Licensure of a Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus, and Haemophilus b Conjugate Vaccine and Guidance for Use in Infants and Children

On June 20, 2008 the Food and Drug Administration (FDA) licensed a combined diphtheria and tetanus toxoids and acellular pertussis adsorbed (DTaP), inactivated poliovirus vaccine (IPV), and Haemophilus influenzae type b conjugate (tetanus toxoid [TT] conjugate) vaccine, DTaP-IPV/Hib (Pentacel, Sanofi Pasteur, Swiftwater, Pennsylvania), for use as a four-dose series in infants and children at ages 2, 4, 6, and 15 -- 18 months (1,2). This report summarizes the indications for Pentacel and provides guidance from the Advisory Committee on Immunization Practices (ACIP) for its use.

ACIP reviewed data on the safety and immunogenicity of DTaP-IPV/Hib (Pentacel). On the basis of these data, expert opinion of the ACIP Combination Vaccines Workgroup, and feedback from ACIP liaison organizations including the American Academy of Pediatrics and the American Academy of Family Physicians, ACIP endorsed the licensed indications and offered the following guidance for use of DTaP-IPV/Hib. On June 26, ACIP voted to include DTaP-IPV/Hib in the federal Vaccines for Children Program.

Each dose of DTaP-IPV/Hib contains the same diphtheria and tetanus toxoids and pertussis antigens (inactivated pertussis toxin [PT], filamentous hemagglutinin [FHA], pertactin, and fimbriae types 2 and 3) as the FDA-licensed DTaP vaccine Daptacel (Sanofi Pasteur, Toronto, Canada) but contains an increased amount of inactivated PT and FHA (2). The poliovirus component of DTaP-IPV/Hib contains the same strains and amount of inactivated poliovirus types 1, 2, and 3 as the polio vaccine Poliovax (Sanofi Pasteur, Toronto, Canada) (2). The Hib component is identical to ActHib (Haemophilus influenzae type b capsular polysaccharide [polyribosyl-ribitol-phosphate {PRP}] covalently bound to tetanus toxoid) (Sanofi Pasteur, Swiftwater, Pennsylvania) (2). The DTaP-IPV component is supplied as a sterile liquid used to reconstitute a lyophilized ActHIB vaccine component. Components should not be administered separately. DTaP-IPV/Hib does not contain thimerosal.

In comparative studies, the frequency of solicited local and systemic adverse events and of serious adverse events after administration of DTaP-IPV/Hib was similar to that observed following separately administered DTaP, IPV, and Hib component vaccines (2,3). The immunologic responses after the third dose or the fourth dose of DTaP-IPV-Hib generally were comparable to those following separately administered component vaccines, and have been published (2,3). Immune responses following the first and second doses were not measured.

Indications and Guidance for Use

DTaP-IPV/Hib is licensed for use in children aged 6 weeks through 4 years. DTaP-IPV/Hib is indicated for use in infants and children at ages 2, 4, 6, and 15 -- 18 months (1). DTaP-IPV/Hib is not licensed for use in children aged >5 years, and is not indicated for the booster dose at age 4 -- 6 years (2). However, DTaP-IPV/Hib that is inadvertently administered to children aged >5 years should be counted as a valid dose.

For prevention of diphtheria, tetanus, and pertussis, all children are recommended to receive 4 doses of DTaP, at ages 2, 4, 6, and 15 -- 18 months, and a booster dose at age 4 -- 6 years. Although an 8-week interval between doses is preferred, if an accelerated schedule is needed, a minimum interval of 4 weeks should occur between the first and second doses, and the third dose should not be administered before age 14 weeks (4). The fourth dose of DTaP-IPV/Hib may be administered as early as 12 months of age if the clinician feels an opportunity to vaccinate may be missed later and if 6 months has elapsed since the third dose of DTaP-IPV/Hib (1).

Data are limited on the safety and immunogenicity of interchanging DTaP vaccines from different manufacturers (2). ACIP recommends that, whenever feasible, the same manufacturer's DTaP product should be used for the pertussis series; however, that vaccination should not be deferred if the specific DTaP vaccine brand previously administered is unavailable or unknown (2).

