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Indications/Dosage
Description/Classification
Administration Information
Contraindications/Precautions
Pregnancy/Breast-feeding
Monitoring Parameters
US Drug Names
Aspirin, ASA
Labeled
arterial thromboembolism prophylaxis
dental pain
mild pain
myocardial infarction prophylaxis
prosthetic heart valves
reduction of cardiovascular mortality
stroke prophylaxis
Off-Label
claudication
colorectal cancer prophylaxis
migraine prophylaxis
multisystem inflammatory syndrome in children (MIS-C)
percutaneous coronary intervention (PCI)
preeclampsia prophylaxis
thrombosis prophylaxis
† Off-label indication
For the treatment of mild pain associated with arthralgia, dental pain, dysmenorrhea, headache, musculoskeletal pain (including backache), and/or the common cold
Oral dosage
325 or 650 mg PO every 4 hours as needed, or alternatively, 975 mg PO every 6 hours, as needed. Max: 3,900 g/day. Discontinue use if pain gets worse or lasts more than 10 days.[49579] [64835]
Children and Adolescents 12 to 17 years
Rectal dosage
300 or 600 mg PR every 4 to 6 hours, as needed. Max: 3,600 mg/day. Discontinue use if pain gets worse or lasts more than 10 days.[66829]
For the treatment of acute ischemic stroke†
Oral dosage (immediate-release tablets or capsules)
160 to 325 mg PO once daily starting within 24 to 48 hours of stroke symptom onset.[55211] [64716] In patients with minor noncardioembolic ischemic stroke who did not receive a thrombolytic, use aspirin for first 21 days in combination with clopidogrel.[64716] [64742] Aspirin is not recommended as a substitute for acute stroke treatment in patients eligible for thrombolytic therapy or mechanical thrombectomy.[64716]
Infants, Children, and Adolescents
1 to 5 mg/kg/dose PO once daily.[49232] [54220] [54221] If dissection and cardioembolic causes are excluded, continue aspirin for a minimum of 2 years. Transition to clopidogrel, LMWH, or warfarin in those who have recurrent acute ischemic stroke (AIS) or transient ischemic attacks. For acute AIS due to non-Moyamoya vasculopathy, continue aspirin for 3 months; guide ongoing antithrombotic therapy with repeat cerebrovascular imaging.[49232]
Neonates
1 to 5 mg/kg/dose PO once daily. Aspirin is recommended for neonates with recurrent acute ischemic stroke.[49232]
For secondary stroke prophylaxis in patients who have had an ischemic stroke or transient ischemic attack (TIA)
for stroke prophylaxis and to reduce the risk of death in patients with a history of ischemic stroke or TIA
Oral dosage (extended-release capsules)
162.5 mg PO once daily.[60438]
for stroke prophylaxis in patients with a history of noncardioembolic ischemic stroke or TIA
50 to 325 mg PO once daily.[55211] [64742] Antiplatelet agents are recommended over oral anticoagulation.[64742]
for stroke prophylaxis in patients with a history of ischemic stroke or TIA and atrial fibrillation who are unable to take oral anticoagulants
75 to 100 mg PO once daily in combination with clopidogrel.[55211] [64742]
for stroke prophylaxis in pregnant or breast-feeding women with low-risk situations in which antiplatelet therapy is recommended
Pregnant or Breast-feeding Female Adults
50 to 150 mg PO once daily after the first trimester of pregnancy.[64742]
for stroke prophylaxis in pediatric patients with a history of ischemic stroke or TIA†
1 to 5 mg/kg/dose PO once daily for a minimum of 2 years.[49232] [52706] [54221] [54222] Transition to clopidogrel, LMWH, or warfarin in those who have recurrent acute ischemic stroke or transient ischemic attacks.[49232]
For the coronary artery thrombosis prophylaxis† in patients with acute coronary syndrome (ACS)
for emergency (EMS) management of ACS prior to hospital arrival
160 mg to 325 mg PO non-enteric coated tablet, chewed and swallowed immediately, may be provided by emergency medical services (EMS) prior to hospital arrival for patients without aspirin allergy.[32435]
for acute coronary syndrome without ST-segment elevation (NSTEMI) including patients with unstable angina (UA)
75 mg to 325 mg PO non-enteric coated tablet, chewed and swallowed immediately, for patients without aspirin allergy.[32416] The maintenance dosage for secondary prevention is 75 mg to 162 mg PO once daily indefinitely.[32395] [32416] Hospitalized ACS patients should also be treated with unfractionated heparin (UFH) or low-molecular weight heparin (LMWH) in addition to aspirin.[24978] [32416] Patients with moderate to high-risk features should also receive early concomitant therapy with tirofiban or eptifibatide.[32416] For dosage of aspirin when combined with clopidogrel, see clopidogrel monograph.
for treatment of an evolving acute myocardial infarction with ST segment elevation (STEMI)
160 mg to 325 mg PO non-enteric coated tablet, chewed and swallowed immediately, regardless of concomitant fibrinolytic therapy.[31689] [32417] The maintenance dosage is 75 mg to 162 mg PO once daily.[32416]
for thrombosis prophylaxis† in patients undergoing percutaneous coronary intervention (PCI)† to reduce the frequency of early ischemic complications
Pretreat with aspirin 75 mg to 325 mg PO, then 75 mg to 162 mg PO once daily given indefinitely.[32423] If warfarin or another antithrombotic is used for long-term treatment after PCI, use aspirin at a dosage of 75 mg/day to 100 mg/day PO.[32423] The 2006 AHA/ACC guidelines for secondary prevention in patients with coronary or other atherosclerotic vascular disease recommend that clopidogrel should be given to patients with ACS for up to 12 months in combination with aspirin (75 mg/day to 162 mg/day PO).[32395] Combination therapy with aspirin and clopidogrel should be given for at least 1 month, 3 months, and 6 months after PCI with placement of a bare metal, sirolimus-eluting, or paclitaxel-eluting stent, respectively; an initial higher dose of aspirin (325 mg/day) should be given for 1 month, 3 months, and 6 months, respectively.
For long-term myocardial infarction prophylaxis
for primary prevention in patients with low to moderate risk for a coronary event in patients not receiving warfarin
75 mg to 162 mg PO once daily. Moderate risk of a coronary event is based on age and 10-year cardiac risk greater than 10%.[32416]
for secondary prevention and a reduction of cardiovascular mortality in patients with stable coronary artery disease including angina or previous myocardial infarction or acute coronary syndrome
75 mg to 162 mg PO once daily indefinitely. Lower doses of 100 mg/day or less are recommended for patients with a history of aspirin-induced bleeding or with risk factors for bleeding. In those patients with a high likelihood of a myocardial infarction, administer aspirin in combination with clopidogrel.[32395] [32416]
For arterial thromboembolism prophylaxis
in combination with warfarin for patients with mechanical prosthetic heart valves and increased risk for thromboembolism:
75 to 100 mg PO once daily in combination with warfarin (target INR 3).[32419] A randomized, double-blind, placebo-controlled study has demonstrated that the addition of enteric-coated, slow-release aspirin 100 mg/day PO to warfarin provided better reduction of morbidity and mortality than warfarin alone after heart valve replacement.[23499] The combination of warfarin with aspirin was also associated with an increased risk of bleeding as compared to warfarin alone.
for patients with bioprosthetic valves who are in sinus rhythm and do not have atrial fibrillation
75 to 100 mg PO once daily as long-term therapy.[32419]
for patients with rheumatic mitral valve disease with atrial fibrillation or a history of systemic embolism, who suffer systemic embolism while receiving oral anticoagulant therapy at a therapeutic INR
75 to 100 mg PO once daily in addition to warfarin.[32419]
for patients with mitral valve prolapse with documented but unexplained transient ischemic attacks (TIA)
50 to 162 mg PO once daily indefinitely.[32419]
for chronic limb ischemia or intermittent claudication† or other patients with atherosclerotic peripheral arterial occlusive disease of the lower extremity
According to the AHA/ACC guidelines for secondary prevention in patients with coronary or other atherosclerotic vascular disease including patients with peripheral arterial disease, aspirin is generally recommended at a dosage of 75 to 162 mg/day PO.[32395] A higher dose range of 75 to 325 mg/day PO is recommended as safe and effective antiplatelet therapy for atherosclerotic peripheral arterial disease of the lower extremity for the management of peripheral arterial disease.[63801] Aspirin is also recommended following prosthetic infrainguinal bypass surgery.[30263]
for patients who are at high-risk of graft thrombosis following infrainguinal bypass
Low dose aspirin (75 to 80 mg/day PO) in combination with warfarin.[24625] [30263]
for all patients undergoing balloon angioplasty of the lower extremity (with or without stenting)
75 to 162 mg PO once daily as long-term therapy.
for antiplatelet therapy prior to and following carotid endarterectomy
The American College of Chest Physicians (ACCP) recommends 75 to 325 mg PO once daily for patients undergoing endarterectomy prior to and continued indefinitely following the procedure.[30263] The ACCP review of acute ischemic stroke provides a similar recommendation for endarterectomy patients, aspirin 81 to 325 mg once daily to reduce cerebral ischemic events.[30259] In the ACE trial, lower doses (81 or 325 mg daily) versus higher doses (650 or 1300 mg daily) of aspirin were evaluated in 2,804 patients with carotid endarterectomy.[30262] This study reported a lower rate of stroke, MI, and death at 3 months for patients receiving low doses of aspirin (81 or 325 mg daily).
