Although highly selective
cyclooxygenase (COX)-2 inhibitors have been shown to be less toxic to the gastrointestinal tract than conventional non-steroidal anti-inflammatory drugs (
NSAIDs), their overall safety profile is questioned. Since different selective
COX-2 inhibitors were found to be associated with increased cardiovascular thrombotic events, the thrombotic hazard may be a class effect. Furthermore, warnings have been issued regarding serious skin and
hypersensitivity reactions associated with
valdecoxib.
Lumiracoxib is a novel COX-2 selective inhibitor (
coxib) with improved biochemical selectivity over that of currently available
coxibs. It is structurally distinct from other drugs in the class and has weakly acidic properties. Clinical studies support a once-daily dosing regimen, despite its relatively short plasma elimination half-life (3 - 6 h). In randomised, controlled clinical trials,
lumiracoxib 100 - 200 mg/day has been shown to be superior to placebo in patients with symptomatic
osteoarthritis, with clinical efficacy similar to
diclofenac 150 mg/day,
celecoxib 200 mg/day or
rofecoxib 25 mg/day. Furthermore,
lumiracoxib 200 - 400 mg/day appeared to be effective in patients with
rheumatoid arthritis. In patients with
acute pain related to primary dysmenorrhoea, dental or orthopaedic surgery,
lumiracoxib 400 mg/day was found to be at least as effective as standard doses of traditional
NSAIDs and other
coxibs. Endoscopic studies have indicated that
lumiracoxib is associated with a rate of
gastroduodenal ulcer formation that is significantly lower than with
ibuprofen and does not differ from
celecoxib. In the Therapeutic
Arthritis Research and Gastrointestinal Trial, which enrolled 18,325 patients with
osteoarthritis, the cumulative 1-year incidence of
ulcer complications (primary end point) was significantly reduced by approximately threefold on
lumiracoxib 400 mg/day compared with
naproxen 1000 mg/day or
ibuprofen 2400 mg/day (0.32 versus 0.91%). Reduction in
ulcer complications was more pronounced in the population not taking low-dose
aspirin (0.2 versus 0.92%, respectively). Conversely, the gastrointestinal advantage of
lumiracoxib was abrogated in patients receiving low-dose
aspirin (0.69 versus 0.88%, respectively, p = 0.49). Regarding cardiovascular events contributing to the trialists' composite end point (
myocardial infarction,
stroke or cardiovascular death), there was no significant difference between
lumiracoxib (0.65%) versus combined comparator
NSAIDs (0.55%). Similarly, no significant difference was recorded in rates of
myocardial infarction (clinical and silent) between the
lumiracoxib (0.25%) and the combined
NSAID (0.19%) treatment groups. Liver function test abnormalities were more frequent with
lumiracoxib (2.57%) than with the comparator
NSAIDs (0.63%). Whether or not this would result in an increased risk of clinical
hepatitis in the real world setting is unforeseeable.