Oxaprozin

Oxaprozin, also known as oxaprozinum, is a nonsteroidal anti-inflammatory drug (NSAID),[1] used to relieve the inflammation, swelling, stiffness, and joint pain associated with osteoarthritis and rheumatoid arthritis. Chemically, it is a propionic acid derivative. Safety and efficacy has been established in children over 6 years with juvenile rheumatoid arthritis only, and there is an increased risk of adverse reactions in the elderly population.

Oxaprozin
Clinical data
Trade namesDaypro, Dayrun, Duraprox, others
AHFS/Drugs.comMonograph
MedlinePlusa693002
Pregnancy
category
  • C
Routes of
administration		By mouth
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability95%
Protein binding99%
MetabolismLiver—65% oxidation and 35% glucuronic acid conjugation. 5% are active phenolic metabolites.
Elimination half-life54.9 hours
Identifiers
IUPAC name
  • 3-(4,5-diphenyl-1,3-oxazol-2-yl)propanoic acid
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.040.254
Chemical and physical data
FormulaC18H15NO3
Molar mass293.322 g·mol−1
3D model (JSmol)
SMILES
  • O=C(O)CCc1nc(c(o1)c2ccccc2)c3ccccc3
InChI
  • InChI=1S/C18H15NO3/c20-16(21)12-11-15-19-17(13-7-3-1-4-8-13)18(22-15)14-9-5-2-6-10-14/h1-10H,11-12H2,(H,20,21) Y
  • Key:OFPXSFXSNFPTHF-UHFFFAOYSA-N Y
 NY (what is this?)  (verify)

It was patented in 1967 and approved for medical use in 1983.[2]

Medical uses

In 2015, oxaprozin was one of twenty NSAIDs included in a clinical trial to compare the efficacy of NSAIDs in the short-term treatment of ankylosing spondylitis (AS). The NSAIDs were compared by completing randomized controlled trials of NSAIDs in patients with active AS. Efficacy reported at 2–12 weeks and adverse effects were examined. Efficacy was measured by change in pain score and change in the duration of morning stiffness. A total of 26 trials with a total of 3410 participants were completed (58% of the trials had fewer than 50 participants). While all 20 NSAIDs were found to reduce more pain than the placebo, 15 were found to be significantly better. In regards to the decrease of morning stiffness and the likelihood of adverse events, there was no significant difference between NSAIDs. It was concluded that etoricoxib was more effective in reducing pain of AS, however due to small studies and insufficient evidence, no one NSAID could be determined to be the most effective treatment of AS. After etoricoxib, patients taking oxaprozin experienced the least amount of pain with fewer adverse effects than naproxen.[3]

Adverse effects

In October 2020, the U.S. Food and Drug Administration (FDA) required the drug label to be updated for all nonsteroidal anti-inflammatory medications to describe the risk of kidney problems in unborn babies that result in low amniotic fluid.[4][5] They recommend avoiding NSAIDs in pregnant women at 20 weeks or later in pregnancy.[4][5]

History

Oxaprozin was developed and patented by Wyeth-Ayerst.[6] The US patent 3578671, Oxazoles, was filed November 6, 1967 and published May 11, 1971.[7] Following the filing of the patent, the first description of oxaprozin exhibiting anti-inflammatory properties was outlined in the article Diaryloxazole and diaylthiazolealkanoci acids: two novel series of non-steroidal anti-inflammatory agents. This article was published in Nature in 1968.[8][9] In December 1988, Wyeth-Ayerst licensed the marketing rights for the US, Canada, Puerto Rico, and the Caribbean to Searle.[6]

Daypro became available January 5, 1993. Upon its release, “The Pink Sheet” estimated that the average whole sale price of Searle's Daypro was $112.30 for 100 (600 mg) tablets.[6] The price was comparable to other prescription NSAIDs.

Society and culture

FDA approval

The oxaprozin new drug application (NDA 18-841) was submitted to the FDA on August 10, 1982. The drug was granted an “NDA Day” review on June 15–16, 1992. After Searle agreed to complete seven Phase IV postmarketing studies on October 22, the FDA approved Daypro on October 29, 1992.[6]

Since the approval of Daypro by Searle, other companies have submitted abbreviated new drug applications (ANDAs) to the FDA. Daypro by Searle is listed as the Reference Listed Drug to prove the bioequivalence of the ANDAs. Below is a table listing all of the approved oxaprozin products.

Company[10] FDA Approval Date[10]
GD Searle Oct 29, 1992
Apotex Inc Sep 2, 2004
Dr. Reddy's Labs LTD Jan 31, 2001
Ivax Sub Teva May 13, 2002
Sandoz Jan 31, 2002
Sun Pharm Inds Inc Jan 3, 2002
Teva Jul 3, 2002

Recalls

Advantage Dose LLC recalled oxaprozin tablets on November 26, 2008. The company was not in conformance with cGMP. (Recall #D-837-2009)[11]

References
  1. Greenblatt DJ, Matlis R, Scavone JM, Blyden GT, Harmatz JS, Shader RI (March 1985). "Oxaprozin pharmacokinetics in the elderly". British Journal of Clinical Pharmacology. 19 (3): 373–8. doi:10.1111/j.1365-2125.1985.tb02656.x. PMC 1463728. PMID 3986088.
  2. Fischer, Jnos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 520. ISBN 9783527607495.
  3. Wang, Runsheng (6 Aug 2015). "Comparative efficacy of non-steroidal anti-inflammatory drugs in ankylosing spondylitis: a Bayesian network meta-analysis of clinical trials". Annals of the Rheumatic Diseases. 75 (6): 1152–1160. doi:10.1136/annrheumdis-2015-207677. PMID 26248636. S2CID 20375113.
  4. "FDA Warns that Using a Type of Pain and Fever Medication in Second Half of Pregnancy Could Lead to Complications". U.S. Food and Drug Administration (FDA) (Press release). 15 October 2020. Retrieved 15 October 2020. This article incorporates text from this source, which is in the public domain.
  5. "NSAIDs may cause rare kidney problems in unborn babies". U.S. Food and Drug Administration. 21 July 2017. Retrieved 15 October 2020. This article incorporates text from this source, which is in the public domain.
  6. The NDA Pipeline 1992. Chevy Chase, MD: F-D-C Reports, Inc. 1992. pp. I-462.
  7. Oxazoles, retrieved 2015-12-07
  8. Brown, K. (July 13, 1968). "Diaryloxazole and Diarylthiazolealkanoic Acids: Two Novel Series of Non-steroidal Anti-inflammatory Agents". Nature. 219 (5150): 164. Bibcode:1968Natur.219..164B. doi:10.1038/219164a0. PMID 5301713. S2CID 4214027.
  9. The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck Research Laboratories. 2001.
  10. "Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations". www.accessdata.fda.gov. Retrieved 2015-12-02.
  11. "FDA Enforcement Report" (PDF). FDA.gov. June 24, 2009. Retrieved Dec 2, 2015.
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