for nonoperative patients with asymptomatic or recurrent carotid stenosis
for patients following saphenous vein artery bypass grafting performed for coronary artery disease (CAD)
The optimal dosage and timing of aspirin therapy for patients following coronary bypass graft surgery (CABG) has not been established. Perioperative aspirin improves vein graft patency but increases the risk of perioperative transfusions.[32443] According to the AHA/ACC guidelines for secondary prevention in patients with coronary and other atherosclerotic vascular disease, aspirin is recommended at a dosage of 100 to 325 mg/day PO, starting within 48 hours of surgery to reduce saphenous vein graft occlusion; doses greater than 162 mg/day PO can be continued for up to 1 year.[32395] The American College of Chest Physicians (ACCP) has previously recommended a dosage range of 75 to 325 mg PO once daily beginning 6 hours after surgery or, if delayed by bleeding, as soon as possible.[32422] For long-term secondary prevention, 75 to 162 mg PO once daily is generally recommended for all CAD patients.[32395] [32416]
for patients following internal mammary artery bypass grafting performed for coronary artery disease (CAD)
Although a demonstrated effect of aspirin on arterial graft patency has not been established, a long-term maintenance dosage of 75 to 162 mg PO once daily is recommended for secondary prevention due to the underlying CAD.[32416] [32422] [32437]
For the treatment of fever
325 or 650 mg PO every 4 hours as needed, or alternatively, 975 mg PO every 6 hours, as needed. Max: 3,900 g/day. Discontinue use if fever gets worse or lasts more than 3 days.[49579] [64835]
300 or 600 mg PR every 4 to 6 hours, as needed. Max: 3,600 mg/day. Discontinue use if fever gets worse or lasts more than 3 days.[66829]
For the treatment of Kawasaki disease†
80 to 100 mg/kg/day PO in 4 divided doses during the acute phase (often until patient has been afebrile for 24 to 72 hours, for up to 14 days), then decrease to 3 to 5 mg/kg/day PO once daily (Max: 325 mg/day) until 4 to 6 weeks after the onset of illness. High-dose IVIG should be given concurrently within 10 days of illness onset but as soon as possible after diagnosis. For those who develop coronary abnormalities, low-dose aspirin may continue indefinitely.[49232] [54229] [54230] [54234] [61950] Duration of high-dose aspirin varies in clinical practice; while many clinicians reduce the aspirin dose after the patient is afebrile for 24 to 72 hours, others continue high-dose aspirin until day 14 of illness and at least 48 to 72 hours after cessation of fever.[54229] [61950] There is also debate over the optimal dose of aspirin in the acute phase of treatment. High-dose is recommended in the clinical guidelines. However, moderate doses (30 to 50 mg/kg/day) are commonly used in Asia and Western Europe during the acute phase to minimize aspirin toxicity. There are no data to suggest either dose is superior.[54229] [61950] Additionally, some data suggests low-dose aspirin (3 to 5 mg/kg/day or less than 10 mg/kg/day) is not inferior to high-dose aspirin (80 mg/kg/day or more than 10 mg/kg/day) in reducing the risk of CAA when given concomitantly with IVIG during the acute phase.[62162]
For the treatment of idiopathic or viral pericarditis†
750 to 1,000 mg PO 3 times daily for 1 to 2 weeks for acute pericarditis and 2 to 4 weeks for recurrent pericarditis, then tapered over 3 to 4 weeks. Treatment duration is dependent on resolution of symptoms and the normalization of markers of inflammation (e.g., C-reactive protein).[60439] Concomitant use of colchicine improves remission rates at 1 week and reduces recurrence.[33628] [33629] [60439] [60440]
For colorectal cancer prophylaxis†
Adults 50 to 69 years
81 mg PO once daily for patients who have a 10% or more 10-year CVD risk, are not at increased risk for bleeding, have a life expectancy of at least 10 years, and are willing to take low-dose aspirin daily for at least 10 years.[66811]
For preeclampsia prophylaxis†
for preeclampsia prophylaxis† in high-risk pregnant patients
Adult Females
81 mg PO once daily starting at 12 weeks gestation.[46190] [57086] [58826] [66488] In pregnant women with pre-existing diabetes mellitus, 162 mg PO once daily may be appropriate.[64926]
for preeclampsia prophylaxis† in pregnant patients with low to moderate risk
Dosage not established. 65 to 100 mg PO once daily initiated at various times during pregnancy (e.g., 12 weeks) and continued until 34 weeks or delivery has been used.[24348] [58824] [58825]
For the acute treatment of migraine†
500 mg PO once. Guidelines classify aspirin as having established efficacy for the treatment of acute migraine.[64551] [64565]
For migraine prophylaxis†
100 or 325 mg PO every other day, or alternately, 300 mg PO once daily.[59202] [59203] [59204] Clinical practice guidelines classify aspirin as having inadequate or conflicting data to support or refute use for migraine prophylaxis.[58130]
For the management of multisystem inflammatory syndrome in children (MIS-C) post SARS-CoV-2 exposure†
Available data are limited, and efficacy has not been established. Doses varying from 3 to 5 mg/kg/day PO (low dose) to 30 to 100 mg/kg/day PO (moderate to high dose) have been reported and are being used in combination with IVIG with or without methylprednisolone.[65545] [65546] [65547] [65577] [65706] Although ranges are provided in clinical studies, the optimal duration of treatment or recommendations on dividing larger doses is not always described. However, when treating other conditions, high doses of aspirin are divided into 2 to 4 doses. At a minimum, low dose aspirin is recommended for patients with Kawasaki disease-like syndrome.[65720] In 1 institutional protocol, aspirin 20 to 25 mg/kg/dose every 6 hours (80 to 100 mg/kg/day) is recommended in patients with Kawasaki disease-like illness, evidence of excessive inflammation (ferritin more than 700 ng/mL, CRP more than 300 g/dL, or multisystem organ failure), or cardiac involvement. Once patients are afebrile for 24 hours or more, the aspirin dose is reduced to 3 to 5 mg/kg/day.[65577] Low dose aspirin (3 to 5 mg/kg/day; max 81 mg/day) has been recommended in patients with MIS-C and Kawasaki disease-like features and/or thrombocytosis (platelet count 450,000/microliter or more). Continuation is recommended until platelet count and coronary arteries are normal for at least 4 weeks after diagnosis with avoidance in patients with a platelet count of 80,000/microliter or less. Additionally, it is recommended that patients with coronary artery aneurysms and a maximal z-score of 2.5 to 10 be treated with low dose aspirin, whereas patients with a z-score of 10 or more be treated with low dose aspirin and therapeutic anticoagulation with enoxaparin or warfarin.[65707] In a prospective observational study, 21 patients received low dose aspirin 3 to 5 mg/kg/day in combination with IVIG.[65546] In retrospective studies and case series, 30 to 100 mg/kg/day PO (moderate to high dose) was usually administered initially, followed by 3 to 5 mg/kg/day PO (low dose).[65545] [65615] [65616] In 1 study, moderate to high dose aspirin was continued until 48 hours after defervescence and then continued at a low dose for 8 weeks.[65545]
Most patients experience signs of acute salicylate toxicity when the total salicylate concentration is more than 300 mcg/mL. In chronic salicylism, signs of toxicity may occur at lower concentrations (150 mcg/mL or more).[54310]
Maximum Dosage Limits
Patients with Hepatic Impairment Dosing
Avoid aspirin in patients with severe hepatic insufficiency.[54023] Patients with any degree of hepatic disease are at increased risk of salicylate-induced adverse reactions.
Patients with Renal Impairment Dosing
CrCl less than 10 mL/minute: Avoid analgesic doses.[32569] Use of low-dose aspirin for primary and secondary prevention of atherosclerotic events in patients with cardiovascular disease is recommended.[60881]
Intermittent hemodialysis
Avoid analgesic doses. Use of low-dose aspirin for primary and secondary prevention of atherosclerotic events in patients with cardiovascular disease is recommended.[60881] If use is necessary, doses should be administered after hemodialysis; aspirin is 50% to 100% dialyzable.[32569]
Continuous ambulatory peritoneal dialysis (CAPD)
Avoid analgesic doses.[32569] Use of low-dose aspirin for primary and secondary prevention of atherosclerotic events in patients with cardiovascular disease is recommended.[60881]
Continuous renal replacement therapy (CRRT)
No dosage adjustment needed; monitor serum salicylate concentrations if possible.[32569]
Revision Date: 07/28/2021, 01:02:30 PM
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BMJ 2020; 369m2094. Published 2020 Jun 3. doi: 10.1135/bmj.m209465547 - Chiotos K, Bassiri H, Behrens EM, et al. Multisystem inflammatory syndrome in children during the COVID-19 pandemic: a case series [published online ahead of print, 2020 May 28]. J Pediatric Infect Dis Soc. 2020; piaa069. doi:10.1093/jpids/piaa06965577 - Hennon TR, Penque MD, Abdul-Aziz R, et al. COVID-19 associated multisystem inflammatory syndrome in children (MIS-C) guidelines; a western New York approach. Prog Pediatric Cardiol 2020 May 23.65615 - Pouletty M, Borocco C, Ouldali N, et al. Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 mimicking Kawasaki disease (Kawa-COVID-19): a multicentre cohort. [published online ahead of print, 2020 May 28]. Ann Rheum Dis. doi: 10.1136/annrheumdis-2020-217960.65616 - Ramcharan T, Nolan O, Lai C, at al. Paediatric inflammatory multisystem syndrome: temporally associated with SARS-COV-2 (PIMS-TS): cardiac features, management and short term outcomes at a UK tertiary pediatric hospital. [published online ahead of print, 2020 June]. Pediatric Cardiology. doi: 10.1007/s00246-020-02391-265706 - Nakra NA, Blumberg DA, Herrera-Guerra A, Lakshminrusimha S. Multisystem inflammatory syndrome in children (MIS-C) following SARS-CoV-2 infection: review of clinical presentation, hypothetical pathogenesis, and proposed management. Children 2020; 7(7): 69.65707 - Henderson LA, Canna SW, Friedman KG, et al. American college of rheumatology clinical guidance for multisystem inflammatory syndrome in children associated with SARS-CoV-2 and hyperinflammation in pediatric COVID-19: Version 2. Arthritis Rheumatol 2021;73(4):e13-e29.65720 - American Academy of Pediatrics (AAP). Multisystem inflammatory syndrome in children (MIS-C) interim guidance. Accessed May 3, 2021. Available on the World Wide Web at: https://services.aap.org/en/pages/2019-novel-coronavirus-covid-19-infections/clinical-guidance/multisystem-inflammatory-syndrome-in-children-mis-c-interim-guidance/66488 - American College of Obstetricians and Gynecologists. ACOG Practice Bulletin Number 743: Low-Dose Aspirin Use During Pregnancy. Obstet Gynecol 2018;132:e44-52.66811 - Bibbins-Domingo K et al. Aspirin Use for the Primary Prevention of Cardiovascular Disease and Colorectal Cancer: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med 2016;164:836-845.66829 - Aspirin suppository package insert. Minneapolis, MN: Paddock Laboratories, LLC; 2019 Jul.
