Editing Celecoxib (section)

==Adverse effects==
* Cardiovascular events: <!-- [US Boxed Warning]: --> 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 before 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. Celecoxib may cause sodium and fluid retention, so its use in patients with edema or heart failure warrants caution. 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 the risk of cardiovascular events; alternative therapies should be considered for patients at high risk.<ref>{{cite journal | vauthors = Solomon SD, McMurray JJ, Pfeffer MA, Wittes J, Fowler R, Finn P, Anderson WF, [[Ann Zauber|Zauber A]], Hawk E, Bertagnolli M | title = Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention | journal = The New England Journal of Medicine | volume = 352 | issue = 11 | pages = 1071–80 | date = March 2005 | pmid = 15713944 | doi = 10.1056/NEJMoa050405 | doi-access = free }}</ref> The increased risk is about 37%.<ref name=Coxib2013/>
* Gastrointestinal events: <!-- [US Boxed Warning]: --> NSAIDs may increase the 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 (drug)|alcohol]], and the elderly or debilitated patients. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce the risk of GI adverse events; alternate therapies should be considered for patients at high risk. When used concomitantly with ≤325&nbsp;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.<ref name="Celebrex FDA label">{{cite web | title=Celebrex- celecoxib capsule | website=DailyMed | date=31 May 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8d52185d-421f-4e34-8db7-f7676db2a226 | access-date=5 May 2020 | archive-date=24 February 2021 | archive-url=https://web.archive.org/web/20210224181140/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8d52185d-421f-4e34-8db7-f7676db2a226 | url-status=live }}</ref> The increased risk is about 81%.<ref name=Coxib2013/>
* Hematologic effects: Anemia may occur; monitor hemoglobin or hematocrit in people on long-term treatment. Celecoxib does not usually affect [[prothrombin time]], [[partial thromboplastin time]], or [[platelet]] counts; it does not inhibit platelet aggregation at approved doses.

People with a prior history of ulcer disease or GI bleeding require special precautions. 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 labelling|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.<ref name="FDA PR 20201015" /><ref name="FDA safety 20201015" /> They recommend avoiding NSAIDs in pregnant women at 20 weeks or later in pregnancy.<ref name="FDA PR 20201015">{{cite press release | title=FDA Warns that Using a Type of Pain and Fever Medication in Second Half of Pregnancy Could Lead to Complications | website=U.S. [[Food and Drug Administration]] (FDA) | date=15 October 2020 | url=https://www.fda.gov/news-events/press-announcements/fda-warns-using-type-pain-and-fever-medication-second-half-pregnancy-could-lead-complications | access-date=15 October 2020 | archive-date=16 October 2020 | archive-url=https://web.archive.org/web/20201016180003/https://www.fda.gov/news-events/press-announcements/fda-warns-using-type-pain-and-fever-medication-second-half-pregnancy-could-lead-complications | url-status=dead }} {{PD-notice}}</ref><ref name="FDA safety 20201015">{{cite web | title=NSAIDs may cause rare kidney problems in unborn babies | website=U.S. Food and Drug Administration | date=21 July 2017 | url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-recommends-avoiding-use-nsaids-pregnancy-20-weeks-or-later-because-they-can-result-low-amniotic | access-date=15 October 2020 | archive-date=17 October 2020 | archive-url=https://web.archive.org/web/20201017014419/https://www.fda.gov/drugs/drug-safety-and-availability/fda-recommends-avoiding-use-nsaids-pregnancy-20-weeks-or-later-because-they-can-result-low-amniotic | url-status=dead }} {{PD-notice}}</ref>

===Allergy===
Celecoxib contains a [[sulfonamide (chemistry)|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|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 the 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 celecoxib) increase the risk of major cardiovascular problems by about 37% over placebo.<ref name=Coxib2013>{{cite journal | vauthors = Bhala N, Emberson J, Merhi A, Abramson S, Arber N, Baron JA, Bombardier C, Cannon C, Farkouh ME, FitzGerald GA, Goss P, Halls H, Hawk E, Hawkey C, Hennekens C, Hochberg M, Holland LE, Kearney PM, Laine L, Lanas A, Lance P, Laupacis A, Oates J, Patrono C, Schnitzer TJ, Solomon S, Tugwell P, Wilson K, Wittes J, Baigent C | title = Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials | journal = Lancet | volume = 382 | issue = 9894 | pages = 769–79 | date = August 2013 | pmid = 23726390 | pmc = 3778977 | doi = 10.1016/S0140-6736(13)60900-9 }}</ref> In 2016, a randomized trial provided strong evidence that treatment with celecoxib is not more likely to result in poor cardiovascular outcomes than treatment with naproxen or ibuprofen.<ref name="NissenYeomans2016">{{cite journal | vauthors = Nissen SE, Yeomans ND, Solomon DH, Lüscher TF, Libby P, Husni ME, Graham DY, Borer JS, Wisniewski LM, Wolski KE, Wang Q, Menon V, Ruschitzka F, Gaffney M, Beckerman B, Berger MF, Bao W, Lincoff AM | title = Cardiovascular Safety of Celecoxib, Naproxen, or Ibuprofen for Arthritis | journal = The New England Journal of Medicine | volume = 375 | issue = 26 | pages = 2519–29 | date = December 2016 | pmid = 27959716 | doi = 10.1056/NEJMoa1611593 | doi-access = free }}</ref> As a result, in 2018 an FDA advisory panel concluded that celecoxib 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 celecoxib's safety.<ref name=NPR2018/>

