INFANRIX (Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed)

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.

Approval Status:

January 1997

Specific Treatments:

diphtheria, tetanus and pertussis

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General Information

INFANRIX has been approved as new vaccine for infants and children. INFANRIX is indicated for active immunization against diphtheria, tetanus and pertussis (whooping cough) in infants and children 6 weeks to 7 years of age (prior to seventh birthday).

Clinical 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.

Additional Information

Pertussis (whooping cough) is caused by infection of the respiratory tract by the Gram-negative bacterium Bordetella pertussis and is highly contagious. pertussis causes violent spells of coughing that may be followed by difficulty in breathing. Symptoms progress to paroxysmal coughs followed by a long, deep breath ("whoop").

Pertussis was a major cause of morbidity and mortality among infants and children in the United States during the prevaccine era (i.e., before the mid-1940s). Since pertussis became a nationally reportable disease in 1922, the highest number of pertussis cases (approximately 260,000) was reported in 1934; the highest number of pertussis related deaths (approximately 9,000) occurred in 1923. Following the licensure of and widespread use of whole-cell DTP among infants and children, the incidence of reported pertussis declined to a historical low of 1,010 cases in 1976. However, since the early 1980s, reported pertussis incidence has increased cyclically with each successive peak.

Acellular pertussis vaccines contain only those purified parts of the pertussis bacterium believed to be important in conferring immunity. Whole-cell vaccines, by contrast, incorporate entire, inactivated bacteria. Although whole-cell vaccines have been effective in reducing the incidence of pertussis, they are more likely to cause side effects, such as redness, pain and swelling at the site infection, fever, drowsiness, fretfulness and loss of appetite. A fear of side effects associated with whole-cell pertussis vaccines, and in some countries the lack of mandatory immunization, has led to an increase in the incidence of pertussis.

Beginning in the early 1980s, collaboration between scientists and vaccine manufacturers to improve pertussis vaccines led to the development of acellular vaccines. The first acellular vaccine was developed in Japan in the mid-seventies. In 1991, the Food and Drug Administration licensed an acellular vaccine to be used as booster doses at 15-18 months and 4-6 years of age. Now INFANRIX, the newest advance in DTP vaccines, has shown improved tolerability with significantly lower local and systemic reactions than whole-cell DTP vaccines.