Etoricoxib
Encyclopedia
Etoricoxib is a COX-2 selective inhibitor (approx. 106.0 times more selective for COX-2 inhibition over COX-1) from Merck & Co.
Currently it is approved in more than 70 countries worldwide but not in the US, where the Food and Drug Administration
(FDA) requires additional safety and efficacy data for etoricoxib before it will issue approval. Current therapeutic indications are: treatment of rheumatoid arthritis
, psoriatic arthritis
, osteoarthritis
, ankylosing spondylitis
, chronic low back pain
, acute pain and gout
. Note that approved indications differ by country.
Like any other COX-2 selective inhibitor ("coxib"), etoricoxib selectively inhibits isoform 2 of the enzyme cyclo-oxigenase (COX-2). This reduces the generation of prostaglandins (PGs) from arachidonic acid
. Among the different functions exerted by PGs, their role in the inflammation cascade should be highlighted.
COX-2 selective inhibitors showed less marked activity on type 1 cycloxigenase compared to traditional non-steroidal anti-inflammatory drug
s (NSAID). This reduced activity is the cause of reduced gastrointestinal side effects, as demonstrated in several large clinical trials performed with different coxibs.
Some clinical trials and meta-analysis showed that treatment with some coxibs (in particular rofecoxib
) led to increased incidence of adverse cardiovascular events compared to placebo. Because of these results, some drugs were withdrawn from the market (rofecoxib, in September 2004 and valdecoxib
in April 2005). In addition, the FDA and EMA (USA and European Community health authorities respectively) started a revision process of the entire class of both NSAID and COX-2 inhibitors.
The FDA concluded its revision on April 6, 2005: the final document can be found here.
The EMA concluded its revision on June 27, 2005: the final document can be found here.
On April 27, 2007, the Food and Drug Administration issued Merck a "non-approvable letter" for etoricoxib. The letter said Merck needs to provide more test results showing that the drug's benefits outweigh its risks before it has another chance of getting approved.
Merck & Co.
Merck & Co., Inc. , also known as Merck Sharp & Dohme or MSD outside the United States and Canada, is one of the largest pharmaceutical companies in the world. The Merck headquarters is located in Whitehouse Station, New Jersey, an unincorporated area in Readington Township...
Currently it is approved in more than 70 countries worldwide but not in the US, where the Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
(FDA) requires additional safety and efficacy data for etoricoxib before it will issue approval. Current therapeutic indications are: treatment of rheumatoid arthritis
Rheumatoid arthritis
Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
, psoriatic arthritis
Psoriatic arthritis
Psoriatic arthritis is a type of inflammatory arthritis that, according to the National Psoriasis Foundation, will develop in up to 30 percent of people who have the chronic skin condition psoriasis...
, osteoarthritis
Osteoarthritis
Osteoarthritis also known as degenerative arthritis or degenerative joint disease, is a group of mechanical abnormalities involving degradation of joints, including articular cartilage and subchondral bone. Symptoms may include joint pain, tenderness, stiffness, locking, and sometimes an effusion...
, ankylosing spondylitis
Ankylosing spondylitis
Ankylosing spondylitis , previously known as Bekhterev's disease, Bekhterev syndrome, and Marie-Strümpell disease is a chronic inflammatory disease of the axial skeleton with variable involvement of peripheral joints and nonarticular structures...
, chronic low back pain
Low back pain
Low back pain or lumbago is a common musculoskeletal disorder affecting 80% of people at some point in their lives. In the United States it is the most common cause of job-related disability, a leading contributor to missed work, and the second most common neurological ailment — only headache is...
, acute pain and gout
Gout
Gout is a medical condition usually characterized by recurrent attacks of acute inflammatory arthritis—a red, tender, hot, swollen joint. The metatarsal-phalangeal joint at the base of the big toe is the most commonly affected . However, it may also present as tophi, kidney stones, or urate...
. Note that approved indications differ by country.
Like any other COX-2 selective inhibitor ("coxib"), etoricoxib selectively inhibits isoform 2 of the enzyme cyclo-oxigenase (COX-2). This reduces the generation of prostaglandins (PGs) from arachidonic acid
Arachidonic acid
Arachidonic acid is a polyunsaturated omega-6 fatty acid 20:4.It is the counterpart to the saturated arachidic acid found in peanut oil, Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega-6 fatty acid 20:4(ω-6).It is the counterpart to the saturated arachidic acid found in peanut oil,...
. Among the different functions exerted by PGs, their role in the inflammation cascade should be highlighted.
COX-2 selective inhibitors showed less marked activity on type 1 cycloxigenase compared to traditional non-steroidal anti-inflammatory drug
Non-steroidal anti-inflammatory drug
Nonsteroidal anti-inflammatory drugs, usually abbreviated to NSAIDs or NAIDs, but also referred to as nonsteroidal anti-inflammatory agents/analgesics or nonsteroidal Anti-inflammatory medicines , are drugs with analgesic and antipyretic effects and which have, in higher doses, anti-inflammatory...
s (NSAID). This reduced activity is the cause of reduced gastrointestinal side effects, as demonstrated in several large clinical trials performed with different coxibs.
Some clinical trials and meta-analysis showed that treatment with some coxibs (in particular rofecoxib
Rofecoxib
Rofecoxib is a nonsteroidal anti-inflammatory drug that has now been withdrawn over safety concerns. It was marketed by Merck & Co. to treat osteoarthritis, acute pain conditions, and dysmenorrhoea...
) led to increased incidence of adverse cardiovascular events compared to placebo. Because of these results, some drugs were withdrawn from the market (rofecoxib, in September 2004 and valdecoxib
Valdecoxib
Valdecoxib is a non-steroidal anti-inflammatory drug used in the treatment of osteoarthritis, rheumatoid arthritis, and painful menstruation and menstrual symptoms. It is a cyclooxygenase-2 selective inhibitor....
in April 2005). In addition, the FDA and EMA (USA and European Community health authorities respectively) started a revision process of the entire class of both NSAID and COX-2 inhibitors.
The FDA concluded its revision on April 6, 2005: the final document can be found here.
The EMA concluded its revision on June 27, 2005: the final document can be found here.
On April 27, 2007, the Food and Drug Administration issued Merck a "non-approvable letter" for etoricoxib. The letter said Merck needs to provide more test results showing that the drug's benefits outweigh its risks before it has another chance of getting approved.