Minimising the Adverse Effects of Ketorolac

Abstract

Gastrointestinal bleeding and perforation, platelet inhibition with altered haemostasis, and renal impairment are among the list of adverse effects associated with the administration of ketorolac. The incidence of serious adverse events has declined since dosage guidelines were revised. Most of the published literature suggests that the overall risk of gastrointestinal or operative site bleeding related to ketorolac therapy is only slightly higher than with opioids. The risk for adverse events, however, increases with high doses, with prolonged therapy (>5 days) or in vulnerable patients (e.g. the elderly). Acute renal failure has been reported after ketorolac treatment but is usually reversible after discontinuation of the drug. As with other nonsteroidal anti-inflammatory drugs (NSAIDs), ketorolac may trigger allergic or hypersensitivity reactions. Careful patient selection is essential if use of ketorolac is considered. Contraindications to ketorolac use include a history of, or current risk of, gastrointestinal bleeding, risk of renal failure, compromised haemostasis, hypersensitivity to aspirin (acetylsalicylic acid) or other NSAIDs, labour, delivery and nursing. Ketorolac should be prescribed at the lowest dosage necessary to control pain; the duration of therapy should also be limited to as few days as possible. Practitioners should be familiar with, and follow, label warnings and dosage guidelines.

Retrospective analysis of perioperative ketorolac and postoperative bleeding in reduction mammoplasty

“…When used as an adjunct, there may be a 25-50% reduction in opioid requirements, which may reduce the incidence of adverse side effects associated with opioid consumption. 1,5 Similar to other NSAIDs, ketorolac may prolong bleeding through inhibition of prostaglandin synthesis 6,7 via a mechanism of non-selective cyclooxygenase inhibition. 4 In 1991, shortly after the introduction of ketorolac, Garcha raised concerns surrounding an unusual cluster of postoperative hematomas following breast procedures.…”

Potential of Cyclodextrin Complexation and Liposomes in Topical Delivery of Ketorolac: In Vitro and In Vivo Evaluation

“…Oral bioavailability of KTRM is reported to be 90% with a very low first pass metabolism. However, the drug is reported to cause severe gastrointestinal side effects such as gastrointestinal bleeding, perforation, peptic ulceration, and acute renal failure (3,4). Therefore, parenteral administration of KTRM is the preferred route of administration for moderate to severe pain management.…”

Pharmacological Management of Cancer-Related Pain

“…22 Ketorolac use in the advanced patient with cancer is not recommended for more than 1 week. 23 Acetaminophen has not been shown to work synergistically with opioids but has not been shown to be opioid-sparing with opioid doses of more than 200 mg of morphine equivalents. 22 NSAIDs are useful for pain originating in tissues such as connective tissue, joints, serous membranes, and the periosteum; in addition, visceral pain may also respond to NSAIDs.…”