View source for Ketorolac

{{Short description|Nonsteroidal anti-inflammatory drug (NSAID; analgesic)}}
{{Use dmy dates|date=February 2024}}
{{Drugbox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 461740251
| image = Ketorolac.svg
| image_class = skin-invert-image
| alt = 
| chirality = [[Racemic mixture]]
| caption = Above: molecular structure of ketorolac
Below: 3D representation of a ketorolac molecule
| image2 = Ketorolac 3D.png
| image_class2 = bg-transparent
| alt2 = <!-- Clinical data -->
| tradename = Toradol, Acular, Sprix, others
| Drugs.com = {{drugs.com|monograph|ketorolac-tromethamine}}
| MedlinePlus = a693001
| DailyMedID = Ketorolac
| pregnancy_AU = C
| pregnancy_category = 
| routes_of_administration = [[Oral administration|By mouth]], [[Sublingual administration|under the tongue]], [[intramuscular]], [[intravenous]], [[Ophthalmic drug administration|eye drops]], nasal spray
| ATC_prefix = M01
| ATC_suffix = AB15
| ATC_supplemental = {{ATC|S01|BC05}}
| legal_AU = S4
| 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>
| legal_CA = Rx-only
| legal_US = Rx-only
| legal_UK = [[Prescription drug|POM]]<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>
| legal_status = <!-- Pharmacokinetic data -->
| bioavailability = 80–100% (oral)
100% IV/IM
| metabolism = [[Liver]]
| 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 = [[Kidney]]: 91.4% (mean)<br />[[Bile|Biliary]]: 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 [[nonsteroidal anti-inflammatory drug]] (NSAID) used to treat [[pain]].<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 [[injection into a vein]] or [[intramuscular|muscle]], 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 [[antipyretic]] (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 -->
Common side effects include sleepiness, dizziness, abdominal pain, swelling, and nausea.<ref name=AHFS2019/> Serious side effects may include [[stomach bleeding]], [[kidney failure]], [[heart attacks]], [[bronchospasm]], [[heart failure]], and [[anaphylaxis]].<ref name=AHFS2019/> Use is not recommended during the last part of [[pregnancy]] or during [[breastfeeding]].<ref name=AHFS2019/> Ketorolac works by blocking [[cyclooxygenase]] 1 and 2 (COX1 and COX2), thereby decreasing production of [[prostaglandin]]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 -->
Ketorolac was patented in 1976 and approved for medical use in 1989. It is available as a [[generic medication]]. In 2022, it was the 223rd most commonly prescribed medication in the United States, with more than 1{{nbsp}}million prescriptions.

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 [[opioid]] replacement in pain therapy because its side effects were perceived as much less severe, it did not produce any [[Substance dependence|dependence]], 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 [[vasoconstriction]]-related effects, e.g. during blood loss or high endogenous [[catecholamine]] 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>

==Medical uses==
[[File:Ketorolac (Toradol).jpg|thumb|left|Ketorolac package from Russia]]

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}}

Ketorolac is effective when administered with [[paracetamol]] (acetaminophen) to control pain in newborns because it does not depress [[Breathing|respiration]] as do [[opioid]]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 [[dysmenorrhea]].<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>

Ketorolac also has [[antipyretic]] (fever-reducing) properties.<ref name="pmid9010653"/><ref name="pmid38333494"/>

For systemic use, ketorolac can be administered [[oral medication|orally]], [[Sublingual administration|under the tongue]], by intramuscular injection, intravenously, and by [[nasal spray]].<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"/>

Ketorolac is also used as an [[eye drop]]. 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 [[corneal abrasion]]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>

During treatment with ketorolac, clinicians monitor for the manifestation of adverse effects. Lab tests, such as [[liver function tests]], bleeding time, [[BUN]], [[serum creatinine]] 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>

