Editing Aspirin (section)

==Adverse effects==
[[File:Side effects of aspirin.svg|thumb|Main side effects of aspirin]]

In October 2020, the US [[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">{{citation-attribution|1={{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}} }}</ref><ref name="FDA safety 20201015">{{citation-attribution|1={{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}} }}</ref> One exception to the recommendation is the use of low-dose 81{{nbsp}}mg aspirin at any point in pregnancy under the direction of a health care professional.<ref name="FDA safety 20201015" />

===Contraindications===
<!-- Note that Contraindications is spelled correctly! It does not need to be changed. -->

Aspirin should not be taken by people who are allergic to [[ibuprofen]] or [[naproxen]],<ref name="drugs.com" /><ref name="personalmd">{{cite web |url=http://www.personalmd.com/drgdb/3.htm |archive-url=https://web.archive.org/web/20000918231717/http://personalmd.com/drgdb/3.htm |url-status=dead |archive-date=18 September 2000 |title=Oral Aspirin information |access-date=8 May 2008 |publisher=First DataBank }}</ref> or who have [[salicylate intolerance]]<ref name="pmid16247191">{{cite journal | vauthors = Raithel M, Baenkler HW, Naegel A, Buchwald F, Schultis HW, Backhaus B, Kimpel S, Koch H, Mach K, Hahn EG, Konturek PC | title = Significance of salicylate intolerance in diseases of the lower gastrointestinal tract | journal = Journal of Physiology and Pharmacology | volume = 56 | issue = Suppl 5 | pages = 89–102 | date = September 2005 | pmid = 16247191 | url = http://www.jpp.krakow.pl/journal/archive/09_05_s5/pdf/89_09_05_s5_article.pdf | url-status = live | archive-url = https://web.archive.org/web/20110409093851/http://www.jpp.krakow.pl/journal/archive/09_05_s5/pdf/89_09_05_s5_article.pdf | archive-date = 9 April 2011 }}</ref><ref name="pmid8566739">{{cite journal | vauthors = Senna GE, Andri G, Dama AR, Mezzelani P, Andri L | title = Tolerability of imidazole salycilate in aspirin-sensitive patients | journal = Allergy Proceedings | volume = 16 | issue = 5 | pages = 251–254 | year = 1995 | pmid = 8566739 | doi = 10.2500/108854195778702675 }}</ref> 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 ulcer]]s, mild diabetes, or [[gastritis]] seek medical advice before using aspirin.<ref name="drugs.com" /><ref name="mercksource">{{cite web |title = PDR guide to over the counter (OTC) drugs |url=http://www.mercksource.com/pp/us/cns/cns_hl_pdr.jspzQzpgzEzzSzppdocszSzuszSzcnszSzcontentzSzpdrotczSzotc_fullzSzdrugszSzfgotc036zPzhtm |access-date =28 April 2008 |archive-url= https://web.archive.org/web/20080410223441/http://www.mercksource.com/pp/us/cns/cns_hl_pdr.jspzQzpgzEzzSzppdocszSzuszSzcnszSzcontentzSzpdrotczSzotc_fullzSzdrugszSzfgotc036zPzhtm |archive-date= 10 April 2008 |url-status= live}}</ref> Even if none of these conditions is present, the risk of [[gastrointestinal hemorrhage|stomach bleeding]] is still increased when aspirin is taken with [[alcoholic beverage|alcohol]] or [[warfarin]].<ref name="drugs.com" /><ref name="personalmd" /> People with [[hemophilia]] or other bleeding tendencies should not take aspirin or other salicylates.<ref name="drugs.com" /><ref name="mercksource" /> Aspirin 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.<ref>{{cite book |title = Frequencies of hemoglobin variants: thalassemia, the glucose-6-phosphate dehydrogenase deficiency, G6PD variants, and ovalocytosis in human populations |url=https://books.google.com/books?id=OjqNeJERhWwC&q=0195036344|publisher=Oxford University Press |isbn = 978-0-19-503634-3 |vauthors = Livingstone FB |year = 1985}}</ref> Use of aspirin during [[dengue fever]] is not recommended owing to increased bleeding tendency.<ref>{{cite web |title= Dengue and dengue hemorrhagic fever: information for health care practitioners |url = https://www.cdc.gov/NCIDOD/dvbid/dengue/dengue-hcp.htm |access-date =28 April 2008 |archive-url = https://web.archive.org/web/20080317070305/http://www.cdc.gov/Ncidod/dvbid/dengue/dengue-hcp.htm |archive-date = 17 March 2008 }}</ref> Aspirin taken at doses of ≤325&nbsp;mg and ≤100&nbsp;mg per day for ≥2 days can increase the odds of suffering a gout attack by 81% and 91% respectively. This effect may potentially be worsened by high purine diets, diuretics, and kidney disease, but is eliminated by the urate lowering drug allopurinol.<ref>{{cite journal | vauthors = Zhang Y, Neogi T, Chen C, Chaisson C, Hunter DJ, Choi H | title = Low-dose aspirin use and recurrent gout attacks | journal = Annals of the Rheumatic Diseases | volume = 73 | issue = 2 | pages = 385–390 | date = February 2014 | pmid = 23345599 | pmc = 3902644 | doi = 10.1136/annrheumdis-2012-202589 }}</ref> Daily low dose aspirin does not appear to worsen kidney function.<ref>{{cite journal | vauthors = Polkinghorne KR, Wetmore JB, Thao LT, Wolfe R, Woods RL, Ernst ME, Nelson MR, Reid CM, Shah RC, McNeil JJ, Murray AM | title = Effect of Aspirin on CKD Progression in Older Adults: Secondary Analysis From the ASPREE Randomized Clinical Trial | journal = American Journal of Kidney Diseases | volume = 80 | issue = 6 | pages = 810–813 | date = December 2022 | pmid = 35430328 | pmc = 9562592 | doi = 10.1053/j.ajkd.2022.02.019 }}</ref> Aspirin may reduce cardiovascular risk in those without established cardiovascular disease in people with moderate CKD, without significantly increasing the risk of bleeding.<ref>{{cite journal | vauthors = Mann JF, Joseph P, Gao P, Pais P, Tyrwhitt J, Xavier D, Dans T, Jaramillo PL, Gamra H, Yusuf S | title = Effects of aspirin on cardiovascular outcomes in patients with chronic kidney disease | journal = Kidney International | volume = 103 | issue = 2 | pages = 403–410 | date = February 2023 | pmid = 36341885 | doi = 10.1016/j.kint.2022.09.023 | s2cid = 253194139 | doi-access = free }}</ref> Aspirin should not be given to children or adolescents under the age of 16 to control cold or influenza symptoms, as this has been linked with [[Reye syndrome]].<ref name="BMJ2002-Macdonald">{{cite journal | vauthors = Macdonald S | title = Aspirin use to be banned in under 16 year olds | journal = BMJ | volume = 325 | issue = 7371 | pages = 988c–988 | date = November 2002 | pmid = 12411346 | pmc = 1169585 | doi = 10.1136/bmj.325.7371.988/c }}</ref>

