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. One exception to the recommendation is the use of low-dose 81 mg<unk>  at any point in pregnancy under the direction of a health care professional. Contraindications<unk>  should not be taken by people who are allergic to ibuprofen or naproxen, or who have salicylate intolerance or a more generalized drug intolerance to NSAIDs, and caution should be exercised in those with asthma or NSAID-precipitated bronchospasm. Owing to its effect on the stomach lining, manufacturers recommend people with peptic ulcers, mild diabetes, or gastritis seek medical advice before using<unk> . Even if none of these conditions is present, the risk of stomach bleeding is still increased when<unk>  is taken with alcohol or warfarin. People with hemophilia or other bleeding tendencies should not take<unk>  or other salicylates.<unk>  is known to cause hemolytic anemia in people who have the genetic disease glucose-6-phosphate dehydrogenase deficiency, particularly in large doses and depending on the severity of the disease. Use of<unk>  during dengue fever is not recommended owing to increased bleeding tendency. People with kidney disease, hyperuricemia, or gout should not take<unk>  because it inhibits the kidneys' ability to excrete uric acid, thus may exacerbate these conditions.<unk>  should not be given to children or adolescents to control cold or influenza symptoms, as this has been linked with Reye's syndrome. Gastrointestinal<unk>  use has been shown to increase the risk of gastrointestinal bleeding. Although some enteric-coated formulations of<unk>  are advertised as being "gentle to the stomach", in one study, enteric coating did not seem to reduce this risk. Combining<unk>  with other NSAIDs has also been shown to further increase this risk. Using<unk>  in combination with clopidogrel or warfarin also increases the risk of upper gastrointestinal bleeding. Blockade of COX-1 by<unk>  apparently results in the upregulation of COX-2 as part of a gastric defense. Several trials suggest that the simultaneous use of a COX-2 inhibitor with<unk>  may increase the risk of gastrointestinal injury. However, currently available evidence has been unable to prove that this effect is consistently repeatable in everyday clinical practice. More dedicated research is required to provide greater clarity on the subject. Therefore, caution should be exercised if combining<unk>  with any "natural" supplements with COX-2-inhibiting properties, such as garlic extracts, curcumin, bilberry, pine bark, ginkgo, fish oil, resveratrol, genistein, quercetin, resorcinol, and others. In addition to enteric coating, "buffering" is the other main method companies have used to try to mitigate the problem of gastrointestinal bleeding. Buffering agents are intended to work by preventing the<unk>  from concentrating in the walls of the stomach, although the benefits of buffered<unk>  are disputed. Almost any buffering agent used in antacids can be used; Bufferin, for example, uses magnesium oxide. Other preparations use calcium carbonate. Gas-forming agents in effervescent tablet and powder formulations can also double as a buffering agent, one example being sodium bicarbonate found in Alka-Seltzer. Taking it with vitamin C has been investigated as a method of protecting the stomach lining. Taking equal doses of vitamin C and<unk>  may decrease the amount of stomach damage that occurs compared to taking<unk>  alone. Retinal vein occlusion It is a widespread habit among eye specialists (ophthalmologists) to prescribe<unk>  as an add-on medication for patients with retinal vein occlusion (RVO), such as central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO). The reason of this widespread use is the evidence of its proven effectiveness in major systemic venous thrombotic disorders, and it has been<unk> umed that may be similarly beneficial in various types of retinal vein occlusion. However, a large-scale investigation based on data of nearly 700 patients showed "that<unk>  or other antiplatelet aggregating agents or anticoagulants adversely influence the visual outcome in patients with CRVO and hemi-CRVO, without any evidence of protective or beneficial effect". Several expert groups, including the Royal College of Ophthalmologists, recommended against the use of antithrombotic drugs (incl.