Aspirin Chewable tablet
Aspirin 81mg Chewable Tablet (65162-0014) (Akyma Pharmaceuticals, a subsidiary of Amneal Pharmaceuticals) (off market)
Aspirin 81mg Chewable Tablet (52297-0146) (Cardinal Health, Inc.) (off market)
Aspirin 81mg Chewable Tablet (57896-0510) (Geri-Care Pharmaceuticals) (off market)
Aspirin 81mg Chewable Tablet (57896-0911) (Geri-Care Pharmaceuticals) null
Aspirin 81mg Chewable Tablet (00904-4040) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)
Aspirin 81mg Chewable Tablet (00904-4040) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) null
Aspirin 81mg Chewable Tablet (null) (Mason Vitamins) (off market)
Aspirin 81mg Chewable Tablet (49348-0757) (McKesson Corporation) null
Aspirin 81mg Chewable Tablet (63739-0434) (McKesson Packaging) null
Aspirin 81mg Chewable Tablet (63739-0025) (McKesson Packaging Inc) (off market)
Aspirin 81mg Chewable Tablet (49614-0467) (Medicine Shoppe) null
Aspirin 81mg Chewable Tablet (51079-0659) (Mylan Institutional LLC ) (off market)
Aspirin 81mg Chewable Tablet (55966-0028) (PDK Labs Inc) null
Aspirin 81mg Chewable Tablet (43063-0278) (PD-Rx Pharmaceuticals, Inc.) (off market)
Aspirin 81mg Chewable Tablet (62107-0026) (Prime Marketing) null
Aspirin 81mg Chewable Tablet (17236-0014) (R&S Northeast, LLC, formerly Dixon-Shane Drug Company) (off market)
Aspirin 81mg Chewable Tablet (69618-0014) (Reliable 1 Laboratories LLC) (off market)
Aspirin 81mg Chewable Tablet (60814-0175) (Rexall Group) (off market)
Aspirin 81mg Chewable Tablet (00536-1008) (Rugby Laboratories a Division of The Harvard Drug Group, LLC) null
Aspirin 81mg Chewable Tablet (00677-1854) (Sun Pharmaceutical Industries, Inc.) (off market)
Aspirin 81mg Chewable Tablet (00364-0023) (Teva/Actavis US) (off market)
Aspirin Low Dose 81mg Chewable Tablet (16103-0366) (Pharbest Pharmaceuticals) null
Aspirin Low Dose 81mg Chewable Tablet (68752-0003) (TriMarc Laboratories) null
Aspirin Low Dose 81mg Chewable Tablet (Orange) (49483-0334) (Time Cap Laboratories Inc) null
Bayer Aspirin 81mg Low Dose Chewable Tablet (Orange) (12843-0101) (Bayer Corp Consumer Care Div) null
Bayer Aspirin 81mg Low Dose Chewable Tablet (Orange) (12843-0131) (Bayer Corp Consumer Care Div) (off market)
Bayer Aspirin Regimen 81mg Low Dose Chewable Tablet (Orange) (12843-0101) (Bayer Corp Consumer Care Div) null
Bayer Children's Aspirin 81mg Low Dose Chewable Tablet (Cherry) (12843-0132) (Bayer Corp Consumer Care Div) null
Bayer Children's Aspirin 81mg Low Dose Chewable Tablet (Mint) (12843-0512) (Bayer Corp Consumer Care Div) (off market)
Children's Aspirin 81mg Chewable Tablet (55154-6752) (Cardinal Health, Inc.) null
Children's Aspirin 81mg Chewable Tablet (63739-0434) (McKesson Packaging Inc) (off market)
Children's Aspirin 81mg Chewable Tablet (00603-0024) (Par Pharmaceuticals, an Endo Company) (off market)
Children's Aspirin 81mg Chewable Tablet (00536-3297) (Rugby Laboratories a Division of The Harvard Drug Group, LLC) (off market)
Children's Aspirin 81mg Chewable Tablet (00677-1977) (Sun Pharmaceutical Industries, Inc.) (off market)
Children's Aspirin 81mg Chewable Tablet (00182-1420) (Teva Pharmaceuticals USA) (off market)
CVS Aspirin Low Dose 81mg Chewable Tablet (Cherry) (59779-0274) (CVS Health) null
CVS Aspirin Low Dose 81mg Chewable Tablet (Cherry) (59779-0274) (CVS Health) (off market)
CVS Aspirin Low Dose 81mg Chewable Tablet (Orange) (null) (CVS Health) (off market)
CVS Aspirin Low Dose 81mg Chewable Tablet (Orange) (59779-0467) (CVS Health) (off market)
CVS Aspirin Low Dose 81mg Chewable Tablet (Orange) (59779-0467) (CVS Health) null
CVS Aspirin Low Strength 81mg Chewable Tablet (null) (CVS Health) null
Equaline Children's Aspirin 81mg Chewable Tablet (Cherry) (41163-0274) (Albertson's, Inc) (off market)
Equaline Children's Aspirin 81mg Chewable Tablet (Orange) (41163-0467) (Albertson's, Inc) (off market)
GNP Aspirin 81mg Chewable Tablet (Cherry) (24385-0278) (AmerisourceBergen Corporation) null
GNP Aspirin 81mg Chewable Tablet (Orange) (24385-0028) (AmerisourceBergen Corporation) null
GoodSense Aspirin 81mg Chewable Tablet (00113-0467) (Goodsense a Division of Perrigo) null
GoodSense Aspirin 81mg Chewable Tablet (Cherry) (00113-0274) (Goodsense a Division of Perrigo) null
Health Mart Aspirin Low Dose 81mg Chewable Tablet (Cherry) (62011-0212) (McKesson Corporation) null
Health Mart Aspirin Low Dose 81mg Chewable Tablet (Orange) (62011-0028) (McKesson Corporation) null
Leader Aspirin 81mg Chewable Tablet (Orange) (37205-0369) (Cardinal Health, Inc.) null
Leader Aspirin Low Dose 81mg Chewable Tablet (Cherry) (37205-0708) (Cardinal Health, Inc.) null
Leader Aspirin Low Dose 81mg Chewable Tablet (Orange) (37205-0467) (Cardinal Health, Inc.) null
Premier Value Aspirin 81mg Chewable Tablet (Cherry) (68016-0024) (Pharmacy Value Alliance LLC formerly Chain Drug Consortium , LLC) null
Premier Value Aspirin 81mg Chewable Tablet (Orange) (68016-0690) (Pharmacy Value Alliance LLC formerly Chain Drug Consortium , LLC) null
Premier Value Children's Aspirin 81mg Chewable Tablet (Orange) (68016-0013) (Pharmacy Value Alliance LLC formerly Chain Drug Consortium , LLC) null
Publix Aspirin 81mg Low Dose Chewable Tablet (Orange) (56062-0467) (Publix Super Markets, Inc) null
Quality Choice Aspirin Low Dose 81mg Chewable Tablet (Orange) (63868-0240) (Chain Drug Marketing Association) null
RITE AID Aspirin Low Dose 81mg Chewable Tablet (Cherry) (null) (Rite Aid Corp) null
RITE AID Aspirin Low Dose 81mg Chewable Tablet (Orange) (null) (Rite Aid Corp) null
RITE AID Low Dose Aspirin 81mg Chewable Tablet (null) (Rite Aid Corp) null
Select Brand Children's Aspirin 81mg Chewable Tablet (15127-0241) (Select Brand) null
St. Joseph Adult Aspirin 81mg Chewable Tablet (69536-0281) (Foundation Consumer Healthcare, LLC) null
St. Joseph Adult Aspirin 81mg Chewable Tablet (00045-0173) (McNeil Consumer Healthcare Division of McNEIL-PPC, Inc.) (off market)
Sunmark Aspirin Adult Low Strength 81mg Chewable Tablet (Orange) (49348-0498) (McKesson Corporation) null
Sunmark Aspirin Low Dose 81mg Chewable Tablet (Cherry) (49348-0191) (McKesson Corporation) null
Today's Health Aspirin 81mg Chewable Tablet (null) (Today's Health, Inc.) null
Top Care Aspirin 81mg Chewable Tablet (36800-0259) (Topco Associates LLC) null
Top Care Aspirin 81mg Chewable Tablet (Cherry) (36800-0274) (Topco Associates LLC) null
Walgreens Aspirin Adult Low Strength 81mg Chewable Tablet (00363-0218) (Walgreens Co) null
Walgreens Children's Aspirin 81mg Chewable Tablet (00363-0397) (Walgreens Co) null
Aspirin Chewing gum, medicated
Aspergum 227mg Chewing Gum (Cherry) (null) (Medtech Products, Inc a Prestige Brands Company formerly Insight Pharmaceuticals) (off market)
Aspergum 227mg Chewing Gum (Orange) (null) (Medtech Products, Inc a Prestige Brands Company formerly Insight Pharmaceuticals) (off market)
Aspirin Oral capsule, extended release
DURLAZA 162.5mg Extended Release Capsule (58487-0001) (New Haven Pharmaceuticals, Inc.) null
Aspirin Oral capsule, liquid filled
VAZALORE 81mg Low Dose Liquid Filled Capsule (73089-0081) (PLx Pharma Inc.) null
VAZALORE 325mg Liquid Filled Capsule (73089-0325) (PLx Pharma Inc.) null
Aspirin Oral tablet
Aspirin 81mg Tablet (52297-0507) (Cardinal Health, Inc.) (off market)
Aspirin 81mg Tablet (52735-0761) (Family Pharmacy) (off market)
Aspirin 81mg Tablet (null) (Mason Vitamins) (off market)
Aspirin 81mg Tablet (51079-0845) (Mylan Institutional LLC ) (off market)
Aspirin 81mg Tablet (00084-0046) (Natural Nutritionals Company) (off market)
Aspirin 81mg Tablet (45802-0642) (Perrigo Pharmaceuticals Company) (off market)
Aspirin 81mg Tablet (60814-0172) (Rexall Group) (off market)
Aspirin Low Strength 81mg Tablet (58948-0535) (Goodsense a Division of Perrigo) (off market)
Bayer Women's Aspirin 81mg Plus Calcium Buffered Caplet (12843-0500) (Bayer Corp Consumer Care Div) null
Bufferin Low Dose 81mg Tablet (00067-6424) (GlaxoSmithKline Consumer Healthcare ) (off market)
Aspirin 325mg Buffered Tablet (65162-0380) (Akyma Pharmaceuticals, a subsidiary of Amneal Pharmaceuticals) (off market)
Aspirin 325mg Buffered Tablet (57896-0931) (Geri-Care Pharmaceuticals) null
Aspirin 325mg Buffered Tablet (00820-0137) (Logen Pharmaceuticals Inc.) (off market)
Aspirin 325mg Buffered Tablet (null) (Mason Vitamins) null
Aspirin 325mg Buffered Tablet (51079-0021) (Mylan Institutional LLC ) (off market)
Aspirin 325mg Buffered Tablet (00084-0196) (Natural Nutritionals Company) (off market)
Aspirin 325mg Buffered Tablet (17236-0380) (R&S Northeast, LLC, formerly Dixon-Shane Drug Company) (off market)
Aspirin 325mg Buffered Tablet (00536-3300) (Rugby Laboratories a Division of The Harvard Drug Group, LLC) (off market)
Aspirin 325mg Buffered Tablet (00781-1200) (Sandoz Inc. a Novartis Company) (off market)
Aspirin 325mg Buffered Tablet (00182-1060) (Teva Pharmaceuticals USA) (off market)
Aspirin 325mg Coated Tablet (00536-1284) (Rugby Laboratories a Division of The Harvard Drug Group, LLC) (off market)
Aspirin 325mg Micro-Coated Tablet (00536-3305) (Rugby Laboratories a Division of The Harvard Drug Group, LLC) (off market)
Aspirin 325mg Micro-Coated Tablet (49483-0011) (Time Cap Laboratories Inc) null
Aspirin 325mg Tablet (65162-0378) (Akyma Pharmaceuticals, a subsidiary of Amneal Pharmaceuticals) (off market)
Aspirin 325mg Tablet (24385-0429) (AmerisourceBergen Corporation) (off market)
Aspirin 325mg Tablet (52297-0137) (Cardinal Health, Inc.) (off market)