===Gastrointestinal===

Aspirin increases the risk of [[upper gastrointestinal bleeding]].<ref name="Sorensen 2000">{{cite journal | vauthors = Sørensen HT, Mellemkjaer L, Blot WJ, Nielsen GL, Steffensen FH, McLaughlin JK, Olsen JH | title = Risk of upper gastrointestinal bleeding associated with use of low-dose aspirin | journal = The American Journal of Gastroenterology | volume = 95 | issue = 9 | pages = 2218–2224 | date = September 2000 | pmid = 11007221 | doi = 10.1016/s0002-9270(00)01040-6 }}</ref> Enteric coating on aspirin may be used in manufacturing to prevent release of aspirin into the stomach to reduce gastric harm, but enteric coating does not reduce gastrointestinal bleeding risk.<ref name="Sorensen 2000" /><ref name="Kedir 2021">{{cite journal | vauthors = Kedir HM, Sisay EA, Abiye AA | title = Enteric-Coated Aspirin and the Risk of Gastrointestinal Side Effects: A Systematic Review | journal = International Journal of General Medicine | volume = 14 | pages = 4757–4763 | year = 2021 | pmid = 34466020 | doi = 10.2147/ijgm.s326929 | pmc = 8403009 | doi-access = free }}</ref> Enteric-coated aspirin may not be as effective at reducing blood clot risk.<ref>{{cite web | vauthors = Torborg L | title=Mayo Clinic Q and A: Coated aspirin may not be as effective at reducing blood clot risk | website=Mayo Clinic News Network | date=4 December 2018 | url=https://newsnetwork.mayoclinic.org/discussion/mayo-clinic-q-and-a-coated-aspirin-may-not-be-as-effective-at-reducing-blood-clot-risk/}}</ref><ref>{{cite journal | vauthors = Cox D, Maree AO, Dooley M, Conroy R, Byrne MF, Fitzgerald DJ | title = Effect of enteric coating on antiplatelet activity of low-dose aspirin in healthy volunteers | journal = Stroke | volume = 37 | issue = 8 | pages = 2153–2158 | date = August 2006 | pmid = 16794200 | doi = 10.1161/01.STR.0000231683.43347.ec | s2cid = 8034371 | doi-access = free }}</ref> Combining aspirin with other [[Nonsteroidal anti-inflammatory drug|NSAIDs]] has been shown to further increase the risk of gastrointestinal bleeding.<ref name="Sorensen 2000" /> Using aspirin in combination with clopidogrel or warfarin also increases the risk of upper gastrointestinal bleeding.<ref>{{cite journal | vauthors = Delaney JA, Opatrny L, Brophy JM, Suissa S | title = Drug drug interactions between antithrombotic medications and the risk of gastrointestinal bleeding | journal = CMAJ | volume = 177 | issue = 4 | pages = 347–351 | date = August 2007 | pmid = 17698822 | pmc = 1942107 | doi = 10.1503/cmaj.070186 }}</ref>

