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Revision as of 06:56, 8 August 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Script assisted update of identifiers for the Chem/Drugbox validation project (updated: 'ChEBI').← Previous edit		Latest revision as of 10:57, 17 December 2024 edit undo139.47.117.13 (talk) →Ecological effects: linksTag: Visual edit
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			{{Short description|Nonsteroidal anti-inflammatory drug}}
	{{drugbox | verifiedrevid = 420108706
			{{Redirect|Diclo|the organic solvent sometimes called Di-clo|Dichloromethane}}
	|
			{{Redirect|Dichronic|common misspellings|Diachronic (disambiguation)}}
	| IUPAC_name = 2-(2-(2,6-dichlorophenylamino)phenyl)acetic acid
			{{Use dmy dates|date=January 2024}}
			{{cs1 config |name-list-style=vanc |display-authors=6}}
			{{Infobox drug
			| Verifiedfields = changed
			| Watchedfields = changed
			| verifiedrevid = 443636249
	| image = Diclofenac.svg		| image = Diclofenac.svg
	| width= 200px		| width = 250
			| alt =
	| image2 = Diclofenac 3D 2ek.png
			| caption = Structure of diclofenac with ball and stick model
	| width2 = 200px
			| image2 = Diclofenac-from-xtal-3D-bs-17.png
	| CASNo_Ref = {{cascite|correct|CAS}}
			| width2 = 250
			| alt2 =
			<!-- Clinical data -->
			| pronounce = {{IPAc-en|d|aɪ|'|k|l|oʊ|f|ə|n|æ|k}}<ref name=tn /> or {{IPAc-en|d|ɪ|k|l|ɒ|'|f|ɛ|n|æ|k}}<ref>{{cite book|title=]| veditors = O'Toole MT |page=536 |edition=10th |year=2017 |publisher=Elsevier|location=|isbn=978-0-323-22205-1}}</ref>
			| tradename = Voltaren, ]<ref name=tn/>
			| Drugs.com = {{drugs.com|monograph|diclofenac-epolamine}}
			| MedlinePlus = a689002
			| DailyMedID = Diclofenac
			| pregnancy_AU = C
			| pregnancy_AU_comment = <ref name="Drugs.com pregnancy">{{cite web|title=Diclofenac Use During Pregnancy|website=Drugs.com|date=16 January 2000|url=https://www.drugs.com/pregnancy/diclofenac.html|access-date=18 February 2024}}</ref>
			| routes_of_administration = ], ], ], ], ], ]
			| class = ]s
			| ATC_prefix = D11
			| ATC_suffix = AX18
			| ATC_supplemental = {{ATC|M01|AB05}}, {{ATC|M02|AA15}}, {{ATC|S01|BC03}}
			<!-- Legal status -->
			| legal_AU = S4
			| legal_AU_comment = /&nbsp;S3&nbsp;/&nbsp;S2
			| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C5, D1, D2, E, F1, F2, F3, F4 -->
			| legal_BR_comment =
			| legal_CA = Rx-only
			| legal_CA_comment = <ref>{{cite web | title=Product monograph brand safety updates | website=] | date=6 June 2024 | url=https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/drug-product-database/label-safety-assessment-update/product-monograph-brand-safety-updates.html | access-date=8 June 2024}}</ref>
			| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
			| legal_DE_comment =
			| legal_NZ = <!-- Class A, B, C -->
			| legal_NZ_comment =
			| legal_UK = POM
			| legal_UK_comment = /&nbsp;P&nbsp;/&nbsp;GSL
			| legal_US = Rx-only
			| legal_US_comment = /&nbsp;OTC<ref name="Voltaren FDA label">{{cite web | title=Voltaren Arthritis Pain- diclofenac sodium gel; Voltaren Arthritis Pain- diclofenac sodium kit | website=DailyMed | date=13 March 2024 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=30a94282-0892-442a-aa10-6525cbd4fe88 | access-date=13 October 2024}}</ref><ref name="Cambia FDA label">{{cite web | title=Cambia- diclofenac potassium powder, for solution | website=DailyMed | date=25 April 2024 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d249ced1-4ca0-4f57-adcb-23440f58f659 | access-date=13 October 2024}}</ref><ref name=FDAswitch>{{cite web|title=FDA Approves Three Drugs for Nonprescription Use Through Rx-to-OTC Switch Process|website=U.S. ] (FDA) |date=14 February 2020|url=http://www.fda.gov/news-events/press-announcements/fda-approves-three-drugs-nonprescription-use-through-rx-otc-switch-process|access-date=18 February 2024}} {{PD-notice}}</ref>
			| legal_EU =
			| legal_EU_comment =
			| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
			| legal_UN_comment =
			| legal_status = Rx-only
			<!-- Pharmacokinetic data -->
			| bioavailability =
			| protein_bound = More than 99%
			| metabolism = Liver, oxidative, primarily by ], also by ], ], as well as conjugative by ] (]) and ];<ref>{{cite web|url=http://www.medicinereviews.ooo/2018/08/diclofenac-oral-uses-dosage-side.html|title=Diclofenac Oral Uses, Dosage, Side Effects And Composition|publisher=Medicine Reviews Agency|author=Sayyad M|date=23 August 2018|access-date=18 February 2024|archive-date=24 August 2018|archive-url=https://web.archive.org/web/20180824135214/https://www.medicinereviews.ooo/2018/08/diclofenac-oral-uses-dosage-side.html|url-status=dead}}</ref> no active metabolites exist
			| metabolites =
			| onset = Within 4 hours (gel), 30 min (non-gel)<ref name=AHFS2018/>
			| elimination_half-life = 1.2–2 ] (35% of the drug enters enterohepatic recirculation)
			| duration_of_action =
			| excretion = 35% ], 65% ]<ref>{{cite book|vauthors=Williams BS, Buvanendran A|chapter=Nonopioid analgesics: NSAIDs, COX-2 inhibitors, and acetaminophen|date=1 January 2011|chapter-url=https://www.sciencedirect.com/science/article/pii/B9781437722420000262|title=Essentials of Pain Medicine|edition=3|pages=130–139|veditors=Benzon HT, Raja SN, Liu SS, Fishman SM|publisher=W.B. Saunders|doi=10.1016/b978-1-4377-2242-0.00026-2|isbn=978-1-4377-2242-0|access-date=10 January 2023|archive-date=10 January 2023|archive-url=https://web.archive.org/web/20230110202200/https://www.sciencedirect.com/science/article/pii/B9781437722420000262|url-status=live}}</ref>
			<!-- Identifiers -->
			| CAS_number_Ref = {{cascite|correct|??}}
			| CAS_number = 15307-86-5
			| PubChem = 3033
			| IUPHAR_ligand = 2714
			| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
			| DrugBank = DB00586
			| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
			| ChemSpiderID = 2925
	| UNII_Ref = {{fdacite|correct|FDA}}		| UNII_Ref = {{fdacite|correct|FDA}}
	| UNII = 144O8QL0L1		| UNII = 144O8QL0L1
			| KEGG_Ref = {{keggcite|correct|kegg}}
	| InChI = 1/C14H11Cl2NO2.C6H13NO/c15-10-5-3-6-11(16)14(10)17-12-7-2-1-4-9(12)8-13(18)19;8-6-5-7-3-1-2-4-7/h1-7,17H,8H2,(H,18,19);8H,1-6H2
			| KEGG = D07816
	| smiles = O=C(O)Cc1ccccc1Nc2c(Cl)cccc2Cl.OCCN1CCCC1
			| ChEBI_Ref = {{ebicite|correct|EBI}}
	| InChIKey = DCERVXIINVUMKU-UHFFFAOYAN
			| ChEBI = 47381
	| ChEMBL_Ref = {{ebicite|correct|EBI}}		| ChEMBL_Ref = {{ebicite|correct|EBI}}
	| ChEMBL = 139		| ChEMBL = 139
			| NIAID_ChemDB =
			| PDB_ligand = DIF
			| synonyms =
			<!-- Chemical and physical data -->
			| IUPAC_name = acetic acid <!-- the locant '2' for acetic acid is not cited, see P-14.3.4.3 Nomenclature of Organic Chemistry – IUPAC Recommendations and Preferred Names 2013 (Blue Book) -->
			| C = 14
			| H = 11
			| Cl = 2
			| N = 1
			| O = 2
			| SMILES = O=C(O)Cc1ccccc1Nc2c(Cl)cccc2Cl
	| StdInChI_Ref = {{stdinchicite|correct|chemspider}}		| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
	| StdInChI = 1S/C14H11Cl2NO2/c15-10-5-3-6-11(16)14(10)17-12-7-2-1-4-9(12)8-13(18)19/h1-7,17H,8H2,(H,18,19)		| StdInChI = 1S/C14H11Cl2NO2/c15-10-5-3-6-11(16)14(10)17-12-7-2-1-4-9(12)8-13(18)19/h1-7,17H,8H2,(H,18,19)
			| StdInChI_comment =
	| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}		| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
	| StdInChIKey = DCOPUUMXTXDBNB-UHFFFAOYSA-N		| StdInChIKey = DCOPUUMXTXDBNB-UHFFFAOYSA-N
			| density =
	| smiles1 = c1ccc(c(c1)CC(=O)O)Nc2c(cccc2Cl)Cl
			| density_notes =
	| CAS_number = 15307-86-5
			| melting_point =
	| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
	| ChemSpiderID = 2925		| melting_high =
	| ATC_prefix = D11		| melting_notes =
	| ATC_suffix = AX18		| boiling_point =
			| boiling_notes =
	| ATC_supplemental = {{ATC|M01|AB05}}, {{ATC|M02|AA15}}, {{ATC|S01|BC03}}
	| ChEBI = 47381		| solubility =
	| PubChem = 3033		| sol_units =
			| specific_rotation =
	| DrugBank = APRD00527
	| KEGG_Ref = {{keggcite|correct|kegg}}
	| KEGG = D07816
	| C=14 |H=11 |Cl=2 |N=1 |O=2
	| molecular_weight = 296.148 g/mol
	| Oral Bioavailability = 60%
	| protein_bound = more than 99%
	| metabolism = hepatic, no active metabolites exist
	| elimination_half-life = 1.2-2 hr (35% of the drug enters enterohepatic recirculation)
	| excretion = biliary, only 1% in urine
	| pregnancy_AU = C
	| pregnancy_US =
	| pregnancy_category = C (1st. and 2nd. trimenon), D (third trimenon)
	| legal_AU =
	| legal_UK = P
	| legal_US =
	| legal_status = Rx-only most preparations/countries. Limited OTC some countries. Manufacture and veterinary use is banned in India, Nepal and Pakistan due to imminent extinction of local vultures.
	| routes_of_administration = oral, rectal, ], ] (renal- and gallstones), topical
	}}		}}
	'''Diclofenac''' (marketed under many ] names, see below: ]) is a ] (NSAID) taken to reduce ] and as an ] reducing pain in certain conditions.
