Bextra (valdecoxib) — Pfizer’s COX-2 Pulled in 2005 and a Record $2.3 Billion Fraud Settlement

When Pfizer pulled Bextra from the U.S. market on 7 April 2005 — not voluntarily, but at the written request of the U.S. Food and Drug Administration — the company described a balanced judgment about risks and benefits; the documented record shows a drug whose dangers had been measurable for at least a year and whose marketing had outrun every safety signal it generated. Bextra (valdecoxib), a COX-2 selective anti-inflammatory developed by G. D. Searle/Pharmacia and co-promoted by Pfizer after approval on 20 November 2001 for osteoarthritis, rheumatoid arthritis, and menstrual pain, was withdrawn for two converging harms: an excess of heart attacks and strokes, and a rare but lethal class of skin reactions. The FDA concluded the drug offered no demonstrated advantage over existing NSAIDs to justify either.

The cardiovascular signal was not theoretical. A randomized trial in 1,671 cardiac-surgery patients — Nussmeier et al., published in The New England Journal of Medicine on 17 March 2005 — found that patients given parecoxib followed by valdecoxib after coronary-artery-bypass-graft surgery suffered cardiovascular events at a risk ratio of 3.7 (95% confidence interval 1.0–13.5; P=0.03), roughly 2.0 percent versus 0.5 percent on placebo. This was the same COX-2 hazard that had condemned Vioxx six months earlier, surfacing in Pfizer’s own franchise.

The dermatologic harm was, if anything, more distinctive. Because valdecoxib is a sulfonamide, it carried a strong association with Stevens-Johnson syndrome and toxic epidermal necrolysis — conditions in which the skin blisters and sloughs and which kill a meaningful fraction of those who develop them. By the end of March 2004 the FDA had logged on the order of 63 reported cases of SJS/TEN tied to the drug, several of them fatal. In mid-October 2004, Pfizer sent physicians a warning letter; a boxed warning followed; the withdrawal followed that. The verdict is therefore plain at the outset: a me-too painkiller with no proven edge over cheap generics was kept on the market and aggressively promoted while it accumulated both a cardiac body count and a roster of fatal skin reactions — and the reckoning, when it came, took the form of the largest health-care fraud prosecution the Justice Department had ever brought.