Aspirin 325mg Tablet (00436-0416) (Century Pharmaceuticals Inc) (off market)
Aspirin 325mg Tablet (00295-1236) (Denison Pharmaceuticals Inc) null
Aspirin 325mg Tablet (52735-0702) (Family Pharmacy) null
Aspirin 325mg Tablet (52735-0703) (Family Pharmacy) (off market)
Aspirin 325mg Tablet (57896-0501) (Geri-Care Pharmaceuticals) (off market)
Aspirin 325mg Tablet (57896-0901) (Geri-Care Pharmaceuticals) null
Aspirin 325mg Tablet (60809-0108) (Glasgow Pharmaceutical Corporation) (off market)
Aspirin 325mg Tablet (59618-0099) (Global Source Management & Consulting) (off market)
Aspirin 325mg Tablet (00820-0134) (Logen Pharmaceuticals Inc.) (off market)
Aspirin 325mg Tablet (00904-2009) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)
Aspirin 325mg Tablet (10135-0150) (Marlex Pharmaceuticals) (off market)
Aspirin 325mg Tablet (null) (Mason Vitamins) null
Aspirin 325mg Tablet (49348-0001) (McKesson Corporation) null
Aspirin 325mg Tablet (63739-0024) (McKesson Packaging Inc) (off market)
Aspirin 325mg Tablet (57480-0104) (Medirex Inc) (off market)
Aspirin 325mg Tablet (51079-0018) (Mylan Institutional LLC ) (off market)
Aspirin 325mg Tablet (54629-0801) (National Vitamin Company Inc) (off market)
Aspirin 325mg Tablet (00084-0408) (Natural Nutritionals Company) (off market)
Aspirin 325mg Tablet (10244-0562) (Otis Clapp and Son) (off market)
Aspirin 325mg Tablet (00603-0031) (Par Pharmaceuticals, an Endo Company) null
Aspirin 325mg Tablet (55966-0048) (PDK Labs Inc) null
Aspirin 325mg Tablet (55289-0743) (PD-Rx Pharmaceuticals, Inc.) null
Aspirin 325mg Tablet (16103-0365) (Pharbest Pharmaceuticals) null
Aspirin 325mg Tablet (17236-0378) (R&S Northeast, LLC, formerly Dixon-Shane Drug Company) (off market)
Aspirin 325mg Tablet (69618-0016) (Reliable 1 Laboratories LLC) (off market)
Aspirin 325mg Tablet (00122-0821) (Rexall Group) (off market)
Aspirin 325mg Tablet (00536-1053) (Rugby Laboratories a Division of The Harvard Drug Group, LLC) (off market)
Aspirin 325mg Tablet (00536-1054) (Rugby Laboratories a Division of The Harvard Drug Group, LLC) null
Aspirin 325mg Tablet (00182-0444) (Teva Pharmaceuticals USA) (off market)
Aspirin 325mg Tablet (00364-0835) (Teva/Actavis US) (off market)
Aspirin 325mg Tablet (47682-0116) (UniFirst First-Aid Corporation) null
Aspirin 325mg Tablet (11383-0148) (Weeks and Leo) null
Aspirtab 325mg Tablet (51469-0301) (Dover Pharmaceutical) (off market)
Aspir-Trin 325mg Tablet (null) (Mason Vitamins) (off market)
Bayer Advanced Aspirin 325mg Tablet (12843-0545) (Bayer Corp Consumer Care Div) null
Bayer Aspirin 325mg Caplet (12843-0102) (Bayer Corp Consumer Care Div) (off market)
Bayer Aspirin 325mg Tablet (12843-0101) (Bayer Corp Consumer Care Div) (off market)
Bayer Genuine Aspirin 325mg Tablet (12843-0545) (Bayer Corp Consumer Care Div) null
Bayer Genuine Aspirin 325mg Tablet (12843-0555) (Bayer Corp Consumer Care Div) (off market)
Bufferin 325mg Tablet (null) (Bristol Myers Squibb Co) (off market)
Bufferin 325mg Tablet (00067-2063) (GlaxoSmithKline Consumer Healthcare ) null
Bufferin 325mg Tablet (19810-0005) (GlaxoSmithKline Consumer Healthcare ) (off market)
CVS Aspirin 325mg Buffered Tablet (59779-0183) (CVS Health) (off market)
CVS Aspirin 325mg Buffered Tablet (59779-0183) (CVS Health) null
CVS Aspirin 325mg Coated Tablet (null) (CVS Health) (off market)
CVS Aspirin 325mg Coated Tablet (null) (CVS Health) null
CVS Aspirin 325mg Coated Tablet (59779-0733) (CVS Health) null
CVS Aspirin 325mg Tablet (null) (CVS Health) null
CVS Aspirin 325mg Tablet (null) (CVS Health) (off market)
CVS Aspirin 325mg Tablet (59779-0772) (CVS Health) null
CVS Genuine Aspirin 325mg Tablet (null) (CVS Health) null
Equaline Aspirin 325mg Buffered Tablet (41163-0642) (Albertson's, Inc) (off market)
Equaline Aspirin 325mg Tablet (41163-0416) (Albertson's, Inc) (off market)
GNP Aspirin 325mg Coated Tablet (46122-0292) (AmerisourceBergen Corporation) null
GNP Aspirin 325mg Tablet (24385-0416) (AmerisourceBergen Corporation) null
GoodSense Aspirin 325mg Tablet (00113-0416) (Goodsense a Division of Perrigo) null
Health Mart Aspirin 325mg Tablet (62011-0020) (McKesson Corporation) null
Leader Aspirin 325mg Buffered Tablet (37205-0150) (Cardinal Health, Inc.) (off market)
Leader Aspirin 325mg Tablet (37205-0145) (Cardinal Health, Inc.) (off market)
Leader Aspirin 325mg Tablet (37205-0668) (Cardinal Health, Inc.) null
Premier Value Aspirin 325mg Tablet (68016-0011) (Pharmacy Value Alliance LLC formerly Chain Drug Consortium , LLC) null
Publix Aspirin 325mg Coated Tablet (56062-0416) (Publix Super Markets, Inc) null
Quality Choice Aspirin 325mg Coated Tablet (63868-0352) (Chain Drug Marketing Association) null
RITE AID Aspirin 325mg Coated Tablet (null) (Rite Aid Corp) null
RITE AID Aspirin 325mg Tri-Buffered Tablet (null) (Rite Aid Corp) null
Select Brand Aspirin 325mg Tablet (15127-0738) (Select Brand) null
Today's Health Aspirin 325mg Tablet (null) (Today's Health, Inc.) null
Tri-Buffered Aspirin 325mg Tablet (00904-2015) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) null
Walgreens Aspirin 325mg Tablet (00363-0157) (Walgreens Co) null
Walgreens Aspirin 325mg Tri-Buffered Tablet (00363-0183) (Walgreens Co) null
Aspirin 500mg Tablet (12843-0005) (Bayer Corp Consumer Care Div) (off market)
Bayer Advanced Aspirin 500mg Extra Strength Tablet (12843-0552) (Bayer Corp Consumer Care Div) (off market)
Bayer Aspirin 500mg Extra Strength Caplet (12843-0202) (Bayer Corp Consumer Care Div) (off market)
Bayer Aspirin 500mg Extra Strength Gelcap (12843-0363) (Bayer Corp Consumer Care Div) (off market)
Bayer Aspirin Extra Strength 500mg Gelcap (00280-2140) (Bayer Corp Consumer Care Div) (off market)
Bayer Aspirin Plus 500mg Extra Strength Caplet (12843-0124) (Bayer Corp Consumer Care Div) null
Bayer Extra Strength 500mg Caplet (12843-0555) (Bayer Corp Consumer Care Div) (off market)
Bayer Extra Strength Plus 500mg Caplet (12843-0555) (Bayer Corp Consumer Care Div) null
Bufferin Extra Strength 500mg Tablet (null) (Bristol Myers Squibb Co) (off market)
Bufferin Extra Strength 500mg Tablet (00067-2065) (GlaxoSmithKline Consumer Healthcare ) null
Aspirin 650mg Tablet (00677-0772) (Sun Pharmaceutical Industries, Inc.) (off market)
Aspir-Trin 650mg Tablet (null) (Mason Vitamins) null
Aspirin 800mg Tablet (64125-0106) (Excellium Pharmaceutical Inc, a Leading Pharma Company) (off market)
Aspirin Oral tablet, extended release
Aspirin 800mg Extended-Release Tablet (00677-1799) (Sun Pharmaceutical Industries, Inc.) (off market)
Zero Order Release Aspirin Controlled-Release 800mg Tablet (60258-0052) (Cypress Pharmaceutical Inc. a wholly-owned subsidiary of Currax Pharmaceuticals, LLC) (off market)
Zorprin 800mg Extended-Release Tablet (49884-0657) (Par Pharmaceuticals, an Endo Company) (off market)
Aspirin Oral tablet, gastro-resistant
Adult Aspirin Low Dose 81mg Enteric Coated Tablet (57896-0985) (Geri-Care Pharmaceuticals) null
Adult Low Dose Aspirin 81mg Enteric Coated Tablet (57896-0981) (Geri-Care Pharmaceuticals) (off market)
Anacin Adult Low Strength 81mg Tablet (null) (Medtech Products, Inc a Prestige Brands Company formerly Insight Pharmaceuticals) (off market)
Aspirin 81mg Delayed-Release Enteric Coated Tablet (63739-0212) (McKesson Packaging) (off market)
Aspirin 81mg Delayed-Release Tablet (10135-0173) (Marlex Pharmaceuticals) (off market)
Aspirin 81mg Delayed-Release Tablet (55966-0089) (PDK Labs Inc) null
Aspirin 81mg Delayed-Release Tablet (17236-0705) (R&S Northeast, LLC, formerly Dixon-Shane Drug Company) (off market)
Aspirin 81mg Enteric Coated Tablet (71406-0128) (AACE Pharmaceuticals, Inc.) null
Aspirin 81mg Enteric Coated Tablet (65162-0241) (Akyma Pharmaceuticals, a subsidiary of Amneal Pharmaceuticals) (off market)
Aspirin 81mg Enteric Coated Tablet (46122-0615) (AmerisourceBergen Corporation) null
Aspirin 81mg Enteric Coated Tablet (65162-0241) (Amneal Pharmaceuticals LLC) (off market)
Aspirin 81mg Enteric Coated Tablet (70882-0122) (Cambridge Therapeutics Technologies, LLC) null
Aspirin 81mg Enteric Coated Tablet (00904-6713) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)
Aspirin 81mg Enteric Coated Tablet (10135-0729) (Marlex Pharmaceuticals) null
Aspirin 81mg Enteric Coated Tablet (63739-0522) (McKesson Packaging) (off market)
Aspirin 81mg Enteric Coated Tablet (63739-0272) (McKesson Packaging Inc) (off market)
Aspirin 81mg Enteric Coated Tablet (43063-0724) (PD-Rx Pharmaceuticals, Inc.) null
Aspirin 81mg Enteric Coated Tablet (69618-0046) (Reliable 1 Laboratories LLC) (off market)
Aspirin 81mg Enteric Coated Tablet (69618-0066) (Reliable 1 Laboratories LLC) null
Aspirin 81mg Enteric Coated Tablet (00536-3086) (Rugby Laboratories a Division of The Harvard Drug Group, LLC) (off market)
Aspirin 81mg Enteric Coated Tablet (00536-1149) (Rugby Laboratories a Division of The Harvard Drug Group, LLC ) (off market)
Aspirin 81mg Enteric Coated Tablet (00677-1855) (Sun Pharmaceutical Industries, Inc.) (off market)
Aspirin 81mg Enteric Coated Tablet (00182-1061) (Teva Pharmaceuticals USA) (off market)
Aspirin 81mg Enteric Coated Tablet (49483-0387) (Time Cap Laboratories Inc) null
Aspirin Adult Low Dose 81mg Enteric Coated Tablet (43063-0862) (PD-Rx Pharmaceuticals, Inc.) null
Aspirin Adult Low Dose 81mg Enteric Coated Tablet (16103-0356) (Pharbest Pharmaceuticals) null
Aspirin Low Dose 81mg Delayed-Release Enteric Coated Tablet (63739-0212) (McKesson Packaging) null
