Administration Site Conditions: Asthenia^b, malaise^b.

Hepatobiliary Disorders: Jaundice^b.

Immune System Disorders: Anaphylactic shock^a, serum sickness-like disease^b.

Musculoskeletal and Connective Tissue Disorders: Arthralgia^b, arthritis^b, muscular weaknessb, myalgia^b.

Nervous System Disorders: Encephalopathy^a, headache^a, meningitis^b, neuritis^b, neuropathy^b, paralysis^b.

Skin and Subcutaneous Tissue Disorders: Alopecia^b, erythema multiforme^b, lichen planus^b, pruritus^a,b, Stevens Johnson syndrome^a.

Vascular Disorders: Vasculitis^b.

^a Following INFANRIX (licensed in the United States in 1997).
^b Following ENGERIX-B (licensed in the United States in 1989).

Read the entire FDA prescribing information for Pediarix (Diphtheria, Tetanus Toxoids and Acellular Pertussis Adsorbed, Hepatitis B and Inactivated Poliovirus Vaccine)