Merck letter re safety of proquad, increased risk of febrile seizures. Wait until 4 yrs

Select Safety Information

ProQuad' (Measles, Mumps, Rubella and Varicella Virus Vaccine Live) should not be administered to certain individuals, including those with any of the following: a history of anaphylactic reactions to neomycin; a history of hypersensitivity to gelatin or any other component of the vaccine; blood dyscrasias, leukemia, lymphomas of any type, or other malignant neoplasms affecting the bone marrow or lymphatic system; an immunodeficient condition or receiving immunosuppressive therapy; active untreated tuberculosis; an active febrile illness (>101.3°F); or those who are pregnant.

In clinical trials with ProQuad involving children 12 to 23 months of age, the most frequently reported injection-site adverse experiences (>1% of children) were pain/tenderness/soreness, erythema, swelling, ecchymosis, and rash. The most frequently reported systemic vaccine-related adverse experiences (1% of children) were fever (102°F), irritability, measles-like rash, varicella-like rash, rash (not otherwise specified), upper respiratory infection, viral exanthema, and diarrhea.

In these trials, the only systemic vaccine-related adverse experiences that were reported at a significantly greater rate in individuals who received ProQuad than in individuals who received M-M-R₁₁ (Measles, Mumps, and Rubella Virus Vaccine Live) and VARIVAX'' [Varicella Virus Vaccine Live (Oka/Merck)] were fever (102°F f38.9°CJ oral equivalent or abnormal) (21.5% versus 14.9%, respectively), and measles-like rash (3.0% versus 2.1%, respectively).

Febrile seizures have been reported in children receiving ProQuad. Consistent with clinical study data on the timing of fever and measles-like rash, an interim analysis of a postmarketing observational study in children (N=14,263) receiving their first dose of vaccine has shown that febrile seizures occurred more frequently 5 to 12 days following vaccination with ProQuad (0.5 per 1000) when compared with data from children in a historical, age- and gender-matched, control group vaccinated with M-M-R'₁₁ and VARIVAX (N=14,263) concomitantly (0.2 per 1000). In the 0- to 30-day time period following vaccination, the incidence of febrile seizures with ProQuad (1.0 per 1000) was not greater than that observed in children receiving M-M-R"^-₁₁ and VARIVAX concomitantly (1.3 per 1000).

The duration of protection from measles, mumps, rubella, and varicella infections after vaccination with ProQuad is unknown.

Vaccination with ProQuad may not offer 100% protection from measles, mumps, rubella, and varicella infection.

Before administering ProQuad, VARIVAX, or _M-M-R'11, please read the enclosed appropriate Prescribing Information. For additional copies of the Prescribing Information, call 1-800-672-6372, visit MerckVaccines.com', or contact your Merck representative.

If you have further questions, please visit MerckVaccines.com', call 1-877-VAX-MERCK (1-877-829-6372) or contact your Merck representative.

Sincerely,

Dennis A. Brooks, MD, MPH

 

Dennis A. Brooks, MD, MPH    Merck & Co.. Inc.

Senior Director    770 Sumneytown Pike

Pediatric Medical Affairs    P.O. Box 250

Policy, Public Health & Medical Affairs    West Point PA 19486-0250

0 MERCK

March 7, 2008

Dear Health Care Practitioner:

I am writing to inform you thatthe Advisory Committee on Immunization Practices IACIP), at its meeting on

February 27, 2008, after reviewing preliminary data from two postlicensure safety studies on febrile seizures following administration of MMRV vaccine compared with MMR and varicella vaccines, voted to change the language regarding the use of combination measles, mumps, rubella, varicella vaccine (marketed by Merck & Co., Inc., as ProQuad- (Measles, Mumps, Rubella and Varicella Virus Vaccine Live). As stated on the Web site of the Centers for Disease Control and Prevention (CDC) at http://www.cdc.goviod/science/iso/vsdimmrv.htm, the ACIP recommends that there is no preference for use of combination MMRV vaccine over separate administration of MMR and varicella vaccines.

Preliminary results from an MMRV vaccine safety study among children aged 12 to 23 months implemented by the CDC found that the rates of febrile seizures during the 7 to 10 days after vaccine was about 2 times higher in children who received MMRV vaccine I9/10,000 children vaccinated) compared with children who received mumps, measles, and rubella (MMR) and varicella vaccines separately at the same visit (4/10,600 children vaccinated).

An interim analysis of a postmarketing observational study conducted by Merck in children (N=14,253) receiving their first dose of vaccine has shown that febrile seizures occurred more frequently 5 to 12 days following vaccination with ProO.uad (0.5 per 1000) when compared with data from children in a historical, age- and gender-matched, control group vaccinated with M-M-R^-₁₁ (Measles, Mumps, and Rubella Virus Vaccine Live) and VARIVAX' [Varicella Virus Vaccine Live (Oka/Merck)) IN.14,263) concomitantly (0.2 per 1000). In the 0- to 30-day time period following vaccination, the incidence of febrile seizures with ProGuad (1.0 per 10001 was not greater than that observed in children receiving M-M-R'₁₁ and VARIVAX concomitantly (1.3 per 1000).

The interim results from the Merck observational study have been recently added to the Adverse Reactions section of the label for ProGuad. A copy of the label for ProQuad is included with this letter.

Merck supports the recommendations of the ACIP on the use of ProCluad, M-M-19₁₁ and VARIVAX for appropriate patients in the United States and supports the appropriate use of ProGuad as an option for simultaneous vaccination against measles, mumps, rubella, and chickenpox in children 12 months through 12 years of age.

I would also like to take this opportunity to remind you that the current unavailability of ProQuad is due to a manufacturing issue and is unrelated to these postmarketing analyses or any safety or efficacy issue with the vaccine. Merck remains committed to resupplying ProQuad as soon as possible and, as previously stated, expects to bring ProQuad back to the US market in early 2009.

About ProQuad

ProGuad is indicated for simultaneous vaccination against measles, mumps, rubella, and varicella in children 12 months through 12 years of age. ProGuad may be used in children 12 months through 12 years of age if a second dose of measles, mumps, and rubella vaccine is to be administered.

• At least 1 month should elapse between a dose of a measles-containing vaccine such as M-M-R _II and a dose of ProQuad.
  
• If for any reason a second dose of varicella-containing vaccine is required, at least 3 months should elapse between administration of the 2 doses.