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Revision as of 11:25, 18 January 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,081 edits Script assisted update of identifiers from ChemSpider, CommonChemistry and FDA for the Chem/Drugbox validation project - Updated: ChEMBL.← Previous edit		Latest revision as of 19:41, 14 January 2025 edit undoRickyCourtney (talk | contribs)Extended confirmed users, Pending changes reviewers47,033 edits CleanupTag: Visual edit
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			{{Short description|Nonsteroidal anti-inflammatory drug (NSAID; analgesic)}}
	{{drugbox
			{{Use dmy dates|date=February 2024}}
	| verifiedrevid = 400417780
			{{Drugbox
	| drug_name = Ketorolac
			| Verifiedfields = changed
	| IUPAC_name =(±)-5-benzoyl-2,3-dihydro-<BR>1<u>H</u>-pyrrolizine-1-carboxylic acid,<BR>2-amino-2-(hydroxymethyl)-1,3-propanediol
			| Watchedfields = changed
	| ChEMBL = 469
			| verifiedrevid = 461740251
	| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
			| image = Ketorolac.svg
	| StdInChI = 1S/C15H13NO3/c17-14(10-4-2-1-3-5-10)13-7-6-12-11(15(18)19)8-9-16(12)13/h1-7,11H,8-9H2,(H,18,19)
			| image_class = skin-invert-image
	| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
			| alt =
	| StdInChIKey = OZWKMVRBQXNZKK-UHFFFAOYSA-N
			| chirality = ]
	| smiles = O=C(c1ccc2n1CCC2C(=O)O)c3ccccc3
			| image2 = Ketorolac ball-and-stick.png
	| CAS_number =74103-06-3
			| image_class2 = bg-transparent
	| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
			| alt2 =
	| ChemSpiderID = 3694
	| ATC_code =M01AB15
			<!-- Clinical data -->
	| ATC_prefix=M01
			| tradename = Toradol, Acular, Sprix, others
	| ATC_suffix=AB15
			| Drugs.com = {{drugs.com|monograph|ketorolac-tromethamine}}
	| image=Ketorolac.png
			| MedlinePlus = a693001
	| imagename = 1 : 1 mixture (racemate)
			| DailyMedID = Ketorolac
	| width = 250px
			| pregnancy_AU = C
	| PubChem=3826
			| pregnancy_category =
	| DrugBank=DB00465
			| routes_of_administration = ], ], ], ], ], nasal spray
	| KEGG = D08104
	| C=15 | H=13 | N=1 | O=3		| ATC_prefix = M01
			| ATC_suffix = AB15
	| molecular_weight =255.27 g/mol
			| ATC_supplemental = {{ATC|S01|BC05}}
	| bioavailability = 100% (All routes)
	| metabolism = ]
			| legal_AU = S4
	| elimination_half-life =3.5-9.2 ]s, young adults;<br>4.7-8.6 hrs, elderly (mean age 72)
			| legal_AU_comment = <ref name="Therapeutic Goods Administration (TGA)-2022">{{cite web | title=Prescription medicines: registration of new generic medicines and biosimilar medicines, 2017 | website=Therapeutic Goods Administration (TGA) | date=21 June 2022 | url=https://www.tga.gov.au/resources/publication/publications/prescription-medicines-registration-new-generic-medicines-and-biosimilar-medicines-2017 | access-date=30 March 2024 | archive-date=6 July 2023 | archive-url=https://web.archive.org/web/20230706023149/https://www.tga.gov.au/resources/publication/publications/prescription-medicines-registration-new-generic-medicines-and-biosimilar-medicines-2017 | url-status=live }}</ref>
	| excretion = ]:91.4% (mean)<br>]:6.1% (mean)
			| legal_CA = Rx-only
	| pregnancy_AU = C
			| legal_US = Rx-only
	| pregnancy_US = C
			| legal_UK = ]<ref>{{Cite web |title=Ketorolac Trometamol 30 mg/ml solution for injection - Summary of Product Characteristics (SmPC) - (emc) |url=https://www.medicines.org.uk/emc/product/11547/smpc |access-date=2024-10-26 |website=www.medicines.org.uk}}</ref>
	| pregnancy_category =
	| legal_status = Rx-only		| legal_status =
	| routes_of_administration = oral, ], ]
			<!-- Pharmacokinetic data -->
			| bioavailability = 80–100% (oral)
			100% IV/IM
			| metabolism = ]
			| elimination_half-life = 3.5 h to 9.2 h, young adults;<br />4.7 h to 8.6 h, elderly (mean age 72)
			| excretion = ]: 91.4% (mean)<br />]: 6.1% (mean)
			<!-- Identifiers -->
			| CAS_number_Ref = {{cascite|changed|??}}
			| CAS_number = 74103-06-3
			| PubChem = 3826
			| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
			| DrugBank = DB00465
			| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
			| ChemSpiderID = 3694
			| ChEBI_Ref = {{ebicite|changed|EBI}}
			| ChEBI = 6129
			| UNII_Ref = {{fdacite|correct|FDA}}
			| UNII = YZI5105V0L
			| KEGG_Ref = {{keggcite|correct|kegg}}
			| KEGG = D08104
			| ChEMBL_Ref = {{ebicite|correct|EBI}}
			| ChEMBL = 469
			| PDB_ligand = KTR
			| synonyms = Ketorolac tromethamine
			<!-- Chemical data -->
			| IUPAC_name = (±)-5-benzoyl-2,3-dihydro-1''H''-pyrrolizine-1-carboxylic acid
			| C = 15
			| H = 13
			| N = 1
			| O = 3
			| smiles = O=C(c1ccc2n1CCC2C(=O)O)c3ccccc3
			| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
			| StdInChI = 1S/C15H13NO3/c17-14(10-4-2-1-3-5-10)13-7-6-12-11(15(18)19)8-9-16(12)13/h1-7,11H,8-9H2,(H,18,19)
			| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
			| StdInChIKey = OZWKMVRBQXNZKK-UHFFFAOYSA-N