<unk>  for patients with RVO. Central effects Large doses of salicylate, a metabolite of<unk> , cause temporary tinnitus (ringing in the ears) based on experiments in rats, via the action on arachidonic acid and NMDA receptors cascade. Reye's syndrome Reye's syndrome, a rare but severe illness characterized by acute encephalopathy and fatty liver, can occur when children or adolescents are given<unk>  for a fever or other illness or infection. From 1981 to 1997, 1207 cases of Reye's syndrome in people younger than 18 were reported to the U.S. Centers for Disease Control and Prevention. Of these, 93% reported being ill in the three weeks preceding the onset of Reye's syndrome, most commonly with a respiratory infection, chickenpox, or diarrhea. Salicylates were detectable in 81.9% of children for whom test results were reported. After the<unk> ociation between Reye's syndrome and<unk>  was reported, and safety measures to prevent it (including a Surgeon General's warning, and changes to the labeling of<unk> -containing drugs) were implemented,<unk>  taken by children declined considerably in the United States, as did the number of reported cases of Reye's syndrome; a similar decline was found in the United Kingdom after warnings against pediatric<unk>  use were issued. The U.S. Food and Drug Administration now recommends<unk>  (or<unk> -containing products) should not be given to anyone under the age of 12 who has a fever, and the UK National Health Service recommends children who are under 16 years of age should not take<unk> , unless it is on the advice of a doctor. Skin For a small number of people, taking<unk>  can result in symptoms including hives, swelling, and headache.<unk>  can exacerbate symptoms among those with chronic hives, or create acute symptoms of hives. These responses can be due to allergic reactions to<unk> , or more often due to its effect of inhibiting the COX-1 enzyme. Skin reactions may also tie to systemic contraindications, seen with NSAID-precipitated bronchospasm, or those with atopy.<unk>  and other NSAIDs, such as ibuprofen, may delay the healing of skin wounds. Earlier findings from two small, low-quality trials suggested a benefit with<unk>  (alongside compression therapy) on venous leg ulcer healing time and leg ulcer size, however larger, more recent studies of higher quality have been unable to corroborate these outcomes. As such, further research is required to clarify the role of<unk>  in this context. Other adverse effects<unk>  can induce swelling of skin tissues in some people. In one study, angioedema appeared one to six hours after ingesting<unk>  in some of the people. However, when the<unk>  was taken alone, it did not cause angioedema in these people; the<unk>  had been taken in combination with another NSAID-induced drug when angioedema appeared.<unk>  causes an increased risk of cerebral microbleeds having the appearance on MRI scans of 5 to 10mm or smaller, hypointense (dark holes) patches. Such cerebral microbleeds are important, since they often occur prior to ischemic stroke or intracerebral hemorrhage, Binswanger disease, and Alzheimer's disease. A study of a group with a mean dosage of<unk>  of 270mg per day estimated an average absolute risk increase in intracerebral hemorrhage (ICH) of 12 events per 10,000 persons. In comparison, the estimated absolute risk reduction in myocardial infarction was 137 events per 10,000 persons, and a reduction of 39 events per 10,000 persons in ischemic stroke. In cases where ICH already has occurred,<unk>  use results in higher mortality, with a dose of about 250mg per day resulting in a relative risk of death within three months after the ICH around 2.5 (95% confidence interval 1.3 to 4.6).<unk>  and other NSAIDs can cause abnormally high blood levels of potassium by inducing a hyporeninemic hypoaldosteronic state via inhibition of prostaglandin synthesis; however, these agents do not typically cause hyperkalemia by themselves in the setting of normal renal function and euvolemic state.<unk>  can cause prolonged bleeding after operations for up to 10 days. In one study, 30 of 6499 people having elective surgery required reoperations to control bleeding. Twenty had diffuse bleeding and 10 had bleeding from a site. Diffuse, but not discrete, bleeding was<unk> ociated with the preoperative use of<unk>  alone or in combination with other NSAIDS in 19 of the 20 diffuse bleeding people. On 9 July 2015, the FDA toughened warnings of increased heart attack and stroke risk<unk> ociated with nonsteroidal anti-inflammatory drugs (NSAID).<unk>  is an NSAID but is not affected by the new warnings. Overdose<unk>  overdose can be acute or chronic. In acute poisoning, a single large dose is taken; in chronic poisoning, higher than normal doses are taken over a period of time. Acute overdose has a mortality rate of 2%. Chronic overdose is more commonly lethal, with a mortality rate of 25%; chronic
Aspirin
Clopidogrel
Warfarin
Ticagrelor
Ticlopidine
Palladin
Heparin
Tafamidis