Parecoxib, sold under the brand name Dynastat among others, is a water-soluble and
injectable prodrug of
valdecoxib. Parecoxib is a
COX2 selective inhibitor. It is injectable. It is approved through much of Europe for short term perioperative pain control.
It was patented in 1996 and approved for medical use in 2002.
Approval
In 2005, the
U.S. Food and Drug Administration (FDA) issued a letter of non-approval for parecoxib in the United States. No reasons were ever documented publicly for the non-approval, although one study noted increased occurrences of
heart attacks following
cardiac bypass surgery
Coronary artery bypass surgery, also known as coronary artery bypass graft (CABG, pronounced "cabbage") is a surgical procedure to treat coronary artery disease (CAD), the buildup of plaques in the arteries of the heart. It can relieve chest pai ...
compared to placebo when high doses of parecoxib were used to control pain after surgery. Importantly, rare but severe
allergic reactions (
Stevens–Johnson syndrome,
Lyell syndrome) have been described with
valdecoxib, the
molecule
A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bio ...
to which parecoxib is converted. The drug is not approved for use after cardiac surgery in Europe.
All anti-inflammatory medications in the U.S. carry the same warning regarding skin reactions, and none are approved for use during CABG surgery, so the reason for the FDA denying the approval of parecoxib remains unknown, but was likely related to political pressure from the US Congress to not approve another
COX-2 selective inhibitor in the wake of the
Vioxx affair. No COX-2 selective inhibitor has been approved in the US since that time, regardless of the safety profile of parecoxib in Europe. Efforts to find out the scientific rationale, or more likely the lack thereof, that the FDA used to justify the non-approval of parecoxib in the USA have proven futile due to secrecy issues.
The political motivation to not approve parecoxib was further supported by a 2017 pooled analysis of safety data in 28 published studies, which showed after 69,567,300 units of parecoxib, skin rash and cardiac complications were minimal, if at all, different from placebo.
Parecoxib, along with other COX-2 selective inhibitors,
celecoxib
Celecoxib, sold under the brand name Celebrex among others, is a COX-2 inhibitor and nonsteroidal anti-inflammatory drug (NSAID). It is used to treat the pain and inflammation in osteoarthritis, acute pain in adults, rheumatoid arthritis, ...
,
valdecoxib, and
mavacoxib, were discovered by a team at the
Searle division of
Monsanto
The Monsanto Company () was an American agrochemical and agricultural biotechnology corporation founded in 1901 and headquartered in Creve Coeur, Missouri. Monsanto's best known product is Roundup, a glyphosate-based herbicide, developed i ...
led by
John Talley.
Parecoxib is the first parenteral COX-2 selective inhibitor available for clinical use in pain management. Its first perceptible analgesic effect occurs within seven to thirteen minutes, with clinically meaningful analgesia demonstrated within twenty-three to thirty-nine minutes and a peak effect within two hours following administration of single doses of 40 mg by IV or IM injection.
See also
*
Discovery and development of cyclooxygenase 2 inhibitors
References
Further reading
*
*
{{Prostanoidergics
Prodrugs
COX-2 inhibitors
Nonsteroidal anti-inflammatory drugs
Isoxazoles
Propionamides