			<!-- Definition and medical uses -->
	The name is derived from its chemical name: 2-(2,6-'''dichlo'''ranilino) '''phen'''ylacetic '''ac'''id.
			'''Diclofenac''', sold under the brand name '''Voltaren''' among others, is a ] (NSAID) used to treat ] and ] such as ].<ref name="Voltaren FDA label" /><ref name=AHFS2018>{{cite web|title=Diclofenac epolamine Monograph for Professionals|website=]
			|url=https://www.drugs.com/monograph/diclofenac-epolamine.html|access-date=18 February 2024}}</ref> It can be taken ] (swallowed by mouth), inserted ] as a ], injected ], injected ], ], or ].<ref name=AHFS2018/><ref name=inject>{{cite journal|author=Chung CH|title=The use of Injectable Nonsteroidal Anti-Inflammatory Drugs in Local Accident & Emergency Practice|journal=Hong Kong Journal of Emergency Medicine|year=2017|volume=9|issue=2|pages=65–71|doi=10.1177/102490790200900201|s2cid=74032271}}</ref><ref>{{Cite web |date=2016-07-15 |title=Diclofenac Ophthalmic |url=https://medlineplus.gov/druginfo/meds/a606003.html |access-date=2024-10-08 |website=medlineplus.gov}}</ref> Improvements in pain last up to eight hours.<ref name=AHFS2018/> It is also available as the ] ] (Arthrotec) to help protect the stomach.<ref>{{cite web | title=Arthrotec- diclofenac sodium and misoprostol tablet, film coated | website=DailyMed | date=16 August 2023 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=600fe842-45d9-4d68-9ef2-456dbbebaa11 | access-date=13 October 2024}}</ref><ref name=BNF74/>
			<!-- Side effects and mechanism -->
	In the ], ], ] and the ], it may be supplied as either the ] or ] ], in China most often as the sodium salt, while in some other countries only as the potassium salt. Diclofenac is available as a generic drug in a number of formulations. ] (OTC) use is approved in some countries for minor aches and pains and fever associated with common infections.
			Common side effects include ], ], nausea, dizziness, headache, and swelling.<ref name=AHFS2018/> Serious side effects may include ], ], ], and ].<ref name=BNF74/><ref name=AHFS2018/> Use is not recommended in the ].<ref name=AHFS2018/> It is likely safe during ].<ref name=BNF74/> Diclofenac is believed to work by decreasing the production of ]s, like other drugs in this class.<ref>{{cite book|title=Mosby's Drug Reference for Health Professions|year=2017|publisher=Elsevier Health Sciences|location=|isbn=978-0-323-56682-7|page=398|url=https://books.google.com/books?id=KOM2DwAAQBAJ&pg=PA398}}</ref>
			<!-- History and culture -->
			In 2022, it was the 51st most commonly prescribed medication in the United States, with more than 12{{nbsp}}million prescriptions.<ref>{{cite web | title=The Top 300 of 2022 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=30 August 2024 | archive-date=30 August 2024 | archive-url=https://web.archive.org/web/20240830202410/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Diclofenac Drug Usage Statistics, United States, 2013 - 2022 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Diclofenac | access-date = 30 August 2024 }}</ref> It is available as its acid or in two salts, as either diclofenac sodium or potassium.<ref name=BNF74>{{cite book|title=British national formulary: BNF 74|year=2017|publisher=British Medical Association|isbn=978-0-85711-298-9|pages=1033–1035|edition=74}}</ref>
	==Medical uses==		==Medical uses==
			Diclofenac is used to ] ] related to ], ], ] and other ],<ref name=AHFS2018/> ]s and ]s. An additional indication is the treatment of acute ]s.<ref name="Cambia FDA label" /> Diclofenac is used to treat mild to moderate postoperative or post-traumatic pain, in particular when inflammation is also present.
	] tablets]]
	]) 50 mg tablets]]
	] and ] administration]]
	] administration]]
			Diclofenac ophthalmic is indicated for the treatment of postoperative inflammation in people who have undergone cataract extraction and for the temporary relief of pain and photophobia in people undergoing corneal refractive surgery.<ref>{{cite web | title=Voltaren- diclofenac sodium solution | website=DailyMed | date=1 October 2012 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=65037222-146c-493d-aa1c-e6df89bf5b8d | access-date=13 October 2024}}</ref>
	Diclofenac is used to treat ], inflammatory disorders, and ].<ref name=AHFS>{{cite web|title=Diclofenac Epolamine|url=http://www.drugs.com/monograph/diclofenac-epolamine.html|work=The American Society of Health-System Pharmacists|accessdate=3 April 2011}}</ref>
			Diclofenac is also available in topical forms and is useful for ] but not other types of long-term musculoskeletal pain.<ref name=Dutta2007>{{cite journal|vauthors=Dutta NK, Mazumdar K, Dastidar SG, Park JH|title=Activity of diclofenac used alone and in combination with streptomycin against Mycobacterium tuberculosis in mice|journal=International Journal of Antimicrobial Agents|volume=30|issue=4|pages=336–340|year=2007|pmid=17644321|doi=10.1016/j.ijantimicag.2007.04.016}}</ref> Diclofenac may also help with ] and with acute pain caused by minor strains, sprains and ].<ref>{{cite web |url= http://www.mayoclinic.com/health/drug-information/DR600545 |title= Diclofenac (Topical Application Route) Description and Brand Names |website= MayoClinic.com |publisher= ] |date= |accessdate= |archive-date= 23 November 2013 |archive-url= https://web.archive.org/web/20131123224442/http://www.mayoclinic.com/health/drug-information/DR600545 |url-status= live }}</ref>
	Inflammatory disorder may include musculoskeletal complaints, especially ], ], ], ], ], dental pain, ], ], ], ] attacks,<ref name="BPC">
	"RUFENAL", Birzeit Pharmaceutical Company, BPC.ps, web:
	.
	</ref> and ] in cases of ]s and ]s. An additional indication is the treatment of acute migraines.<ref>http://www.cambiarx.com/</ref> Diclofenac is used commonly to treat mild to moderate post-operative or post-traumatic pain, in particular when inflammation is also present,<ref name=BPC/> and is effective against menstrual pain and ].
			In many countries, eye drops are sold to treat acute and chronic nonbacterial inflammation of the anterior part of the eyes (such as postoperative states).<ref>{{cite web |title=Naclof, oogdruppels 1 mg/ml |url=http://db.cbg-meb.nl/IB-teksten/h12800.pdf |archive-url=https://web.archive.org/web/20160304033446/http://db.cbg-meb.nl/IB-teksten/h12800.pdf |archive-date=4 March 2016 |work=Laboratoires THEA |publisher=Netherlands Medicines Authority MEB |via=Medicines Information Bank |location=Netherlands}}</ref> The eye drops have also been used to manage pain for ].<ref name="Wakai">{{cite journal | vauthors = Wakai A, Lawrenson JG, Lawrenson AL, Wang Y, Brown MD, Quirke M, Ghandour O, McCormick R, Walsh CD, Amayem A, Lang E, Harrison N | title = Topical non-steroidal anti-inflammatory drugs for analgesia in traumatic corneal abrasions | journal = The Cochrane Database of Systematic Reviews | volume = 2017 | issue = 5 | pages = CD009781 | date = May 2017 | pmid = 28516471 | pmc = 6481688 | doi = 10.1002/14651858.CD009781.pub2 }}</ref>
	As long-term use of diclofenac and similar NSAIDs predisposes for ], many patients at risk for this complication are prescribed a combination (]) of diclofenac and ], a synthetic prostaglandin analogue, to protect the gastric mucosa.{{Citation needed|date=May 2010}}
			Diclofenac is often used to treat chronic ], especially if inflammation is present.<ref>{{cite web | title=WHO's cancer pain ladder for adults | website=] (WHO) | date=27 November 2013 | url= https://www.who.int/cancer/palliative/painladder/en/ | archive-url= https://web.archive.org/web/20030807014332/http://www.who.int/cancer/palliative/painladder/en/ | url-status=dead | archive-date=7 August 2003 | access-date=26 April 2020}}</ref>
	An external, gel-based formulation containing 3% of diclofenac (Solaraze) is available for the treatment of facial ] caused by over-exposure to sunlight. Some countries have also approved the external use of diclofenac 1% gel to treat ] conditions.
			<gallery>
	In many countries{{Where|date=July 2011}}, eye-drops are sold to treat acute and chronic non-bacterial inflammations of the anterior part of the eyes (e.g., postoperative states).{{Citation needed|date=May 2010}} A common brand name is Voltaren-optha.
			File:Voltaren tablets.jpg|Voltaren (diclofenac) 50&nbsp;mg ] tablets
			File:Diclofenac sodium IV 75mg.jpg|Dyloject (diclofenac) 2&nbsp;ml for ] and ] administration
			File:Diclofenac sodium 100mg.jpg|Sintofarm (diclofenac) for ] administration
			File:Diclofenac Topical Gel.jpg|150 gram tube diclofenac ] U.S. package generic
			</gallery>
			==Contraindications==
	=== Investigational uses ===
			Diclofenac is contraindicated for pregnant women; for people with active stomach and/or duodenal ] or ]; and for people undergoing ].<ref name=AHFS2018 /><ref>{{cite web | title=Diclofenac Sodium Topical Solution: PI | website=Drugs.com | date=5 August 2024 | url=https://www.drugs.com/pro/diclofenac-sodium-topical-solution.html | access-date=13 October 2024}}</ref><ref>{{cite web | title=Diclofenac Sodium- diclofenac gel | website=DailyMed | date=30 March 2018 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f64b68a5-d6d2-4e92-87e7-90af04c1f9db | access-date=13 October 2024}}</ref>
	Diclofenac is often used to treat chronic pain associated with ], in particular if inflammation is also present (Step I of the ] (WHO) Scheme for treatment of chronic pain). Good results (sometimes better than those with opioids) have been seen in female breast cancer and in the pain associated with bony metastases.{{Citation needed|date=May 2010}} Diclofenac can be combined with opioids if needed. Combaren, a fixed combination of diclofenac and codeine (50&nbsp;mg each), is available for cancer treatment in Europe.{{Citation needed|date=May 2010}} Combinations with psychoactive drugs such as ] and/or ] have also been investigated and found useful in a number of cancer patients.{{Citation needed|date=May 2010}}
			==Adverse effects==
	Fever due to malignant lymphogranulomatosis (]) often responds to diclofenac.{{Citation needed|date=May 2010}} Treatment can be terminated as soon as the usual treatment with radiation and/or chemotherapy causes remission of fever.