The blockade of COX-1 by aspirin apparently results in the upregulation of COX-2 as part of a gastric defense.<ref>{{cite journal |vauthors = Wallace JL |title = Prostaglandins, NSAIDs, and gastric mucosal protection: why doesn't the stomach digest itself? |journal = Physiological Reviews |volume = 88 |issue = 4 |pages = 1547–65 |date = October 2008 |pmid = 18923189 |doi = 10.1152/physrev.00004.2008 |s2cid = 448875 }}</ref> There is no clear evidence that simultaneous use of a COX-2 inhibitor with aspirin may increase the risk of gastrointestinal injury.<ref name="Rostom-2007">{{cite journal |vauthors = Rostom A, Muir K, Dubé C, Jolicoeur E, Boucher M, Joyce J, Tugwell P, Wells GW |title = Gastrointestinal safety of cyclooxygenase-2 inhibitors: a Cochrane Collaboration systematic review |journal = Clinical Gastroenterology and Hepatology |volume = 5 |issue = 7 |pages = 818–28, 828.e1-5; quiz 768 |date = July 2007 |pmid = 17556027 |doi = 10.1016/j.cgh.2007.03.011 |doi-access = free }}</ref>

"[[Buffer solution|Buffering]]" is an additional method used with the intent to mitigate gastrointestinal bleeding, such as by preventing aspirin from concentrating in the walls of the stomach, although the benefits of buffered aspirin are disputed.<ref name="Clerici_2023">{{cite journal | vauthors = Clerici B, Cattaneo M | title = Pharmacological Efficacy and Gastrointestinal Safety of Different Aspirin Formulations for Cardiovascular Prevention: A Narrative Review | journal = Journal of Cardiovascular Development and Disease | volume = 10 | issue = 4 | date = March 2023 | page = 137 | pmid = 37103016 | pmc = 10145431 | doi = 10.3390/jcdd10040137 | doi-access = free }}</ref> Almost any buffering agent used in antacids can be used; Bufferin, for example, uses [[magnesium oxide]]. Other preparations use [[calcium carbonate]].<ref>{{cite web |url=http://antoine.frostburg.edu/chem/senese/101/acidbase/faq/buffered-aspirin.shtml |title=General chemistry online: FAQ: Acids and bases: What is the buffer system in buffered aspirin? |publisher=Antoine.frostburg.edu |access-date=11 May 2011 |url-status=live |archive-url=https://web.archive.org/web/20110414145143/http://antoine.frostburg.edu/chem/senese/101/acidbase/faq/buffered-aspirin.shtml |archive-date=14 April 2011}}</ref> Gas-forming agents in [[effervescent tablet|effervescent tablet and powder]] formulations can also double as a buffering agent, one example being [[sodium bicarbonate]], used in [[Alka-Seltzer]].<ref>{{cite journal | vauthors = Davison C, Smith BW, Smith PK | title = Effects of buffered and unbuffered acetylsalicylic acid upon the gastric acidity of normal human subjects | journal = Journal of Pharmaceutical Sciences | volume = 51 | issue = 8 | pages = 759–763 | date = August 1962 | pmid = 13883982 | doi = 10.1002/jps.2600510813 }}</ref>

Taking vitamin C with aspirin has been investigated as a method of protecting the stomach lining. In trials, vitamin C-releasing aspirin (ASA-VitC) or a buffered aspirin formulation containing vitamin C was found to cause less stomach damage than aspirin alone.<ref name="Dammann">{{cite journal |vauthors = Dammann HG, Saleki M, Torz M, Schulz HU, Krupp S, Schürer M, Timm J, Gessner U |title = Effects of buffered and plain acetylsalicylic acid formulations with and without ascorbic acid on gastric mucosa in healthy subjects |journal = Alimentary Pharmacology & Therapeutics |volume = 19 |issue = 3 |pages = 367–74 |date = February 2004 |pmid = 14984384 |doi = 10.1111/j.1365-2036.2004.01742.x |s2cid = 22688422 |doi-access = free | title-link = doi }}</ref><ref name="Konturek">{{cite journal |vauthors = Konturek PC, Kania J, Hahn EG, Konturek JW |title = Ascorbic acid attenuates aspirin-induced gastric damage: role of inducible nitric oxide synthase |journal = Journal of Physiology and Pharmacology |volume = 57 |issue = Suppl 5 |pages = 125–36 |date = November 2006 |pmid = 17218764 }}</ref>