For prevention of poliomyelitis, all children are recommended to receive 4 doses of IPV, at ages 2, 4, 6 -- 18 months, and 4 -- 6 years. DTaP-IPV/Hib may be used for 1 or more doses of the IPV series, including in children who have received 1 or more doses of another licensed IPV vaccine and who also are scheduled to receive DTaP and Hib vaccination. When an accelerated or catch-up schedule is needed, IPV doses may be administered at 4-week intervals and the fourth dose counted as valid if administered as early as age 18 weeks when the proper spacing of prior doses is maintained (1). Therefore, DTaP-IPV/Hib (Pentacel) doses administered at 2, 4, 6, and 12 -- 18 months would provide 4 valid doses of IPV under these circumstances.

The recommended vaccination schedule for Hib-TT vaccines (e.g., Pentacel) consists of a 3-dose primary series at ages 2, 4, and 6 months, and a booster dose at age 12 -- 15 months (1). Intervals between doses of the primary series as short as 1 month are acceptable but not optimal. Minimum intervals for the booster dose vary by age at first vaccination and have been published (5). DTaP-IPV/Hib may be administered at 12 months and counted as a valid Hib-TT dose if the minimum intervals are followed; however, the safety and efficacy of DTaP-IPV/Hib in this circumstance have not been evaluated. DTaP-IPV/Hib may be administered at separate injection sites with other vaccines administered at age 12 -- 18 months, such as hepatitis A, hepatitis B, pneumococcal conjugate, measles, mumps, and rubella (MMR), and varicella vaccines (2).

Special Considerations

Certain American Indian/Alaska Native (AI/AN) children are at increased risk for Hib disease, particularly in the first 6 months of life (6). Furthermore, the immunologic response to different Hib conjugate vaccine preparations can vary. Compared with other Hib conjugate vaccines (e.g., Hib-TT), administration of polyribosylribitol phosphate-meningococcal outer membrane protein (PRP-OMP)-containing Hib vaccine preparations leads to a more rapid seroconversion to protective antibody concentrations within the first 6 months of life. Although for subsequent doses, PRP-OMP and other Hib conjugate vaccines appear to have equal efficacy, failure to use PRP-OMP vaccines for the first dose has been associated with excess cases of Hib disease in AI/AN infants living in communities where Hib transmission is ongoing and exposure to colonized persons is likely (6,7). In addition, stocking of both PRP-OMP and other Hib conjugate vaccine preparations in the same clinic might lead to inadvertent administration of another vaccine for the first Hib dose. For this reason, clinics that serve predominantly AI/AN children might elect to stock and use only PRP-OMP-containing Hib vaccines (6).

Different lot numbers for the different components of DTaP-IPV/Hib are included on the DTaP-IPV vial and on the Hib powder vial. Providers should record lot numbers separately for the DTaP-IPV and Hib components.

References

1. CDC. Recommended immunization schedules for persons aged 0 -- 18 years -- United States, 2008. MMWR 2008;57(1).
2. Food and Drug Administration. Product approval information: package insert. Pentacel (diphtheria and tetanus toxoids and acellular pertussis adsorbed, inactivated poliovirus and Haemophilus b conjugate [tetanus toxoid conjugate] vaccine. Available at http://www.fda.gov/cber/products/pentacel.htm.
3. Black S, Greenberg DP. A combined diphtheria, tetanus, five-component acellular pertussis, poliovirus and Haemophilus influenzae type b vaccine. Expert Rev Vaccines 2005;4:793 -- 805.
4. CDC. General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2006;55(No. RR-15).
5. 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 ACIP. MMWR 1991;40(No. RR-1).
6. Pickering LK, ed. 2006 red book: report of the Committee on Infectious Diseases. 25th ed. Elk Grove Village, IL: Academy of Pediatrics; 2006.
7. Galil K, Singleton R, Levine OS, et al. Reemergence of invasive Haemophilus influenzae type b disease in a well-vaccinated population in remote Alaska. J Infect Dis 1999;179:101 -- 6.

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Date last reviewed: 10/1/2008