	}}		}}
			<!-- Definition and medical uses -->
			'''Ketorolac''', sold under the brand name '''Toradol''', '''Acular''' and '''Sprix''', among others, is a ] (NSAID) used to treat ].<ref name="researchgate.net">{{cite journal |vauthors=Mallinson T |title=A review of ketorolac as a prehospital analgesic |journal=Journal of Paramedic Practice |date=2017 |volume=9 |issue=12 |pages=522–526 |url=https://www.researchgate.net/publication/321640488 |access-date=2 June 2018 |doi=10.12968/jpar.2017.9.12.522 |doi-access= |archive-date=5 June 2018 |archive-url=https://web.archive.org/web/20180605033254/https://www.researchgate.net/publication/321640488_A_review_of_ketorolac_as_a_prehospital_analgesic |url-status=live }}</ref><ref name="AHFS2019">{{cite web |title=Ketorolac Tromethamine Monograph for Professionals |url=https://www.drugs.com/monograph/ketorolac-tromethamine.html |url-status=live |archive-url=https://web.archive.org/web/20190408214139/https://www.drugs.com/monograph/ketorolac-tromethamine.html |archive-date=8 April 2019 |access-date=13 April 2019 |website=Drugs.com |publisher=American Society of Health-System Pharmacists}}</ref> Specifically it is recommended for moderate to severe pain.<ref name=BNF76/> Recommended duration of treatment is less than six days,<ref name=AHFS2019/> and in Switzerland not more than seven days (parenterally two days).<ref name="Kompendium-2022">{{Cite web |url=https://compendium.ch/product/30303-tora-dol-inj-los-30-mg-ml/mpro |title=TORA-DOL Inj Lös 30 mg/ml |date=1 March 2022 |website=Kompendium |language=de |quote=Die Behandlung mit Ampullen ist bei akuten und schweren Schmerzzuständen angezeigt und sollte nicht länger als 2 Tage dauern. |access-date=24 March 2023 |archive-date=7 June 2023 |archive-url=https://web.archive.org/web/20230607181444/https://compendium.ch/product/30303-tora-dol-inj-los-30-mg-ml/mpro |url-status=live }}</ref> It is used by mouth, by nose, by ] or ], and as eye drops.<ref name=AHFS2019/><ref name=BNF76>{{cite book|title=British national formulary: BNF 76|date=2018|publisher=Pharmaceutical Press|isbn=9780857113382|pages=1144, 1302–1303|edition=76}}</ref> Effects begin within an hour and last for up to eight hours.<ref name=AHFS2019/> Ketorolac also has ] (fever-reducing) properties.<ref name="pmid9010653">{{cite journal |vauthors=Gillis JC, Brogden RN |title=Ketorolac. A reappraisal of its pharmacodynamic and pharmacokinetic properties and therapeutic use in pain management |journal=Drugs |volume=53 |issue=1 |pages=139–88 |date=January 1997 |pmid=9010653 |doi=10.2165/00003495-199753010-00012 |url=}}</ref><ref name="pmid38333494">{{cite journal |vauthors=Mehmood KT, Al-Baldawi S, Zúñiga Salazar G, Zúñiga D, Balasubramanian S |title=Antipyretic Use in Noncritically Ill Patients With Fever: A Review |journal=Cureus |volume=16 |issue=1 |pages=e51943 |date=January 2024 |pmid=38333494 |pmc=10851038 |doi=10.7759/cureus.51943 |doi-access=free |url=}}</ref>
			<!-- Side effects and mechanisms -->
	'''Ketorolac''' or '''ketorolac tromethamine''' (marketed under the trademarks '''Toradol''' and '''Acular''' in the US, where ] have also been approved, and various other brand names around the world) is a ] (NSAID) in the family of ] ] ], often used as an ], ] (] reducer), and anti-]. Ketorolac acts by ] the ] of ]. Ketorolac in its oral (] or ]) and ] (]) preparations is a ] of both (''S'')-(−)-ketorolac, the active ], and (''R'')-(+)-ketorolac. An ophthalmic (i.e., ]) solution of ketorolac is available and is used to treat eye pain and to relieve the itchiness and burning of seasonal ].The FDA has approved an intranasal formulation of ketorolac tromethamine (Sprix Nasal Spray) for short-term management of moderate to moderately severe pain requiring analgesia at the opioid level.
			Common side effects include sleepiness, dizziness, abdominal pain, swelling, and nausea.<ref name=AHFS2019/> Serious side effects may include ], ], ], ], ], and ].<ref name=AHFS2019/> Use is not recommended during the last part of ] or during ].<ref name=AHFS2019/> Ketorolac works by blocking ] 1 and 2 (COX1 and COX2), thereby decreasing production of ]s.<ref name=AHFS2019/><ref name=Daily2019>{{cite web |title=DailyMed - ketorolac tromethamine tablet, film coated |url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2837a082-3a34-6f81-5e43-45a70295686b |website=dailymed.nlm.nih.gov |access-date=14 April 2019 |archive-date=13 August 2020 |archive-url=https://web.archive.org/web/20200813001442/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2837a082-3a34-6f81-5e43-45a70295686b |url-status=live }}</ref>
			<!-- History and culture -->
	==Chemistry==
			Ketorolac was patented in 1976 and approved for medical use in 1989. It is available as a ]. In 2022, it was the 223rd most commonly prescribed medication in the United States, with more than 1{{nbsp}}million prescriptions.