			{{See also|Nonsteroidal anti-inflammatory drug#Adverse effects}}
			Diclofenac consumption has been associated with significantly increased vascular and coronary risk in a study including coxib, diclofenac, ] and ].<ref name="BhalaEmbersonEtAl">{{cite journal | vauthors = Bhala N, Emberson J, Merhi A, Abramson S, Arber N, Baron JA, Bombardier C, Cannon C, Farkouh ME, FitzGerald GA, Goss P, Halls H, Hawk E, Hawkey C, Hennekens C, Hochberg M, Holland LE, Kearney PM, Laine L, Lanas A, Lance P, Laupacis A, Oates J, Patrono C, Schnitzer TJ, Solomon S, Tugwell P, Wilson K, Wittes J, Baigent C | title = Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials | journal = Lancet | volume = 382 | issue = 9894 | pages = 769–779 | date = August 2013 | pmid = 23726390 | pmc = 3778977 | doi = 10.1016/S0140-6736(13)60900-9 }}</ref> Upper gastrointestinal complications were also reported.<ref name="BhalaEmbersonEtAl" /> ] were increased by about a third by diclofenac, chiefly due to an increase in major coronary events.<ref name="BhalaEmbersonEtAl" /> Compared with placebo, of 1000 patients allocated to diclofenac for a year, three more had major vascular events, one of which was fatal.<ref name="BhalaEmbersonEtAl" /> Vascular death is increased significantly by diclofenac.<ref name="BhalaEmbersonEtAl" />
	Diclofenac has been found to increase the blood pressure in patients with ] and ]. Currently, this use is highly investigative and cannot be recommended as routine treatment.
			In October 2020, the US ] (FDA) required the ] to be updated for all nonsteroidal anti-inflammatory medications to describe the risk of kidney problems in fetuses that result in low amniotic fluid.<ref name="FDA PR 20201015">{{cite press release | title=FDA Warns that Using a Type of Pain and Fever Medication in Second Half of Pregnancy Could Lead to Complications | website=U.S. ] (FDA) | date=15 October 2020 | url=https://www.fda.gov/news-events/press-announcements/fda-warns-using-type-pain-and-fever-medication-second-half-pregnancy-could-lead-complications | access-date=15 October 2020 | archive-date=16 October 2020 | archive-url=https://web.archive.org/web/20201016180003/https://www.fda.gov/news-events/press-announcements/fda-warns-using-type-pain-and-fever-medication-second-half-pregnancy-could-lead-complications | url-status=live }} {{PD-notice}}</ref><ref name="FDA safety 20201015">{{cite web | title=NSAIDs may cause rare kidney problems in unborn babies | website=U.S. ] (FDA) | date=21 July 2017 | url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-recommends-avoiding-use-nsaids-pregnancy-20-weeks-or-later-because-they-can-result-low-amniotic | access-date=15 October 2020 | archive-date=17 October 2020 | archive-url=https://web.archive.org/web/20201017014419/https://www.fda.gov/drugs/drug-safety-and-availability/fda-recommends-avoiding-use-nsaids-pregnancy-20-weeks-or-later-because-they-can-result-low-amniotic | url-status=live }} {{PD-notice}}</ref>
	Diclofenac has been found to be effective against all strains of multi drug resistant E. coli, with a MIC of 25 micrograms/mL. Therefore, it may be suggested that diclofenac has the capacity to treat uncomplicated urinary tract infections (UTI) caused by '']''.<ref name="pmid17091768">{{cite journal |author=Mazumdar K, Dutta NK, Dastidar SG, Motohashi N, Shirataki Y |title=Diclofenac in the management of ''E. coli'' urinary tract infections |journal=In Vivo |volume=20 |issue=5 |pages=613–619 |year=2006 |pmid=17091768 |doi=}}</ref> It has also been shown to be effective in treating Salmonella infections in mice<ref name="Dutta2007">{{cite journal |author=Dutta NK, Annadurai S, Mazumdar K, Dastidar SG, Kristiansen JE, Molnar J, Martins M, Amaral L. |title=Potential management of resistant microbial infections with a novel non-antibiotic: the anti-inflammatory drug diclofenac sodium |journal= Int. J. Antimicrob. Agents |volume=30 |issue=3 |pages=242–249 |year=2007|doi=10.1016/j.ijantimicag.2007.04.018 |pmid=17644318}}</ref> and is under investigation for the treatment of tuberculosis.<ref name="Dutta2007a">{{cite journal |author=Dutta NK, Mazumdar K, Dastidar SG, Park JH |title=Activity of diclofenac used alone and in combination with streptomycin against ''Mycobacterium tuberculosis'' in mice |journal= Int. J. Antimicrob. Agents |volume=30 |issue=4 |pages=336–340 |year=2007|doi=10.1016/j.ijantimicag.2007.04.016 |pmid=17644321}}</ref>
			===Heart===
	Diclofenac is an ].<ref name="pmid18727958">{{cite journal
			In 2013, a study found major vascular events were increased by about a third by diclofenac, chiefly due to an increase in major coronary events.<ref name="BhalaEmbersonEtAl" /> Compared with placebo, of 1000 people allocated to diclofenac for a year, three more had major vascular events, one of which was fatal.<ref name="BhalaEmbersonEtAl" /> Vascular death was increased by diclofenac (1·65).<ref name="BhalaEmbersonEtAl" />
	| author = Naidoo V, Swan GE
	| title = Diclofenac toxicity in Gyps vulture is associated with decreased uric acid excretion and not renal portal vasoconstriction
	| journal = Comp. Biochem. Physiol. C Toxicol. Pharmacol.
	| volume = 149
	| issue = 3
	| pages = 269–74
	| year = 2008
	| month = August
	| pmid = 18727958
	| doi = 10.1016/j.cbpc.2008.07.014
	| url =
	| issn =
	}}</ref>
			Following the identification of increased risks of heart attacks with the selective ] ] in 2004, attention has focused on all the other members of the nonsteroidal anti-inflammatory drug group, including diclofenac. Research results are mixed, with a meta-analysis of papers and reports up to April 2006 suggesting a relative increased rate of heart disease of 1.63 compared to nonusers.<ref name="BMJ2006-Kearney">{{cite journal | vauthors = Kearney PM, Baigent C, Godwin J, Halls H, Emberson JR, Patrono C | title = Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials | journal = BMJ | volume = 332 | issue = 7553 | pages = 1302–1308 | date = June 2006 | pmid = 16740558 | pmc = 1473048 | doi = 10.1136/bmj.332.7553.1302 }}</ref> Professor Peter Weissberg, medical director of the British Heart Foundation said, "However, the increased risk is small, and many patients with chronic debilitating pain may well feel that this small risk is worth taking to relieve their symptoms". Only ] was found not to increase the risk of heart disease; however, this is known to have a higher rate of gastric ulceration than diclofenac. As of January 2015, the MHRA announced that diclofenac would be reclassified as a prescription-only medicine (POM) due to the risk of cardiovascular adverse events.<ref>{{cite web |url=http://www.mhra.gov.uk/NewsCentre/Pressreleases/CON500341 |title=Press release: Diclofenac tablets now only available as a prescription medicine |date=14 January 2015 |access-date=14 January 2015 |website=Medicines and Healthcare products Regulatory Agency |archive-date=22 January 2015 |archive-url=https://web.archive.org/web/20150122224346/http://www.mhra.gov.uk/NewsCentre/Pressreleases/CON500341 |url-status=live }}</ref>
	==Contraindications==
	* Hypersensitivity against diclofenac
	* History of allergic reactions (bronchospasm, shock, rhinitis, urticaria) following the use of Aspirin or another NSAID
	* ]
	* Active stomach and/or duodenal ulceration or gastrointestinal bleeding
	* Inflammative intestinal disorders such as Crohn's disease or ulcerative colitis
	* Severe insufficiency of the heart (NYHA III/IV)
	* Recently, a warning has been issued by FDA not to use to treat patients recovering from heart surgery
	* Severe liver insufficiency (Child-Pugh Class C)
	* Severe renal insufficiency (creatinine clearance <30 ml/min)
	* Caution in patients with preexisting hepatic porphyria, as diclofenac may trigger attacks
	* Caution in patients with severe, active bleeding such as cerebral hemorrhage
	* NSAIDs in general should be avoided during ].
	* On animals which after death may be eaten by ]s or other scavenging birds.
	==Side-effects==
	* Diclofenac is among the better tolerated NSAIDs. Though 20% of patients on long-term treatment experience side-effects, only 2% have to discontinue the drug, mostly due to gastrointestinal complaints.
			A subsequent large study of 74,838 Danish users of nonsteroidal anti-inflammatory drugs or ]s found no additional cardiovascular risk from diclofenac use.<ref name="ArthritisRheum2006-Solomon">{{cite journal | vauthors = Solomon DH, Avorn J, Stürmer T, Glynn RJ, Mogun H, Schneeweiss S | title = Cardiovascular outcomes in new users of coxibs and nonsteroidal antiinflammatory drugs: high-risk subgroups and time course of risk | journal = Arthritis and Rheumatism | volume = 54 | issue = 5 | pages = 1378–1389 | date = May 2006 | pmid = 16645966 | doi = 10.1002/art.21887 | s2cid = 2082359 | doi-access = }}</ref> A very large study of 1,028,437 Danish users of various nonsteroidal anti-inflammatory drugs or coxibs found the "Use of the nonselective NSAID diclofenac and the selective cyclooxygenase-2 inhibitor rofecoxib was associated with an increased risk of cardiovascular death (], 1.91; 95% confidence interval, 1.62 to 2.42; and odds ratio, 1.66; 95% confidence interval, 1.06 to 2.59, respectively), with a dose-dependent increase in risk."<ref name="pmid20530789">{{cite journal | vauthors = Fosbøl EL, Folke F, Jacobsen S, Rasmussen JN, Sørensen R, Schramm TK, Andersen SS, Rasmussen S, Poulsen HE, Køber L, Torp-Pedersen C, Gislason GH | title = Cause-specific cardiovascular risk associated with nonsteroidal antiinflammatory drugs among healthy individuals | journal = Circulation: Cardiovascular Quality and Outcomes | volume = 3 | issue = 4 | pages = 395–405 | date = July 2010 | pmid = 20530789 | doi = 10.1161/CIRCOUTCOMES.109.861104 | doi-access = free }}</ref>
	===Cardiac===
	* Following the identification of increased risks of heart attacks with the selective ] ] in 2004, attention has focused on all the other members of the ] group, including diclofenac. Research results are mixed with a meta-analysis of papers and reports up to April 2006 suggesting a relative increased rate of heart disease of 1.63 compared to non-users.<ref name="BMJ2006-Kearney">{{cite journal | author=
	Kearney P, Baigent C, Godwin J, Halls H, Emberson J, Patrono C
	| title=Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials
	| journal=BMJ | volume=332 | issue=7553 | pages=1302–8
	| year=2006 | pmid=16740558 | doi=10.1136/bmj.332.7553.1302
	| pmc=1473048}}</ref> Professor Peter Weissberg, Medical Director of the British Heart Foundation said, "However, the increased risk is small, and many patients with chronic debilitating pain may well feel that this small risk is worth taking to relieve their symptoms". Only ] was found not to increase the risk of heart disease; however, this is known to have a higher rate of gastric ulceration than diclofenac.