===Retinal vein occlusion===
It is a widespread habit among eye specialists (ophthalmologists) to prescribe aspirin 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).{{medical citation needed|date=April 2025}} The reason of this widespread use is the evidence of its proven effectiveness in major systemic venous [[Thrombosis|thrombotic]] disorders, and it has been assumed that may be similarly beneficial in various types of retinal vein occlusion.{{medical citation needed|date=April 2025}}

However, a large-scale investigation based on data of nearly 700 patients showed "that aspirin 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".<ref name="pmid24769221">{{cite journal |vauthors = Hayreh SS |title = Ocular vascular occlusive disorders: natural history of visual outcome |journal = Progress in Retinal and Eye Research |volume = 41 |pages = 1–25 |date = July 2014 |pmid = 24769221 |pmc = 4073304 |doi = 10.1016/j.preteyeres.2014.04.001 }}</ref> Several expert groups, including the [[Royal College of Ophthalmologists]], recommended against the use of antithrombotic drugs (incl. aspirin) for patients with RVO.<ref name="pmid26780742">{{cite journal |vauthors = Ageno W, Beyer-Westendorf J, Garcia DA, Lazo-Langner A, McBane RD, Paciaroni M |title = Guidance for the management of venous thrombosis in unusual sites |journal = Journal of Thrombosis and Thrombolysis |volume = 41 |issue = 1 |pages = 129–43 |date = January 2016 |pmid = 26780742 |pmc = 4715841 |doi = 10.1007/s11239-015-1308-1 }}</ref>

===Central effects===
Large doses of [[salicylate]], a metabolite of aspirin, cause temporary [[tinnitus]] (ringing in the ears) based on experiments in rats, as the action on [[arachidonic acid]] and [[NMDA receptor]]s cascade.<ref name="Gutton">{{cite journal |vauthors = Guitton MJ, Caston J, Ruel J, Johnson RM, Pujol R, Puel JL |title = Salicylate induces tinnitus through activation of cochlear NMDA receptors |journal = The Journal of Neuroscience |volume = 23 |issue = 9 |pages = 3944–52 |date = May 2003 |pmid = 12736364 |pmc = 6742173 |doi = 10.1523/JNEUROSCI.23-09-03944.2003 }}</ref>

===Reye syndrome===
{{Main|Reye syndrome}}
Reye syndrome, a rare but severe illness characterized by acute [[encephalopathy]] and [[fatty liver]], can occur when children or adolescents are given aspirin for a fever or other illness or infection. From 1981 to 1997, 1207 cases of Reye syndrome in people younger than 18 were reported to the US [[Centers for Disease Control and Prevention]] (CDC). Of these, 93% reported being ill in the three weeks preceding the onset of Reye syndrome, most commonly with a [[Respiratory tract infection|respiratory infection]], [[chickenpox]], or [[diarrhea]]. Salicylates were detectable in 81.9% of children for whom test results were reported.<ref name=Belay>{{cite journal |vauthors = Belay ED, Bresee JS, Holman RC, Khan AS, Shahriari A, Schonberger LB |title = Reye's syndrome in the United States from 1981 through 1997 |journal = The New England Journal of Medicine |volume = 340 |issue = 18 |pages = 1377–82 |date = May 1999 |pmid = 10228187 |doi = 10.1056/NEJM199905063401801 |doi-access = free }}</ref> After the association between Reye syndrome and aspirin was reported, and safety measures to prevent it (including a [[Surgeon General of the United States|Surgeon General]]'s warning, and changes to the labeling of aspirin-containing drugs) were implemented, aspirin taken by children declined considerably in the United States, as did the number of reported cases of Reye syndrome; a similar decline was found in the United Kingdom after warnings against pediatric aspirin use were issued.<ref name=Belay/> The US [[Food and Drug Administration]] recommends aspirin (or aspirin-containing products) should not be given to anyone under the age of 12 who has a fever,<ref name="BMJ2002-Macdonald"/> and the UK [[National Health Service]] recommends children who are under 16 years of age should not take aspirin, unless it is on the advice of a doctor.<ref>{{cite web |url=https://www.nhs.uk/conditions/reyes-syndrome/|title= Reye's syndrome |publisher=National Health Service |work=Health A to Z|date= 14 September 2023|access-date=24 August 2024}}</ref>