	Although its name does not suggest similarity with propionic acid derivatives (including ], ], ], ], etc.), ketorolac is an ] of ketoprofen. More precisely, it is a dihydropyrrolizine carboxylic acid derivative structurally related to ].<ref>Martindale, The Complete Drug Reference,35th Edition, 2007</ref>.
			Due to a series of deaths due to gastrointestinal bleeding and kidney failure, ketorolac as a pain medication was removed from the German market in 1993.<ref name="Abverkauf von Ketorolac-1993">{{Cite web |url=https://www.arznei-telegramm.de/html/1993_08/9308084_02.html |title=Abverkauf von Ketorolac (TORATEX) gestoppt |year=1993 |trans-title=Sale of Ketorolac (TORATEX) stopped |access-date=24 March 2023 |archive-date=3 October 2023 |archive-url=https://web.archive.org/web/20231003042337/https://www.arznei-telegramm.de/html/1993_08/9308084_02.html |url-status=live }}</ref> When ketorolac was introduced into Germany, it was often used as an ] replacement in pain therapy because its side effects were perceived as much less severe, it did not produce any ], and a dose was effective for 7–8 hours compared to morphine with 3–4 hours. As a very potent prostaglandin inhibitor, ketorolac diminishes the kidney's own defenses against ]-related effects, e.g. during blood loss or high endogenous ] levels.<ref name="Arznei-Telegramm-1993">{{Cite web |url=https://www.arznei-telegramm.de/html/1993_06/9306061_05.html |title=Warnhinweis: Wie lange noch Analgetikum Ketorolac (Toratex)? |publisher=Arznei-Telegramm |year=1993 |language=de |trans-title=Warning notice: How long anymore analgesic Ketorolac (Toratex)? |access-date=24 March 2023 |archive-date=24 March 2023 |archive-url=https://web.archive.org/web/20230324114422/https://www.arznei-telegramm.de/html/1993_06/9306061_05.html |url-status=live }}</ref>
	NSAIDs (non-steroidal anti-inflammatory drug) are not recommended for use with other NSAIDs because of the potential for additive side effects.
			==Medical uses==
	The protein-binding effect of most non-] NSAIDs are inhibited by the presence of aspirin in the blood.
			]
			Ketorolac is used for short-term management of moderate to severe pain.<ref name="researchgate.net"/> It is usually not prescribed for longer than five days,<ref name=Vallertand>{{cite book | vauthors = Vallerand AH |publisher= F.A. Davis Company |location= Philadelphia |year= 2017 |title= Davis's Drug Guide for Nurses|page=730 | isbn = 9780803657052}}</ref><ref name=PDR/><ref name=AHFS>{{cite web |title= Ketorolac-tromethamine |url= https://www.drugs.com/monograph/ketorolac-tromethamine.html |work= The American Society of Health-System Pharmacists |access-date= 3 April 2011 |archive-date= 8 April 2019 |archive-url= https://web.archive.org/web/20190408214139/https://www.drugs.com/monograph/ketorolac-tromethamine.html |url-status= live }}</ref><ref name = "Henry_2016">{{cite book | vauthors = Henry N | title = RN pharmacology for nursing: review module | publisher = Assessment Technologies Institute | location = Overland Park, KS | year = 2016 | isbn = 978-1-56533-573-8 }}</ref>{{rp|291}} due to its potential to cause kidney damage.<ref name = "Henry_2016" />{{rp|280}}
	==Mechanism of action==
	The primary ] responsible for ketorolac's anti-inflammatory, antipyretic and analgesic effects is the inhibition of prostaglandin synthesis by competitive blocking of the ] ] (COX). Like most NSAIDs, ketorolac is a non-selective COX inhibitor.
			Ketorolac is effective when administered with ] (acetaminophen) to control pain in newborns because it does not depress ] as do ]s.<ref name="pmid28232869">{{cite journal | vauthors = Martin LD, Jimenez N, Lynn AM | title = A review of perioperative anesthesia and analgesia for infants: updates and trends to watch | journal = F1000Research | volume = 6 | pages = 120 | year = 2017 | pmid = 28232869 | pmc = 5302152 | doi = 10.12688/f1000research.10272.1 | doi-access = free }}</ref> Ketorolac is also an adjuvant to opioid medications and improves pain relief. It is also used to treat ].<ref name = "Henry_2016" />{{rp|291}} Ketorolac is used to treat idiopathic pericarditis, where it reduces inflammation.<ref name="SchwierTran2016">{{cite journal | vauthors = Schwier N, Tran N | title = Non-Steroidal Anti-Inflammatory Drugs and Aspirin Therapy for the Treatment of Acute and Recurrent Idiopathic Pericarditis | journal = Pharmaceuticals | volume = 9 | issue = 2 | pages = 17 | date = March 2016 | pmid = 27023565 | pmc = 4932535 | doi = 10.3390/ph9020017 | doi-access = free }}</ref>
	==Indications==
	Ketorolac is ] for short-term management of moderate to severe postoperative pain. Concerns about the high incidence of reported side effects led to restriction in its dosage and maximum duration of use. In the UK, treatment should be initiated only in hospital. Maximum duration of treatment should not exceed 5 days for tablets (per package insert), or 2 days for continuous daily dosing with intravenous or intramuscular formulations<ref>MHRA Drug Safety Update October 2007, Volume 1, Issue 3, pp 3-4</ref>. The ophthalmic formulation can be used instead of steroidal anti inflammatories in cases where a raised intraocular pressure (]) is to be avoided.