==Contraindications==
Ketorolac is [[Contraindication|contraindicated]] in those with [[hypersensitivity]], allergies to the medication, cross-sensitivity to other NSAIDs, before surgery, history of [[peptic ulcer disease]], gastrointestinal bleeding, [[alcohol intolerance]], renal impairment, cerebrovascular bleeding, [[nasal polyps]], [[angioedema]], and [[bronchospasm|asthma]].<ref name=Vallertand/><ref name=PDR/> Recommendations exist for cautious use of ketorolac in those who have experienced [[cardiovascular disease]], [[myocardial infarction]], stroke, [[heart failure]], [[coagulation]] disorders, [[renal impairment]], and [[hepatic impairment]].<ref name=Vallertand/><ref name=PDR/>

==Adverse effects==
A common (>10%) side effect is [[drowsiness]]. Infrequent (<1%) side effects include [[paresthesia]], prolonged [[bleeding time]], [[intramuscular injection|injection]] site pain, [[purpura]], [[sweat]]ing, abnormal thinking, increased production of [[tears]], [[edema]], [[pallor]], [[dry mouth]], [[Taste|abnormal taste]], [[urinary frequency]], [[Liver function tests|increased liver enzymes]], [[itching]] 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 [[stroke]], myocardial infarction, [[GI bleeding]], [[Stevens–Johnson syndrome]], [[toxic epidermal necrolysis]] and [[anaphylaxis]]. 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" />

Like all NSAIDs, ketorolac can cause premature constriction of the [[ductus arteriosus]] in the infant if taken by the mother during the third trimester of pregnancy.<ref name=Vallertand/><ref name=PDR/>

In October 2020, the U.S. [[Food and Drug Administration]] (FDA) required the [[Drug labelling|drug label]] to be updated for all nonsteroidal anti-inflammatory medications to describe the risk of kidney problems in unborn babies that result in low amniotic fluid.<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. [[Food and Drug Administration]] (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=dead }} {{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=dead }} {{PD-notice}}</ref>

== Interactions ==
Ketorolac can interact with other medications. [[Probenecid]] can increase the probability of having an adverse reaction when taken with ketorolac. [[Pentoxifylline]] 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, [[corticosteroids]], or [[alcohol (drug)|alcohol]] 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 [[clopidogrel]], [[cefoperazone]], [[valproic acid]], [[cefotetan]], [[eptifibatide]], [[tirofiban]], and [[ticlopidine]]. 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 [[cyclosporine]].<ref name=Vallertand/><ref name=PDR/>

Interactions with ketorolac also exist with some [[herbal supplement]]s. The use of ''[[Panax ginseng]]'', [[clove]], [[ginger]], [[arnica]], [[feverfew]], [[dong quai]], [[chamomile]], and ''[[Ginkgo biloba]]'' increases the risk of bleeding.<ref name=Vallertand/><ref name=PDR/>

==Mechanism of action==
Chemically ketorolac functions as a carboxylic acid derivative serving non-selectively to block the prostaglandin synthesis by inhibition of [[prostaglandin]] 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 [[mechanism of action]] responsible for ketorolac's anti-inflammatory, [[antipyretic]], and analgesic effects is the inhibition of prostaglandin synthesis by competitive blocking of the [[enzyme]] [[cyclooxygenase]] (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 ==
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 [[generic medication]].<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 ([[Eye drop|eye-drop]]), was developed by the [[Syntex]] company, of [[Palo Alto, California]] around 2006, which is currently licensed by [[Allergan]].<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>

Sprix, an intranasal formulation ([[nasal spray]]), 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>

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>

Ketorolac has also been used in collegiate and professional sports and is reported to be routinely used in the [[National Football League]] and [[National Hockey League]]. 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>

== References ==
{{Reflist}}

== Further reading ==
{{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}}

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[[Category:Wikipedia medicine articles ready to translate]]
[[Category:Aromatic ketones]]
[[Category:Nasal sprays]]
[[Category:Drugs developed by AbbVie]]
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[[Category:Ophthalmology]]
[[Category:Pyrrolizines]]
[[Category:Syntex]]