Notice to Readers
FDA Approval of a Haemophilus b Conjugate Vaccine Combined by
Reconstitution with an Acellular Pertussis Vaccine
On September 27, 1996, the Food and Drug Administration (FDA)
licensed a Haemophilus b Conjugate Vaccine (ActHIB{Registered} * )
combined by reconstitution with diphtheria and tetanus toxoids and
acellular pertussis vaccine (DTaP) (Tripedia{Registered} ** ) for
use as the fourth dose in the childhood vaccination series. This
combination vaccine will be sold under the trade name
TriHIBit{Trademark}. On July 31, 1996, Tripedia{Registered} was
licensed for the initial four doses of the diphtheria, tetanus, and
pertussis vaccination series (1). TriHIBit{Trademark} is the first
vaccine to be licensed in the United States that combines DTaP with
a Haemophilus b Conjugate Vaccine.
The Advisory Committee on Immunization Practices (ACIP), the
Committee on Infectious Diseases of the American Academy of
Pediatrics, and the American Academy of Family Physicians recommend
that children routinely receive a series of five doses of vaccine
against diphtheria, tetanus, and pertussis before age 7 years and
four doses of vaccine against Haemophilus influenzae type b (Hib)
disease before age 2 years (2-7). The first four doses of the
diphtheria, tetanus, and pertussis vaccination series should be
administered at ages 2, 4, 6, and 15-18 months and the fifth dose
at age 4-6 years. If diphtheria, tetanus, and whole-cell pertussis
vaccine (DTP) is used as a fourth dose, it may be administered as
early as 12 months of age provided that 6 months have elapsed since
the third dose.
The following evidence supports the use of TriHIBit{Trademark}
for the fourth dose of the diphtheria, tetanus, pertussis, and Hib
vaccination series:
In clinical studies, children aged 15-20 months who previously
had received three doses of Haemophilus b Conjugate Vaccine and DTP
were administered either Tripedia{Registered} and
ActHIB{Registered} vaccines at separate sites or combined as a
single injection. In both groups, following administration of the
fourth dose, 100% of children had serologic evidence of long-term
protection from invasive Hib disease, diphtheria, and tetanus
(Connaught Laboratories, Inc., unpublished data). The proportions
of children who had at least fourfold antibody responses to
pertussis toxin measured by enzyme-linked immunosorbent assay or
Chinese hamster ovary cell assay were greater than or equal to 85%
in both groups; a smaller proportion of children who had received
the combined vaccine had at least fourfold antibody response to
filamentous hemagglutinin, but the clinical importance of this
difference is not known.
The rates of local reactions, fever, and other common systemic
symptoms following receipt of Tripedia{Registered} inoculations
were lower than those following DTP vaccination for each of the
first four doses in the series (5,8; Connaught Laboratories, Inc.,
unpublished data). In randomized trials, the local reactions were
mild following administration of TriHIBit{Trademark} as a fourth
dose as a single injection or ActHIB{Registered} simultaneously
with Tripedia{Registered} as two injections at separate sites.
Rates of both local and systemic reactions were similar between
children who had received vaccines combined or separate (Connaught
Laboratories, Inc., unpublished data).
Protective efficacy of TriHIBit{Trademark} when used as a fourth
dose in the childhood vaccination series has not been evaluated in
a clinical trial. This vaccine has been licensed for use as the
fourth dose on the basis of seroconversion and safety data.
Because of the reduced frequency of adverse reactions and high
efficacy, ACIP recommends DTaP for routine use for all doses of the
pertussis vaccination series (1). TriHIBit{Trademark} can be
administered as the fourth dose of the vaccination series at age
15-18 months following administration of either DTaP or DTP.
TriHIBit{Trademark} has not been licensed for use as the first
three doses of the vaccination series. Vaccine should be used
immediately (within 30 minutes) after reconstitution. A complete
ACIP statement providing recommendations for use of DTaP and DTaP
combined with Haemophilus b Conjugate Vaccine is being developed.
References
CDC. Food and Drug Administration approval of an acellular
pertussis vaccine for the initial four doses of the diphtheria,
tetanus, and pertussis vaccination series. MMWR 1996;45:676-7.
CDC. Diphtheria, tetanus, and pertussis: recommendations for
vaccine use and other preventive measures: recommendations of
the
Immunization Practices Advisory Committee (ACIP). MMWR
1991;40(no.
RR-10).
American Academy of Pediatrics. Report of the Committee on
Infectious Diseases. Elk Grove Village, Illinois: American
Academy
of Pediatrics, Committee on Infectious Diseases, 1991.
CDC. Pertussis vaccination: acellular pertussis vaccine for
reinforcing and booster use -- supplementary ACIP statement:
recommendations of the Immunization Practices Advisory Committee
(ACIP). MMWR 1992;41(no. RR-1).
CDC. Pertussis vaccination: acellular pertussis vaccine for the
fourth and fifth doses of the DTP series: update to the
supplementary ACIP statement: recommendations of the Advisory
Committee on Immunization Practices (ACIP). MMWR 1992;41(no.
RR-15).
CDC. Haemophilus b conjugate vaccines for prevention of
Haemophilus influenzae type b disease among infants and children
two months of age and older: recommendations of the Immunization
Practices Advisory Committee (ACIP). MMWR 1991;40(no. RR-1).
CDC. Recommendations for use of Haemophilus b conjugate vaccines
and a combined diphtheria, tetanus, pertussis, and Haemophilus b
vaccine: recommendations of the Advisory Committee on
Immunization
Practices (ACIP). MMWR 1993;42(no. RR-13).
Decker MD, Edwards KM, Steinhoff MC, et al. Comparison of 13
acellular pertussis vaccines: adverse reactions. Pediatrics
1995;96(suppl):557-66.
* Haemophilus b Conjugate Vaccine (Tetanus Toxoid Conjugate) is
manufactured by Pasteur Merieux Serums & Vaccines S.A. ActHIB is
identical to Haemophilus b Conjugate Vaccine (Tetanus Toxoid
Conjugate) -- OmniHIB (distributed by SmithKline Beecham
Pharmaceuticals). Use of trade names and commercial sources is for
identification only and does not imply endorsement by the Public
Health Service or the U.S. Department of Health and Human Services.
** Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine
Adsorbed, prepared and distributed as Tripedia{Registered} by
Connaught Laboratories, Inc. (Swiftwater, Pennsylvania), was
licensed July 31, 1996, for use in infants. The purified acellular
pertussis vaccine component is produced by BIKEN/Tanabe Corporation
(Osaka, Japan) and is combined with diphtheria and tetanus toxoids
manufactured by Connaught Laboratories, Inc.
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