			Ketorolac also has ] (fever-reducing) properties.<ref name="pmid9010653"/><ref name="pmid38333494"/>
	==Contraindications==
	Ketorolac is ] in patients with a previously demonstrated ] to ketorolac, and in patients with the complete or partial ] of ], ], ] reactivity or other allergic manifestations to aspirin or other non-]al anti-inflammatory drugs (due to possibility of severe ]). As with all NSAIDs, ketorolac should be avoided in patients with renal (]) dysfunction. (Prostaglandins are needed to dilate the ]; NSAIDs effectively reverse this.) The patients at highest risk, especially in the elderly, are those with ] imbalances or with compromised renal function (e.g., ], ] use, ], ], and ]).
			For systemic use, ketorolac can be administered ], ], by intramuscular injection, intravenously, and by ].<ref name=Vallertand/> Usually, it is initially administered by intramuscular injection or intravenously,<ref name="researchgate.net"/> with oral therapy used as a continuation after the initial IM or IV dose.<ref name=Vallertand/><ref name="pmid28232869"/>
	==Adverse effects==
	Concerns over the high incidence of reported side effects with ketorolac trometamol has led to its withdrawal (apart for the ophthalmic formulation) in several countries, while in others its permitted dosage and maximum duration of treatment have been reduced. From 1990 to 1993, 97 reactions with a fatal outcome were reported worldwide<ref>Committee on the Safety of Medicines, Medicines Control Agency: Ketorolac: new restrictions on dose and duration of treatment. ''Current Problems in Pharmacovigilance:'' June 1993; '''Volume 19''' (pages 5-8)</ref>. A post-marketing surveillance study<ref>Strom BL ''et al.'' Parenteral Ketorolac and risk of gastrointestinal and operative site bleeding: a postmarketing surveillance study ''JAMA'' 1996; '''275''':376-82</ref> indicated a dose-response relationship with average daily dose for both gastrointestinal bleeding and operative site bleeding, and an association between gastrointestinal bleeding and therapy for more than five days. Allergic reactions (anaphylactoid reactions, asthma, bronchospasm, Stevens Johnson syndrome, Lyell syndrome) have been reported. Fluid retention and edema have been reported with the use of ketorolac and it should therefore be used with caution in patients with cardiac decompensation, hypertension or similar conditions. When this ophthalmic formulation is instilled into the eye it can lead to an unpleasant short term burning pain for 4–5 seconds. Other adverse effects are similar to the ones associated with other NSAIDs. ''See inset "Ketorolac adverse effects."''
			Ketorolac is also used as an ]. It can be given during eye surgery to help with pain,<ref name="Saenz-de-ViteriGonzalez-Salinas2016">{{cite journal | vauthors = Gonzalez-Salinas R, Guarnieri A, Guirao Navarro MC, Saenz-de-Viteri M | title = Patient considerations in cataract surgery - the role of combined therapy using phenylephrine and ketorolac | journal = Patient Preference and Adherence | volume = 10 | pages = 1795–1801 | year = 2016 | pmid = 27695298 | pmc = 5029911 | doi = 10.2147/PPA.S90468 | doi-access = free }}</ref> and is effective in treating ocular itching.<ref name=Karch>{{cite book | vauthors = Karch A |page = 272| title = Focus on nursing pharmacology | publisher = Wolters Kluwer | location = Philadelphia | year = 2017 | isbn = 9781496318213 }}</ref> There is not enough evidence to decide that non-steroidal anti-inflammatory drugs help in preventing cystoid macular edema.<ref name="LimLim2016">{{cite journal | vauthors = Lim BX, Lim CH, Lim DK, Evans JR, Bunce C, Wormald R | title = Prophylactic non-steroidal anti-inflammatory drugs for the prevention of macular oedema after cataract surgery | journal = The Cochrane Database of Systematic Reviews | volume = 2016 | pages = CD006683 | date = November 2016 | issue = 11 | pmid = 27801522 | pmc = 6464900 | doi = 10.1002/14651858.CD006683.pub3 | url = http://discovery.ucl.ac.uk/1529414/ | access-date = 22 November 2018 | archive-date = 28 August 2021 | archive-url = https://web.archive.org/web/20210828134945/https://discovery.ucl.ac.uk/id/eprint/1529414/ | url-status = live }}</ref><ref name="pmid36520144">{{cite journal |vauthors=Wingert AM, Liu SH, Lin JC, Sridhar J |date=December 2022 |title=Non-steroidal anti-inflammatory agents for treating cystoid macular oedema following cataract surgery |journal=The Cochrane Database of Systematic Reviews |volume=2022 |issue= 12|pages= CD004239|doi=10.1002/14651858.CD004239.pub4 |pmid=36520144|pmc=9754896 }}</ref> Ketorolac eye drops have also been used to manage pain from ]s.<ref name="pmid28516471">{{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 | display-authors = 6 | title = Topical non-steroidal anti-inflammatory drugs for analgesia in traumatic corneal abrasions | journal = The Cochrane Database of Systematic Reviews | volume = 2017 | pages = CD009781 | date = May 2017 | issue = 5 | pmid = 28516471 | pmc = 6481688 | doi = 10.1002/14651858.CD009781.pub2 }}</ref>
	{| border="1" cellpadding="3" cellspacing="0" width="350px" align="right" style="border-collapse: collapse; margin: 0 0 0 0.5em"
	!colspan="2"|Ketorolac adverse effects
	|-
	!width=100|Body system
	!width=250|Effects
	|-
	! General
	| ]. Less frequently, ] reactions (such as ], ], ] edema, ] edema, ]), ], ], or ]. Very infrequently, ].