The COX-2 inhibitor [[rofecoxib]] (Vioxx) was removed from the market in 2004 due to its risk. Like all NSAIDs on the US market, celecoxib 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."<ref name="AHA2007"/>

In 2005, a study published in the ''[[Annals of Internal Medicine]]'' found that cardiovascular effects of COX-2 inhibitors differ, depending on the drug.<ref name="pmid15684203">{{cite journal | vauthors = Kimmel SE, Berlin JA, Reilly M, Jaskowiak J, Kishel L, Chittams J, Strom BL | title = Patients exposed to rofecoxib and celecoxib have different odds of nonfatal myocardial infarction | journal = Annals of Internal Medicine | volume = 142 | issue = 3 | pages = 157–64 | date = February 2005 | pmid = 15684203 | doi = 10.7326/0003-4819-142-3-200502010-00005 | doi-access = free }}</ref> Other COX-2-selective inhibitors, such as rofecoxib, have significantly higher myocardial infarction rates than celecoxib.<ref name="pmid11509060">{{cite journal | vauthors = Mukherjee D, Nissen SE, Topol EJ | title = Risk of cardiovascular events associated with selective COX-2 inhibitors | journal = JAMA | volume = 286 | issue = 8 | pages = 954–9 | year = 2001 | pmid = 11509060 | doi = 10.1001/jama.286.8.954 }}</ref> 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".<ref name="Jenkins">{{cite web |vauthors=Jenkins JK, Seligman PJ | title=Analysis and recommendations for Agency action regarding nonsteroidal anti-inflammatory drugs and cardiovascular risk [decision memorandum] | url=https://www.fda.gov/cder/drug/infopage/cox2/NSAIDdecisionMemo.pdf | archive-url=https://web.archive.org/web/20050909082236/https://www.fda.gov/cder/drug/infopage/cox2/NSAIDdecisionMemo.pdf | url-status=dead | archive-date=9 September 2005 | date=6 April 2005 | publisher=U.S. [[Food and Drug Administration]] (FDA) }}</ref> In a 2006 [[meta-analysis]] of randomized control studies, the [[cerebrovascular disease|cerebrovascular events]] associated with COX-2 inhibitors were examined, but no significant risks were found when compared to nonselective NSAIDs or placebos.<ref name="pmid17176361">{{cite journal | vauthors = Chen LC, Ashcroft DM | title = Do selective COX-2 inhibitors increase the risk of cerebrovascular events? A meta-analysis of randomized controlled trials | journal = Journal of Clinical Pharmacy and Therapeutics | volume = 31 | issue = 6 | pages = 565–76 | date = December 2006 | pmid = 17176361 | doi = 10.1111/j.1365-2710.2006.00774.x | s2cid = 40738580 | doi-access = free }}</ref>

===Drug interactions===
Celecoxib undergoes metabolism primarily by the enzymes [[CYP2C9]] and [[CYP3A4]], but it also interacts with [[CYP2D6]], inhibiting its activity without being metabolized by it.<ref name="Shkundin_2025">{{cite journal | vauthors = Shkundin A, Wheeler HE, Sinacore J, Halaris A | title = BDNF/BDNF-AS Gene Polymorphisms Modulate Treatment Response and Remission in Bipolar Disorder: A Randomized Clinical Trial | journal = Journal of Personalized Medicine | volume = 15 | issue = 2 | pages = 62 | year = 2025 | doi = 10.3390/jpm15020062 | doi-access = free| pmid = 39997339 | pmc = 11856652 }}</ref> The CYP2C9 gene exhibits considerable genetic variability, with common polymorphisms, such as [[CYP2C9 | rs1799853]] and [[CYP2C9 | rs1057910]], linked to reduced enzyme activity and altered pharmacokinetics of celecoxib.<ref name="Shkundin_2025"/> Additionally, the influence of CYP2D6 on celecoxib metabolism is inconsistent, with its effect varying depending on the individual’s CYP2C9 genetic profile.<ref name="Shkundin_2025"/>

Caution must be exercised with concomitant use of 2C9 inhibitors, such as [[fluconazole]], which can greatly elevate celecoxib serum levels.<ref name="Celebrex FDA label"/> If used concomitantly with lithium, celecoxib increases lithium plasma levels.<ref name="Celebrex FDA label"/> If used concomitantly with warfarin, celecoxib may result in an increased risk of bleeding complications.<ref name="Celebrex FDA label"/> The risk of bleeding and gastric ulcers also increases further when [[selective serotonin reuptake inhibitor]]s (SSRI) are used in combination with celecoxib.<ref>{{cite journal | vauthors = Turner MS, May DB, Arthur RR, Xiong GL | title = Clinical impact of selective serotonin reuptake inhibitors therapy with bleeding risks | journal = Journal of Internal Medicine | volume = 261 | issue = 3 | pages = 205–213 | date = March 2007 | pmid = 17305643 | doi = 10.1111/j.1365-2796.2006.01720.x | s2cid = 41772614 | doi-access = free }}</ref> The drug may increase the risk of kidney failure with [[angiotensin]]-converting enzyme-inhibitors, such as [[lisinopril]], and [[diuretic]]s, such as [[hydrochlorothiazide]].<ref name="Celebrex FDA label"/>