Etoricoxib, sold under brand names including Arcoxia, Exinef and Nucoxia is a selective COX-2 inhibitor developed and commercialized by Merck. It is approved in 63 countries worldwide as of 2007, except the United States where the Food and Drug Administration sent a Non Approvable Letter to Merck and required them to provide additional data.
It was patented in 1996 and approved for medical use in 2002.
Medical uses
Etoricoxib is indicated for "the symptomatic relief of
osteoarthritis (OA), rheumatoid arthritis (RA), ankylosing spondylitis, and the pain and signs of inflammation associated with acute gouty arthritis."
Efficacy
A
Cochrane review assessed the benefits of single-dose etoricoxib in the reduction of acute post-operative pain in adults.
Single-dose oral etoricoxib provides four times more pain relief post-operatively than placebo, with equivalent levels of adverse events.
[ Etoricoxib given at a dose of 120 mg is as effective or even better than other analgesics that are commonly used.][
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Adverse effects
Like all other NSAIDs, the COX-2 inhibitors too have their share of adverse effects. Fixed drug eruption and generalised erythema,
Mechanism of action
Like any other selective COX-2 inhibitor ("coxib"), etoricoxib selectively inhibits isoform 2 of the enzyme cyclooxygenase (COX-2). It has approximately 106-fold selectivity for COX-2 inhibition over COX-1.
Selective COX-2 inhibitors show less activity on COX-1 compared to traditional non-steroidal anti-inflammatory drugs (NSAID). This reduced activity is the cause of reduced gastrointestinal side effects, as demonstrated in several large clinical trials performed with different coxibs.
Cardiovascular safety and concerns
Etoricoxib's safety on the gastrointestinal tract and cardiovascular was evaluated in the MEDAL Program consisting of three clinical trials: MEDAL ( Multinational Etoricoxib Versus Diclofenac Arthritis Long-term Study), EDGE ( Etoricoxib versus Diclofenac Sodium Gastrointestinal Tolerability and Effectiveness) and EDGE II.
Like rofecoxib's VIGOR trial, the MEDAL Program was also criticized, this time due to Merck's choice of comparator group. In a testimony before the FDA Arthritis Advisory Committee, Sidney M. Wolfe pointed out that unlike the VIGOR trial, in which the active comparator was naproxen, three trials in the MEDAL Program used diclofenac as an active comparator. Wolfe showed that when etoricoxib is compared to naproxen (which is a nonselective COX inhibitor), etoricoxib significantly increases the risks of cardiovascular events to such a degree that they "are similar to rofecoxib/naproxen comparison". However, when etoricoxib is compared to diclofenac (which inhibits COX-2 more preferentially and has a worse CV safety profile than placebo), the difference was not statistically significant. He also noted the increase in other cardiac events, such as heart failure and high blood pressure.