Aspirin Low Dose 81mg Enteric Coated Tablet (57896-0981) (Geri-Care Pharmaceuticals) null
Aspirin Low Dose 81mg Enteric Coated Tablet (57896-0981) (Geri-Care Pharmaceuticals) (off market)
Aspirin Low Dose 81mg Enteric Coated Tablet (00904-6751) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) null
Aspirin Low Dose 81mg Enteric Coated Tablet (00603-0025) (Par Pharmaceuticals, an Endo Company) (off market)
Aspirin Low Dose 81mg Enteric Coated Tablet (00536-1234) (Rugby Laboratories a Division of The Harvard Drug Group, LLC) null
Aspirin Low Dose 81mg Safely Coated Tablet (71399-8627) (Akron Pharma Inc.) null
Aspirin Low Dose 81mg Safety Coated Tablet (72789-0039) (PD-Rx Pharmaceuticals, Inc.) null
Aspir-Low 81mg Enteric Coated Tablet (00904-7704) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)
Bayer Low Dose Aspirin Regimen 81mg Tablet (12843-0106) (Bayer Corp Consumer Care Div) (off market)
Bayer Low Dose Aspirin Regimen 81mg Tablet (12843-0536) (Bayer Corp Consumer Care Div) null
Bayer Low Dose Aspirin Regimen 81mg Tablet (00280-2100) (Bayer HealthCare LLC) null
BeneHealth Aspirin 81mg Low Dose Enteric Coated Tablet (65155-0981) (BeneHealth) null
CVS Aspirin Adult Low Dose 81mg Enteric Coated Tablet (59779-0600) (CVS Health) null
CVS Aspirin Adult Low Strength 81mg Enteric Coated Tablet (null) (CVS Health) (off market)
CVS Aspirin Adult Low Strength 81mg Enteric Coated Tablet (null) (CVS Health) null
CVS Aspirin Adult Low Strength 81mg Enteric Coated Tablet (59779-0945) (CVS Health) (off market)
CVS Aspirin Low Dose 81mg Enteric Coated Tablet (59779-0600) (CVS Health) null
CVS Aspirin Low Dose 81mg Enteric Coated Tablet (59779-0439) (CVS Health) (off market)
CVS Aspirin Low Dose 81mg Enteric Coated Tablet (null) (CVS Health) null
CVS Aspirin Low Dose 81mg Enteric Coated Tablet (null) (CVS Health) (off market)
CVS Aspirin Low Dose Sugar Free 81mg Enteric Coated Tablet (null) (CVS Health) null
CVS Aspirin Low Strength 81mg Enteric Coated Tablet (59779-0945) (CVS Health) null
CVS Aspirin Low Strength 81mg Enteric Coated Tablet (null) (CVS Health) null
Ecotrin 81mg Low Strength Enteric Coated Tablet (00135-0117) (GlaxoSmithKline Consumer Healthcare) (off market)
Ecotrin 81mg Low Strength Enteric Coated Tablet (49692-0903) (Medtech Products, Inc a Prestige Consumer Healthcare Company) (off market)
Ecotrin 81mg Low Strength Enteric Coated Tablet (63029-0301) (Medtech Products, Inc a Prestige Consumer Healthcare Company) null
Equaline Enteric Coated Aspirin 81mg Tablet (41163-0535) (Albertson's, Inc) (off market)
Equate Aspirin Adult Low Strength 81mg Enteric Coated Tablet (49035-0535) (Wal-Mart Stores, Inc.) (off market)
Equate Aspirin Low Dose 81mg Safety Coated Tablet (49035-0563) (Wal-Mart Stores, Inc.) null
GNP Aspirin 81mg Enteric Coated Tablet (24385-0535) (AmerisourceBergen Corporation) null
GNP Aspirin 81mg Enteric Coated Tablet (46122-0180) (AmerisourceBergen Corporation) (off market)
GoodSense Aspirin 81mg Enteric Coated Tablet (00113-0277) (Goodsense a Division of Perrigo) (off market)
GoodSense Aspirin 81mg Safety Coated Tablet (50804-0227) (Geiss, Destin & Dunn, Inc.) (off market)
GoodSense Aspirin 81mg Safety Coated Tablet (50804-0880) (Perrigo Company) null
Halfprin 81mg Enteric Coated Tablet (null) (Kramer Laboratories) (off market)
Health Mart Aspirin Low Dose 81mg Enteric Coated Tablet (62011-0019) (McKesson Corporation) null
Health Mart Safety Coated Aspirin 81mg Tablet (62011-0003) (McKesson Corporation) null
Leader Adult Aspirin Regimen 81mg Enteric Coated Tablet (70000-0218) (Cardinal Health, Inc.) null
Leader Aspirin Adult Low Strength 81mg Enteric Coated Tablet (37205-0510) (Cardinal Health, Inc.) null
Leader Aspirin Low Dose 81mg Enteric Coated Tablet (70000-0428) (Cardinal Health, Inc.) (off market)
Member's Mark Aspirin Low Dose 81mg Enteric Coated Tablet (68196-0901) (Sam's West/Wal-Mart Stores, Inc.) null
MiniPrin 81mg Enteric Coated Tablet (49483-0054) (Time Cap Laboratories Inc) (off market)
MiniPrin Low Dose 81mg Enteric Coated Tablet (49483-0330) (Time Cap Laboratories Inc) null
Premier Value Aspirin 81mg Enteric Coated Tablet (68016-0089) (Pharmacy Value Alliance LLC formerly Chain Drug Consortium , LLC) null
Premier Value Low Dose Aspirin 81mg Enteric Coated Tablet (68016-0642) (Pharmacy Value Alliance LLC formerly Chain Drug Consortium , LLC) null
Quality Choice Aspirin 81mg Enteric Coated Tablet (63868-0363) (Chain Drug Marketing Association) null
Quality Choice Low Dose Aspirin 81mg Enteric-Coated Tablet (63868-0363) (Chain Drug Marketing Association) null
RITE AID Aspirin Low Dose 81mg Enteric Coated Tablet (null) (Rite Aid Corp) null
RITE AID Aspirin Low Strength 81mg Enteric Coated Tablet (null) (Rite Aid Corp) null
Select Brand Aspirin 81mg Enteric Coated Tablet (15127-0228) (Select Brand) null
St. Joseph Aspirin Adult Low Strength 81mg Safety Coated Tablet (69536-0181) (Foundation Consumer Healthcare, LLC) null
St. Joseph Aspirin Adult Low Strength 81mg Safety Coated Tablet (00045-0126) (McNeil Consumer Healthcare Division of McNEIL-PPC, Inc.) (off market)
Sunmark Aspirin Adult Low Strength 81mg Enteric Coated Tablet (49348-0980) (McKesson Corporation) null
Sunmark Aspirin Adult Low Strength 81mg Safety Coated Tablet (49348-0981) (McKesson Corporation) null
Sunmark Aspirin Low Dose 81mg Enteric Coated Tablet (49348-0756) (McKesson Corporation) null
Today's Health Aspirin Low Dose 81mg Enteric Coated Tablet (null) (Today's Health, Inc.) null
Top Care Aspirin 81mg Enteric Coated Tablet (36800-0277) (Topco Associates LLC) null
Walgreens Aspirin 81mg Enteric Coated Tablet (00363-0414) (Walgreens Co) null
Walgreens Dye-Free Aspirin 81mg Enteric Coated Tablet (00363-0587) (Walgreens Co) null
Walgreens Low Dose Aspirin 81mg Tablet (00363-0563) (Walgreens Co) null
Halfprin 162mg Enteric Coated Tablet (null) (Kramer Laboratories) (off market)
Aspirin 300mg Delayed-Release Tablet (00781-1603) (Sandoz Inc. a Novartis Company) (off market)
Aspirin 325mg Delayed-Release Tablet (52297-0918) (Cardinal Health, Inc.) (off market)
Aspirin 325mg Delayed-Release Tablet (00904-2011) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)
Aspirin 325mg Delayed-Release Tablet (10135-0126) (Marlex Pharmaceuticals) (off market)
Aspirin 325mg Delayed-Release Tablet (57480-0106) (Medirex Inc) (off market)
Aspirin 325mg Delayed-Release Tablet (55966-0045) (PDK Labs Inc) null
Aspirin 325mg Delayed-Release Tablet (00182-0448) (Teva Pharmaceuticals USA) (off market)
Aspirin 325mg Enteric Coated Tablet (65162-0382) (Akyma Pharmaceuticals, a subsidiary of Amneal Pharmaceuticals) (off market)
Aspirin 325mg Enteric Coated Tablet (62584-0127) (American Health Packaging) null
Aspirin 325mg Enteric Coated Tablet (68084-0848) (American Health Packaging) (off market)
Aspirin 325mg Enteric Coated Tablet (57896-0921) (Geri-Care Pharmaceuticals) (off market)
Aspirin 325mg Enteric Coated Tablet (57896-0921) (Geri-Care Pharmaceuticals) null
Aspirin 325mg Enteric Coated Tablet (00904-2013) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)
Aspirin 325mg Enteric Coated Tablet (63739-0523) (McKesson Packaging) (off market)
Aspirin 325mg Enteric Coated Tablet (63739-0023) (McKesson Packaging Inc) (off market)
Aspirin 325mg Enteric Coated Tablet (00574-0002) (Paddock Laboratories Inc, a Perrigo Family) (off market)
Aspirin 325mg Enteric Coated Tablet (00603-0167) (Par Pharmaceuticals, an Endo Company) (off market)
Aspirin 325mg Enteric Coated Tablet (69618-0015) (Reliable 1 Laboratories LLC) null
Aspirin 325mg Enteric Coated Tablet (00536-3313) (Rugby Laboratories a Division of The Harvard Drug Group, LLC) (off market)
Aspirin 325mg Enteric Coated Tablet (00536-1232) (Rugby Laboratories a Division of The Harvard Drug Group, LLC ) null
Aspirin 325mg Enteric Coated Tablet (00536-1148) (Rugby Laboratories a Division of The Harvard Drug Group, LLC ) (off market)
Aspirin 325mg Enteric Coated Tablet (00677-1971) (Sun Pharmaceutical Industries, Inc.) (off market)
Aspirin 325mg Enteric Coated Tablet (49483-0331) (Time Cap Laboratories Inc) null
Aspirin 325mg Safety Coated Tablet (00904-6712) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)
Aspirin 325mg Safety Coated Tablet (16103-0357) (Pharbest Pharmaceuticals) null
Aspirin Lite Coat 325mg Enteric Coated Tablet (57394-0286) (Apothecary Products) (off market)
Aspirin Lite Coat 325mg Enteric Coated Tablet (00677-1853) (Sun Pharmaceutical Industries, Inc.) (off market)
Bayer Aspirin Regimen 325mg Caplet (12843-0103) (Bayer Corp Consumer Care Div) null
CVS Aspirin 325mg Enteric Coated Tablet (59779-0137) (CVS Health) null
CVS Aspirin 325mg Enteric Coated Tablet (null) (CVS Health) null
CVS Enteric Aspirin 325mg Tablet (59726-0370) (CVS Health) (off market)
CVS Enteric Aspirin 325mg Tablet (59726-0370) (CVS Health) null
Ecotrin 325mg Enteric Coated Tablet (00135-0014) (GlaxoSmithKline Consumer Healthcare) (off market)
Ecotrin 325mg Enteric Coated Tablet (63029-0302) (Medtech Products, Inc a Prestige Consumer Healthcare Company) null
Ecotrin 325mg Enteric Coated Tablet (49692-0903) (Medtech Products, Inc a Prestige Consumer Healthcare Company) (off market)
Equaline Enteric Coated Aspirin 325mg Tablet (41163-0429) (Albertson's, Inc) (off market)
Equate Aspirin 325mg Safety Coated Tablet (49035-0416) (Wal-Mart Stores, Inc.) null
Equate Aspirin 325mg Safety-coated Tablet (49035-0370) (Sam's West/Wal-Mart Stores, Inc.) null
