Vioxx

Rofecoxib is a nonsteroidal anti-inflammatory drug (NSAID) that was used in the treatment of osteoarthritis, acute pain conditions, and dysmenorrhoea. Formerly marketed by Merck & Co. under the trade names Vioxx, Ceoxx and Ceeoxx, it was voluntarily withdrawn from the market in 2004 because of concerns about increased risk of heart attack and stroke. more...

Rofecoxib was one of the most widely used drugs ever to be withdrawn from the market. Worldwide, over two million people were prescribed Vioxx at the time. In the year before withdrawal, Merck had a sales revenue of US$2.5 billion from Vioxx.

Rofecoxib was available on prescription as tablets and as an oral suspension.

COX-2 selective inhibitor

Rofecoxib belongs to the group of NSAIDs known as COX-2 selective inhibitors or coxibs (CycloOXygenase-2 InhiBitors). Being COX-2 selective means that these drugs act specifically on one form of the cyclooxygenase (COX) enzyme, namely the COX-2, whereas previous NSAIDs inhibited both COX-1 and COX-2. This specificity allows rofecoxib and other COX-2 inhibitors to reduce inflammation and pain while minimizing undesired gastrointestinal adverse effects - peptic ulcers - that are common with non-selective NSAIDs such as aspirin, naproxen, and ibuprofen.

Interestingly, at the time of its withdrawal, rofecoxib was the only coxib with clinical evidence of its superior gastrointestinal adverse effect profile over conventional NSAIDs. This was largely based on the VIGOR (Vioxx GI Outcomes Research) study, which compared the efficacy and adverse effect profiles of rofecoxib and naproxen. (Bombardier et al., 2000).

Adverse drug reactions

Aside from the reduced incidence of gastric ulceration, rofecoxib exhibits a similar adverse effect profile to other NSAIDs.

Withdrawal from the market

VIGOR study

The VIGOR study, published in 2000, had indicated a significant 4-fold increased risk of acute myocardial infarction (heart attack) in rofecoxib patients when compared with naproxen patients (0.4% vs 0.1%, RR 0.25) over the 12 month span of the study. There was no significant difference in the mortality from cardiovascular events between the two groups. Nor was there any significant difference in the rate of myocardial infarction between the rofecoxib and naproxen treatment groups in patients without high cardiovascular risk. The difference in overall risk was accounted for by the patients meeting the criteria for low-dose aspirin prophylaxis of secondary cardiovascular events (previous myocardial infarction, angina, cerebrovascular accident, transient ischemic attack, or coronary bypass), but who were excluded from taking low-dose aspirin in the initial design study. Once this risk was noted, Merck notified investigators in other rofecoxib studies to modify allow high-risk patients to take low-dose aspirin. (Bombardier et al., 2000)

Merck's scientists interpreted the finding as a protective effect of naproxen in reducing the risk of MI in high cardiovascular risk patients by 80 percent (which some commentators have noted would make naproxen three times as effective as aspirin). The results of the VIGOR study were submitted to the United States Food and Drug Administration (FDA) in February 2001, which led to the introduction, in April 2002, of warnings on Vioxx labelling concerning the increased risk of cardiovascular events (heart attack and stroke).

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