Ketorolac is an NSAID used to treat moderate to severe acute pain. It works by inhibiting prostaglandins to reduce pain from inflammation. Ketorolac can be administered intravenously, intramuscularly, or orally. It has a short half-life and analgesic effects last 4-6 hours. Side effects include an increased risk of bleeding and kidney problems. Ketorolac should not be used for more than 5 days or in combination with other NSAIDs or anticoagulants due to drug-drug interactions and safety concerns.

1. Understanding Ketorolac: An
Interprofessional Approach
Ben Roberts
Lamar University
Last edited: November 4, 2017

2. Description and Indications for Use
 Ketorolac – belongs to a group of meds known as NSAIDs
(non-steroidal anti inflammatory drugs)
 Used to treat moderately severe pain that is acute, not
chronic due to increased risk of adverse drug reactions
 Mechanism of action: inhibits prostaglandins thus
reducing pains associated with inflammatory process

3. Intended Drug Response from Usage
 Manage acute moderately severe pain through the IV, IM, or oral routes of
administration
 Oral route of administration intended to be given after IV or IM administration
 Drug may not be used for greater than 5 days
 Regardless of route
 Important teaching opportunity for patients
 More is not always better!
 Higher doses do not create greater analgesic effect but it will increase the
likelihood of adverse drug reactions!
 Higher doses are associated with increased duration of analgesia effects
 Ketorolac usage associated with decreased opiate requirements to manage
acute pain
 Do you think this would contribute positively to the drug epidemic seen in the
United States? (5 minute class discussion)

4. The Nitty Gritty
(nitty gritty refers to side effects & contraindications)
 Inhibits platelet function
 Decreased platelet function = greater risk of bleeding!
 Not to be used in conjunction with anticoagulants or NSAIDs
 Contraindications
 Increased risk of myocardial infarction and CVA
 Mechanism not fully understood
 Patients with history of gi bleeding’
 Peptic ulcer
 Intestinal perforation
 Renal insufficiency
 Drug has risk of nephrotoxicity

5. Drug-Drug Interactions
 Aspirin – both inhibit platelet function and compete for binding sites
 SSRI – increased risk of hallucination and gi bleed
 Lithium – decreased renal clearance of Lithium
 Decreased renal clearance means higher serum levels
 Can lead to seizures (Ain’t nobody got time for that!)
 Probenecid
 Both drugs use same excretion pathway in kidney
 Imagine everyone in a concert trying to go out the same exit at the same time! It would
be slow, cause delays, and increase likelihood of harm!!

6. Pharmacokinetics
 Pharmacokinetics
 100% bioavailability despite administration route
 You have two hands….ketorolac has two parts
 S-enantiomer – possess analgesic effect
 Cleared by kidneys quickly causing shorter half life (2.5 hours)
 Peak analgesic effect 1-2 hours after administration
 Analgesic effect experienced for 4-6 hours by patient
 R-enantiomer – does not have therapeutic effect
 Highly protein bound (99% protein bound)
 Decreased albumin levels cause more free drug
 Metabolized by liver
 Glucuronidation – removes toxic substance
 Excreted by kidneys
 60% is nonmetabolized
 40% is metabolized liver by products

7. Pharmacogenomics
 Pharmacogenomics – the study of genetics affect pharmacological responses
 New field of study….little research on ketorolac’s pharmacgenomic
 Pharmocogenomic can be used to our benefit
 Celebrex use decrease colon cancer relapse in patients with CYP2C9 mutation
 No study found to see if ketorolac has same effect
 Current evidence is conflicting
 Some studies show ketorolac has no pharmacogenomic considerations
 Some studies show the opposite:
 CYP2C9 mutations affect drug metabolism and increased risk of gi bleed
 ABCC2 mutations can affect biliary excretion of ketorolac and lead to hepatotoxicity

8. Knowledge is power…so do something with it!
(Ketorolac Clinical Applications)
 Provide patient education
 Example: sign/symptoms of gi bleed, 5 day use only
 Provide suggestions to other healthcare team members
 Example: has baseline or recent kidney functions tests been performed
 Be aware of contraindications
 Examples:
 Has your patient had a history of gi bleed?
 Does your patient have decreased kidney impairment?
 Is your patient also on aspirin?

9. References
 Baxter Healthcare Corporation (2006 January). Intravenous dilution guideline – ketorolac tromethamine. Retrieved from http://www.globalrph.com/ketorolac_dilution.htm
 Benedict, D. (2017, November 2). Personal interview
 Brocks, D.R. & Jamali, F. (1992 December). Clinical pharmacokinetics of ketorolac tromethamine. Clinical Pharmacokinetics, 23(6), 415-427. Retrieved from
https://link.sprnger.com/article/10.2165%2F00003088-199223060-00003
 DrugLib (n.d.). Toradol – description and clinical pharmacology. Retrieved from http://www.druglib.com/druginfo/toradol/description_pharmacology
 Fresenius Kabi USA, LLC (2017 March). Ketorolac tromethamine [PDF file]. Retrieved from https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=950b7295-3f68-4027-ac2b
-2f7d0f5f8ef9
 G.D. Searle LLC (2005, June 15). Toradol. Retrieved from https://www.rxlist.com/toradol-drug.htm
 Genetic Home Reference (2017, October 24). What is pharmacogenomics? Retrieved from https://ghr.nlm.nih.gov/primer/genomicresearch/pharmacogenomics
 Institute of Safe Medication Practices (n.d.). About ISMP. Retrieved from http://www.ismp.org/about/default.aspx
 King, N. (2016, June 22). GeneSight analgesic combinatorial pharmacogenomic test. Retrieved from https://genesight.com/wp-content/uploads/2017/05/GeneSight-Sample
-Reports.pdf
 Morell, S. (2017, November 2). Personal interview
 Prescribers’ Digital Reference (n.d.). Ketorolac tromethamine – drug summary. Retrieved from http://www.pdr.net/drug-summary/Ketorolac-Tromethamine-Tablets-
ketorolactrometham ine-1793.3935
 Reactome (2011, September 20). Pathway: glucuronidation. Retrieved from http://www.pathwaycommons.org/pc/record2.do?id=486025
 Ricciotti, E., & FitzGerald, G. (2012, May 1). Prostaglandins and inflammation. Arteriosclerosis, Thrombosis, and Vascular Biology, 31(5), 986-1000. doi: 10.1161/ATVBAHA.110.2074 49
 Roche (2008, December). Ketorolac [PDF file]. Retrieved from https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/019645s019lbl.pdf
 RxList (2017). Drug interactions with ketorolac iv and probenecid oral. Retrieved from https://www.rxlist.com/drug-interactions/ketorolac-iv-and-probenecid-oral-interaction.htm
 United States National Library of Medicine (2017, September 21). Ketorolac. Retrieved from https://medlineplus.gov/druginfo/meds/a693001.html
 Yiannakopoulou, E. (2013). Pharmacogenomics of acetylsalicylic acid and other nonsteroidal anti-inflammatory agents: clinical implications. European Journal of Clinical
Pharmacology, 69(7), 1369-1373. doi:10.1007/s00228-013-1477-9