General Information

INFANRIX is a vaccine indicated for active immunization against diphtheria, tetanus, and pertussis as a 5-dose series in infants and children aged 6 weeks through 6 years (prior to the 7th birthday).

A 0.5-mL dose of INFANRIX is approved for intramuscular administration in infants and children aged 6 weeks through 6 years (prior to the 7th birthday) as a 5-dose series. The series consists of a primary immunization course of 3 doses administered at 2, 4, and 6 months of age (at intervals of 4 to 8 weeks), followed by 2 booster doses, administered at 15 to 20 months of age and at 4 to 6 years of age. The first dose may be given as early as 6 weeks of age.

The preferred administration site is the anterolateral aspect of the thigh for most infants aged younger than 12 months and the deltoid muscle of the upper arm for most children aged 12 months through 6 years.

Mechanism of Action

INFANRIX (Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed) is a noninfectious, sterile vaccine for intramuscular administration. Each 0.5-mL dose is formulated to contain 25 Lf of diphtheria toxoid, 10 Lf of tetanus toxoid, 25 mcg of inactivated pertussis toxin (PT), 25 mcg of filamentous hemagglutinin (FHA), and 8 mcg of pertactin (69 kiloDalton outer membrane protein). 

Diphtheria

• Diphtheria is an acute toxin-mediated infectious disease caused by toxigenic strains of C. diphtheriae. Protection against disease is due to the development of neutralizing antibodies to the diphtheria toxin. A serum diphtheria antitoxin level of 0.01 IU/mL is the lowest level giving some degree of protection; a level of 0.1 IU/mL is regarded as protective.

Tetanus

• Tetanus is an acute toxin-mediated infectious disease caused by a potent exotoxin released by C. tetani. Protection against disease is due to the development of neutralizing antibodies to the tetanus toxin. A serum tetanus antitoxin level of at least 0.01 IU/mL, measured by neutralization assays, is considered the minimum protective level. 2,3 A level of 0.1 IU/mL is considered protective.

Pertussis

• Pertussis (whooping cough) is a disease of the respiratory tract caused by B. pertussis. The role of the different components produced by B. pertussis in either the pathogenesis of, or the immunity to, pertussis is not well understood. There is no well-established serological correlate of protection for pertussis.

Side Effects

Adverse effects associated with the use of the INFANRIX vaccine may include, but are not limited to, the following:

• injection site reaction
• fever
• drowsiness
• irritability/fussiness
• loss of appetite

Clinical Trial Results

INFANRIX, which contains three pertussis antigens (pertactin (PRN), pertussis toxoid (PT) and filamentous hemagglutinin (FHA)) demonstrated an absolute efficacy of 89 percent in preventing pertussis in a German household contact study. Furthermore, INFANRIX is the only acellular DTP proven more effective at 84 percent than a whole-cell DTP (36 percent effective). INFANRIX also includes antigens to protect against two other childhood diseases (diphtheria and tetanus). INFANRIX demonstrated a superior safety profile as compared to that of whole-cell DTP vaccines. Whole-cell vaccines, although effective, are associated with relatively high rates of side effects. Acellular vaccines such as INFANRIX cause significantly fewer local and systemic reactions.

The National Institute of Health pertussis trials conducted in 1992-95 were a benchmark in the evaluation of acellular pertussis vaccines. The efficacy and safety of acellular vaccines were well established in the trials, which were conducted in Italy and Sweden and together enrolled more than 25,000 children. The trials were randomized, double-blinded with a whole-cell DTP control group and a placebo control group. Results of the trials, reported in The New England Journal of Medicine in February, 1996, supported SB’s choice of a three-component vaccine.

The Swedish study (N = 9,829) found a two-component (PT and FHA) acellular DTO manufactured by SB to be 59 percent effective. The whole-cell DTP vaccine was found to be 48 percent effective.

In the Italian study (N = 14,751), INFANRIX, containing three pertussis antigens, PT, FHA and pertactin, was found to be 84 percent effective against WHO-defined typical pertussis (21 days or more of paroxysmal cough plus laboratory confirmation). The Italian study confirmed the superior efficacy of INFANRIX by demonstrating that it is more effective than a U.S. licensed whole-cell vaccine which was proven 36 percent effective.

Although the role of the pertussis antigens in providing protection is not well understood, the NIH trials which evaluated candidate acellular DTPs manufactured by SB Biologicals supported the efficacy of three-component INFANRIX.

The superior efficacy of INFANRIX was confirmed in a large, blinded, prospective household contact study that enrolled more than 22,000 infants in six different areas in Germany. INFANRIX demonstrated a protective efficacy of 89 percent for WHO-defined typical pertussis. This study was free of detectable bias from potentially confounding factors (age, socioeconomic status, family size and erythromycin treatment) and was conducted under stringent conditions. These findings were published in The Journal of the American Medical Association (JAMA) in January 1996.