As he has been doing for years, Richard Peters, R.Ph., pharmacy manager of Glen Raven Pharmacy in Burlington, N.C., arrived at work early to prepare for the day ahead. Imagine his surprise when he reads the daily blogs on his Internet home page on Sept. 30 and learns of the voluntary withdrawal of the blockbuster arthritis drug rofecoxib (Vioxx, Merck), from U.S. and worldwide markets. By 9:05 am the calls start pouring in from panicked customers. "What's this about Vioxx?" "What's going to happen to me? I've been taking Vioxx for so long!"
As he has been doing for years, Richard Peters, R.Ph., pharmacy manager of Glen Raven Pharmacy in Burlington, N.C., arrived at work early to prepare for the day ahead. Imagine his surprise when he reads the daily blogs on his Internet home page on Sept. 30 and learns of the voluntary withdrawal of the blockbuster arthritis drug rofecoxib (Vioxx, Merck), from U.S. and worldwide markets. By 9:05 AM the calls start pouring in from panicked customers. "What's this about Vioxx?" "What's going to happen to me? I've been taking Vioxx for so long!"
"Is there some reason why we as healthcare professionals do not receive a warning even one day before the general public?" asked Peters. His frustration was echoed by other retail pharmacists interviewed by Drug Topics, who felt angry that Merck had not provided an earlier warning. Most felt they were "stuck in the middle," and, though they are professionals, they were not armed with the knowledge to give professional answers. Peters didn't receive his letter from Merck until the day after the Merck announcement, and some of his colleagues received it two days later, leaving him to wonder why there couldn't have been an e-mail or fax alert sent out, rather than snail mail to deliver the news.
Interestingly enough, Jim Jorgenson, R.Ph., M.S., director of pharmacy at the University of Utah Hospital and Clinics, did receive the press release via e-mail. "We looked at it as a voluntary recall and didn't extend it to patients right away," he said. The medication was removed from the shelves and physicians were notified, but most didn't immediately convert their patients.
So what's going to happen to the two million patients who have been taking rofecoxib? "Everybody has been switching to Celebrex [celecoxib, Pfizer]," said Peters. Jeffrey Fudin, Pharm.D., DAAPM, clinical pharmacist at the Stratton VA Medical Center in Albany, explained that "the more COX-2- selective a drug is, the higher the probability it will cause cardiovascular problems." Published reports have indicated that rofecoxib is a more highly selective inhibitor of the COX-2 isoenzyme (276 times more selective for COX-2 than COX-1) than is celecoxib (30 times). Jorgenson, on the other hand, has seen physicians convert patients equally to either celecoxib or valdecoxib (Bextra, Pfizer).
Merck's decision to withdraw the drug came after new data found it doubled the risk of heart attacks and strokes in patients taking the drug for more than 18 months. The big question is whether these adverse events stem from a class effect or drug effect.
The first indication the Food & Drug Administration received that rofecoxib could pose a cardiovascular risk was in 2001, when Merck submitted data from the Vioxx Gastrointestinal Outcomes Research (VIGOR) study. The study demonstrated a gastrointestinal benefit for rofecoxib, but it also showed an increase in thrombotic events. The VIGOR study data were added to rofecoxib labeling in April 2002. In contrast, Pfizer's Celecoxib Long-term Arthritis Safety Study (CLASS) verified celecoxib's cardiovascular safety but did not confirm a GI benefit. Pfizer has been emphasizing the safety of celecoxib, and to date the Pfizer drug has not been found to have the same level of cardiac risk as rofecoxib.
FDA's Center for Drug Evaluation & Research acting director, Steven Galson, M.D., indicated that FDA would seek long-term data for COX-2 drugs already on the market. In addition, "we're going to be more interested in looking at long-term data of the new products coming down the pike," Galson said during a recent media call.
Merck's rofecoxib follow-up compound eterocoxib (Arcoxia) is under review at the FDA, and Novartis expects to submit an NDA for its COX-2 lumiracoxib (Prexige) by 2006.