			Diclofenac is similar in COX-2 selectivity to ].<ref name="pmid11496855">{{cite journal | vauthors = FitzGerald GA, Patrono C | title = The coxibs, selective inhibitors of cyclooxygenase-2 | journal = The New England Journal of Medicine | volume = 345 | issue = 6 | pages = 433–442 | date = August 2001 | pmid = 11496855 | doi = 10.1056/NEJM200108093450607 }}</ref>{{Contradictory inline|reason=This contradicts the later (also substantiated) statement that diclofenac and naproxen have relatively equipotent COX inhibition. Diclofenac is not usually categorised as COX-2-selective, but this source would seem to suggest that it is.|date=November 2022|section=Mechanism of action}}
	A subsequent large study of 74,838 users of NSAIDs or ]s, published in May 2006, found no additional cardiovascular risk from diclofenac use.<ref name="ArthritisRheum2006-Solomon">{{cite journal | author=Solomon D, Avorn J, Stürmer T, Glynn R, Mogun H, Schneeweiss S | title=Cardiovascular outcomes in new users of coxibs and nonsteroidal antiinflammatory drugs: high-risk subgroups and time course of risk | journal=Arthritis Rheum | volume=54 | issue=5 | pages=1378–89 | year=2006 | pmid=16645966 | doi=10.1002/art.21887}}</ref> A very large study of 1,028,437 Danish users of various NSAIDs or coxibs, published online on June 8, 2010, found that "Use of the nonselective NSAID diclofenac and the selective cyclooxygenase-2 inhibitor rofecoxib was associated with an increased risk of cardiovascular death (odds ratio, 1.91; 95% confidence interval, 1.62 to 2.42; and odds ratio, 1.66; 95% confidence interval, 1.06 to 2.59, respectively), with a dose-dependent increase in risk." .<ref name="pmid20530789">{{cite journal | author=Fosbøl EL, Folke F, Jacobsen S, Rasmussen JN, Sørensen R, Schramm TK, Andersen SS, Rasmussen S, Poulsen HE, Køber L, Torp-Pedersen C, Gislason GH | title=Cause-Specific Cardiovascular Risk Associated With Nonsteroidal Antiinflammatory Drugs Among Healthy Individuals | journal=Circ Cardiovasc Qual Outcomes | volume=3 | issue=4 | pages=395–405 | year=2010 | pmid=20530789 | doi=10.1161/CIRCOUTCOMES.109.861104}}</ref>
	* Diclofenac has similar COX-2 selectivity to ].<ref name="pmid11496855">{{cite journal
	| author=FitzGerald G, Patrono C
	| title=The coxibs, selective inhibitors of cyclooxygenase-2
	| journal=N Engl J Med |volume=345 |issue=6 |pages=433–42
	| year=2001 |pmid=11496855 |doi=10.1056/NEJM200108093450607}}</ref> Perhaps related to this selectivity, a review of this constantly-changing topic by FDA Medical Officer David Graham concluded in September, 2006 that diclofenac does increase the risk of ].<ref name="pmid16968830">{{cite journal |author=Graham D |title=COX-2 inhibitors, other NSAIDs, and cardiovascular risk: the seduction of common sense |journal=JAMA |volume=296 |issue=13 |pages=1653–6 |year=2006 |pmid=16968830 | doi=10.1001/jama.296.13.jed60058 | url=http://jama.ama-assn.org/cgi/content/full/296/13/1653}}</ref>
	===Gastrointestinal===		===Gastrointestinal===
			{{unreferenced section|date=October 2024}}
	* Gastrointestinal complaints are most often noted (see above). The development of ulceration and/or bleeding requires immediate termination of treatment with diclofenac. Most patients receive an ulcer-protective drug as prophylaxis during long-term treatment (], ] 150&nbsp;mg at bedtime or ] 20&nbsp;mg at bedtime).
			* Gastrointestinal complaints are most often noted. Most patients receive a gastro-protective drug as prophylaxis during long-term treatment (], ], or ]).
	===Hepatic===		===Liver===
	* Liver damage occurs infrequently, and is usually reversible. ] may occur rarely without any warning symptoms and may be fatal. Patients with ] more often develop symptomatic liver disease than patients with rheumatoid arthritis. Liver function should be monitored regularly during long-term treatment. If used for the short-term treatment of pain or fever, diclofenac has not been found to be more hepatotoxic than other NSAIDs.		* Liver damage occurs infrequently, and is usually reversible. ] may occur rarely without any warning symptoms and may be fatal. Patients with ] more often develop symptomatic liver disease than patients with rheumatoid arthritis. If used for the short-term treatment of pain or fever, diclofenac has not been found more hepatotoxic than other nonsteroidal anti-inflammatory drugs.{{medical citation needed|date=April 2020}}
	* As of 12/2009 Endo, Novartis and FDA notified healthcare professionals to add new warnings and precautions about the potential for elevation in liver function tests during treatment with all products containing diclofenac sodium.<ref>http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm193047.htm</ref>		* {{As of|December 2009}}, Endo, Novartis, and the US FDA notified healthcare professionals to add new warnings and precautions about the potential for elevation in liver function tests during treatment with all products containing diclofenac sodium.<ref>{{cite web |title= Voltaren Gel (diclofenac sodium topical gel) 1% – Hepatic Effects Labeling Changes|website=U.S. ] (FDA) |url= https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm193047.htm |archive-url= https://web.archive.org/web/20150329100526/https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm193047.htm |url-status= dead|date= 4 December 2009|archive-date= 29 March 2015}}</ref>
	* Cases of drug-induced hepatotoxicity have been reported in the first month, but can occur at any time during treatment with diclofenac. Postmarketing surveillance has reported cases of severe hepatic reactions, including liver necrosis, jaundice, fulminant hepatitis with and without jaundice, and liver failure. Some of these reported cases resulted in fatalities or liver transplantation.		* Cases of drug-induced hepatotoxicity have been reported in the first month but can occur at any time during treatment with diclofenac. ] has reported cases of severe hepatic reactions, including liver necrosis, jaundice, fulminant hepatitis with and without jaundice, and liver failure. Some of these reported cases resulted in fatalities or liver transplantation.{{medical citation needed|date=April 2020}}
	* Physicians should measure transaminases periodically in patients receiving long-term therapy with diclofenac. Based on clinical trial data and postmarketing experiences, transaminases should be monitored within 4 to 8 weeks after initiating treatment with diclofenac.
	===Renal===		===Kidney===
			* Nonsteroidal anti-inflammatory drugs "are associated with adverse renal effects caused by the reduction in synthesis of renal ]s"<ref name="Brater2002">{{cite journal | vauthors = Brater DC | title = Renal effects of cyclooxygyenase-2-selective inhibitors | journal = Journal of Pain and Symptom Management | volume = 23 | issue = 4 Suppl | pages = S15–20; discussion S21–23 | date = April 2002 | pmid = 11992745 | doi = 10.1016/S0885-3924(02)00370-6 | doi-access = free }}</ref> in sensitive persons or animal species, and potentially during long-term use in nonsensitive persons if resistance to side effects decreases with age. However, this side effect cannot be avoided merely by using a COX-2 selective inhibitor because, "Both isoforms of COX, COX-1, and COX-2, are expressed in the kidney...
	* Studies in Pakistan showed that diclofenac caused acute kidney failure in vultures when they ate the carcasses of animals that had recently been treated with it (see below at ]). Species and individual humans that are drug sensitive are initially assumed to lack genes expressing specific drug detoxification enzymes.
	* NSAIDs "are associated with adverse renal effects caused by the reduction in synthesis of renal prostaglandins"<!--
	--><ref name="Brater2002">{{cite journal | author=Brater DC | title=Renal effects of cyclooxygyenase-2-selective inhibitors | journal=J Pain Symptom Manage | year=2002 | pages=S15–20; discussion S21–3 | volume=23 | issue=4 Suppl | pmid=11992745 | doi=10.1016/S0885-3924(02)00370-6}}</ref><!--
	--> in sensitive persons or animal species, and potentially during long-term use in non-sensitive persons if resistance to side-effects decreases with age. However, this side-effect cannot be avoided merely by using a COX-2 selective inhibitor because, "Both isoforms of COX, COX-1 and COX-2, are expressed in the kidney... Consequently, the same precautions regarding renal risk that are followed for nonselective NSAIDs should be used when selective COX-2 inhibitors are administered."<ref name="Brater2002"/> However, diclofenac appears to have a different mechanism of renal toxicity.<ref name="pmid18727958"/>
	===Other===		===Mental health===
			* Mental health side effects have been reported. These symptoms are rare but exist in significant enough numbers to include as potential side effects. These include depression, anxiety, irritability, nightmares, and psychotic reactions.<ref>{{cite web |url=https://www.drugs.com/sfx/diclofenac-side-effects.html |title=Diclofenac Side Effects |work=Drugs.com |access-date=21 January 2013 |archive-date=5 February 2013 |archive-url=https://web.archive.org/web/20130205085428/http://www.drugs.com/sfx/diclofenac-side-effects.html |url-status=live }}</ref>
	* Bone marrow depression is noted infrequently (], ], ] with/without purpura, ]). These conditions may be life-threatening and/or irreversible, if detected too late. All patients should be monitored closely. Diclofenac is a weak and reversible inhibitor of thrombocytic aggregation needed for normal coagulation.
			==Pharmacology==
	*Induces warm antibody hemolytic anemia by inducing antibodies to Rh antigens, ] also does this.<ref></ref>
			As with other nonsteroidal anti-inflammatory drugs, the primary ] responsible for its ], ] and ] action is thought to be inhibition of prostaglandin synthesis through ]-inhibition.