===Skin===
For a small number of people, taking aspirin can result in symptoms including [[hives]], swelling, and headache.<ref>{{cite web |url=https://health.clevelandclinic.org/are-you-sensitive-to-aspirin-here-are-some-reasons-why/ |title=Are You Sensitive to Aspirin? Here are Some Reasons Why |date=5 February 2015 |website=Health Essentials from Cleveland Clinic |access-date=5 March 2020 |archive-date=25 October 2020 |archive-url=https://web.archive.org/web/20201025171549/https://health.clevelandclinic.org/are-you-sensitive-to-aspirin-here-are-some-reasons-why/ |url-status=dead }}</ref> Aspirin can exacerbate symptoms among those with chronic hives, or create acute symptoms of hives.<ref name="Doña-2018">{{cite journal |vauthors = Doña I, Barrionuevo E, Salas M, Laguna JJ, Agúndez J, García-Martín E, Bogas G, Perkins JR, Cornejo-García JA, Torres MJ |title = NSAIDs-hypersensitivity often induces a blended reaction pattern involving multiple organs |journal = Scientific Reports |volume = 8 |issue = 1 |pages = 16710 |date = November 2018 |pmid = 30420763 |pmc = 6232098 |doi = 10.1038/s41598-018-34668-1 |bibcode = 2018NatSR...816710D }}</ref> These responses can be due to allergic reactions to aspirin, or more often due to its effect of inhibiting the COX-1 enzyme.<ref name="Doña-2018" /><ref name="Kowalski-2019">{{cite journal |vauthors = Kowalski ML, Agache I, Bavbek S, Bakirtas A, Blanca M, Bochenek G, Bonini M, Heffler E, Klimek L, Laidlaw TM, Mullol J, Niżankowska-Mogilnicka E, Park HS, Sanak M, Sanchez-Borges M, Sanchez-Garcia S, Scadding G, Taniguchi M, Torres MJ, White AA, Wardzyńska A |title = Diagnosis and management of NSAID-Exacerbated Respiratory Disease (N-ERD)-a EAACI position paper |journal = Allergy |volume = 74 |issue = 1 |pages = 28–39 |date = January 2019 |pmid = 30216468 |doi = 10.1111/all.13599 |s2cid = 52276808 |doi-access = free | title-link = doi }}</ref> Skin reactions may also tie to systemic contraindications, seen with NSAID-precipitated [[bronchospasm]],<ref name="Doña-2018" /><ref name="Kowalski-2019" /> or those with [[atopy]].<ref>{{cite journal |vauthors = Sánchez-Borges M, Capriles-Hulett A |title = Atopy is a risk factor for non-steroidal anti-inflammatory drug sensitivity |journal = Annals of Allergy, Asthma & Immunology |volume = 84 |issue = 1 |pages = 101–6 |date = January 2000 |pmid = 10674573 |doi = 10.1016/S1081-1206(10)62748-2 }}</ref>

Aspirin and other NSAIDs, such as ibuprofen, may delay the healing of skin wounds.<ref>{{cite journal |vauthors=Stadelmann WK, Digenis AG, Tobin GR |title=Impediments to wound healing |journal=American Journal of Surgery |volume=176 |issue=2A Suppl |pages=39S–47S |date=August 1998 |pmid=9777971 |doi=10.1016/S0002-9610(98)00184-6}}</ref> Earlier findings from two small, low-quality trials suggested a benefit with aspirin (alongside compression therapy) on venous leg ulcer healing time and leg ulcer size,<ref>{{cite journal |vauthors=Layton AM, Ibbotson SH, Davies JA, Goodfield MJ |title=Randomised trial of oral aspirin for chronic venous leg ulcers |journal=Lancet |volume=344 |issue=8916 |pages=164–5 |date=July 1994 |pmid=7912767 |doi=10.1016/s0140-6736(94)92759-6 |s2cid=912169}}</ref><ref>{{cite journal |vauthors=del Río Solá ML, Antonio J, Fajardo G, Vaquero Puerta C |title=Influence of aspirin therapy in the ulcer associated with chronic venous insufficiency |journal=Annals of Vascular Surgery |volume=26 |issue=5 |pages=620–9 |date=July 2012 |pmid=22437068 |doi=10.1016/j.avsg.2011.02.051 | hdl=10324/2904 |hdl-access=free }}</ref><ref>{{cite journal |vauthors=de Oliveira Carvalho PE, Magolbo NG, De Aquino RF, Weller CD |title=Oral aspirin for treating venous leg ulcers |journal=The Cochrane Database of Systematic Reviews |volume=2016 |pages=CD009432 |date=February 2016 |issue=2 |pmid=26889740 |doi=10.1002/14651858.CD009432.pub2 |pmc=8627253 |collaboration=Cochrane Wounds Group}}</ref> however, larger, more recent studies of higher quality have been unable to corroborate these outcomes.<ref>{{cite journal |vauthors=Jull A, Wadham A, Bullen C, Parag V, Kerse N, Waters J |title=Low dose aspirin as adjuvant treatment for venous leg ulceration: pragmatic, randomised, double blind, placebo controlled trial (Aspirin4VLU) |journal=BMJ |volume=359 |pages=j5157 |date=November 2017 |pmid=29175902 |pmc=5701114 |doi=10.1136/bmj.j5157}}</ref><ref>{{cite journal|vauthors=Tilbrook H, Clark L, Cook L, Bland M, Buckley H, Chetter I, Dumville J, Fenner C, Forsythe R, Gabe R, Harding K, Layton A, Lindsay E, McDaid C, Moffatt C, Rolfe D, Sbizzera I, Stansby G, Torgerson D, Vowden P, Williams L, Hinchliffe R|date=October 2018|title=AVURT: aspirin versus placebo for the treatment of venous leg ulcers - a Phase II pilot randomised controlled trial|journal=Health Technology Assessment|volume=22|issue=55|pages=1–138|doi=10.3310/hta22550|pmc=6204573|pmid=30325305}}</ref>