Genacote Aspirin 325mg Enteric Coated Tablet (00182-1415) (Teva Pharmaceuticals USA) (off market)
GNP Aspirin 325mg Enteric Coated Tablet (24385-0429) (AmerisourceBergen Corporation) null
GoodSense Aspirin 325mg Enteric Coated Tablet (00113-0429) (Goodsense a Division of Perrigo) (off market)
Health Mart Aspirin 325mg Enteric Coated Tablet (62011-0040) (McKesson Corporation) null
Leader Aspirin 325mg Enteric Coated Tablet (70000-0359) (Cardinal Health Inc.) (off market)
Leader Aspirin 325mg Enteric Coated Tablet (37205-0429) (Cardinal Health, Inc.) (off market)
Leader Aspirin 325mg Enteric Coated Tablet (37205-0429) (Cardinal Health, Inc.) null
Premier Value Aspirin 325mg Enteric Coated Tablet (68016-0722) (Pharmacy Value Alliance LLC formerly Chain Drug Consortium , LLC) null
Publix Enteric Aspirin 325mg Tablet (56062-0429) (Publix Super Markets, Inc) null
Quality Choice Enteric Aspirin 325mg Tablet (63868-0898) (Chain Drug Marketing Association) null
RITE AID Pain Relief Aspirin 325mg Enteric Coated Tablet (null) (Rite Aid Corp) null
Select Brand Aspirin 325mg Enteric Coated Tablet (15127-0011) (Select Brand) (off market)
Select Brand Aspirin 325mg Enteric Coated Tablet (15127-0760) (Select Brand) null
Sunmark Aspirin 325mg Enteric Coated Tablet (49348-0937) (McKesson Corporation) null
Today's Health Enteric Aspirin 325mg Tablet (null) (Today's Health, Inc.) null
Top Care Aspirin 325mg Enteric Coated Tablet (36800-0429) (Topco Associates LLC) null
Walgreens Aspirin 325mg Enteric Coated Caplet (00363-0691) (Walgreens Co) null
Walgreens Aspirin 325mg Enteric Coated Tablet (00363-0227) (Walgreens Co) null
Leader Aspirin 500mg Maximum Strength Enteric Coated Tablet (37205-0511) (Cardinal Health, Inc.) (off market)
Aspirin 650mg Enteric Coated Tablet (00182-0449) (Teva Pharmaceuticals USA) (off market)
Aspirin 975mg Delayed-Release Tablet (00677-1347) (Sun Pharmaceutical Industries, Inc.) (off market)
Easprin 975mg Delayed-Release Tablet (59417-0975) (Shire LLC) (off market)
Aspirin Rectal suppository
Aspirin 60mg Rectal Suppository (45802-0701) (Perrigo Pharmaceuticals Company) (off market)
Aspirin 125mg Rectal Suppository (51079-0551) (Mylan Institutional LLC ) (off market)
Aspirin 125mg Rectal Suppository (45802-0702) (Perrigo Pharmaceuticals Company) (off market)
Aspirin 125mg Rectal Suppository (00536-1330) (Rugby Laboratories a Division of The Harvard Drug Group, LLC) (off market)
Aspirin 125mg Rectal Suppository (00182-0264) (Teva Pharmaceuticals USA) (off market)
Aspirin 300mg Rectal Suppository (00839-5531) (HL Moore Drug Exchange) (off market)
Aspirin 300mg Rectal Suppository (00574-7034) (Paddock Laboratories Inc, a Perrigo Family) null
Aspirin 600mg Rectal Suppository (00574-7036) (Paddock Laboratories Inc, a Perrigo Family) (off market)
Aspirin 1200mg Rectal Suppository (45802-0706) (Perrigo Pharmaceuticals Company) (off market)
Aspirin is an oral and rectal nonsteroidal antiinflammatory drug (NSAID) indicated for the temporary relief of minor aches and pains associated with headache, backache, muscular aches, a cold, toothache, minor pain of arthritis, premenstrual and menstrual cramps, to reduce the risk of death and myocardial infarction (MI) in patients with chronic coronary artery disease, such as patients with a history of MI or angina pectoris or chronic stable angina, and to reduce the risk of death and recurrent stroke in patients who have had an ischemic stroke or transient ischemic attack (TIA).[60438][64835] Aspirin increases the risk of bleeding and may cause gastric ulceration and bleeding.[64835] Reye's syndrome, a potentially fatal disease, has been associated with aspirin use after active varicella infection or other viral illnesses in children; hence, aspirin use is children is primarily limited to the treatment of Kawasaki disease, for thrombosis prophylaxis, particularly in those with congenital heart disease after cardiac surgery, and for the treatment and secondary prevention of arterial ischemic stroke.[49232][54240][52706][61950] Guidelines for the treatment of juvenile idiopathic arthritis in children no longer recommend aspirin as a treatment option due to the availability of other NSAIDs (i.e., ibuprofen, naproxen) that are just as effective, safer, and better tolerated.[54236][54237][54238][54239] Observational studies have suggested that aspirin reduces the risk of colorectal cancer. However, long-term follow-up of the randomized Physicians' Health Study found no association between aspirin use and colorectal cancer.[27349] In contrast, randomized trials have shown that aspirin reduces the risk of recurrent adenomas in persons with a history of colorectal cancer or adenomas.[27351][27352] The role of aspirin in the chemoprevention of colorectal cancer, either as primary or secondary prophylaxis, has not been determined.
Blood and Blood Forming Organs
Antithrombotic Agents
Platelet Aggregation Inhibitors
Cyclo-oxygenase Inhibitor Platelet Aggregation Inhibitors
Analgesics with Antipyretic Activity
Revision Date: 12/17/2019, 09:57:50 AM
27349 - Sturmer T, Glynn RJ, Lee IM, et al. Aspirin use and colorectal cancer: post-trial follow-up data from the Physicians' Health Study. Ann Intern Med 1998;128:713-20.27351 - Sandler RS, Halabi S, Baron JA, et al. A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer. N Engl J Med 2003;348:883-90.27352 - Baron JA, Cole BF, Sandler RS, et al. A randomized trial of aspirin to prevent colorectal adenomas. N Engl J Med 2003;348:891-9.49232 - Monagle P, Chan A, Goldenberg NA, et al. Antithrombotic therapy in neonates and children: American College of Physicians Evidence-Based Clinical Practice Guidelines (9th Edition). Chest 2012;141:e737S-801S.52706 - Roach ES, Golomb MR, Adams R, et al. Management of stroke in infants and children: a scientific statement from a special writing group of the American Heart Association Stroke Council and the Council on Cardiovascular Disease in the Young. Stroke 2008;39:2644-91.54236 - Dueckers G, Guellac N, Arbogast M, et al. Evidence and consensus based GKJR guidelines for the treatment of juvenile idiopathic arthritis. Clin Immunol 2012;142:176-193.54237 - Beukelman T, Patkar NM, Saag KG, et al. 2011 American College or Rheumatology recommendations for the treatment of juvenile idiopathic arthritis: initation and safety monitoring of therapeutic agents for the treatment of arthritis and systemic features. Arthritis Care Res (Hoboken) 2011;63:465-482.54238 - Hashkes PJ, Tauber T, Somekh E, et al. Naproxen as an alternative to aspirin for the treatment of arthritis of rheumatic fever: A randomized trial. J Pediatr 2003;143:399-401.54239 - Giannini EH, Brewer EJ, Miller ML, et al. Ibuprofen suspension in the treatment of juvenile rheumatoid arthritis. Pediatric Rheumatology Collaborative Study Group. J Pediatr 1990;117:645-5254240 - Schror K. Aspirin and Reye syndrome. A review of the evidence. Pediatr Drugs 2007;9:195-204.60438 - Durlaza (aspirin extended-release capsule) prescribing information. North Haven, CT; New Haven Pharmaceuticals: 2015 Sept.61950 - McCrindle BW, Rowley AH, Newburger JW, et al. Diagnosis, treatment, and long-term management of Kawasaki disease: A scientific statement for health professionals from the American Heart Association. Circulation 2017;135:e927-e999.64835 - Vazalore (aspirin) capsules package insert. Sparta, NJ: PLx Pharma Inc.; 2021 Nov.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
Administer with food or large amounts (240 mL) of water or milk to minimize gastric irritation.
Oral Solid Formulations
Film-coated tablets: May help to reduce the unpleasant taste or aftertaste, burning in the throat, or difficulty in swallowing associated with uncoated tablets.
Enteric-coated or extended-release tablets: Swallow whole; do not crush, cut, or chew.[53771] May help to reduce gastric irritation and/or symptomatic GI disturbances associated with uncoated tablets.
Chewable tablets: May be chewed, crushed, and/or dissolved in a liquid, or swallowed whole, followed by approximately 120 mL of water, milk, or fruit juice immediately after administration.
Capsules: Swallow whole; do not crush, cut, or chew.[64835]
Rectal Administration
For use in patients unable to take or retain oral aspirin; however, absorption may be slow and incomplete.[54242] Do not use aspirin tablets rectally because they are likely to cause irritation and erosion of rectal mucosa.
Instruct patient or caregiver on proper use of suppository.
Prior to insertion, carefully remove the wrapper. Avoid excessive handling as to avoid melting of the suppository.
If suppository is too soft to insert, chill in the refrigerator for 30 minutes or run cold water over it before removing the wrapper.
Moisten the suppository with cool water prior to insertion.
Have patient lie down on their side, usually in the Sim's lateral position to provide support and comfort.
Apply gentle pressure to insert the suppository completely into the rectum, pointed end first, using a gloved, lubricated index finger.
After insertion, keep the patient lying down to aid retention and gently hold the buttock cheeks close to keep the child from immediately expelling the suppository. The suppository must be retained in rectum to ensure complete absorption.
Clinical Pharmaceutics Information
From Trissel's 2'Ñ¢ Clinical Pharmaceutics Database
Revision Date: 07/06/2021, 12:12:35 PMCopyright 2004-2022 by Lawrence A. Trissel. All Rights Reserved.