			The main target in the inhibition of prostaglandin synthesis appears to be the transiently expressed prostaglandin-endoperoxide synthase-2 (PGES-2), also known as ] (COX-2). That is, diclofenac is partially selective for COX-2. The reported selectivity for COX-2 varies from 1.5 to 30 depending on the source.<ref>{{cite journal | title = Diclofenac | date = 15 January 2024 | pmid = 32491802 | url = https://www.ncbi.nlm.nih.gov/books/NBK557879/ | website = National Library of Medicine | access-date = 15 January 2024 | publication-date = 22 May 2023 | vauthors = Alfaro RA, Davis DD }}</ref><ref>{{cite journal | vauthors = Patrono C, Patrignani P, García Rodríguez LA | title = Cyclooxygenase-selective inhibition of prostanoid formation: transducing biochemical selectivity into clinical read-outs | journal = The Journal of Clinical Investigation | volume = 108 | issue = 1 | pages = 7–13 | date = July 2001 | pmid = 11435450 | doi = 10.1172/JCI13418 | pmc = 209347 }}</ref><ref>{{cite journal | vauthors = Warner TD, Giuliano F, Vojnovic I, Bukasa A, Mitchell JA, Vane JR | title = Nonsteroid drug selectivities for cyclo-oxygenase-1 rather than cyclo-oxygenase-2 are associated with human gastrointestinal toxicity: a full in vitro analysis | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 96 | issue = 13 | pages = 7563–7568 | date = June 1999 | pmid = 10377455 | pmc = 22126 | doi = 10.1073/pnas.96.13.7563 | doi-access = free | bibcode = 1999PNAS...96.7563W }}</ref><ref>{{cite journal | vauthors = Mitchell JA, Akarasereenont P, Thiemermann C, Flower RJ, Vane JR | title = Selectivity of nonsteroidal antiinflammatory drugs as inhibitors of constitutive and inducible cyclooxygenase | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 90 | issue = 24 | pages = 11693–11697 | date = December 1993 | pmid = 8265610 | pmc = 48050 | doi = 10.1073/pnas.90.24.11693 | bibcode = 1993PNAS...9011693M | doi-access = free }}</ref>
	* Diclofenac may disrupt the normal menstrual cycle.
			The drug may be bacteriostatic via inhibiting bacterial DNA synthesis.<ref name="Dutta2000">{{cite journal | vauthors = Dastidar SG, Ganguly K, Chaudhuri K, Chakrabarty AN | title = The anti-bacterial action of diclofenac shown by inhibition of DNA synthesis | journal = International Journal of Antimicrobial Agents | volume = 14 | issue = 3 | pages = 249–251 | date = April 2000 | pmid = 10773497 | doi = 10.1016/S0924-8579(99)00159-4 }}</ref>
	==Mechanism of action==
	The exact mechanism of action is not entirely known, but it is thought that the primary mechanism responsible for its ], ], and ] action is inhibition of ] synthesis by inhibition of ] (COX). It also appears to exhibit bacteriostatic activity by inhibiting bacterial DNA synthesis.<ref name="Dutta2000">{{cite journal |author=Dutta NK, Annadurai S, Mazumdar K, Dastidar SG, Kristiansen JE, Molnar J, Martins M, Amaral L |title=The anti-bacterial action of diclofenac shown by inhibition of DNA synthesis |journal= Int. J. Antimicrob. Agents |volume=14 |issue=3 |pages=249–51|year=2000|doi=10.1016/S0924-8579(99)00159-4 |pmid=10773497}}</ref>
			Diclofenac has a relatively high lipid solubility, making it one of the few nonsteroidal anti-inflammatory drugs that are able to enter the brain by crossing the ].<ref name="Diclofenac: novità su tollerabilità">{{cite journal | vauthors = Sandri A | title = Diclofenac: update on tolerableness and spinal anti-inflammatory action | journal = Minerva Medica | volume = 105 | issue = 4 | pages = 313–318 | date = August 2014 | pmid = 25078485 | url = https://www.minervamedica.it/en/journals/minerva-medica/article.php?cod=R10Y2014N04A0313 | access-date = 23 April 2023 | archive-date = 23 April 2023 | archive-url = https://web.archive.org/web/20230423165313/https://www.minervamedica.it/en/journals/minerva-medica/article.php?cod=R10Y2014N04A0313 | url-status = live }}</ref> As in the rest of the body, it is thought to exert its effect in the brain through inhibition of COX-2.<ref name="Diclofenac: novità su tollerabilità"/> In addition, it may have effects inside the spinal cord.<ref>{{cite journal | vauthors = Sandri A | title = Spinal antinflammatory action of Diclofenac | journal = Minerva Medica | volume = 107 | issue = 3 | pages = 167–172 | date = June 2016 | pmid = 27014880 | url = https://www.minervamedica.it/en/journals/minerva-medica/article.php?cod=R10Y2016N03A0167 | access-date = 23 April 2023 | archive-date = 23 April 2023 | archive-url = https://web.archive.org/web/20230423165313/https://www.minervamedica.it/en/journals/minerva-medica/article.php?cod=R10Y2016N03A0167 | url-status = live }}</ref>
	Inhibition of COX also decreases ]s in the ] of the stomach, making it more sensitive to corrosion by ].{{Citation needed|date=May 2010}} This is also the main side-effect of diclofenac. Diclofenac has a low to moderate preference to block the COX2-isoenzyme (approximately 10-fold) and is said to have, therefore, a somewhat lower incidence of gastrointestinal complaints than noted with ] and ].{{Citation needed|date=March 2009}}
			Diclofenac may be a unique member of the nonsteroidal anti-inflammatory drugs in other aspects. Some evidence indicates it inhibits the ] pathways,<ref>{{cite journal | vauthors = Gan TJ | title = Diclofenac: an update on its mechanism of action and safety profile | journal = Current Medical Research and Opinion | volume = 26 | issue = 7 | pages = 1715–1731 | date = July 2010 | pmid = 20470236 | doi = 10.1185/03007995.2010.486301 }}</ref><ref>{{cite journal | vauthors = Ku EC, Lee W, Kothari HV, Scholer DW | title = Effect of diclofenac sodium on the arachidonic acid cascade | journal = The American Journal of Medicine | volume = 80 | issue = 4B | pages = 18–23 | date = April 1986 | pmid = 3085488 | doi = 10.1016/0002-9343(86)90074-4 }}</ref> thus reducing the formation of ]s (also pro-inflammatory ]s). It also may inhibit ], which may be relevant to its mechanism of action. These additional actions may explain its high potency – it is the most potent NSAID on a broad basis.<ref name="pmid3085490">{{cite journal | vauthors = Scholer DW, Ku EC, Boettcher I, Schweizer A | title = Pharmacology of diclofenac sodium | journal = The American Journal of Medicine | volume = 80 | issue = 4B | pages = 34–38 | date = April 1986 | pmid = 3085490 | doi = 10.1016/0002-9343(86)90077-x }}</ref>
	The action of one single dose is much longer (6 to 8 hours) than the very short half-life that the drug indicates.{{Citation needed|date=May 2010}} This could be partly because it persists for over 11 hours in ]s.<ref name="pmid6628528">{{cite journal |author=Fowler PD, Shadforth MF, Crook PR, John VA |title=Plasma and synovial fluid concentrations of diclofenac sodium and its major hydroxylated metabolites during long-term treatment of rheumatoid arthritis |journal=Eur. J. Clin. Pharmacol. |volume=25 |issue=3 |pages=389–94 |year=1983 |pmid=6628528 |doi= 10.1007/BF01037953|url=}}</ref>
			Marked differences exist among nonsteroidal anti-inflammatory drugs in their selective inhibition of the two subtypes of cyclooxygenase, COX-1, and COX-2.<ref name="Cryer1998">{{cite journal | vauthors = Cryer B, Feldman M | title = Cyclooxygenase-1 and cyclooxygenase-2 selectivity of widely used nonsteroidal anti-inflammatory drugs | journal = The American Journal of Medicine | volume = 104 | issue = 5 | pages = 413–421 | date = May 1998 | pmid = 9626023 | doi = 10.1016/S0002-9343(98)00091-6 }}</ref> Drug developers have focused on selective COX-2 inhibition, particularly as a way to minimize the gastrointestinal side effects of nonsteroidal anti-inflammatory drugs. In practice, the use of some ]s with their ] has led to massive numbers of lawsuits alleging wrongful death by ], yet other significantly COX-selective nonsteroidal anti-inflammatory drugs, such as diclofenac, have been well tolerated by most of the population.{{Citation needed|date=May 2010}}
	Diclofenac may also be a unique member of the ]s. There is some evidence that diclofenac inhibits the ] pathways,{{Citation needed|date=March 2009}} thus reducing formation of the ]s (also pro-inflammatory ]s). There is also speculation{{By whom|date=May 2010}} that diclofenac may inhibit ] as part of its mechanism of action. These additional actions may explain the high potency of diclofenac – it is the most potent NSAID on a broad basis.{Scholer. Pharmacology of Diclofenac Sodium. Am J of Medicine Volume 80 April 28, 1986}
			Besides the COX-inhibition, several other molecular targets of diclofenac possibly contributing to its pain-relieving actions have recently been identified. These include:
	There are marked differences among NSAIDs in their selective inhibition of the two subtypes of cyclo-oxygenase, ] and ].{{Citation needed|date=May 2010}} Much pharmaceutical drug design has attempted to focus on selective COX-2 inhibition as a way to minimize the gastrointestinal side-effects of NSAIDs like aspirin. In practice, use of some ]s with their ] has led to massive numbers of patient family lawsuits alleging wrongful death by ], yet other significantly COX-selective NSAIDs such as diclofenac have been well-tolerated by most of the population.{{Citation needed|date=May 2010}}
			* Blockage of voltage-dependent ]s (after activation of the channel, diclofenac inhibits its reactivation, also known as phase inhibition)<ref>{{cite journal | vauthors = Fei XW, Liu LY, Xu JG, Zhang ZH, Mei YA | title = The non-steroidal anti-inflammatory drug, diclofenac, inhibits Na(+) current in rat myoblasts | journal = Biochemical and Biophysical Research Communications | volume = 346 | issue = 4 | pages = 1275–1283 | date = August 2006 | pmid = 16806078 | doi = 10.1016/j.bbrc.2006.06.034 }}</ref><ref name=":0">{{cite journal | vauthors = Gwanyanya A, Macianskiene R, Mubagwa K | title = Insights into the effects of diclofenac and other non-steroidal anti-inflammatory agents on ion channels | journal = The Journal of Pharmacy and Pharmacology | volume = 64 | issue = 10 | pages = 1359–1375 | date = October 2012 | pmid = 22943167 | doi = 10.1111/j.2042-7158.2012.01479.x }}</ref>
			* Blockage of acid-sensing ]s (ASICs)<ref>{{cite journal | vauthors = Voilley N, de Weille J, Mamet J, Lazdunski M | title = Nonsteroid anti-inflammatory drugs inhibit both the activity and the inflammation-induced expression of acid-sensing ion channels in nociceptors | journal = The Journal of Neuroscience | volume = 21 | issue = 20 | pages = 8026–8033 | date = October 2001 | pmid = 11588175 | pmc = 6763876 | doi = 10.1523/JNEUROSCI.21-20-08026.2001 }}</ref>
