Vioxx should be allowed back on the market advises expert panel
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* Barbara Sibbald

Rofecoxib (Vioxx) ought to be allowed back on the market, concludes Health Canada's Expert Advisory Panel on the Safety of COX-2 Selective Non-steroidal Anti-Inflammatory Drugs (NSAIDs).

After Merck & Co. withdrew rofecoxib from the world marketplace on Sept. 30, 2004 (*CMAJ* 2004;171[9]:1027-8), Health Canada launched a review of the cardiovascular (CV) risks associated with COX-2-selective NSAIDs, including rofecoxib, valdecoxib (Bextra), celecoxib (Celebrex) and meloxicam (Mobicox and other generics). The 400-page review includes pre-clinical and clinical trials, adverse drug reaction reports and other data.

In its comments on that review, released in June 2006, Health Canada decided that both rofecoxib and valdecoxib (which was withdrawn in December 2005 following evidence of increase CV events and severe cutaneous adverse reactions) will remain off the market unless a new drug submission is received and approved by Health Canada.

“At this time, we have not made a decision about whether to resubmit,” says Merck Frosst spokesperson Marlene Gauthier.

The 13 members of the Expert Advisory Panel, who met for 2 days in Ottawa in June 2005, included people with backgrounds in rheumatology, cardiology, gastroenterology, internal medicine, family medicine, clinical trial methodology and epidemiology, plus 2 patients with rheumatoid arthritis. The report was released in July 2005.

The panel voted 12 to 1 in favour of potential future sales for rofecoxib, noting that most NSAIDs carry cardiovascular risk and that rofecoxib has a decreased frequency of both gastrointestinal intolerance and peptic ulcer diseases compared with traditional non-selective NSAIDs, and that “patients benefit from having a variety of drugs to choose from.” The panel did not recommend that valdeocoxib go back on the market due to the rare but severe skin reactions.

“There's no question [rofecoxib] increases cardiovascular risk compared to placebo,” says Dr. Andreas Laupacis, who headed Health Canada's Expert Advisory Panel. “But the absolute increase is very small.”

Given that the risk is comparable to that of traditional NSAIDs, such as ibuprofen (see article on page [233](http://www.cmaj.ca/lookup/volpage/175/233)), but that it has a lower incidence of gastrointestinal problems, “What's the rationale for not making it available?” asked Laupacis the president and CEO of the Institute for Clinical Evaluative Sciences.

Health Canada's comments on that review and own scientific review of certain COX-2s, recommend shorter and lower doses of all COX-2s and traditional NSAIDs. 

“That's clear in the report,” says Dr. Marc Berthiaume, director of Marketing Pharmaceuticals and Medical Devices Bureau.

During public consultations, Berthiaume says people indicated they wanted to know the risk, but they also wanted to be able to “make that choice.”

Health Canada's review concludes that the “benefit–risk balance favours” the continued sale of celecoxib and meloxicam. In accordance with the panel's recommendations, the labels were revised in September 2005 to warn of the increased risk of CV adverse events and to suggest using these drugs at the “lowest effective dose for the shortest possible duration of treatment.”

Since the COX-2 withdrawals in 2003, the estimated number of filled prescriptions in Canada has plummeted from 7.3 million (worth about $476 million) to 3.5 million (valued at about $199 million) in 2005.