Pfizer Says Bextra, Heart Problems Linked

Pfizer Inc. on Friday said two small clinical trials showed heart bypass surgery patients taking Bextra, an anti-inflammatory in the same class as the recently withdrawn drug Vioxx, had an increased risk of stroke and heart attack.

The company also updated its warning that Bextra can cause a rare, but sometimes fatal, skin disorder called Stevens-Johnson syndrome to note that cases of the condition are being seen more often with Bextra than with other drugs in the same class. Pfizer’s shares fell 2.8 percent on concerns that sales of Bextra would be hurt and that an experimental intravenous version of the drug, called parecoxib, may never now reach the U.S. market. “This definitely tarnishes Bextra and diminishes the prospects for parecoxib,” said Shaojing Tong, an analyst at Mehta Partners. Parecoxib is sold outside the United States under the name Dynastat. Bextra, which was launched in 2001, had sales last year of $687 million. It is approved to treat pain from arthritis and, like Merck & Co.’s Vioxx, is a COX-2 inhibitor. A recent trial showed Vioxx doubled the risk of heart attack and stroke in patients who took the drug for more than 18 months. The Vioxx withdrawal has cast a cloud over the entire class of COX-2 inhibitors, which also includes Pfizer’s Celebrex and an experimental drug from Novartis AG called Prexige. Pfizer said that following the Vioxx withdrawal, it re-examined its clinical data base of 8,000 patients with rheumatoid arthritis and osteoarthritis and found no increased risk of dangerous heart events in those taking Bextra for up to a year. The company also found no increased risk in a trial of patients taking Bextra in a general surgery setting. Doctors said it is too early to quantify the potential risk of Bextra or Celebrex, as neither have been tested for long enough. Pfizer said it is conducting longer term trials in arthritis patients. The coronary bypass trials are ones that Dr. Eric Topol, of the Cleveland Clinic Foundation and an early and outspoken critic of Vioxx, said he found concerning as they show a cluster of heart attacks and strokes. He said the danger signal does not appear to be as strong as it was with Vioxx. “Celebrex and Bextra do appear safer than Vioxx but whether they are really safe, especially in patients with heart risk, that’s an open question,” Topol said. Pfizer has updated the label on several occasions since Bextra was approved to reflect the risk of Stevens-Johnson syndrome, a form of allergic reaction caused usually by certain types of drug. Symptoms usually begin as a blistering of the mouth and lips, spreading to the throat, tongue and other parts of the body. The blisters sometimes become so extensive as to be fatal.The company said the risk did not start to appear until the drug hit the market. It updated the label in April to say that deaths have occurred. The company said the number is “very small,” but declined to be more specific. Gail Cawkwell, Pfizer’s COX-2 worldwide medical team leader, said the company has reported the number of deaths to regulators, but does not believe it is “meaningful” enough to report to the general public. Jean Farrell, founder of the Stevens-Johnson Foundation, a non-profit organization that provides information to patients and the medical community, said that within weeks of Bextra hitting the market she had a “huge” increase in calls. “I had never even heard of the drug and within three weeks we already had six cases of SJS reported to us.” Shares of Pfizer fell 80 cents to $28.28 in afternoon trading on the New York Stock Exchange. (Source: Reuters Health: Toni Clarke: Ocotber 2004.)