General Information

Pediarix [Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Hepatitis B (Recombinant) and Inactivated Poliovirus Vaccine Combined] is a noninfectious, sterile, multivalent pediatric vaccine for intramuscular administration.

Pediarix is specifically indicated for active immunization against diphtheria, tetanus, pertussis, infection caused by all known subtypes of hepatitis B virus, and poliomyelitis.

Pediarix is approved for use as a 3-dose series in infants born of hepatitis B surface antigen (HBsAg)-negative mothers. Pediarix may be given as early as 6 weeks of age through 6 years of age (prior to the 7th birthday). Pediarix is administered as three doses (0.5-mL each) by intramuscular injection at 2, 4, and 6 months of age.

Mechanism of Action

The diphtheria toxin is produced by growing Corynebacterium diphtheriae in Fenton medium containing a bovine extract. Tetanus toxin is produced by growing Clostridium tetani in a modified Latham medium derived from bovine casein. Both toxins are detoxified with formaldehyde, concentrated by ultrafiltration, and purified by precipitation, dialysis, and sterile filtration.

The 3 acellular pertussis antigens (PT, FHA, and pertactin) are isolated from Bordetella pertussis culture grown in modified Stainer-Scholte liquid medium. The antigens are purified in successive chromatographic and precipitation steps. PT is detoxified using glutaraldehyde and formaldehyde. FHA and pertactin are treated with formaldehyde.

The hepatitis B surface antigen (HBsAg) is obtained by culturing genetically engineered Saccharomyces cerevisiae cells, which carry the surface antigen gene of the hepatitis B virus, in synthetic medium. The surface antigen expressed in the S. cerevisiae cells is purified by several physiochemical steps, which include precipitation, ion exchange chromatography, and ultrafiltration.

The inactivated poliovirus component of Pediatrix is an enhanced potency component. Each of the 3 strains of poliovirus is individually grown in VERO cells, a continuous line of monkey kidney cells, cultivated on microcarriers.

Clinical Trial Results

Approval of Pediarix was based on 12 clinical trials worldwide, in which 20,739 doses of vaccine were administered to 7,028 infants.

In a double blind study conducted at 5 sites in the U.S., 484 infants were randomized into 4 groups to receive 3 different new production lots or 1 earlier production lot of Pediarix vaccine. In the 482 infants assessable for reactogenicity, rates of local injection site reactions, restlessness, and fever did not increase over the 3-dose primary series. Severe adverse reactions (grade 3), defined as events that would prevent normal daily activity or in the case of redness or swelling > 20 mm area and a rectal temperature >103.1°F, occurred at rates of 3.4% or less.

In an open, randomized study conducted in the U.S., the immunogenicity of Pediarix was compared with that of Infanrix and Engerix-B. Immunogenicity was analyzed 1 month after the third vaccine dose. One month after the third dose of Pediarix, vaccine response rates to each antigen, with the exception of FHA, were similar to the rates of separately administered vaccines. The immune responses for each antigen contained in Pediarix were considered similar to the comparator group if there was no more than a 10% difference in vaccine response (pertussis antigens) or seroprotection rates (diphtheria, tetanus, hepatitis B, and poliovirus) between the 2 groups. The vaccine response to FHA slightly exceeded the 10% limit for the difference between the groups. The anti-FHA response in the Pediarix group in this study was higher than the anti-FHA response observed in both studies that demonstrated the clinical efficacy of Infanrix.