	|-
	! ]
	| ]. Less frequently, ], ], or ] (syncope).
	|-
	! ]
	| ] or ]. Less frequently, ], ], ]-] ], ], or ].
	|-
	! ]
	| ], ], gastrointestinal ], ], ], ], gastrointestinal fullness, ]ing or ]. Less frequently, ]ation, gastrointestinal ], gastrointestinal perforation, ], ] bleeding, ], ], ], or increased ]. Very infrequently, ].
	|-
	! ] and ]
	| ]. Less frequently, postoperative wound hemorrhage, ], ], or ]. Very infrequently, ] or ].
	|-
	! ]
	| ], ], ], ], ] site pain. Less frequently ]s, ], ], abnormal ], ], or ]. Very infrequently, ], ], ], inability to concentrate, ], excessive thirst, dry mouth, abnormal thinking, ], or ].
	|-
	! ]
	| Less frequently, ], ] and ] ]. Very infrequently, ] or ].
	|-
	! ]
	| Less frequently, acute ]. Very infrequently ] or increased ] frequency.
	|}
			During treatment with ketorolac, clinicians monitor for the manifestation of adverse effects. Lab tests, such as ], bleeding time, ], ] and electrolyte levels are often used and help to identify potential complications.<ref name=Vallertand/><ref name=PDR>{{cite book | title = Physician's Desk Reference 2017 | pages = S–474–5|publisher = PDR, LLC| location = Montvale, New Jersey | year = 2017 | isbn = 9781563638381| title-link = Physicians' Desk Reference}}</ref>
	==Warnings and precautions==
	The most serious risks associated with ketorolac are, as with other NSAIDs, ] ], bleeding and perforation; renal (]) events ranging from interstitial ] to complete ]; ], and hypersensitivity ].
			==Contraindications==
	As with other NSAIDs, ] and ] have been reported with ketorolac. Ketorolac also elevates liver protein levels.
			Ketorolac is ] in those with ], allergies to the medication, cross-sensitivity to other NSAIDs, before surgery, history of ], gastrointestinal bleeding, ], renal impairment, cerebrovascular bleeding, ], ], and ].<ref name=Vallertand/><ref name=PDR/> Recommendations exist for cautious use of ketorolac in those who have experienced ], ], stroke, ], ] disorders, ], and ].<ref name=Vallertand/><ref name=PDR/>
			==Adverse effects==
	When ] through the same IV ] as ], the two drugs have been known to sometimes combine to form a ] in the IV, which may block the line. Line flushing with a ] of ] can push the blockage through.
			A common (>10%) side effect is ]. Infrequent (<1%) side effects include ], prolonged ], ] site pain, ], ]ing, abnormal thinking, increased production of ], ], ], ], ], ], ], ] and others. Platelet function can be decreased by the use of ketorolac.<ref name = "Henry_2016" />{{rp|279}}
			Though uncommon, potentially fatal adverse effects include ], myocardial infarction, ], ], ] and ]. In terms of safety, ketorolac has been assessed to be a relatively higher-risk NSAID when compared to aceclofenac, celecoxib, and ibuprofen.<ref name="SchwierTran2016" />
	Ketorolac is not recommended for pre-] analgesia or co-administration with ] because it inhibits ] aggregation and thus may be associated with an increased risk of bleeding.
			Like all NSAIDs, ketorolac can cause premature constriction of the ] in the infant if taken by the mother during the third trimester of pregnancy.<ref name=Vallertand/><ref name=PDR/>
	Ketorolac is not recommended for ] analgesia because it has not been ] for obstetrical administration and has demonstrable ] ] in ].
			In October 2020, the U.S. ] (FDA) required the ] 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.<ref name="FDA PR 20201015" /><ref name="FDA safety 20201015" /> They recommend avoiding NSAIDs in pregnant women at 20 weeks or later in pregnancy.<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. Food and Drug Administration | 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>
	Ketorolac is not recommended for long-term ] patients.
			== Interactions ==
	However, ketorolac has been co-administered with ] and morphine without apparent adverse effects on patients.
			Ketorolac can interact with other medications. ] can increase the probability of having an adverse reaction when taken with ketorolac. ] can increase the risk of bleeding. When aspirin is taken at the same time as ketorolac, the effectiveness is decreased. Problematic GI effects are additive and become more likely if potassium supplements, aspirin, other NSAIDs, ], or ] is taken at the same time. The effectiveness of antihypertensives and diuretics can be lowered. The use of ketorolac can increase serum lithium levels to the point of toxicity. Toxicity to methotrexate is more likely if ketorolac is taken at the same time. The risk of bleeding increases with the concurrent medications ], ], ], ], ], ], and ]. Anticoagulants and thrombolytic medications also increase the likelihood of bleeding. Medications used to treat cancer can interact with ketorolac along with radiation therapy. The risk of toxicity to the kidneys increases when ketorolac is taken with ].<ref name=Vallertand/><ref name=PDR/>
			Interactions with ketorolac also exist with some ]s. The use of '']'', ], ], ], ], ], ], and '']'' increases the risk of bleeding.<ref name=Vallertand/><ref name=PDR/>
	==Dosage, availability and cost==
	Oral dosage is 10&nbsp;mg; United States price for 20 tablets hovers around US$28. Australian pricing for 20 tablets is around AU$44.<ref name="epharmacy">{{cite web | url = http://www.epharmacy.com.au/searchresults.asp?searchsection=products&terms=toradol&stype=NP&expand=0 | title = Search for Toradol | publisher = ePharmacy | accessdate = 2007-10-16}}</ref> It is considerably less expensive in ] (where it is called ''ketorolaco'', and marketed under various brand names, such as Glicima, from Atlantis Pharma, Dolac, from ], and Supradol, from Laboratorios Liamont), costing approximately US$10 for 20 tablets. De jure prescription only, but de facto OTC in Russia, US$1 for 30 tablets (Ketorol by Dr. Reddy's).
