<unk>  consumption has been associated with significantly increased vascular and coronary risk in a study including coxib,<unk> , ibuprofen and naproxen. Upper gastrointestinal complications were also reported. Major adverse cardiovascular events (MACE) were increased by about a third by<unk> , chiefly due to an increase in major coronary events. Compared with placebo, of 1000 patients allocated to<unk>  for a year, three more had major vascular events, one of which was fatal. Vascular death was increased significantly by<unk> . In October 2020, the U.S. Food and Drug Administration (FDA) required the 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. They recommend avoiding NSAIDs in pregnant women at 20 weeks or later in pregnancy. Heart In 2013, a study found major vascular events were increased by about a third by<unk> , chiefly due to an increase in major coronary events. Compared with placebo, of 1000 people allocated to<unk>  for a year, three more had major vascular events, one of which was fatal. Vascular death was increased by<unk>  (1·65). Following the identification of increased risks of heart attacks with the selective COX-2 inhibitor rofecoxib in 2004, attention has focused on all the other members of the NSAIDs group, including<unk> . Research results are mixed, with a meta-analysis of papers and reports up to April 2006 suggesting a relative increased rate of heart disease of 1.63 compared to nonusers. Professor Peter Weissberg, Medical Director of the British Heart Foundation said, "However, the increased risk is small, and many patients with chronic debilitating pain may well feel that this small risk is worth taking to relieve their symptoms". Only aspirin was found not to increase the risk of heart disease; however, this is known to have a higher rate of gastric ulceration than<unk> . In Britain the Medicines and Healthcare products Regulatory Agency (MHRA) said in June 2013 that the drug should not be used by people with serious underlying heart conditionspeople who had suffered heart failure, heart disease or a stroke were advised to stop using it completely. As of 15 January 2015, the MHRA announced that<unk>  will be reclassified as a prescription-only medicine (POM) due to the risk of cardiovascular adverse events. A subsequent large study of 74,838 Danish users of NSAIDs or coxibs found no additional cardiovascular risk from<unk>  use. A very large study of 1,028,437 Danish users of various NSAIDs or coxibs found the "Use of the nonselective NSAID<unk>  and the selective cyclooxygenase-2 inhibitor rofecoxib was associated with an increased risk of cardiovascular death (odds ratio, 1.91; 95% confidence interval, 1.62 to 2.42; and odds ratio, 1.66; 95% confidence interval, 1.06 to 2.59, respectively), with a dose-dependent increase in risk."<unk>  is similar in COX-2 selectivity to celecoxib. Gastrointestinal * Gastrointestinal complaints are most often noted. The development of ulceration and/or bleeding requires immediate termination of treatment with<unk> . Most patients receive a gastro-protective drug as prophylaxis during long-term treatment (misoprostol, ranitidine 150 mg at bedtime or omeprazole 20 mg at bedtime). Liver * Liver damage occurs infrequently, and is usually reversible. Hepatitis may occur rarely without any warning symptoms and may be fatal. Patients with osteoarthritis more often develop symptomatic liver disease than patients with rheumatoid arthritis. Liver function should be monitored regularly during long-term treatment. If used for the short-term treatment of pain or fever,<unk>  has not been found more hepatotoxic than other NSAIDs. * , Endo, Novartis, and the US FDA notified healthcare professionals to add new warnings and precautions about the potential for elevation in liver function tests during treatment with all products containing<unk>  sodium. * Cases of drug-induced hepatotoxicity have been reported in the first month, but can occur at any time during treatment with<unk> . Postmarketing surveillance has reported cases of severe hepatic reactions, including liver necrosis, jaundice, fulminant hepatitis with and without jaundice, and liver failure. Some of these reported cases resulted in fatalities or liver transplantation. * Physicians should measure transaminases periodically in patients receiving long-term therapy with<unk> . Based on clinical trial data and postmarketing experiences, transaminases should be monitored within 4 to 8 week after initiating treatment with<unk> . Kidney * NSAIDs "are associated with adverse renal kidney effects caused by the reduction in synthesis of renal prostaglandins" in sensitive persons or animal species, and potentially during long-term use in nonsensitive persons if resistance to side effects decreases with age. However, this side effect cannot be avoided merely by using a COX-2 selective inhibitor because, "Both isoforms of COX, COX-1 and COX-2, are expressed in the kidney... Consequently, the same precautions regarding renal risk that are followed for nonselective NSAIDs should be used when selective COX-2 inhibitors are administered." However,<unk>  appears to have a different mechanism of renal toxicity. * Studies in Spain showed<unk>  caused acute kidney failure in vultures when they ate the carcasses of animals that had recently been treated with it. Drug-sensitive species and individual humans are initially assumed to lack genes expressing specific drug detoxification enzymes. Mental health * Mental health side effects have been reported. These symptoms are rare, but exist in significant enough numbers to include as potential side effects. These include depression, anxiety, irritability, nightmares, and psychotic reactions.
Diclofenac
Aceclofenac
Ketoprofen
Indoprofen
Loxoprofen
Fenoprofen
Celecoxib
Ibuprofen