===Other adverse effects===
Aspirin can induce [[angioedema|swelling of skin tissues]] in some people. In one study, [[angioedema]] appeared one to six hours after ingesting aspirin in some of the people. However, when the aspirin was taken alone, it did not cause angioedema in these people; the aspirin had been taken in combination with another NSAID-induced drug when angioedema appeared.<ref>{{cite journal |vauthors = Berges-Gimeno MP, Stevenson DD |title = Nonsteroidal anti-inflammatory drug-induced reactions and desensitization |journal = The Journal of Asthma |volume = 41 |issue = 4 |pages = 375–84 |date = June 2004 |pmid = 15281324 |doi = 10.1081/JAS-120037650 |s2cid = 29909460 }}</ref>

Aspirin causes an increased risk of cerebral microbleeds, having the appearance on [[MRI]] scans of 5 to 10{{nbsp}}mm or smaller, hypointense (dark holes) patches.<ref>{{cite journal |vauthors = Vernooij MW, Haag MD, van der Lugt A, Hofman A, Krestin GP, Stricker BH, Breteler MM |title = Use of antithrombotic drugs and the presence of cerebral microbleeds: the Rotterdam Scan Study |journal = Archives of Neurology |volume = 66 |issue = 6 |pages = 714–20 | date = June 2009 |pmid = 19364926 |doi = 10.1001/archneurol.2009.42 |doi-access = free | title-link = doi }}</ref><ref>{{cite journal |vauthors = Gorelick PB |title = Cerebral microbleeds: evidence of heightened risk associated with aspirin use |journal = Archives of Neurology |volume = 66 |issue = 6 |pages = 691–3 |date = June 2009 |pmid = 19506128 |doi = 10.1001/archneurol.2009.85 }}</ref>

A study of a group with a mean dosage of aspirin of 270{{nbsp}}mg per day estimated an average absolute risk increase in [[intracerebral hemorrhage]] (ICH) of 12 events per 10,000 persons.<ref name=He1998/> 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.<ref name=He1998>{{cite journal |vauthors = He J, Whelton PK, Vu B, Klag MJ |title = Aspirin and risk of hemorrhagic stroke: a meta-analysis of randomized controlled trials |journal = JAMA |volume = 280 |issue = 22 |pages = 1930–5 |date = December 1998 |pmid = 9851479 |doi = 10.1001/jama.280.22.1930 |s2cid = 22997730 }}</ref> In cases where ICH already has occurred, aspirin use results in higher mortality, with a dose of about 250{{nbsp}}mg 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).<ref name=Saloheimo2006>{{cite journal |vauthors = Saloheimo P, Ahonen M, Juvela S, Pyhtinen J, Savolainen ER, Hillbom M |title = Regular aspirin-use preceding the onset of primary intracerebral hemorrhage is an independent predictor for death |journal = Stroke |volume = 37 |issue = 1 |pages = 129–33 |date = January 2006 |pmid = 16322483 |doi = 10.1161/01.STR.0000196991.03618.31 |doi-access = free | title-link = doi }}</ref>

Aspirin and other NSAIDs can cause [[hyperkalemia|abnormally high blood levels of potassium]] by inducing a [[hyporeninemic hypoaldosteronism|hyporeninemic hypoaldosteronism 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.<ref>Medical knowledge self-assessment program for students 4, By American College of Physicians, Clerkship Directors in Internal Medicine, Nephrology 227, Item 29</ref>

