FDA Licenses Two New Pediatric Combination Vaccines

FDA officials approved the licensure of two new combination vaccines for children last month. Both vaccines protect against diphtheria, tetanus, pertussis and polio; one of them also protects against invasive disease caused by Haemophilus influenzae type b, or Hib.

The move further raises the tally of combination vaccine products available on the U.S. market, and one FP expert AAFP News Now consulted says he harbors mixed feelings about that prospect.

Manufactured by GlaxoSmithKline, diphtheria and tetanus toxoids and acellular pertussis adsorbed and inactivated poliovirus vaccine, or DTaP-IPV, was approved for use in children ages 4-6 years on June 24. A single dose of the vaccine, marketed as Kinrix, is indicated for active immunization against diphtheria, tetanus, pertussis and poliomyelitis as the fifth dose in the DTaP vaccine series and the fourth dose in the IPV series in children whose previous DTaP vaccine doses have been with Infanrix (DTaP) and/or Pediarix (DTaP plus recombinant hepatitis B vaccine and IPV) for the first three doses and Infanrix for the fourth dose.

Sanofi pasteur's DTaP-IPV and Hib vaccine, approved June 20 or sale in the United States under the trade name Pentacel, is indicated for active immunization against diphtheria, tetanus, pertussis, polio and invasive Hib disease. The vaccine is approved for use in infants and children ages 6 weeks through 4 years (the vaccine should be given before a child's fifth birthday).

The FDA vaccine advisory panel that recommended licensure also endorsed inclusion of these vaccines in the federal Vaccines for Children program, which provides vaccines for approximately 36 million children who are covered by Medicaid, have no insurance or meet other guidelines for eligibility.

Many experts have noted that combination vaccines provide a valuable service by reducing the number of shots young children receive. The CDC's Advisory Committee on Immunization Practices, or ACIP, has stated that the use of these vaccines "is preferred to separate injection of their equivalent component vaccines to reduce the number of injections and missed opportunities to protect through vaccination."

However, there are some drawbacks to combination vaccines, according to Doug Campos-Outcalt, M.D., M.P.A., of Phoenix, an AAFP liaison to the ACIP and a former member of the AAFP Commission on Clinical Policies and Research. He says that combination vaccines can complicate life for busy FPs. The increasing number of combination products available that contain different vaccine combinations; are used for different and frequently overlapping age ranges; and that often must be tailored according to a child's previous vaccinations, can make the immunization process difficult.

The differing age ranges for which Pentacel and Kinrix are approved, for example, as well as other differences in their respective dosing instructions, may have FPs feeling overwhelmed by the task of tracking each vaccine's indications and ensuring patients are the right age and have the correct number and type of previous vaccinations. In short, says Campos-Outcalt, such combination vaccines are "becoming more common and more confusing."

In addition, Campos-Outcalt says, reimbursement issues should be considered. Although payers cover most combination vaccines, many family physicians find that, because of the amount of work it now takes to sort out the many vaccines, it doesn't always pay to give them. Using combination vaccines can reduce the number of injections FPs administer, but it also can reduce reimbursement compared with using separate vaccines. Therefore, says Campos-Outcalt, the effect of combination vaccines on the bottom line is unclear.

Combination vaccines also may present other potential problems, including unexpected side effects and other reactions. Campos-Outcalt points to Merck & Co.'s measles, mumps, rubella and varicella, or MMR-V, vaccine as an example. Preliminary findings from a postmarketing study showed that children receiving their first dose of the MMR-V vaccine, which is sold as ProQuad, had a higher incidence of febrile seizures five to 12 days after immunization than did children who received separate MMR and varicella vaccine products during a single visit. At 30 days postvaccination, however, that difference disappeared.

Campos-Outcalt notes that the same Merck vaccine provides an example of another issue with combination products -- namely, if one component of such a vaccine becomes unavailable for a time, that shortfall can affect supplies of the combination vaccine, as well as the manufacturer's other vaccine products that contain the same component.

In the case of ProQuad, Merck announced last year that because of difficulty producing sufficient amounts of the varicella component of the vaccine, the company would temporarily halt shipment of ProQuad, concentrating instead on maintaining distribution of two of its other varicella-containing vaccines, Varivax (a varicella-only vaccine) and Zostavax (a varicella-zoster vaccine that protects against shingles).

According to a July 11 update on the CDC's "Current Vaccine Shortages & Delays" Web page, ProQuad remains "currently unavailable," and Zostavax "is available for ordering, however, the manufacturer is experiencing shipping delays."

So, are combination vaccines likely to replace single-antigen vaccines? And if they do, will they make physicians' lives easier?

Campos-Outcalt says he thinks these types of vaccines can be both good and bad for busy FPs. They can introduce confusion and complexity into an already complex system. However, they cut down on the number of injections, which can save physicians time and make their patients happier. So, they're likely here to stay, he says, adding, "It's nice to be able to give fewer injections; the price we pay is more confusion over vaccination schedules."