			* Positive allosteric modulation of KCNQ- and BK-]s (diclofenac opens these channels, leading to hyperpolarization of the cell membrane)<ref>{{cite journal | vauthors = Ortiz MI, Torres-López JE, Castañeda-Hernández G, Rosas R, Vidal-Cantú GC, Granados-Soto V | title = Pharmacological evidence for the activation of K(+) channels by diclofenac | journal = European Journal of Pharmacology | volume = 438 | issue = 1–2 | pages = 85–91 | date = March 2002 | pmid = 11906715 | doi = 10.1016/S0014-2999(02)01288-8 }}</ref><ref name=":0" />
			The duration of action (i.e., duration of pain relief) of a single dose is longer (6 to 8&nbsp;]) than the drug's 1.2–2&nbsp;h half-life. This could be partly because it persists for over 11 hours in ]s.<ref name="pmid6628528">{{cite journal | vauthors = Fowler PD, Shadforth MF, Crook PR, John VA | title = Plasma and synovial fluid concentrations of diclofenac sodium and its major hydroxylated metabolites during long-term treatment of rheumatoid arthritis | journal = European Journal of Clinical Pharmacology | volume = 25 | issue = 3 | pages = 389–394 | year = 1983 | pmid = 6628528 | doi = 10.1007/BF01037953 | s2cid = 9803699 }}</ref>
	Besides the well-known and often-cited COX-inhibition, a number of other molecular targets of diclofenac that could contribute to its pain-relieving actions have recently been identified. These include:
			==History==
	* Blockage of voltage-dependent sodium channels (after activation of the channel, diclofenac inhibits its reactivation also known as phase inhibition){{Citation needed|date=March 2009}}
			Diclofenac was first synthesized by Alfred Sallmann and Rudolf Pfister in 1973.<ref name=":1">{{cite journal | vauthors = Altman R, Bosch B, Brune K, Patrignani P, Young C | title = Advances in NSAID development: evolution of diclofenac products using pharmaceutical technology | journal = Drugs | volume = 75 | issue = 8 | pages = 859–877 | date = May 2015 | pmid = 25963327 | pmc = 4445819 | doi = 10.1007/s40265-015-0392-z }}</ref><ref>{{Cite journal | vauthors = Hasan MK, Akhter S, Fatema K, Hossain MR, Sultana T, Uzzaman M |date= January 2023 |title=Selective modification of diclofenac to reduce the adverse effects; A computer-aided drug design approach |journal=Informatics in Medicine Unlocked |volume=36 |pages=101159 |doi=10.1016/j.imu.2023.101159 |issn=2352-9148|doi-access=free }}</ref> The name "diclofenac" derives from its chemical name: 2-(2,6-'''dichlo'''ranilino) '''phen'''yl'''ac'''etic acid. It was patented in Germany in 1978 by Ciba-Geigy (now ]).<ref name=Fischer2006>{{cite book| vauthors = Fischer J |title=Analogue-based drug discovery|page=517|year=2006|publisher=Wiley-VCH|location=|isbn=978-3-527-31257-3}}</ref><ref>{{cite patent|country=DE|number=1793592|url=https://patents.google.com/patent/DE1793592A1/en?oq=DE1793592|inventor=Pfister R, Sallmann A|title=Process for the production of new substituted phenylacetic acids|assign1=Ciba Geigy AG|gdate=26 January 1978}} {{Webarchive|url=https://web.archive.org/web/20230424053935/https://patents.google.com/patent/DE1793592A1/en?oq=DE1793592|date=24 April 2023}}</ref> It came into medical use in the United States in 1988.<ref name=AHFS2018/> ] purchased the rights in 2015.<ref name=":1" /> It is available as a ].<ref name=AHFS2018/>
			==Society and culture==
	* Blockage of acid-sensing ion channels (ASICs){{Citation needed|date=March 2009}}
			===Formulations and brand names===
			Diclofenac formulations are available worldwide under many different brand names.<ref name=tn>{{cite web|title=Diclofenac|url=https://www.drugs.com/international/diclofenac.html|website=Drugs.com|access-date=22 December 2018|archive-date=22 December 2018|archive-url=https://web.archive.org/web/20181222173313/https://www.drugs.com/international/diclofenac.html|url-status=live}}</ref>
			Voltaren and Voltarol contain the sodium salt of diclofenac. In the United Kingdom, Voltarol can be supplied with either the sodium salt or the potassium salt, while Cataflam, sold in some other countries, is the potassium salt only. However, Voltarol Emulgel contains diclofenac diethylammonium 1.16%, being equivalent to 1% sodium salt. In 2016, Voltarol was one of the biggest selling branded over-the-counter medications sold in Great Britain, with sales of £39.3 million.<ref name=Connelly2017>{{cite news|vauthors=Connelly D|title=A breakdown of the over-the-counter medicines market in Britain in 2016|url=https://pharmaceutical-journal.com/article/infographics/a-breakdown-of-the-over-the-counter-medicines-market-in-britain-in-2016|work=The Pharmaceutical Journal|date=28 April 2017|access-date=23 April 2023|archive-date=8 December 2021|archive-url=https://web.archive.org/web/20211208124752/https://pharmaceutical-journal.com/article/infographics/a-breakdown-of-the-over-the-counter-medicines-market-in-britain-in-2016|url-status=live}}</ref>
	* Positive allosteric modulation of KCNQ- and BK-potassium channels (diclofenac opens these channels, leading to hyperpolarization of the cell membrane){{Citation needed|date=March 2009}}
			In the United States, 1% diclofenac gel was approved by the FDA in 2007 as a prescription drug for the temporary relief of the pain of osteoarthritis of joints in the hands, knees, and feet. In 2020, the FDA approved the gel formulation for ] use.<ref name=FDAswitch/>
	==History==
	Diclofenac originated from Ciba-Geigy (now ]) in 1973.<ref>http://www.novartis.com/about-novartis/company-history/index.shtml</ref> Diclofenac was first introduced in the UK in 1979.<ref>http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1434053</ref><ref>{{cite journal | doi = 10.1016/0002-9343(86)90076-8 | author = Salmann AR | year = 1986 | title = The history of diclofenac | url = | journal = ] | volume = 80 | issue = 4B| pages = 29–33 }}</ref>
			In January 2015, diclofenac oral preparations were reclassified as prescription-only medicines in the UK. The topical preparations are available without a prescription.<ref>{{cite web|url=https://www.gov.uk/drug-device-alerts/drug-alert-oral-diclofenac-presentations-with-legal-status-p-reclassified-to-pom|title=Oral diclofenac presentations with legal status 'P' – reclassified to POM|website=www.gov.uk|access-date=31 March 2015|archive-date=2 April 2015|archive-url=https://web.archive.org/web/20150402164113/https://www.gov.uk/drug-device-alerts/drug-alert-oral-diclofenac-presentations-with-legal-status-p-reclassified-to-pom|url-status=live}}</ref>
	Recent research (2010) has linked use of Diclofenac to an increased chance of ]s<ref>ABC News: Study links Voltaren to strokes http://www.abc.net.au/news/stories/2010/09/14/3011102.htm</ref>
	==Ecological effects==		==={{anchor|Ecological problems}}Ecological effects===
			{{missing information|section|environmental buildup, wastewater; try {{PMID|27649472}}|date=December 2022}}
	Use of diclofenac in animals has been reported to have led to a sharp decline in the ] population in the Indian subcontinent, 95% decline in 2003,<ref name="Oaks2004">{{cite journal | author=Oaks JL, Gilbert M, Virani MZ, Watson RT, Meteyer CU, Rideout BA, Shivaprasad HL, Ahmed S, Chaudhry MJ, Arshad M, Mahmood S, Ali A, Khan AA | title=Diclofenac residues as the cause of vulture population decline in Pakistan | journal=Nature | year=2004 | pages=630–3 | volume=427 | issue=6975 | pmid=14745453 | doi=10.1038/nature02317}}</ref> 99.9% decline as of 2008. The mechanism is, it is presumed, ], a known side-effect of diclofenac. Vultures eat the carcasses of ] that have been administered veterinary diclofenac, and are poisoned by the accumulated chemical.<ref name="BBC3">
			{{Main|Indian vulture crisis}}
	"Vet drug 'killing Asian vultures'", BBC News,
	28 January 2004, webpage:
	.
	</ref> At a meeting of the National Wildlife Board in March 2005, the Government of India announced that it intended to phase out the veterinary use of diclofenac.<ref name="PIB2005">{{cite press release | publisher=Press Information Bureau, Government of India | date=2005-05-16 | url=http://pib.nic.in/release/release.asp?relid=9303 | title=Saving the Vultures from Extinction | accessdate=2006-05-12}}</ref> ] is a safer candidate to replace use of diclofenac.<ref name="Swan2006">{{cite journal | author=Swan G, Naidoo V, Cuthbert R, Green RE, Pain DJ, Swarup D, Prakash V, Taggart M, Bekker L, Das D, Diekmann J, Diekmann M, Killian E, Meharg A, Patra RC, Saini M, Wolter K | title=Removing the threat of diclofenac to critically endangered Asian vultures | journal=PLoS Biol | year=2006 | pages=e66 | volume=4 | issue=3 | pmid=16435886 | doi=10.1371/journal.pbio.0040066 | pmc=1351921}}</ref> It is more expensive than diclofenac, but the price is coming down as more drug companies begin to manufacture it.<ref>Gill, V. BBC News December 9, 2009.</ref>
			Use of diclofenac for animals is controversial due to toxicity when eaten by scavenging birds that eat dead animals;<ref name="vulture1"/><ref name=Moreno2021>{{cite journal|vauthors=Moreno-Opo R, Carapeto R, Casimiro R, Rubio C, Muñoz B, Moreno I, Aymerich M|title=The veterinary use of diclofenac and vulture conservation in Spain: Updated evidence and socio-ecological implications|journal=The Science of the Total Environment|volume=796|issue=|page=148851|year=2021|pmid=34271379|doi=10.1016/j.scitotenv.2021.148851|bibcode=2021ScTEn.79648851M }}</ref> the medication has been banned for veterinary use in several countries.<!--Is a medical cite really necessary? This is surely a legal claim, albeit in a medical article. Possibly this EMA will suffice... {{medcn|date=February 2020}}--><ref name="vulture2"/><ref name="vulture3"/>
	"The loss of tens of millions of vultures over the last decade has had major ecological consequences across the Indian subcontinent that pose a potential threat to human health. In many places, populations of feral ]s (''Canis familiaris'') have increased sharply from the disappearance of '']'' vultures as the main scavenger of wild and domestic ] carcasses. Associated with the rise in dog numbers is an increased risk of ]"<ref name="Swan2006"/> and casualties of almost 50,000 people.<ref></ref> The Government of India cites one of those major consequences as a vulture species extinction.<ref name="PIB2005"/> A major shift in transfer of corpse pathogens from vultures to feral dogs and rats can lead to a disease pandemic causing millions of deaths in a crowded country like India; whereas vultures' digestive systems safely destroy many species of such pathogens.
