Etodolac should be avoided by patients with a history of asthma attacks, hives , or other allergic reactions to aspirin or other NSAIDs. Rare but severe allergic reactions have been reported in such individuals. It also should be avoided by patients with peptic ulcer disease or poor kidney function , since this medication can worsen both conditions. Etodolac is used with caution in patients taking blood thinning medications ( anticoagulants ), such as warfarin (Coumadin), because it increases the risk of bleeding . Patients taking both lithium and etodolac may develop toxic blood lithium levels. Additionally, etodolac has been found to interact with certain anti-depressant medications, such as sertraline or fluoxetine , which can increase risks of stroke, heart attack, and other cardiovascular conditions. Patients also taking ciclosporin (Sandimmune) can develop kidney toxicity. Use in children has not been adequately studied. Etodolac is not habit-forming. NSAIDs should be discontinued prior to elective surgery because of a mild interference with clotting that is characteristic of this group of medicines. Etodolac is best discontinued at least four days in advance of surgery.
A number of arguments counted against the COX-3 hypothesis: COX-2-selective inhibitors react weakly with the COX-3 enzymatic site, because the site is identical to that in COX-1, but they are as good at reducing fever as older NSAIDs. The fever response has also been clearly associated with a rapid induction of COX-2 expression and an associated increase in prostaglandin E2 production, with no role for COX-1 or a COX-1 gene product (., COX-3). Finally, the sites of COX-3 expression do not appear to fit in well with those sites associated with fever, and the protein should be present within the hypothalamus rather than the cerebral cortex . All these considerations appeared to argue against COX-3 being the site of the antipyretic actions of NSAIDs and COX-2-selective agents. However, the results could be read as showing that paracetamol acts at a different site than the other NSAIDs and that more than one COX isoform contribute to the fever response.