* Cardiovascular events: NSAIDs are associated with an increased risk of serious (and potentially fatal) adverse cardiovascular thrombotic events, including myocardial infarction and stroke. Risk may be increased with duration of use or pre-existing cardiovascular risk factors or disease. Individual cardiovascular risk profiles should be evaluated prior to prescribing. New-onset hypertension or exacerbation of hypertension may occur (NSAIDs may impair response to thiazide or loop diuretics), and may contribute to cardiovascular events; monitor blood pressure and use with caution in patients with hypertension. May cause sodium and fluid retention, use with caution in patients with edema or heart failure. Long-term cardiovascular risk in children has not been evaluated. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce risk of cardiovascular events; alternative therapies should be considered for patients at high risk. The increased risk is about 37%. * Gastrointestinal events: NSAIDs may increase risk of serious gastrointestinal (GI) ulceration, bleeding, and perforation (may be fatal). These events may occur at any time during therapy and without warning. Use caution with a history of GI disease (bleeding or ulcers), concurrent therapy with aspirin, anticoagulants and/or corticosteroids, smoking, use of alcohol, the elderly or debilitated patients. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce risk of GI adverse events; alternate therapies should be considered for patients at high risk. When used concomitantly with ≤325 mg of aspirin, a substantial increase in the risk of gastrointestinal complications (e.g., ulcer) occurs; concomitant gastroprotective therapy (e.g., proton pump inhibitors) is recommended. The increased risk is about 81%. * Hematologic effects: Anemia may occur; monitor hemoglobin or hematocrit in people on long-term treatment.<unk>  does not usually affect prothrombin time, partial thromboplastin time or platelet counts; it does not inhibit platelet aggregation at approved doses. People with prior history of ulcer disease or GI bleeding require special precaution. Moderate to severe liver impairment or GI toxicity can occur with or without warning symptoms in people treated with NSAIDs. 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. Allergy<unk>  contains a sulfonamide moiety and may cause allergic reactions in those allergic to other sulfonamide-containing drugs. This is in addition to the contraindication in people with severe allergies to other NSAIDs. However, it has a low (reportedly 4%) chance of inducing cutaneous reactions among persons who have a history of such reactions to aspirin or nonselective NSAIDs. NSAIDs may cause serious skin adverse events, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis; events may occur without warning and in patients without prior known sulfa allergy. Use should be discontinued at first sign of rash (or any other hypersensitivity). Heart attack and stroke A 2013 meta-analysis of hundreds of clinical trials found that coxibs (the class of drugs that includes<unk>  increase the risk of major cardiovascular problems by about 37% over placebo. In 2016, a randomized trial provided strong evidence that treatment with<unk>  is not more likely to result in poor cardiovascular outcomes than treatment with naproxen or ibuprofen. As a result, in 2018 an FDA advisory panel concluded that<unk>  poses no greater risk for causing heart attacks and strokes than the commonly-used NSAIDs ibuprofen or naproxen and recommended that the FDA consider changing its advice to physicians regarding<unk> 's safety. The COX-2 inhibitor rofecoxib (Vioxx) was removed from the market in 2004 due to its risk. Like all NSAIDs on the US market,<unk>  carries an FDA-mandated "black box warning" for cardiovascular and gastrointestinal risk. In February 2007, the American Heart Association warned that with respect to "patients with a prior history of or at high risk for cardiovascular disease... use of COX-2 inhibitors for pain relief should be limited to patients for whom there are no appropriate alternatives, and then, only in the lowest dose and for the shortest duration necessary." In 2005, a study published in the Annals of Internal Medicine found that cardiovascular effects of COX-2 inhibitors differ, depending on the drug. Other COX-2-selective inhibitors, such as rofecoxib, have significantly higher myocardial infarction rates than<unk> . In April 2005, after an extensive review of data, the FDA concluded it was likely "that there is a 'class effect' for increased CV risk for all NSAIDs". In a 2006 meta-analysis of randomized control studies, the cerebrovascular events associated with COX-2 inhibitors were examined, but no significant risks were found when compared to nonselective NSAIDs or placebos. Drug interactions<unk>  is predominantly metabolized by cytochrome P450 2C9. Caution must be exercised with concomitant use of 2C9 inhibitors, such as fluconazole, which can greatly elevate<unk>  serum levels. If used concomitantly with lithium,<unk>  increases lithium plasma levels. If used concomitantly with warfarin,<unk>  may result in increased risk of bleeding complications. The risk of bleeding and gastric ulcers also increase further when SSRIs are used in combination with<unk> . The drug may increase the risk of kidney failure with angiotensin-converting enzyme-inhibitors, such as lisinopril, and diuretics, such as hydrochlorothiazide. Pregnancy In the US FDA's pregnancy categories, the drug is category C prior to 30 weeks gestation, and category D starting at 30 weeks gestation.
Celecoxib
Aceclofenac
Ketoprofen
Diclofenac
Fenoprofen
Valdecoxib
Naproxen
Loxoprofen