Use of low-dose aspirin before a surgical procedure has been associated with an increased risk of bleeding events in some patients, however, ceasing aspirin prior to surgery has also been associated with an increase in major adverse cardiac events. An analysis of multiple studies found a three-fold increase in adverse events such as [[myocardial infarction]] in patients who ceased aspirin prior to surgery. The analysis found that the risk is dependent on the type of surgery being performed and the patient indication for aspirin use.<ref>{{cite journal | vauthors = Biondi-Zoccai GG, Lotrionte M, Agostoni P, Abbate A, Fusaro M, Burzotta F, Testa L, Sheiban I, Sangiorgi G | title = A systematic review and meta-analysis on the hazards of discontinuing or not adhering to aspirin among 50,279 patients at risk for coronary artery disease | journal = European Heart Journal | volume = 27 | issue = 22 | pages = 2667–2674 | date = November 2006 | pmid = 17053008 | doi = 10.1093/eurheartj/ehl334 }}</ref>

In July 2015, the US [[Food and Drug Administration]] (FDA) strengthened warnings of increased [[heart attack]] and [[stroke]] risk associated with [[nonsteroidal anti-inflammatory drug]]s (NSAID).<ref name="FDA-20150709" /> Aspirin is an NSAID but is not affected by the revised warnings.<ref name="FDA-20150709">{{cite web |title=FDA strengthens warning of heart attack and stroke risk for non-steroidal anti-inflammatory drugs |url=https://www.fda.gov/consumers/consumer-updates/fda-strengthens-warning-heart-attack-and-stroke-risk-non-steroidal-anti-inflammatory-drugs |date=9 July 2015 |work=U.S. [[Food and Drug Administration]] (FDA) |access-date=9 July 2015 |url-status=dead |archive-url=https://web.archive.org/web/20150711004922/https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm453610.htm |archive-date=11 July 2015}}</ref>

===Overdose===
{{Main|Aspirin poisoning}}
[[File:Symptoms of aspirin overdose.svg|thumb|Symptoms of aspirin overdose]]

Aspirin 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%;<ref>{{cite web |vauthors = Kreplick LW |year=2001 |title=Salicylate toxicity in emergency medicine |publisher=[[Medscape]] |url=http://misc.medscape.com/pi/android/medscapeapp/html/A818242-business.html |url-status=live |archive-url=https://web.archive.org/web/20120831184805/http://misc.medscape.com/pi/android/medscapeapp/html/A818242-business.html |archive-date=31 August 2012}}</ref> chronic overdose may be especially severe in children.<ref name="Pediatrics1982-gaudreault">{{cite journal |vauthors = Gaudreault P, Temple AR, Lovejoy FH |title = The relative severity of acute versus chronic salicylate poisoning in children: a clinical comparison |journal = Pediatrics |volume = 70 |issue = 4 |pages = 566–9 |date = October 1982 |doi = 10.1542/peds.70.4.566 |pmid = 7122154 |s2cid = 12738659 }} (primary source)</ref> Toxicity is managed with a number of potential treatments, including [[activated charcoal]], intravenous dextrose and normal saline, [[sodium bicarbonate]], and [[Kidney dialysis|dialysis]].<ref>{{cite book |title=Rosen's emergency medicine: concepts and clinical practice |vauthors = Marx J |year=2006 |publisher=Mosby/Elsevier |isbn=978-0-323-02845-5 |page=2242 |url=https://archive.org/details/rosensemergencym0002unse/page/2242 }}</ref> The diagnosis of poisoning usually involves measurement of plasma salicylate, the active metabolite of aspirin, by automated spectrophotometric methods. Plasma salicylate levels in general range from 30 to 100{{nbsp}}mg/L after usual therapeutic doses, 50–300{{nbsp}}mg/L in people taking high doses and 700–1400{{nbsp}}mg/L following acute overdose. Salicylate is also produced as a result of exposure to [[bismuth subsalicylate]], [[methyl salicylate]], and [[sodium salicylate]].<ref>{{cite journal |vauthors = Morra P, Bartle WR, Walker SE, Lee SN, Bowles SK, Reeves RA |title = Serum concentrations of salicylic acid following topically applied salicylate derivatives |journal = The Annals of Pharmacotherapy |volume = 30 |issue = 9 |pages = 935–40 |date = September 1996 |pmid = 8876850 |doi = 10.1177/106002809603000903 |s2cid = 9843820 }}</ref><ref>{{cite book |vauthors = Baselt R |title=Disposition of toxic drugs and chemicals in man |edition=9th |publisher=Biomedical Publications |location=Seal Beach, California |year=2011 |pages=20–23|isbn=978-0-9626523-8-7 }}</ref>

