Home » Drug Information » FDA Approved Drugs » 1997
Medical Areas: Immunology | Pediatrics/Neonatology | Family Medicine | Urology
View By:YearCompanyConditionsTherapeutic AreasDrug Names
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.
Company: SmithKline Beecham
Approval Status: January 1997
Treatment Area: diphtheria, tetanus and pertussis
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).
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.
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
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
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.