WASHINGTON -- Despite Celebrex's well-documented link to higher heart risks, Pfizer Inc. wants permission to sell its painkiller to treat children as young as 2 who have arthritis.
Even as critics call for the drug to be removed from the market, Food and Drug Administration advisers will meet Wednesday to consider the company's request to expand Celebrex use.
Celebrex was the first of a class of new-style painkillers, called cox-2 inhibitors , approved in December 1998, and it is the last one to remain on the market. The drugs were designed to relieve pain without causing the stomach distress associated with other treatments, but they have been plagued by safety concerns. Merck & Co. pulled Vioxx from the market in 2004 after its studies showed the painkiller doubled the risk of heart attacks and strokes. Merck now faces more than 20,000 Vioxx lawsuits. Pfizer, under pressure from the FDA, last year halted sales of another cox-2 inhibitor, Bextra , because of heart risks and potentially fatal skin reactions.
Arthur A. Levin , an FDA adviser who has been invited to the Wednesday meeting, has already said sales of Celebrex also should be halted. "Obviously, these drugs remain extremely controversial," said Levin, director of the Center for Medical Consumers in New York. Pfizer must believe it has "some really compelling evidence" that Celebrex could benefit young patients, he said, but "it remains to be seen how compelling."
In considering applications such as Pfizer's, the FDA balances a product's risks against its effectiveness. The drugmaker is expected to present the results from clinical trials involving children to support its application. The company, in a statement, said it is working with the FDA "to determine the most appropriate means to share data that doctors and patients may find useful when making treatment decisions" and has "no plans to actively promote Celebrex" for children.
Pfizer has already faced criticism for heavily promoting the painkiller, transforming Celebrex into a blockbuster product before all its risks were known. The FDA has approved the drug as a treatment for rheumatoid arthritis suffered by adults , osteoarthritis , and painful menstrual cycles, and to prevent a type of colorectal tumor.
Some doctors who treat children with rheumatoid arthritis already prescribe Celebrex for young patients because other painkillers upset their stomachs. Such off- label uses are allowed when considered appropriate by individual doctors, but they cannot be promoted by drugmakers. Though many doctors commonly treat children with scaled-down doses of adult medicines, they would prefer to prescribe drugs whose safety and efficiency has been formally tested in children.
According to the National Institutes of Health , about 1 in 1,000 children in the United States has juvenile rheumatoid arthritis, a chronic ailment. They have swollen, tender joints, and can have enlarged livers and spleens as well as swollen lymph nodes.
"We use Celebrex all the time," said Dr. Marisa Klein-Gitelman , who practices at Children's Memorial Hospital in Chicago and is a member of the pediatric executive committee for the American College of Rheumatology .
In August 2004 , weeks before Merck pulled Vioxx, the FDA approved the company's application to market the drug to children with rheumatoid arthritis . Pediatric-strength Vioxx was a pleasant-tasting liquid.
The FDA received thousands of reports of serious side effects associated with Vioxx during the time it was available for pediatric use, according to a memo written by a safety evaluator from the agency. Of those reports, 16 involved children younger than 16; the FDA reviewed those and concluded that six reports could be linked to Vioxx, including two cases of acute kidney failure. Two reported deaths -- of 12- and 14-year-old girls -- involved heart complications.
But in the two years since the FDA approved Vioxx for pediatric use, evidence of heart problems for cox-2 painkillers has mounted, drug safety researchers say.
A long-term study of Celebrex as a possible way to prevent cancer showed that taking 400 milligrams of the drug twice a day tripled the risk of having a heart attack , stroke , or heart failure , and of dying from other cardiovascular causes . In the United States, the typical daily dose of Celebrex is no higher than 200 milligrams .
The results of an Alzheimer's prevention trial Pfizer finished in 2000 , but released in 2005 , also showed increased cardiovascular risk with Celebrex. And according to a study published this year, patients recovering from heart attacks who then took Celebrex had nearly double the risk of dying and a 1.5 -fold increased risk of having another attack.
"There are more studies confirming that these drugs double the risk of heart attacks. If anything, use should be restricted," said Dr. Curt Furberg , a professor at the Wake Forest University School of Medicine .
Furberg was among the first to cite heart risks associated with Bextra , a warning that ultimately helped to halt sales of the product.
Pfizer, at the request of the FDA, stopped consumer-directed Celebrex ads in December 2004 after the National Institutes of Health ended studies of the drug as a potential cancer prevention treatment because of heart risks. Amid criticism, Pfizer in February restarted print ads for Celebrex.
In October, Pfizer reported US Celebrex third-quarter sales were $419 million, up 24 percent from the previous year.
source - Boston Globe