			Use of diclofenac in animals has been reported to have led to a sharp decline in the ] population in the Indian subcontinent – a 95% decline by 2003<ref name="Oaks2004">{{cite journal | vauthors = Oaks JL, Gilbert M, Virani MZ, Watson RT, Meteyer CU, Rideout BA, Shivaprasad HL, Ahmed S, Chaudhry MJ, Arshad M, Mahmood S, Ali A, Khan AA | title = Diclofenac residues as the cause of vulture population decline in Pakistan | journal = Nature | volume = 427 | issue = 6975 | pages = 630–633 | date = February 2004 | pmid = 14745453 | doi = 10.1038/nature02317 | s2cid = 16146840 | bibcode = 2004Natur.427..630O }}</ref> and a 99.9% decline by 2008. The mechanism is presumed to be ];<ref>{{cite journal | vauthors = Swan GE, Cuthbert R, Quevedo M, Green RE, Pain DJ, Bartels P, Cunningham AA, Duncan N, Meharg AA, Oaks JL, Parry-Jones J, Shultz S, Taggart MA, Verdoorn G, Wolter K | title = Toxicity of diclofenac to Gyps vultures | journal = Biology Letters | volume = 2 | issue = 2 | pages = 279–282|year=2006 | pmid = 17148382 | pmc = 1618889 | doi = 10.1098/rsbl.2005.0425 }}</ref> however, toxicity may be due to direct inhibition of uric acid secretion in vultures.<ref name="pmid18727958">{{cite journal|vauthors=Naidoo V, Swan GE|title = Diclofenac toxicity in Gyps vulture is associated with decreased uric acid excretion and not renal portal vasoconstriction | journal = Comparative Biochemistry and Physiology. Toxicology & Pharmacology|volume=149|issue=3|pages=269–274|year=2009|pmid=18727958|doi=10.1016/j.cbpc.2008.07.014|hdl-access=free|hdl=2263/13907}}</ref> Vultures eat the carcasses of ] that have been administered veterinary diclofenac, and are poisoned by the accumulated chemical,<ref name="BBC3">{{cite news|title=Vet drug 'killing Asian vultures'|work=BBC News|date=28 February 2004|url=http://news.bbc.co.uk/2/hi/science/nature/3437583.stm |access-date=25 August 2010|archive-date=3 December 2013|archive-url=https://web.archive.org/web/20131203033409/http://news.bbc.co.uk/2/hi/science/nature/3437583.stm |url-status=live}}</ref> as vultures do not have a particular enzyme to break down diclofenac. At a meeting of the National Wildlife Board in March 2005, the Government of India announced it intended to phase out the veterinary use of diclofenac.<ref name="PIB2005">{{cite press release | publisher=Press Information Bureau, Government of India | date=16 May 2005 | url=http://pib.nic.in/release/release.asp?relid=9303 | title=Saving the Vultures from Extinction | access-date=12 May 2006 | archive-date=20 December 2005 | archive-url=https://web.archive.org/web/20051220213802/http://pib.nic.in/release/release.asp?relid=9303 | url-status=live }}</ref> ] is a safer alternative to replace use of diclofenac.<ref name="Swan2006">{{cite journal | vauthors = Swan G, Naidoo V, Cuthbert R, Green RE, Pain DJ, Swarup D, Prakash V, Taggart M, Bekker L, Das D, Diekmann J, Diekmann M, Killian E, Meharg A, Patra RC, Saini M, Wolter K | title = Removing the threat of diclofenac to critically endangered Asian vultures | journal = PLOS Biology|volume=4|issue=3| page=e66|year=2006 | pmid = 16435886 | pmc = 1351921 | doi = 10.1371/journal.pbio.0040066 | doi-access = free }}</ref> It is more expensive than diclofenac, but the cost is dropping{{when|date=February 2020}} as more pharmaceutical companies are beginning to manufacture it.{{citation needed|date=February 2020}}
	The resulting multiplication of feral dogs in India and Pakistan has caused a multiplication of ]s feeding on those dogs and invading urban areas looking for dogs to prey on, resulting in occasional attacks on human children.<ref>''Nature Shock'', UK ] television, Tuesday 7 Sept 2010,8 to 9 pm,</ref>
			]s have the same vulnerability to diclofenac as Old World vultures and are therefore at a similar risk from its effects.<ref>{{cite news|title=Eagles fall prey to vulture-killing chemical|vauthors=Phadnis M |work=Pune Mirror|date=28 May 2014|url=http://www.punemirror.in/pune/others/Eagles-fall-prey-to-vulture-killing-chemical/articleshow/35639257.cms|access-date=28 May 2014|archive-date=29 May 2014|archive-url=https://web.archive.org/web/20140529124248/http://www.punemirror.in/pune/others/Eagles-fall-prey-to-vulture-killing-chemical/articleshow/35639257.cms|url-status=live}}</ref> Diclofenac has been shown also to harm freshwater fish species such as rainbow trout.<ref>{{cite journal|vauthors=Schwaiger J, Ferling H, Mallow U, Wintermayr H, Negele RD|title = Toxic effects of the non-steroidal anti-inflammatory drug diclofenac. Part I: histopathological alterations and bioaccumulation in rainbow trout|journal=Aquatic Toxicology|volume=68|issue=2|pages=141–150|year=2004|pmid=15145224|doi=10.1016/j.aquatox.2004.03.014|bibcode = 2004AqTox..68..141S }}</ref><ref>{{cite journal|vauthors=Triebskorn R, Casper H, Heyd A, Eikemper R, Köhler HR, Schwaiger J | title = Toxic effects of the non-steroidal anti-inflammatory drug diclofenac. Part II: cytological effects in liver, kidney, gills and intestine of rainbow trout (Oncorhynchus mykiss)|journal=Aquatic Toxicology|volume=68|issue=2|pages=151–166|year=2004|pmid=15145225|doi=10.1016/j.aquatox.2004.03.015| bibcode = 2004AqTox..68..151T}}</ref><ref>{{cite journal|vauthors=Schwaiger J, Triebskorn R|title=Subletale Wirkungen von Arzneimitteln bei aquatischen Organismen|trans-title=Sublethal effects of drugs in aquatic organisms|language=de|journal=Texte|volume=29|issue=5|year=2005|pages=217–226|url=https://www.umweltbundesamt.de/sites/default/files/medien/publikation/long/2976.pdf}}</ref><ref name="pmid17216161">{{cite journal | vauthors = Triebskorn R, Casper H, Scheil V, Schwaiger J | title = Ultrastructural effects of pharmaceuticals (carbamazepine, clofibric acid, metoprolol, diclofenac) in rainbow trout (Oncorhynchus mykiss) and common carp (Cyprinus carpio) | journal = Analytical and Bioanalytical Chemistry | volume = 387 | issue = 4 | pages = 1405–1416|year=2007 | pmid = 17216161 | doi = 10.1007/s00216-006-1033-x | s2cid = 21170569 }}</ref> In contrast, ]s, such as the ], can tolerate at least 100 times the level of diclofenac that is lethal to '']'' species.<ref>{{cite journal | vauthors = Rattner BA, Whitehead MA, Gasper G, Meteyer CU, Link WA, Taggart MA, Meharg AA, Pattee OH, Pain DJ | title = Apparent tolerance of turkey vultures (Cathartes aura) to the non-steroidal anti-inflammatory drug diclofenac | journal = Environmental Toxicology and Chemistry | volume = 27 | issue = 11 | pages = 2341–2345|year=2008 | pmid = 18476752 | doi = 10.1897/08-123.1 | bibcode = 2008EnvTC..27.2341R | s2cid = 207267290 | url = http://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=1977&context=usgsstaffpub | access-date = 15 July 2019 | archive-date = 28 August 2021 | archive-url = https://web.archive.org/web/20210828062139/https://digitalcommons.unl.edu/cgi/viewcontent.cgi?referer=&httpsredir=1&article=1977&context=usgsstaffpub | url-status = live }}</ref>
	The loss of vultures has had a social impact on the Indian ] Parsi community, who traditionally use vultures to dispose of human corpses in ], but are now compelled to seek alternate methods of disposal.<ref name="Swan2006"/>
			"The loss of tens of millions of vultures over the last decade has had major ecological consequences across the Indian subcontinent that pose a potential threat to human health. In many places, populations of ] have increased sharply from the disappearance of '']'' vultures as the main scavenger of wild and domestic ] carcasses. Associated with the rise in dog numbers is an increased risk of ]"<ref name="Swan2006"/> and casualties of almost 50,000 people.<ref>{{cite news |vauthors=Walker M |title=Rabies tragedy follows loss of India's vultures |url=https://www.newscientist.com/article/mg19926684-400-rabies-tragedy-follows-loss-of-indias-vultures/ |work=New Scientist |date=6 August 2008 |access-date=23 April 2023 |archive-date=23 April 2023 |archive-url=https://web.archive.org/web/20230423164017/https://www.newscientist.com/article/mg19926684-400-rabies-tragedy-follows-loss-of-indias-vultures/ |url-status=live }}</ref> The Government of India cites this as one of the major consequences of a vulture species extinction.<ref name="PIB2005"/> A major shift in the transfer of corpse pathogens from vultures to feral dogs and rats could lead to a disease pandemic, causing millions of deaths in a crowded country like India, whereas vultures' digestive systems safely destroy many species of such pathogens. Vultures are long-lived and slow to breed. They start breeding only at the age of six and only 50% of their young survive. Even if the government ban is fully implemented, it will take many years to revive the vulture population.<ref name="The Indian Express">{{cite news |title='Decline in vulture population has given rise to diseases': Dr. Vibhu Prakash|url=https://indianexpress.com/article/lifestyle/health/decline-in-vulture-population-has-given-rise-to-diseases-dr-vibhu-prakash-3001298/|date=29 August 2016|access-date=12 December 2018|work=The Indian Express|vauthors=Choudhary S|archive-date=15 December 2018|archive-url=https://web.archive.org/web/20181215222409/https://indianexpress.com/article/lifestyle/health/decline-in-vulture-population-has-given-rise-to-diseases-dr-vibhu-prakash-3001298/|url-status=live}}</ref>
	Diclofenac has been shown also to harm freshwater fish species such as rainbow trout.<ref>Schwaiger et al. (2004). Aquat. Toxicol. 68(2): 141-150</ref><ref>Triebskorn et al. (2004). Aquat. Toxicol. 68(2): 151-166</ref><ref>Schwaiger & Triebskorn (2005). UBA-Berichte 29/05: 217-226</ref><ref>
	Triebskorn et al. (2007). Analyt. Bioanalyt. Chem. 387(4):1405–1416</ref>
			The loss of vultures has had a social impact on the Indian ] ], who traditionally use vultures to ] in ], but are now compelled to seek alternative methods of disposal.<ref name=Swan2006/>
	==Formulations==
	Pennsaid is a minimally systemic prescription topical lotion formulation of 1.5% w/w diclofenac sodium, which is approved in the US, Canada and other countries for osteoarthritis of the knee.
