Parecoxib
Encyclopedia
Parecoxib is a water soluble and injectable prodrug
of valdecoxib
. It is marketed as Dynastat in the European Union
. Parecoxib is a COX2 selective inhibitor in the same category as celecoxib
(Celebrex) and rofecoxib
(Vioxx). As it is injectable, it can be used perioperatively when patients are unable to take oral medications. It is approved through much of Europe for short term perioperative pain control much in the same way ketorolac
(Toradol) is used in the United States. However, unlike ketorolac, parecoxib has no effect on platelet
function and therefore does not promote bleeding during or after surgery. In addition, ketorolac has a much higher gastrointestinal toxicity profile compared to most other nonsteroidal antiinflammatory drugs (NSAIDs) including ibuprofen and naprosyn. However, in the United States ketorolac is the only injectable NSAID, although it is banned in many European countries due to concerns about surgical bleeding and stomach ulcers after surgery.
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 compared to placebo when high doses of parecoxib were used to control pain after surgery. It is also important to remember that rare but severe allergic reactions (Stevens-Johnson Syndrome, Lyell Syndrome) have been described with valdecoxib, the molecule to which parecoxib is converted. The drug is not approved for use after cardiac surgery in Europe. Ketorolac, still banned in much of Europe, is therefore the only option in the United States, and it is not clear whether parecoxib will be resubmitted to the FDA in the future.
All antiiflammatory 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.
Prodrug
A prodrug is a pharmacological substance administered in an inactive form. Once administered, the prodrug is metabolised in vivo into an active metabolite, a process termed bioactivation. The rationale behind the use of a prodrug is generally for absorption, distribution, metabolism, and...
of 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....
. It is marketed as Dynastat in the European Union
European Union
The European Union is an economic and political union of 27 independent member states which are located primarily in Europe. The EU traces its origins from the European Coal and Steel Community and the European Economic Community , formed by six countries in 1958...
. Parecoxib is a COX2 selective inhibitor in the same category as celecoxib
Celecoxib
Celecoxib INN is a sulfa non-steroidal anti-inflammatory drug and selective COX-2 inhibitor used in the treatment of osteoarthritis, rheumatoid arthritis, acute pain, painful menstruation and menstrual symptoms, and to reduce numbers of colon and rectum polyps in patients with familial...
(Celebrex) and 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...
(Vioxx). As it is injectable, it can be used perioperatively when patients are unable to take oral medications. It is approved through much of Europe for short term perioperative pain control much in the same way ketorolac
Ketorolac
Ketorolac or ketorolac tromethamine is a non-steroidal anti-inflammatory drug in the family of heterocyclic acetic acid derivative, often used as an analgesic...
(Toradol) is used in the United States. However, unlike ketorolac, parecoxib has no effect on platelet
Platelet
Platelets, or thrombocytes , are small,irregularly shaped clear cell fragments , 2–3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 days...
function and therefore does not promote bleeding during or after surgery. In addition, ketorolac has a much higher gastrointestinal toxicity profile compared to most other nonsteroidal antiinflammatory drugs (NSAIDs) including ibuprofen and naprosyn. However, in the United States ketorolac is the only injectable NSAID, although it is banned in many European countries due to concerns about surgical bleeding and stomach ulcers after surgery.
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 compared to placebo when high doses of parecoxib were used to control pain after surgery. It is also important to remember that rare but severe allergic reactions (Stevens-Johnson Syndrome, Lyell Syndrome) have been described with valdecoxib, the molecule to which parecoxib is converted. The drug is not approved for use after cardiac surgery in Europe. Ketorolac, still banned in much of Europe, is therefore the only option in the United States, and it is not clear whether parecoxib will be resubmitted to the FDA in the future.
All antiiflammatory 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.
See also
- COX-2 selective inhibitor
- Discovery and development of cyclooxygenase 2 inhibitors