The development of
COX2 inhibitors with improved biochemical selectivity (such as
etoricoxib and
valdecoxib) over that of commercially available
coxibs has been driven by the potential advantage of safety using higher
coxib doses for increased efficacy.
Etoricoxib has been approved in the UK as a once-daily medicine for symptomatic relief in the treatment of
osteoarthritis (OA),
rheumatoid arthritis (RA) and acute
gouty arthritis. It is currently approved with additional indications (i.e., for relief of
acute pain associated with dental surgery, for primary dysmenorrhoea and for chronic musculo-skeletal
pain, including chronic
lower-back pain) in Mexico, Brazil and Peru.
Etoricoxib has an in vitro COX1/COX2 IC(50) ratio of 344, the highest of any
coxib. The administration of therapeutic doses of
etoricoxib to healthy subjects does not affect COX1 activity in circulating platelets and gastric biopsies. The profound inhibition of monocyte COX2 activity at 24 h after dosing, as predicted by a pharmacological half-life of approximately 22 h, supports a once-daily dosing regimen of
etoricoxib. In randomised, well-controlled clinical trials,
etoricoxib has been shown to have a comparable clinical efficacy with traditional
NSAIDs. Combined analysis of efficacy trials with
etoricoxib versus non-selective
NSAIDs has shown that the
drug halves both investigator-reported upper gastrointestinal perforation,
ulcers and bleeds (PUBs) and confirmed PUBs, and reduces the need for gastroprotective agents and gastrointestinal comedications by approximately 40%. The risk of lower extremity oedema and
hypertension adverse experiences with
etoricoxib was low and generally similar to comparator
NSAIDs in a combined analysis of eight Phase III studies in OA, RA, chronic
low-back pain and surveillance endoscopy. Large, randomised clinical trials have been planned to confirm the renal, gastrointestinal and cardiovascular safety of
etoricoxib.