Rofecoxib

Rofecoxib
Clinical data
Pronunciation/ˌrɒfɪˈkɒksɪb/
Trade namesVioxx, Ceoxx, Ceeoxx, others
Pregnancy
category
  • AU: C
Routes of
administration		By mouth & i.m
ATC code
Legal status
Legal status
  • withdrawn worldwide
Pharmacokinetic data
Bioavailability93%
Protein binding87%
Metabolismliver
Elimination half-life17 hours
Excretionbile duct/kidney
Identifiers
  • 4-(4-methylsulfonylphenyl)-3-phenyl-5H-furan-2-one
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.230.077 Edit this at Wikidata
Chemical and physical data
FormulaC17H14O4S
Molar mass314.36 g·mol−1
3D model (JSmol)
  • O=C2OCC(=C2\c1ccccc1)\c3ccc(cc3)S(=O)(=O)C
  • InChI=1S/C17H14O4S/c1-22(19,20)14-9-7-12(8-10-14)15-11-21-17(18)16(15)13-5-3-2-4-6-13/h2-10H,11H2,1H3 checkY
  • Key:RZJQGNCSTQAWON-UHFFFAOYSA-N checkY
  (verify)

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 was approved in the US by the US Food and Drug Administration (FDA) in May 1999, and was marketed under the brand names Vioxx, Ceoxx, and Ceeoxx. Rofecoxib was available by prescription in both tablets and as an oral suspension.[1]

Rofecoxib gained widespread use among physicians treating patients with arthritis and other conditions causing chronic or acute pain. Worldwide, over 80 million people were prescribed rofecoxib at some time.[2]

In September 2004, Merck voluntarily withdrew rofecoxib from the market because of concerns about increased risk of heart attack and stroke associated with long-term, high-dosage use. Merck withdrew the drug after disclosures that it withheld information about rofecoxib's risks from doctors and patients for over five years, allegedly resulting in between 88,000 and 140,000 cases of serious heart disease.[3] Rofecoxib was one of the most widely used drugs ever to be withdrawn from the market. In the year before withdrawal, Merck had sales revenue of US$2.5 billion from Vioxx.[4]

In 2005, the FDA issued a memorandum concluding that risks for serious cardiovascular (CV) events seem to be as great for nonselective NSAIDs as for COX-2–selective agents such as rofecoxib, according to long-term, controlled clinical trials.[5] Based on data up to 2015, the FDA reasserted the likelihood of an increased risk of serious adverse CV events from COX-2–selective and nonselective NSAIDs, dependent on dose and duration.[6]

In November 2017, Massachusetts-based Tremeau Pharmaceuticals announced its plan to return rofecoxib (TRM-201) to market as a treatment for hemophilic arthropathy (HA). Tremeau announced that the FDA had granted an orphan designation for TRM-201 (rofecoxib) for the treatment of HA, and that they had received FDA feedback on their development plan.[7] HA is a degenerative joint disease caused by recurrent intra-articular bleeding. It is the largest cause of morbidity in patients with hemophilia and has no currently approved treatment options in the United States. Traditional NSAIDs are avoided in this population due to their effects on platelet aggregation and risk of gastrointestinal ulcers,[8] and high potency opioids are the current standard of care in treating HA.[9]

  1. ^ "Vioxx PI" (PDF). FDA. Archived (PDF) from the original on 2013-08-22. Retrieved 2019-03-27.
  2. ^ Knox R (September 30, 2004), "Merck Pulls Arthritis Drug Vioxx from Market", NPR.org, archived from the original on November 11, 2010, retrieved December 24, 2016
  3. ^ "Up to 140,000 heart attacks linked to Vioxx". New Scientist. 2005-01-25. p. 1.
  4. ^ "Merck Sees Slightly Higher 2007 Earnings". New York Times. Reuters. 2006-12-07. p. A1. Archived from the original on 2018-11-21. Retrieved 2017-02-20.
  5. ^ "Analysis and recommendations for Agency action regarding nonsteroidal anti-inflammatory drugs and cardiovascular risk" (PDF). FDA. Archived (PDF) from the original on 2017-05-06. Retrieved 2019-03-27.
  6. ^ "FDA Drug Safety Communication: FDA strengthens warning that non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) can cause heart attacks or strokes". FDA. 18 June 2019. Archived from the original on 27 March 2019. Retrieved 27 March 2019.
  7. ^ "Tremeau Pharmaceuticals News". Tremeau Pharmaceuticals. Archived from the original on 2019-03-27. Retrieved 2019-03-27.
  8. ^ Srivastava A, Brewer AK, Mauser-Bunschoten EP, Key NS, Kitchen S, Llinas A, et al. (January 2013). "Guidelines for the management of hemophilia". Haemophilia. 19 (1): e1-47. doi:10.1111/j.1365-2516.2012.02909.x. PMID 22776238. S2CID 29659751.
  9. ^ Forsyth AL, Witkop M, Lambing A, Garrido C, Dunn S, Cooper DL, Nugent DJ (October 2015). "Associations of quality of life, pain, and self-reported arthritis with age, employment, bleed rate, and utilization of hemophilia treatment center and health care provider services: results in adults with hemophilia in the HERO study". Patient Preference and Adherence. 9: 1549–1560. doi:10.2147/PPA.S87659. PMC 4631419. PMID 26604708.