			Despite the vulture crisis, diclofenac remains available in other countries including many in Europe.<ref name="European Parliament">{{cite web|title=E-010588/2015: answer given by Mr Andriukaitis on behalf of the Commission|url=http://www.europarl.europa.eu/sides/getAllAnswers.do?reference=E-2015-010588&language=EN|website=European Parliament|access-date=18 February 2024|archive-date=13 May 2016|archive-url=https://web.archive.org/web/20160513232457/http://www.europarl.europa.eu/sides/getAllAnswers.do?reference=E-2015-010588&language=EN|url-status=live}}</ref> It was controversially approved for veterinary use in Spain in 2013 and continues to be available, despite Spain being home to around 90% of the European vulture population and an independent simulation showing that the drug could reduce the population of vultures by 1–8% annually. ] presented simulations suggesting that the number of deaths would be quite small.<ref name=Becker2016/><ref>{{cite web |url=http://www.birdlife.org/europe-and-central-asia/news/vulture-killing-drug-now-available-eu-market |title=Vulture killing drug now available on EU market|work=International BirdLife|access-date=18 February 2024|archive-date=24 April 2014|archive-url=https://web.archive.org/web/20140424125532/http://www.birdlife.org/europe-and-central-asia/news/vulture-killing-drug-now-available-eu-market|url-status=dead}}</ref> A paper published in 2021 identified the first authenticated death of a vulture from diclofenac in Spain, a ].<ref name=Moreno2021/><ref>{{cite web |url= https://www.4vultures.org/first-evidence-of-a-vulture-killed-by-veterinary-diclofenac-in-spain|title=First evidence of a vulture killed by veterinary diclofenac in Spain – will the Spanish government and the EU act after this smoking gun?| work = Vulture Conservation Foundation |date=7 April 2021|access-date=8 April 2021|archive-date=8 April 2021|archive-url= https://web.archive.org/web/20210408082619/https://www.4vultures.org/first-evidence-of-a-vulture-killed-by-veterinary-diclofenac-in-spain/|url-status=dead}}</ref>
	Flector Patch is a minimally systemic topical patch formulation of diclofenac. It is indicated for acute pain due to minor sprains, strains, and contusions. The patch has been approved in many other countries outside the U.S.A under different brand names.
			Diclofenac is on the European Union's watch list because it pollutes the ]. When the substance enters ], it has an environmental impact and is considered more difficult to remove in ] than, for example, ].<ref>{{cite web |vauthors=Fernholm A |date=4 March 2010 |title=Val av smärtstillande påverkar miljön |url=https://www.lakemedelsvarlden.se/val-av-smartstillande-paverkar-miljon/ |access-date=15 March 2023 |website=LäkemedelsVärlden |language=sv-SE |archive-date=15 August 2022 |archive-url=https://web.archive.org/web/20220815220610/https://www.lakemedelsvarlden.se/val-av-smartstillande-paverkar-miljon/ |url-status=live }}</ref> Harmful residues have been found in ] and fish, among others, where it has been found to cause damage to internal organs such as the ], kidneys and liver.<ref>{{cite web |date=10 September 2014 |title=Itämeren kalat häiriintyvät lääkeaineista – Teollisuudella paineita kehittää eettisempiä pillereitä |url=https://yle.fi/a/3-7455669 |access-date=15 March 2023 |website=Yle Uutiset |language=fi |archive-date=15 March 2023 |archive-url=https://web.archive.org/web/20230315175230/https://yle.fi/a/3-7455669 |url-status=live }}</ref>
	Voltaren and Voltarol contain the sodium salt of diclofenac. In the ] Voltarol can be supplied with either the sodium salt or the potassium salt, while Cataflam in some other countries is the potassium salt only.
			==Veterinary use==
	Diclofenac is available in stomach acid resistant formulations (25 and 50&nbsp;]), fast-disintegrating oral formulations (25 and 50&nbsp;mg), powder for oral solution (50&nbsp;mg), slow- and controlled-release forms (75, 100 or 150&nbsp;mg), suppositories (50 and 100&nbsp;mg), and injectable forms (50 and 75&nbsp;mg).
			Diclofenac is used for livestock; such use was responsible for the ], during which in a few years 95% of the country's vulture population was killed, and in many countries, agricultural use is now forbidden.<ref name=vulture1>{{cite journal | vauthors = Cuthbert RJ, Taggart MA, Prakash V, Chakraborty SS, Deori P, Galligan T, Kulkarni M, Ranade S, Saini M, Sharma AK, Shringarpure R, Green RE | title = Avian scavengers and the threat from veterinary pharmaceuticals | journal = Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences | volume = 369 | issue = 1656 | page = 20130574 | date = November 2014 | pmid = 25405963 | pmc = 4213586 | doi = 10.1098/rstb.2013.0574 }}</ref><ref name=Moreno2021/><ref name=vulture2>{{citation|author1=((European Medicines Agency))|author2=((Committee for Medicinal Products for Veterinary Use))|title=Opinion of the Committee pursuant to Article 30(3) of Regulation (EC) No 726/2004 on the risk to vultures and other necrophagous bird populations in the European Union in connection with the use of veterinary medicinal products containing the substance diclofenac|url=https://www.ema.europa.eu/en/documents/other/opinion-committee-medicinal-products-veterinary-use-pursuant-article-303-regulation-ec-no-726/2004-risk-vultures-other-necrophagous-bird-populations-european-union-conne_en.pdf|id=EMA/CVMP/761582/2014|access-date=16 April 2022|archive-date=7 July 2022|archive-url=https://web.archive.org/web/20220707033019/https://www.ema.europa.eu/en/documents/other/opinion-committee-medicinal-products-veterinary-use-pursuant-article-303-regulation-ec-no-726/2004-risk-vultures-other-necrophagous-bird-populations-european-union-conne_en.pdf|url-status=live}}</ref><ref name=vulture3>{{cite news|vauthors=McKie R|title=Rare European vultures being poisoned by livestock drug|url=https://www.theguardian.com/environment/2021/apr/11/rare-european-vultures-being-poisoned-by-livestock-drug|access-date=16 April 2022 |work=]|date=11 April 2021|quote=...diclofenac has already been banned in India, Pakistan, Nepal and Bangladesh|archive-date=16 April 2022|archive-url=https://web.archive.org/web/20220416025605/https://www.theguardian.com/environment/2021/apr/11/rare-european-vultures-being-poisoned-by-livestock-drug|url-status=live}}</ref>
			Diclofenac is approved as a veterinary medication in some countries<ref name=vulture1/><ref name=Moreno2021/><ref name=vulture2/><ref name=vulture3/> for the treatment of pets as well as in livestock. In some species of birds, diclofenac causes accumulation of ] crystals in internal organs—especially the liver and kidneys—resulting in ], as well as cellular damage and ].<ref name=Hussain2008>{{cite journal|vauthors=Hussain I, Khan MZ, Khan A, Javed I, Saleemi MK|title=Toxicological effects of diclofenac in four avian species|journal=Avian Pathology|volume=37|issue=3|pages=315–321|year=2008|pmid=18568659|doi=10.1080/03079450802056439|s2cid=12985124|doi-access=free}}</ref> In South Asia in the 2000s, ] after feeding on carcasses of livestock that had been treated with diclofenac.<ref name=Becker2016>{{cite journal|vauthors=Becker R|title=Cattle drug threatens thousands of vultures|journal=Nature|year=2016|doi=10.1038/nature.2016.19839|s2cid=75173071 }}</ref>
	Diclofenac is also available ] (OTC) in some countries: 12.5&nbsp;mg diclofenac as potassium salt in ], ] ("Voltaren dolo"), ] (since October 2008 as "Voltarol Pain-eze"), and preparations containing 25&nbsp;mg diclofenac as the potassium salt in ], ], ], ("Voltaren Rapid"), and ] ("Voltaren T" and "Diclofenac T"). Diclofenac as potassium salt can be found throughout the Middle East in 25&nbsp;mg and 50&nbsp;mg doses ("Cataflam").
	Solaraze (3% diclofenac sodium gel) is topically applied, twice a day for three months, to manage the skin condition known as actinic or solar keratosis.
	Parazone-DP is combination of Diclofenac potassium and Paracetamol, Mfg. and supplied by Ozone pharmaceuticals and chemicals, Gujarat,India
	==Trade names==
	Trade names include:
	{{Div col|colwidth=20em}}
	*Anuva
	*Abitren
	*Arthrotec (combination with ])
	*Artifen (Pakistan Abbott Laboratories LTD)
	*Berifen
	*Betaren
	*Bufenac Forte
	*Cambia
	*Cataflam
	*Catafast
	*Clafen
	*Clofast
	*Clonac
	*Dedolor
	*Deflamat
	*Deflox
	*Diclac
	*Dicloberl
	*Diclofenac
	*Diclofenac-Asteria (USA and Korea)
	*Diclofenaco Normon (Spain)
	*Diclofenacum
	*Dicloflex
	*Diclogem
	*Diclogesic (Jordan and Romania)
	*Diclohexal
	*Diclomax
	*Diclowin Plus (India)
	*Diclon
	*Diclopar (Tanzania)
	*Diclotab (Laos)
	*Diklofenak T Actavis (Sweden)
	*Difen
	*Difenac (Venezuela)
	*Difene
	*Dioxaflex (Latin America, Central America)
	*Disflam K (diclofenac potassium, Central America)
	*Dolex
	*Dyloject
	*Feloran
	*Flamrase
	*Flector Patch
	*Flogozan (Mexico)
	*Klodifen
	*Modifenac
	*Morbidic (India)
	*Motifene
	*Naklofen
	*Oflam
	*Olfen
	*Ortofen
	*Panamor
	*Parazone-DP (combination of Paracetamol & Diclofenac Potassium
	*Pennsaid
	*Pritaren
	*Rapten-K
	*Rhumalgan
	*Rufenal
	*Safeguard (combination with ])
	*Solaraze
	*Seradic (India)
	*Topac
	*Uno
	*Veltex CR (South Africa)
	*Vetagesic
	*Voldic
	*Volini (India)
	*Volfenac (Thailand)
	*Voltaflam(India)
	*Voltaren
	*Voltarol
	*Voltfast
	*Voren (Taiwan)
	*Voltral (Pakistan)
	*Votrex
	*Vostar
	*Votalin (China)
	*Voveran
	*Vurdon
	*Zipsor
	*Zolterol
	{{Div col end}}
	==References==		==References==
	{{Reflist|2}}		{{Reflist}}
	==External links==		==External links==
	{{Commons category}}		{{Commons category}}
	*
			{{Other dermatological preparations}}
	{{NSAIDs}}
	{{Anti-inflammatory and antirheumatic products}}		{{Anti-inflammatory and antirheumatic products}}
	{{Topical products for joint and muscular pain}}		{{Topical products for joint and muscular pain}}
	{{Analgesics}}		{{Analgesics}}
			{{Prostanoid signaling modulators}}
			{{Portal bar | Medicine}}
			{{Authority control}}
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