Oxaprozin

Oxaprozin
Clinical data
Trade names	Daypro, Dayrun, Duraprox, others
AHFS/Drugs.com	Monograph
MedlinePlus	a693002
Pregnancy; category	C;
Routes of; administration	By mouth
ATC code	M01AE12 (WHO) ;
Legal status
Legal status	AU: S4 (Prescription only); US: WARNING; In general: ℞ (Prescription only);
Pharmacokinetic data
Bioavailability	95%
Protein binding	99%
Metabolism	Liver—65% oxidation and 35% glucuronic acid conjugation. 5% are active phenolic metabolites.
Elimination half-life	54.9 hours
Identifiers
	IUPAC name 3-(4,5-diphenyl-1,3-oxazol-2-yl)propanoic acid;
CAS Number	21256-18-8 ;
PubChem CID	4614;
IUPHAR/BPS	7252;
DrugBank	DB00991 ;
ChemSpider	4453 ;
UNII	MHJ80W9LRB;
KEGG	D00463 ;
ChEBI	CHEBI:7822 ;
ChEMBL	ChEMBL1071 ;
CompTox Dashboard (EPA)	DTXSID1045118 ;
ECHA InfoCard	100.040.254
Chemical and physical data
Formula	C18H15NO3
Molar mass	293.322 g·mol−1
3D model (JSmol)	Interactive image;
	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) ; Key:OFPXSFXSNFPTHF-UHFFFAOYSA-N ;
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Oxaprozin, also known as oxaprozinum, is a nonsteroidal anti-inflammatory drug (NSAID),^[2] 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.

It was patented in 1967 and approved for medical use in 1983.^[3]

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.^[4]

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.^[5]^[6] They recommend avoiding NSAIDs in pregnant women at 20 weeks or later in pregnancy.^[5]^[6]

History

Oxaprozin was developed and patented by Wyeth-Ayerst.^[7] The US patent 3578671, Oxazoles, was filed November 6, 1967 and published May 11, 1971.^[8] 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.^[9]^[10] In December 1988, Wyeth-Ayerst licensed the marketing rights for the US, Canada, Puerto Rico, and the Caribbean to Searle.^[7]

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.^[7] 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.^[7]

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^[11]	FDA Approval Date^[11]
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)^[12]

References

^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
^ 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): 373–378. doi:10.1111/j.1365-2125.1985.tb02656.x. PMC 1463728. PMID 3986088.
^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 520. ISBN 9783527607495.
^ Wang R, Dasgupta A, Ward MM (June 2016). "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. PMC 11034804. PMID 26248636. S2CID 20375113.
^ ^a ^b "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.
^ ^a ^b "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.
^ ^a ^b ^c ^d The NDA Pipeline 1992. Chevy Chase, MD: F-D-C Reports, Inc. 1992. pp. I-462.
^ Oxazoles, retrieved 2015-12-07
^ Brown K, Cavalla JF, Green D, Wilson AB (July 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.
^ The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck Research Laboratories. 2001. ISBN 9780911910131.
^ ^a ^b "Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations". www.accessdata.fda.gov. Retrieved 2015-12-02.
^ "FDA Enforcement Report" (PDF). FDA.gov. June 24, 2009. Retrieved Dec 2, 2015.

[FDA-AllBoxedWarnings-1] "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.

[pmid3986088-2] 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): 373–378. doi:10.1111/j.1365-2125.1985.tb02656.x. PMC 1463728. PMID 3986088.

[Fis2006-3] Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 520. ISBN 9783527607495.

[4] Wang R, Dasgupta A, Ward MM (June 2016). "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. PMC 11034804. PMID 26248636. S2CID 20375113.

[FDA_PR_20201015-5] "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.

[FDA_safety_20201015-6] "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.

[:1-7] The NDA Pipeline 1992. Chevy Chase, MD: F-D-C Reports, Inc. 1992. pp. I-462.

[:2-8] Oxazoles, retrieved 2015-12-07

[9] Brown K, Cavalla JF, Green D, Wilson AB (July 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.

[10] The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck Research Laboratories. 2001. ISBN 9780911910131.

[:3-11] "Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations". www.accessdata.fda.gov. Retrieved 2015-12-02.

[12] "FDA Enforcement Report" (PDF). FDA.gov. June 24, 2009. Retrieved Dec 2, 2015.

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v t e Non-steroidal anti-inflammatory drugs (NSAIDs) (primarily M01A and M02A, also N02BA)
pyrazolones / pyrazolidines	Aminophenazone Ampyrone Azapropazone Clofezone Difenamizole Famprofazone Feprazone Kebuzone Metamizole Mofebutazone Morazone Nifenazone Oxyphenbutazone Phenazone Phenylbutazone Propyphenazone Sulfinpyrazone Suxibuzone^‡
salicylates	Aspirin (acetylsalicylic acid)^# Aloxiprin Benorylate Carbasalate calcium Diflunisal Dipyrocetyl Ethenzamide Guacetisal Magnesium salicylate Methyl salicylate Salsalate Salicin Salicylamide Salicylic acid (salicylate) Sodium salicylate
acetic acid derivatives and related substances	Aceclofenac Acemetacin Alclofenac Amfenac Bendazac Bromfenac Bufexamac Bumadizone Diclofenac Difenpiramide Etodolac Felbinac Fenclozic acid Fentiazac Indometacin Indometacin farnesil Isoxepac Ketorolac Lonazolac Mofezolac Oxametacin Prodolic acid Proglumetacin Sulindac Tiopinac Tolmetin Zomepirac^†
oxicams	Ampiroxicam Droxicam Isoxicam Lornoxicam Meloxicam Piroxicam Pivoxicam Tenoxicam
propionic acid derivatives (profens)	Alminoprofen Benoxaprofen^† Carprofen^‡ Dexibuprofen Dexketoprofen Fenbufen Fenoprofen Flunoxaprofen Flurbiprofen Ibuprofen^# Ibuproxam Indoprofen^† Ketoprofen Loxoprofen Miroprofen Naproxen Oxaprozin Pelubiprofen Piketoprofen Pirprofen Suprofen Tarenflurbil Tepoxalin^‡ Tiaprofenic acid Vedaprofen^‡ Zaltoprofen COX-inhibiting nitric oxide donator: Naproxcinod
n-arylanthranilic acids (fenamates)	Azapropazone Clonixin Etofenamate Floctafenine Flufenamic acid Flunixin Flutiazin Glafenine^† Meclofenamic acid Mefenamic acid Morniflumate Niflumic acid Tolfenamic acid
COX-2 inhibitors (coxibs)	Apricoxib Celecoxib (+tramadol) Cimicoxib^‡ Deracoxib^‡ Etoricoxib Firocoxib^‡ Lumiracoxib^† Mavacoxib^‡ Parecoxib Robenacoxib^‡ Rofecoxib^† Valdecoxib^†
other	Aminopropionitrile Benzydamine Chondroitin sulfate Diacerein Fluproquazone Glucosamine Glycosaminoglycan Hyperforin Nabumetone Nimesulide Oxaceprol Proquazone Superoxide dismutase / orgotein Tenidap
NSAID combinations	Ibuprofen/famotidine Ibuprofen/hydrocodone Ibuprofen/oxycodone Ibuprofen/paracetamol Meloxicam/bupivacaine Naproxen/diphenhydramine Naproxen/esomeprazole
Key: underline indicates initially developed first-in-class compound of specific group; ^#WHO-Essential Medicines; ^†withdrawn drugs; ^‡veterinary use.
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