			==Mechanism of action==
	Injected dosages are 15, 30 and 60&nbsp;mg; US price for 10 vials of 30&nbsp;mg each is around US$45, making the ] preparation considerably more expensive per dose. One 60-mg dose would require the administration by injection of two vials, at about $9 per dose. Australian pricing for 5 vials is around AU$58<ref name="epharmacy"/>, or about $23 per dose. Ketorolac is not available on the ].<ref>{{cite web | url = http://www.pbs.gov.au/html/consumer/search/results?medicine=ketorolac | title = Search for Ketorolac | publisher = Pharmaceutical Benefits Scheme | accessdate = 2007-10-16}}</ref>
			Chemically ketorolac functions as a carboxylic acid derivative serving non-selectively to block the prostaglandin synthesis by inhibition of ] G/H synthesis 1 and 2. Prostaglandin functions in the body as a messenger for contraction/relaxation of smooth muscle and modulation of inflammation. Resultant, inhibition of prostaglandin synthesis prevents inflammation.<ref name="PubChem-2020">{{Cite web|url=https://pubchem.ncbi.nlm.nih.gov/compound/3826|title=Ketorolac|work=PubChem|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine|access-date=18 April 2020|archive-date=13 August 2020|archive-url=https://web.archive.org/web/20200813183146/https://pubchem.ncbi.nlm.nih.gov/compound/3826|url-status=live}}</ref> The primary ] responsible for ketorolac's anti-inflammatory, ], and analgesic effects is the inhibition of prostaglandin synthesis by competitive blocking of the ] ] (COX). Ketorolac is a non-selective COX inhibitor.<ref name="pmid18292448">{{cite journal | vauthors = Lee IO, Seo Y | title = The effects of intrathecal cyclooxygenase-1, cyclooxygenase-2, or nonselective inhibitors on pain behavior and spinal Fos-like immunoreactivity | journal = Anesthesia and Analgesia | volume = 106 | issue = 3 | pages = 972–7, table of contents | date = March 2008 | pmid = 18292448 | doi = 10.1213/ane.0b013e318163f602 | s2cid = 5894373 | doi-access = free }}</ref> It is considered a first-generation NSAID,<ref name = "Henry_2016" />{{rp|279}} a group of drugs that non-selectively inhibit both COX-1 and COX-2 enzymes, which can lead to gastrointestinal side effects.<ref name="pmid12487621"/> In contrast, later generations of NSAIDs are designed to selectively inhibit COX-2, aiming to reduce inflammation with fewer gastrointestinal issues.<ref name="pmid12487621">{{cite journal |vauthors=Stichtenoth DO, Frölich JC |title=The second generation of COX-2 inhibitors: what advantages do the newest offer? |journal=Drugs |volume=63 |issue=1 |pages=33–45 |date=2003 |pmid=12487621 |doi=10.2165/00003495-200363010-00003 |url=}}</ref>
			== History ==
	In the United States,<ref>{{cite web | url = http://redpoll.pharmacy.ualberta.ca/drugbank/drugBank/FDA_labels/019700.pdf | title = FDA Label for Ketorolac | publisher = US Food and Drug Administration | year = 2004 | accessdate = 2007-10-16 |archiveurl = http://web.archive.org/web/20080307182404/http://redpoll.pharmacy.ualberta.ca/drugbank/drugBank/FDA_labels/019700.pdf <!-- Bot retrieved archive --> |archivedate = 2008-03-07}}</ref> ],<ref>{{cite web | url = http://www.netdoctor.co.uk/medicines/effect/pain/prescription_only_medicines.shtml | title = Pain: prescription-only medicines | publisher = NetDoctor.co.uk | accessdate = 2007-10-16 | year = 2007}}</ref> ],<ref>{{cite web | url = http://www.smartmed.ca/content/search.asp?txtsearch=Ketorolac | title = Prescription Drug Search | publisher = Smart Med Canada | accessdate = 2007-10-16}}</ref> and Australia<ref>{{cite web | url = http://www.roche-australia.com/downloads/toradol-pi.cfm?action=get | title = Toradol (ketorolac trometamol) Product Information | year = 2005 | publisher = Roche Australia | accessdate = 2007-10-16 |archiveurl = http://web.archive.org/web/20070828233543/http://www.roche-australia.com/downloads/toradol-pi.cfm?action=get <!-- Bot retrieved archive --> |archivedate = 2007-08-28}}</ref> this drug cannot be sold ] and must be administered only with a ]. It is commonly available over-the-counter in Mexico and other areas of ], at the pharmacist's discretion.