=== Interactions ===
Aspirin is known to [[drug interaction|interact]] with other drugs. For example, [[acetazolamide]] and [[ammonium chloride]] are known to enhance the intoxicating effect of salicylates, and alcohol also increases the gastrointestinal bleeding associated with these types of drugs.<ref name="drugs.com">{{cite web |url=https://www.drugs.com/aspirin.html |title=Aspirin information from Drugs.com |publisher=Drugs.com |access-date=8 May 2008 |url-status=live |archive-url=https://web.archive.org/web/20080509163105/http://www.drugs.com/aspirin.html |archive-date=9 May 2008}}</ref><ref name="personalmd"/> Aspirin is known to displace a number of drugs from protein-binding sites in the blood, including the [[antidiabetic drug]]s [[tolbutamide]] and [[chlorpropamide]], [[warfarin]], [[methotrexate]], [[phenytoin]], [[probenecid]], [[valproic acid]] (as well as interfering with [[beta oxidation]], an important part of valproate metabolism), and other NSAIDs. Corticosteroids may also reduce the concentration of aspirin. Other NSAIDs, such as ibuprofen and naproxen, may reduce the antiplatelet effect of aspirin.<ref name="Alqahtani_2018">{{cite journal | vauthors = Alqahtani Z, Jamali F | title = Clinical Outcomes of Aspirin Interaction with Other Non-Steroidal Anti-Inflammatory Drugs: A Systematic Review | journal = Journal of Pharmacy & Pharmaceutical Sciences | volume = 21 | issue = 1s | pages = 48s–73s | date = 2018 | pmid = 29891025 | doi = 10.18433/jpps29854 | s2cid = 48361086 | doi-access = free }}</ref><ref name="Gladding_2008">{{cite journal | vauthors = Gladding PA, Webster MW, Farrell HB, Zeng IS, Park R, Ruijne N | title = The antiplatelet effect of six non-steroidal anti-inflammatory drugs and their pharmacodynamic interaction with aspirin in healthy volunteers | journal = The American Journal of Cardiology | volume = 101 | issue = 7 | pages = 1060–1063 | date = April 2008 | pmid = 18359332 | doi = 10.1016/j.amjcard.2007.11.054 }}</ref> Although limited evidence suggests this may not result in a reduced cardioprotective effect of aspirin.<ref name="Alqahtani_2018" /> Analgesic doses of aspirin decrease sodium loss induced by spironolactone in the urine, however this does not reduce the antihypertensive effects of spironolactone.<ref>{{cite web | veditors = Baxter K, Preston CL | work = MedicinesComplete: Stockley's Drug Interactions. | location = | publisher = Royal Pharmaceutical Society |title=Aspirin and Spironolactone |url=https://www.medicinescomplete.com}}</ref> Furthermore, antiplatelet doses of aspirin are deemed too small to produce an interaction with spironolactone.<ref>{{cite journal | vauthors = Hollifield JW |title=Failure of aspirin to antagonize the antihypertensive effect of spironolactone in low-renin hypertension. |journal=Southern Medical Journal |date=August 1976 |volume=69 |issue=8 |pages=1034–6 |doi=10.1097/00007611-197608000-00022 |pmid=785608 }}</ref> Aspirin is known to compete with [[penicillin|penicillin G]] for renal tubular secretion.<ref name="interactions">{{cite book |vauthors=Katzung BG |year=1998 |title=Basic and clinical pharmacology |url=https://archive.org/details/basicclinicalph100katz/page/584 |publisher=McGraw-Hill |page=584 |isbn=978-0-8385-0565-6}}</ref> Aspirin may also inhibit the absorption of vitamin C.<ref>{{cite journal | vauthors = Loh HS, Watters K, Wilson CW | title = The effects of aspirin on the metabolic availability of ascorbic acid in human beings | journal = Journal of Clinical Pharmacology | volume = 13 | issue = 11 | pages = 480–486 | date = 1 November 1973 | pmid = 4490672 | doi = 10.1002/j.1552-4604.1973.tb00203.x }}</ref><ref>{{cite journal | vauthors = Basu TK | title = Vitamin C-aspirin interactions | journal = International Journal for Vitamin and Nutrition Research. Supplement | volume = 23 | pages = 83–90 | year = 1982 | pmid = 6811490 }}</ref>{{Unreliable medical source|date=August 2016}}<ref>{{cite journal | vauthors = Ioannides C, Stone AN, Breacker PJ, Basu TK | title = Impairment of absorption of ascorbic acid following ingestion of aspirin in guinea pigs | journal = Biochemical Pharmacology | volume = 31 | issue = 24 | pages = 4035–4038 | date = December 1982 | pmid = 6818974 | doi = 10.1016/0006-2952(82)90652-9 }}</ref>