53771 - Mitchell JF. Institute for Safe Medication Practices: Oral dosage forms that should not be crushed. 2013 Apr. Available on the World Wide Web at: http://www.ismp.org/tools/donotcrush.pdf54242 - Nowak MM, Brundhofer B, Gibaldi M. Rectal absorption from aspirin suppositories in children and adults. Pediatrics 1974;54:23-26.64835 - Vazalore (aspirin) capsules package insert. Sparta, NJ: PLx Pharma Inc.; 2021 Nov.
diaphoresis
cerebral edema
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
interstitial nephritis
intracranial bleeding
renal failure
renal papillary necrosis
Reye's syndrome
elevated hepatic enzymes
hypernatremia
hyperuricemia
medication overuse headache
metabolic acidosis
proteinuria
respiratory alkalosis
Central nervous system adverse effects reported with aspirin include agitation, cerebral edema, coma, confusion, dizziness, headache, lethargy, and seizures.[60438] Tinnitus and hearing loss may occur in patients receiving high-dose and/or long-term aspirin therapy.[28439] Discontinue aspirin if tinnitus or hearing loss occurs.[46973] These effects are early manifestations of salicylate toxicity. However, hearing loss has occurred in patients at low serum salicylate concentrations. Tinnitus and hearing loss are usually dose-related and reversible upon dose reduction or discontinuation. Tinnitus is commonly associated with salicylate concentrations more than 200 to 300 mcg/mL. Maximum hearing loss occurs most frequently at salicylate concentrations of 400 mcg/mL or more.[28439] [54259] The association of hearing loss and regular analgesic therapy (including aspirin) was prospectively assessed over 18 years in a study of 26,917 males age 40 to 74 years at study enrollment. During 369,079 person-years of follow-up, 3,488 cases of hearing loss were reported. After adjustment for confounders, the hazard ratio (HR) for aspirin associated hearing loss was 1.12 (95% CI 1.04 to 1.2, p = 0.005) in patients who were regular users of the drug (2 times weekly or more) compared to those with less use. Men who used aspirin regularly for 1 to 4 years were 28% (17% to 40%) more likely to develop hearing loss than those without regular use; the risk of hearing loss did not further increase with longer duration of use. Regular users of aspirin younger than 60 years were 33% more likely to experience hearing loss compared to non-regular users; no association occurred in those 60 years and older. This study does suggest association; however, data are based on patient reporting of the outcomes. Information regarding noise exposure and analgesic doses was not provided.[53719] Conversely, a similar prospective analysis conducted over 14 years in 62,261 women did not demonstrate an independent association of aspirin therapy with hearing loss. Salicylate ototoxicity may result from damage to the cochlea or auditory nerve through multiple mechanisms, including reduced cochlear blood flow, impairment of outer hair cell function, or inhibition of prostaglandin-forming cyclooxygenase.[53720]
Gastrointestinal adverse effects reported with aspirin include abdominal pain, anorexia, dyspepsia, elevated hepatic enzymes, gastritis, GI bleeding, hepatitis, nausea, and vomiting. Aspirin may cause peptic ulcer.[41561] [60438]
Reye's syndrome has been reported with aspirin use. Aspirin may increase the risk of developing Reye's syndrome, a rare but serious disease which can follow flu or chicken pox in children and adolescents.[57732] [60438] Reye's syndrome has been reported in children of all ages; however, most of the reported cases have occurred in children 5 to 10 years.[54281] Data are not strong to support a dose-dependent association with Reyes's syndrome; however, a case-controlled study reported that patients who developed Reye's syndrome (n = 27) had received larger doses for a longer duration compared with controls who did not develop Reye's syndrome. Of the patients who developed Reye's syndrome, 67% were receiving more than 20 mg/kg/day of salicylates compared with only 22% of controls.[54282] [54283] Reye's syndrome is a multisystem disorder evidenced by persistent vomiting, altered sensorium, elevated hepatic enzymes, hypoprothrombinemia, hyperammonemia, convulsions, and encephalopathy.[54240] [54281] [54282]
Renal adverse effects reported with aspirin include interstitial nephritis, renal papillary necrosis, proteinuria, renal insufficiency and acute renal failure.[41561] [60438]
Dermatologic adverse reactions reported with aspirin include rash, pruritus, and purpura.[41561]
Salicylates, such as aspirin, have dose-dependent effects on plasma uric acid concentrations. At low doses (1 to 2 g/day) decreased urate excretion and hyperuricemia may be seen. Intermediate salicylate doses (2 to 3 g/day) usually do not alter urate excretion, and high doses of salicylates (more than 3 g/day) induce uricosuria and lower plasma uric acid concentrations.[54248]
Intracranial bleeding has been reported with aspirin use.[41561]
At therapeutic doses, salicylates such as aspirin cause changes in acid/base balance and electrolytes resulting in respiratory alkalosis. In patients with normal renal and respiratory function, this is usually compensated for appropriately. Severe acid/base disturbances may occur during salicylate toxicity. Infants and children with salicylate toxicity rarely present clinically with respiratory alkalosis. As salicylate toxicity progresses, changes resembling metabolic acidosis are present (e.g., low blood pH, low plasma bicarbonate concentrations, and normal or nearly normal plasma PaCO2). In reality, a combination of respiratory acidosis and metabolic acidosis is present. Alterations in water and electrolyte balance also occur in salicylate toxicity. Dehydration due to salicylate-induced diaphoresis and hyperventilation occurs. Since more water than electrolytes are lost, dehydration is associated with hypernatremia. Other laboratory changes noted in salicylate toxicity include hyperglycemia or hypoglycemia (especially in children), ketonuria, hypokalemia, and proteinuria. Prolonged exposure to high doses of salicylates also causes hypokalemia through both renal and nonrenal losses. Hyperventilation occurs due to direct stimulation of the respiratory center in the medulla. At high salicylate plasma concentrations (350 mcg/mL or more), marked hyperventilation will occur, and at serum concentrations of about 500 mcg/mL, hyperpnea will be seen. At high or prolonged doses, salicylates also have a depressant effect on the medulla. Toxic doses of salicylates cause central respiratory depression as well as cardiovascular collapse secondary to vasomotor depression. Since enhanced CO2 production continues, respiratory acidosis occurs.[54194] [54260] [54310]
Overuse of drugs for treating acute headaches, including aspirin, may lead to medication overuse headache. Patients may experience migraine-like daily headaches or a significant increase in migraine attack frequency. Discontinuation of the overused drug and treatment of withdrawal symptoms (e.g., transient worsening of headache) may be necessary. Advise patients about the risks of medication overuse (e.g., use of aspirin for at least 15 days/month or any combination of therapy for at least 10 days/month) and encourage them to keep a written record of headache frequency and drug use.[66767] [66803]
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), a multi-organ hypersensitivity reaction, has occurred with NSAIDs. Some of these events have been life-threatening or fatal. DRESS typically presents as fever, rash, and/or lymphadenopathy in conjunction with other organ system involvement including hepatitis, nephritis, hematologic abnormalities, myocarditis, or myositis sometimes resembling an acute viral infection. Eosinophilia is often present. Early manifestations such as fever and lymphadenopathy may be present without evidence of a rash. Discontinue the NSAID in patients presenting with such signs and symptoms in whom an alternative etiology cannot be identified.[41602]
28439 - Aggrenox (aspirin; dipyridamole extended-release) package insert. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; 2021 May.41561 - Carisoprodol, aspirin, and codeine phosphate tablet package insert. Orlando, FL: Ingenus Pharmaceuticals, LLC.; 2019 Oct.41602 - Norgesic and Norgesic Forte (orphenadrine citrate, aspirin, and caffeine) tablet package insert. Bridgewater, NJ: Baush Health US; 2021 Apr.46973 - Blowfish (aspirin; caffeine) effervescent tablet package insert. New York, NY: Rally Labs, LLC.; 2020 Dec.53719 - Curhan SG, Eavey R, Shargorodsky J, et al. Analgesic use and the risk of hearing loss in men. Am J Med 2010;123:231-237.53720 - Curhan SG, Shargorodsky J, Eavey R, et al. Analgesic use and the risk of hearing loss in women. Am J Epidemiol 2012;176:544-554.54194 - Temple AR. Pathophysiology of aspirin overdosage toxicity, with implications for management. Pediatrics 1978;62:873-876.54240 - Schror K. Aspirin and Reye syndrome. A review of the evidence. Pediatr Drugs 2007;9:195-204.54248 - Zhang Y, Neogi T, Chen C, et al. Low-dose aspirin and recurrent gout attacks. Ann Rheum Dis 2013;0:1-6.54259 - Boettcher FA, Salvi RJ. Salicylate ototoxicity: Review and synthesis. Am J Otolaryngol 1991;12:33-47.54260 - Yip L, Dart RC, Gabow PA. Concepts and controversies in salicylate toxicity. Emerg Med Clin North Am 1994;12:351-364.54281 - Maheady DC. Reye's syndrome: Review and update. J Pediatr Health Care 1989;3:246-250.54282 - Hurwitz ES, Barrett MJ, Bregman D, et al. Public health service study of Reye's syndrome and medications. Report of the main study. JAMA 1987;257:1905-1911.54283 - Wei CM, Chen HL, Lee PI, et al. Reye's syndrome developing in an infant on treatment of Kawasaki syndrome. J Paediatr Child Health 2005;41:303-304.54310 - Snodgrass W, Rumack BH, Peterson RG, et al. Salicylate toxicity following therapeutic doses in young children. Clin Toxicol 1981;18:247-259.57732 - Percodan (aspirin; oxycodone) tablet package insert. Malvern, PA: Endo Pharmaceuticals Inc.; 2018 Sept.60438 - Durlaza (aspirin extended-release capsule) prescribing information. North Haven, CT; New Haven Pharmaceuticals: 2015 Sept.66767 - Diener HC, Antonaci F, Braschinsky M, et al. European Academy of Neurology guideline on the management of medication overuse headache. Eur J Neurol 2020;27:1102-1116.66803 - Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition. Cephalalgia 2018;38:1-211.
Absolute contraindications are italicized.
