Parecoxib, sold under the brand name Dynastat among others, is a water-soluble and

injectable An injection (often and usually referred to as a "shot" in US English, a "jab" in UK English, or a "jag" in Scottish English and Scots) is the act of administering a liquid, especially a drug, into a person's body using a needle (usually a hypo ...

prodrug A prodrug is a medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be used to improve how the drug ...

valdecoxib Valdecoxib is a nonsteroidal anti-inflammatory drug (NSAID) used in the treatment of osteoarthritis, rheumatoid arthritis, and painful menstruation and menstrual symptoms. It is a selective cyclooxygenase-2 inhibitor. It was patented in 1995. V ...

. 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 The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

(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 attack A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may tr ...

s following cardiac bypass surgery compared to placebo when high doses of parecoxib were used to control pain after surgery. Importantly, rare but severe

allergic reaction Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derma ...

s (

Stevens–Johnson syndrome Stevens–Johnson syndrome (SJS) is a type of severe skin reaction. Together with toxic epidermal necrolysis (TEN) and Stevens–Johnson/toxic epidermal necrolysis (SJS/TEN), it forms a spectrum of disease, with SJS being less severe. Erythema ...

Lyell syndrome Toxic epidermal necrolysis (TEN) is a type of severe skin reaction. Together with Stevens–Johnson syndrome (SJS) it forms a spectrum of disease, with TEN being more severe. Early symptoms include fever and flu-like symptoms. A few days later th ...

) have been described with

, 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 bioch ...

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 COX-2 inhibitors are a type of nonsteroidal anti-inflammatory drug (NSAID) that directly targets cyclooxygenase-2, COX-2, an enzyme responsible for inflammation and pain. Targeting selectivity for COX-2 reduces the risk of peptic ulceration and ...

in the wake of the

Vioxx Rofecoxib is a COX-2 selective nonsteroidal anti-inflammatory drug (NSAID). It was marketed by Merck & Co. to treat osteoarthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, acute pain conditions, migraine, and dysmenorrhea. Rofecoxib ...

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, ankyl ...

, and

mavacoxib Mavacoxib (trade name Trocoxil) is a veterinary drug used to treat pain and inflammation in dogs with degenerative joint disease. It acts as a COX-2 inhibitor. Mavacoxib, along with other COX-2 selective inhibitors, celecoxib, valdecoxib, and p ...

, were discovered by a team at the

Searle Searle may refer to: __NOTOC__ Persons * Searle (surname) * J. Searle Dawley (1877–1949), American film director, producer, screenwriter, stage actor and playwright * Searle Turton (born 1979), Canadian politician Places * Serle, a comune in Lomb ...

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 in th ...

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.

Approval

See also

References

Further reading