			Ketorolac was patented in 1976 and approved for medical use in 1989.<ref name="Fis2006">{{cite book |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA521 |title=Analogue-based Drug Discovery |vauthors=Fischer J, Ganellin CR |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=521}}</ref><ref name="AHFS2019" /> It is available as a ].<ref name="BNF76" /> As of 2022, it was the 223rd most commonly prescribed medication in the United States, with more than 1{{nbsp}}million prescriptions.<ref>{{cite web |title=The Top 300 of 2022 |url=https://clincalc.com/DrugStats/Top300Drugs.aspx |url-status=live |archive-url=https://web.archive.org/web/20240830202410/https://clincalc.com/DrugStats/Top300Drugs.aspx |archive-date=30 August 2024 |access-date=30 August 2024 |website=ClinCalc}}</ref><ref>{{cite web |title=Ketorolac Drug Usage Statistics, United States, 2013 - 2022 |url=https://clincalc.com/DrugStats/Drugs/Ketorolac |access-date=30 August 2024 |website=ClinCalc}}</ref> In the US, ketorolac is the only widely available intravenous NSAID.<ref name="pmid28232869"/>
			Acular, an ophthalmic formulation (]), was developed by the ] company, of ] around 2006, which is currently licensed by ].<ref name="RxList-2021">{{Cite web|title=Acular (Ketorolac Tromethamine): Uses, Dosage, Side Effects, Interactions, Warning|url=https://www.rxlist.com/acular-drug.htm|access-date=6 May 2021|website=RxList|archive-date=24 February 2024|archive-url=https://web.archive.org/web/20240224233950/https://www.rxlist.com/acular-drug.htm|url-status=live}}</ref><ref name="Label-2011">{{cite web | title = Label: ACULAR® Eye Drops (ketorolac trometamol) | url = https://allergan-web-cdn-prod.azureedge.net/allergan/allergannewzealand/media/allergannewzealand/products/acular-nz-cmi.pdf | date = December 2011 | access-date = 6 May 2021 | archive-date = 24 September 2021 | archive-url = https://web.archive.org/web/20210924221743/https://allergan-web-cdn-prod.azureedge.net/allergan/allergannewzealand/media/allergannewzealand/products/acular-nz-cmi.pdf | url-status = live }}</ref><ref name="Allergan, Inc.-2021">{{cite web | title = Label: ACULAR® (ketorolac tromethamine ophthalmic solution) | url = https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/019700s028lbl.pdf | work = Allergan, Inc. | publisher = U.S. Food and Drug Administration | access-date = 6 May 2021 | archive-date = 16 April 2024 | archive-url = https://web.archive.org/web/20240416185248/https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/019700s028lbl.pdf | url-status = live }}</ref> The formulation was approved by the FDA in 1992.<ref name="Drugs.com-2013">{{cite web |title=Ketorolac ophthalmic medical facts from |url=https://www.drugs.com/mtm/ketorolac-ophthalmic.html |url-status=live |archive-url=https://web.archive.org/web/20130927012914/http://www.drugs.com/mtm/ketorolac-ophthalmic.html |archive-date=27 September 2013 |access-date=6 October 2013 |publisher=Drugs.com}}</ref>
	==Patent controversy==
	The ] company, of ] developed the ophthalmic solution Acular, and holds the registered trademark on that name, as well as on the Toradol. The actual product using this brand name is manufactured and distributed by ] under license from Syntex.<ref name="Allergan Acular info">{{cite web | last = Allergan | authorlink = Allergan | year = 2006 | url = http://www.allergan.com/site/products/consumers/home.asp?id=acular | title = ACULAR Ketorolac tromethamine 0.5% ophthalmic solution Product Information | work = Allergan web site | publisher = Allergan | accessdate = 2006-05-08}}</ref>
			Sprix, an intranasal formulation (]), was approved by the FDA in 2010 for short-term management of moderate to moderately severe pain requiring analgesia at the opioid level.<ref name="Drugs.com-2013-Sprix">{{cite web |url=https://www.drugs.com/sprix.html |title=Sprix Information from |publisher=Drugs.com |access-date=6 October 2013 |archive-date=17 September 2013 |archive-url=https://web.archive.org/web/20130917105809/http://www.drugs.com/sprix.html |url-status=live }}</ref>
	], a Canadian manufacturer, offers generic Ketorolac tromethamine as a 0.5% ophthalmic solution and as 10&nbsp;mg tablets under the name "Apo-Ketorolac"<ref name="Apotex Ketorolac-ophthalmic info">{{cite web
	| last = Apotex Products Canada | authorlink = Apotex | date = 2006-05-08 | url = http://www.apotex.ca/Products/EN/Detail.asp?MaterialNumber=000000000000043869 | title = APO-KETOROLAC Product Information | work = Apotex Products Canada Product Catalogue | publisher = Apotex Products Canada | accessdate = 2006-05-08}}</ref>, in Canada and some other countries. Syntex and Allergan sued Apotex for ] of US ] No. 5,110,493, over the generic ketorolac tomethamine product. In May, 2005, the ] for the Federal Circuit handed Apotex a victory, ruling that a lower court upholding the Syntex patent misapplied the rules for judging whether an invention was obvious. Allergan had claimed that the patent is valid until 2009.<ref name="Patent Baristas Ketorolac">{{cite web | last = Albainy-Jenei | first = Stephen R. | date = May 24, 2005 | url = http://www.patentbaristas.com/archives/000188.php | title = Federal Circuit Reverses Allergan's Patent Validity Decision | work = Patent Baristas web log | accessdate = 2006-05-08}}</ref>
			In 2007, there were concerns about the high incidence of reported side effects. This led to restrictions on its dosage and maximum duration of use. In the UK, treatment was initiated only in a hospital, although this was not designed to exclude its use in prehospital care and mountain rescue settings.<ref name="researchgate.net" /> Dosing guidelines were published at that time.<ref name="MHRA Drug Safety Update-2007">{{cite journal | title = Ketoprofen and ketorolac: gastrointestinal risk | journal = MHRA Drug Safety Update | date = October 2007 | volume = 1 | issue = 3 | pages = 3–4 | publisher = Medicines and Healthcare products Regulatory Agency (MHRA) | url = https://webarchive.nationalarchives.gov.uk/ukgwa/20150110161836mp_/http://www.mhra.gov.uk/home/groups/pl-p/documents/publication/con2032519.pdf | access-date = 15 October 2022 | archive-date = 26 January 2023 | archive-url = https://web.archive.org/web/20230126163050/https://webarchive.nationalarchives.gov.uk/ukgwa/20150110161836mp_/http://www.mhra.gov.uk/home/groups/pl-p/documents/publication/con2032519.pdf | url-status = live }}</ref> Concerns over the high incidence of reported side effects with ketorolac led to its withdrawal (apart from the ophthalmic formulation) in several countries, while in others its permitted dosage and maximum duration of treatment have been reduced. From 1990 to 1993, 97 reactions with fatal outcomes were reported worldwide.<ref name="Committee on Safety of Medicines-1993">{{cite journal | author = Committee on Safety of Medicines | title = Ketorolac: new restrictions on dose and duration of treatment. | journal = Current Problems in Pharmacovigilance | date = 1993 | volume = 19 | pages = 5–6 | url = }}</ref>
	], an Indian manufacturer makes ketorolac in tablets and ampoules under a name "Ketanov". Another Indian manufacturer ] makes ketorolac under a name "Ketorol".
