Increased risk of serious CV thrombotic events, MI, & stroke; serious GI adverse events including bleeding, ulceration, & perforation of the stomach or intestines. Risk of renal papillary necrosis & other renal injury w/ long-term NSAIDs administration. Renal toxicity in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. Not recommended in patients w/ advanced renal disease. Caution during 1st & 2nd trimesters of pregnancy, particularly from the middle to end of 2nd trimester (onset at approx 20 wk) due to possible fetal renal dysfunction leading to oligohydramnios &, in some cases, neonatal renal impairment or failure.