CDC Updates Recommendations for MMRV Vaccination

Merck Expected to Start Shipping ProQuad Again

May 12, 2010 11:45 am David Mitchell

Physicians who provide care for children should be aware that the CDC has published updated recommendations( for vaccination against measles, mumps, rubella and varicella. The recommendations, which have been adopted by the AAFP, offer clinicians insight into the preferred use of combination measles, mumps, rubella and varicella, or MMRV, vaccine versus use of MMR vaccine plus varicella vaccine.

"We have two very good options," said Jonathan Temte, M.D., Ph.D., a member of the CDC's Advisory Committee on Immunization Practices, or ACIP, and chair of the ACIP MMRV Vaccine Safety Workgroup. "There are some known, though slight, risks with use of the combination product for the first dose at younger ages -- specifically, 12-15 months."

When it was first licensed in 2005, Merck & Co.'s MMRV vaccine, which is marketed as ProQuad, was preferred by the ACIP for both the first and second doses, rather than separate injections of MMR and varicella vaccine.

However, the ACIP issued updated recommendations in February 2008 -- stating no preference for the use of MMRV vaccine versus the two component vaccines -- after preliminary data from two studies showed an increased risk for fever and febrile seizures five-12 days after vaccination among children ages 12-23 months who had received their first dose as the combination MMRV vaccine compared with children who received their first dose as separate injections of MMR and varicella vaccines.

Temte, a professor in the department of family medicine at the University of Wisconsin School of Medicine and Public Health, Madison, said the absolute risk of febrile seizure after measles, mumps, rubella and varicella vaccination is low. However, he said, the relative risk with use of the quadrivalent MMRV vaccine is double that associated with MMR plus varicella in separate injections when administering the first dose to children 12-15 months old.

Data from postlicensure studies do not suggest a similar risk for children ages 4-6 years receiving a second dose. Thus, the ACIP's updated recommendations are as follows:

  • For the first dose at age 12-47 months, either the trivalent MMR vaccine and varicella vaccine can be given in separate injections, or the quadrivalent MMRV vaccine may be used. Clinicians considering MMRV vaccine administration should discuss the benefits and risks of both vaccination options with parents. Unless parents express a preference for MMRV vaccine, the CDC recommends that MMR vaccine and varicella vaccine should be administered for the first dose in this age group.
  • For the second dose at age 15 months to 12 years, and for the first dose in children ages 4 years or older, use of MMRV vaccine generally is preferred rather than separate injections of MMR vaccine and varicella vaccine. Considerations should include clinician assessment, patient preference and the potential for adverse events.
  • Children with a personal or family history of seizures of any etiology generally should be vaccinated with MMR vaccine and varicella vaccine.

Overall, Temte said, the MMRV vaccine is safe and effective. He added that although febrile seizures generally are benign events, they can be extremely worrisome for parents.

The ACIP's recommendations for the use of the quadrivalent vaccine have been moot for the past three years because of the unavailability of ProQuad. Merck notified the CDC about a pending shortage of the vaccine in February 2007 because of lower-than-expected yields of varicella-zoster virus. In May 2007, the manufacturer said it expected that supplies of the vaccine would be depleted within two months.

According to a recent update on the CDC's Current Vaccine Shortages & Delays Web page(, Merck planned to begin taking orders for MMRV vaccine beginning May 10. The agency said Merck was expected to have about 1.4 million doses of ProQuad available.

At press time, however, a check of Merck's ProQuad website found that the vaccine was still noted as unavailable.