			Ketorolac has also been used in collegiate and professional sports and is reported to be routinely used in the ] and ]. Competitive athletes, particularly in contact sports, are often expected by their coaches and/or teammates to play through injuries, generally with the help of painkillers. However, more recent research has indicated that encouraging players to play while injured tends to result in more severe injuries.<ref name="Klemko-2020-Sports-Illustrated">{{Cite magazine|url=https://www.si.com/nfl/2017/03/28/nfl-toradol-lawsuit-painkillers-nflpa-union-team-doctor-conflict-interest|title=Toradol Lawsuit: NFL Can't Outrun Legacy of Abuse|vauthors=Klemko R|magazine=Sports Illustrated|access-date=18 April 2020|archive-date=23 April 2020|archive-url=https://web.archive.org/web/20200423072928/https://www.si.com/nfl/2017/03/28/nfl-toradol-lawsuit-painkillers-nflpa-union-team-doctor-conflict-interest|url-status=live}}</ref><ref name="pmid23016110">{{cite journal | vauthors = Matava M, Brater DC, Gritter N, Heyer R, Rollins D, Schlegel T, Toto R, Yates A | display-authors = 6 | title = Recommendations of the national football league physician society task force on the use of toradol(®) ketorolac in the national football league | journal = Sports Health | volume = 4 | issue = 5 | pages = 377–383 | date = September 2012 | pmid = 23016110 | pmc = 3435943 | doi = 10.1177/1941738112457154 }}</ref> A lawsuit alleging widespread league-sanctioned abuse of painkillers was filed by former players against the National Football League in 2017.<ref name="Maese-2017">{{Cite news|vauthors=Maese R|url=https://www.washingtonpost.com/sports/redskins/nfl-abuse-of-painkillers-and-other-drugs-described-in-court-filings/2017/03/09/be1a71d8-035a-11e7-ad5b-d22680e18d10_story.html|title=NFL abuse of painkillers and other drugs described in court filings|date=9 March 2017|newspaper=Washington Post|access-date=18 April 2020|issn=0190-8286|archive-date=22 April 2020|archive-url=https://web.archive.org/web/20200422190330/https://www.washingtonpost.com/sports/redskins/nfl-abuse-of-painkillers-and-other-drugs-described-in-court-filings/2017/03/09/be1a71d8-035a-11e7-ad5b-d22680e18d10_story.html|url-status=live}}</ref>
	==External links==
	* , at DrugLib
	* on ophthalmic ketorolac
	* on nasal ketorolac
	==References==		== References ==
	{{Reflist}}		{{Reflist}}
	{{Refbegin}}
	* Handley, D.A., P. Carvoni, J.E. McCray, J.R. McCullough (1998). "Preclinical Enantioselective Pharmacology of (R)- and (S)- Ketorolac.", ''J Clin Pharmacol'' '''38''', 25-35.
	* 1993. ''Physicians' Desk Reference, Forty-seventh edition''. Montvale, N.J., Medical Economics Co. Inc., 2411-2415.
	{{Refend}}
			== Further reading ==
	{{NSAIDs}}
			{{refbegin}}
			* {{cite book | title = AHFS drug information | publisher = American Society of Health-System Pharmacists | location = Bethesda, MD | year = 2011 | isbn = 9781585282609 }}
			* {{cite book| vauthors = Hamilton R |title=Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition|date=2015|publisher=Jones & Bartlett Learning|isbn=9781284057560|page=9}}
			* {{cite journal | vauthors = Handley DA, Cervoni P, McCray JE, McCullough JR | title = Preclinical enantioselective pharmacology of (R)- and (S)- ketorolac | journal = Journal of Clinical Pharmacology | volume = 38 | issue = 2S | pages = 25S–35S | date = February 1998 | pmid = 9549656 | doi = 10.1002/j.1552-4604.1998.tb04414.x | s2cid = 22508540 }}
			* {{cite book | vauthors = Henry N | title = RN pharmacology for nursing : review module | publisher = Assessment Technologies Institute | location = Overland Park, KS | year = 2016 | isbn = 9781565335738 }}
			* {{cite book | vauthors = Kizior R | title = Saunders nursing drug handbook 2017 | publisher = Elsevier | location = St. Louis, MO | year = 2017 | isbn = 9780323442916 }}<!--pp 666-669 -->
			{{refend}}
			{{Analgesics}}
	{{Anti-inflammatory and antirheumatic products}}		{{Anti-inflammatory and antirheumatic products}}
			{{Prostanoidergics}}
			{{Portal bar | Medicine}}
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