NSAID hypersensitivity
salicylate hypersensitivity
anticoagulant therapy
coagulopathy
obstetric delivery
von Willebrand's disease
Aspirin is contraindicated in patients with salicylate hypersensitivity or NSAID hypersensitivity. Aspirin is also contraindicated in patients with the syndrome of asthma, rhinitis, and nasal polyps; aspirin may cause severe urticaria, angioedema, or bronchospasm in these patients.[60438]
Aspirin is contraindicated in infants and children for viral infection, with or without fever, because of the risks of Reye's syndrome. Do not use aspirin in children recovering from varicella infection or influenza.[46973] [57732] [59638] [66507] If children are receiving chronic aspirin therapy, aspirin should be discontinued immediately if a fever develops, and not resumed until diagnosis confirms that the febrile viral illness has run its course and the absence of Reye's syndrome. Following varicella vaccination, aspirin use should generally be avoided for 6 weeks.[28336] Children receiving long-term aspirin therapy should receive the annual influenza vaccine.[32219]
Avoid aspirin in patients with active peptic ulcer disease due to the risk for gastric ulceration and bleeding. Aspirin increases bleeding risk; risk factors for bleeding include the use of other drugs that increase the risk of bleeding (e.g., anticoagulant therapy, antiplatelet agents, NSAID therapy), inherited (hemophilia, von Willebrand's disease) or acquired (liver disease) coagulopathy, alcoholism, and age 60 years and older.[57732] [60438] [66507] Neonates have a slower clearance of aspirin and therefore are at higher risk for bleeding.[49232]
Avoid aspirin in patients with severe hepatic insufficiency. Hepatic disease increases the risk for bleeding.[60438]
Avoid aspirin in patients with severe renal failure (i.e., GFR less than 10 mL/minute).[60438]
According to the Beers Criteria, aspirin is considered a potentially inappropriate medication (PIM) in geriatric patients. Aspirin may cause new or worsening gastric or duodenal ulcers, and there is an increased risk of GI bleeding and peptic ulcer disease in high-risk groups including those above 75 years of age, or those taking oral or parenteral corticosteroids, anticoagulants, or antiplatelet medications. The Beers panel recommends avoiding chronic use of aspirin doses more than 325 mg/day in high-risk patients unless other alternatives are not effective and the patient can take a gastroprotective agent. Aspirin doses above 325 mg/day should be avoided in patients with a history of gastric or duodenal ulcers unless other alternatives are not effective and the patient can take a gastroprotective agent. The use of a gastroprotective agent, like a proton-pump inhibitor or misoprostol, reduces but does not eliminate, GI risks. The risk of ulcers, gross bleeding, or perforation is cumulative with continued use. Use caution when aspirin is used for the primary prevention of cardiac disease and colorectal cancer in adults 70 years of age and older. Several studies suggest a lack of net benefit when used for primary prevention in older adults with cardiac risk factors, but the evidence is not conclusive. Aspirin is generally indicated for secondary prevention in older adults with established cardiac disease.[63923] The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). According to OBRA, reserve the use of aspirin for symptoms or inflammatory conditions for which lower risk analgesics (e.g., acetaminophen) have either failed or are not clinically indicated. Aspirin may cause GI bleeding in patients with a prior history of, or with increased risk for, GI bleeding, or may worsen renal failure, increase blood pressure, or exacerbate heart failure. According to OBRA, low-dose aspirin (81 to 325 mg/day) may be appropriate as a prophylactic treatment for cardiac events such as myocardial infarction or stroke. Monitor closely for bleeding when aspirin is used in doses greater than 325 mg/day with another NSAID or when used with other platelet inhibitors or anticoagulants. Aspirin can increase the risk of adverse effects from NSAIDs or COX-2 inhibitors on the GI tract. Some NSAIDs, such as ibuprofen, may reduce the cardioprotective effect of aspirin.[60742]
Avoid aspirin use during the third trimester of pregnancy (starting at 30 weeks of gestation) due to the risk of premature closure of the fetal ductus arteriosus and persistent pulmonary hypertension in the neonate.[60438] If NSAID treatment is deemed necessary between 20 to 30 weeks of pregnancy, limit use to the lowest effective dose and shortest duration possible. Consider ultrasound monitoring of amniotic fluid if NSAID treatment extends beyond 48 hours. Discontinue the NSAID if oligohydramnios occurs and follow up according to clinical practice. These recommendations do not apply to low-dose 81 mg aspirin prescribed for certain conditions in pregnancy. Use of NSAIDs around 20 weeks gestation or later in pregnancy may cause fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation. Oligohydramnios is often, but not always, reversible with treatment discontinuation. Complications of prolonged oligohydramnios may include limb contractures and delayed lung maturation. In some postmarketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were required.[66040] Salicylates have also been associated with alterations in maternal and neonatal hemostasis mechanisms, decreased birth weight, and perinatal mortality. Avoid aspirin 1 week prior to and during labor and obstetric delivery because it can result in excessive blood loss at delivery. Prolonged gestation and labor due to prostaglandin inhibition have been reported.[60438]
Salicylates are excreted into breast milk and could cause adverse effects in infants. Mean peak breast milk concentrations of salicylate in 6 nursing mothers after aspirin doses of 500, 1,000, and 1,500 mg were 5.8, 15.8, and 38.8 mg/L, respectively. Salicylate concentrations were detectable in breast milk within 1 hour of dosing and reached maximum concentration within 2 to 6 hours.[49577] Previous American Academy of Pediatrics (AAP) recommended that aspirin be used cautiously during breast-feeding. Alternative analgesics and antipyretics considered to be usually compatible with breast-feeding by the AAP include acetaminophen and ibuprofen.[27500]
27500 - American Academy of Pediatrics (AAP) Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001;108(3):776-789.28336 - Varivax (varicella virus vaccine live, Oka/Merck) package insert. Whitehouse Station, NJ: Merck and Co, Inc.; 2020 March.32219 - Newburger JW, Takahashi M, Gerber MA, et al. Diagnosis, treatment, and long-term management of kawasaki disease: a statement for health professionals from the committee on rheumatic fever, endocarditis and kawasaki disease, council on cardiovascular disease in the young, American Heart Association. Circ 2004;110:2747-71.46973 - Blowfish (aspirin; caffeine) effervescent tablet package insert. New York, NY: Rally Labs, LLC.; 2020 Dec.49232 - Monagle P, Chan A, Goldenberg NA, et al. Antithrombotic therapy in neonates and children: American College of Physicians Evidence-Based Clinical Practice Guidelines (9th Edition). Chest 2012;141:e737S-801S.49577 - Jamali F, Keshavarz E. Salicylate excretion in breast milk. Int J Pharm 1981;8:285-90.57732 - Percodan (aspirin; oxycodone) tablet package insert. Malvern, PA: Endo Pharmaceuticals Inc.; 2018 Sept.59638 - BC Arthritis (aspirin; caffeine) oral powder package insert. Tarrytown, NY: Medtech Products, Inc.; 2012 Jun.60438 - Durlaza (aspirin extended-release capsule) prescribing information. North Haven, CT; New Haven Pharmaceuticals: 2015 Sept.60742 - Health Care Financing Administration. Interpretive Guidelines for Long-term Care Facilities. Title 42 CFR 483.25(l) F329: Unnecessary Drugs. Revised 2015.63923 - The American Geriatrics Society 2019 Beers Criteria Update Expert Panel. American Geriatrics Society 2019 updated AGS Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc 2019;00:1-21.66040 - Food and Drug Administration MedWatch. Nonsteroidal anti-inflammatory drugs (NSAIDs): Drug safety communication - avoid use of NSAIDs in pregnancy at 20 weeks or later. Available at: https://www.fda.gov/safety/medical-product-safety-information/nonsteroidal-anti-inflammatory-drugs-nsaids-drug-safety-communication-avoid-use-nsaids-pregnancy-20. Accessed October 15, 2020.66507 - Anacin (aspirin; caffeine) oral tablet package insert. Tarrytown, NY: Insight Pharmaceuticals LLC; 2020 Jul
The activity of aspirin is due to its ability to inhibit cyclooxygenase (COX). Cyclooxygenase is responsible for the conversion of arachidonic acid to prostaglandin G2 (PGG-2), the first step in prostaglandin synthesis and precursor to prostaglandins of the E and F series. Cyclooxygenase exists in 2 isozymes: cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). In vivo, aspirin is hydrolyzed to salicylic acid and acetate. However, hydrolysis is not required for aspirin activity. Aspirin irreversibly inhibits COX by acetylation of a specific serine moiety (serine 530 of COX-1 and serine 516 of COX-2). Aspirin is about 170-times more potent in inhibiting COX-1 than COX-2. In comparison, salicylic acid has little or no ability to inhibit COX in vitro despite inhibiting prostaglandin synthesis at the site of inflammation in vivo. The exact mechanism of prostaglandin inhibition by salicylic acid is unclear; however, salicylates produce the majority of classic NSAID effects. Theories regarding the potential mechanism for salicylic acid include inactivation of transcriptional regulatory proteins (e.g., NF-kappaB), which regulate expression of inflammatory proteins. Aspirin appears to inhibit COX through two pathways and seems to have a different mechanism of action than other salicylates. Aspirin does not inhibit the peroxidase activity of COX and does not suppress leukotriene synthesis by lipoxygenase pathways.[54023] [54244]
Antithrombotic Actions: Aspirin-induced inhibition of thromboxane A2 (TXA2) and prostacyclin (PGI-2) has opposing effects on hemostasis. TXA2 is a potent vasoconstrictor and platelet agonist, while PGI-2 inhibits platelet aggregation and vascular smooth muscle contraction. However, data suggest that the effects of aspirin-induced TXA2 inhibition predominate clinically. This may be due to the ability of vascular endothelial cells to regenerate new COX and recover normal function, while COX inhibition in platelets is irreversible due to the limited amount of mRNA and protein synthesis in these cells. This distinction also allows for the use of very low doses of aspirin to retard platelet aggregation. The antithrombotic actions of aspirin are primarily mediated by COX-1 inhibition; COX-1 produces TXA2. Aspirin may also inhibit platelet activation by neutrophils. The antiplatelet effects of aspirin result in a prolonged bleeding time, which returns to normal roughly 36 hours after the last dose of the drug. Antiplatelet effects occur before acetylsalicylic acid is detectable in the peripheral blood due to exposure of platelets in the portal circulation.[26402] [54315] In very high and toxic doses, aspirin also exerts a direct inhibitory effect on vitamin K-dependent hemostasis by inhibiting the synthesis of vitamin K-dependent clotting factors. Prothrombin synthesis is impaired, resulting in hypoprothrombinemia.[54310]
Anti-inflammatory Actions: The antiinflammatory action of aspirin is believed to be a result of peripheral inhibition of COX-1 and COX-2, but aspirin may also inhibit the action and synthesis of other mediators of inflammation. It is thought that COX-2 is the more important pathway for the inflammatory response since COX-2 is inducible in settings of inflammation by cytokines. Inhibition of COX-2 by aspirin suppresses the production of prostaglandins of the E and F series. These prostaglandins induce vasodilation and increase tissue permeability, which, in turn, promotes the influx of fluids and leukocytes. Ultimately, the classic symptoms of inflammation result: swelling, redness, warmth, and pain. Aspirin does not only decrease capillary permeability (which reduces swelling and the influx of inflammatory mediators), but it can also reduce the release of destructive enzymes from lysozymes.[54023] [54244]
Analgesic Actions: Salicylates are effective in cases where inflammation has caused sensitivity of pain receptors (hyperalgesia). It appears prostaglandins, specifically prostaglandins E and F, are responsible for sensitizing the pain receptors; therefore, salicylates have an indirect analgesic effect by inhibiting the production of further prostaglandins and do not directly affect hyperalgesia or the pain threshold. Salicylates may also interfere with pain perception centrally by activity within the hypothalamus. The total serum salicylate concentrations associated with analgesic activity are 30 to 100 mcg/mL.[54023] [54244]
Antipyretic Actions: Salicylates promote a return to a normal body temperature set point in the hypothalamus by suppressing the synthesis of prostaglandins, specifically PGE-2, in circumventricular organs in and near the hypothalamus. Salicylates rarely decrease body temperature in afebrile patients. Paradoxically, toxic doses of salicylates may increase body temperature by increasing oxygen consumption and metabolic rate. The total serum salicylate concentrations associated with antipyretic activity are 30 to 100 mcg/mL.[54023] [54244]
Gastrointestinal Effects: Adverse gastrointestinal effects from salicylates may be mediated through decreased prostaglandin synthesis due to inhibition of COX-1. A direct irritant effect on gastric mucosa may also be involved. Salicylates increase the permeability of the gastric mucosa to cations, thus increasing the entry of acid into the mucosa. Salicylates are also known to stimulate the chemoreceptor trigger zone, resulting in nausea and vomiting.[26402] [54244]
Respiratory Effects: The respiratory effects of salicylates lead to acid/base changes and alterations in electrolyte and water balance. Salicylates stimulate respiration directly and indirectly resulting in respiratory alkalosis. This is caused by a salicylate-induced increase in oxygen consumption, primarily in skeletal muscle, leading to increased carbon dioxide production and respiratory stimulation. Increased alveolar ventilation balances the increased carbon dioxide production; therefore, plasma carbon dioxide (PaCO2) does not change. Salicylate-induced respiratory alkalosis is compensated for by increasing renal excretion of bicarbonate, which is accompanied by increased sodium and potassium excretion. The serum bicarbonate concentration is then lowered and the serum pH returns to normal (i.e., compensated respiratory alkalosis). However, if the respiratory response to hypercapnia has been depressed (e.g., administration of a barbiturate or opiate agonist), salicylates will cause a significant increase in PaCO2 and respiratory acidosis. Hyperventilation also occurs due to direct stimulation of the respiratory center in the medulla. At high salicylate plasma concentrations (350 mcg/mL or more), marked hyperventilation will occur, and at serum concentrations of about 500 mcg/mL, hyperpnea will be seen. Finally, at high-therapeutic and at toxic doses, aspirin can affect oxidative phosphorylation, however, this action is insignificant at lower doses. Other changes in acid-base status (e.g., metabolic and respiratory acidosis) and electrolyte and water balance (hypokalemia, hypernatremia, dehydration) may be seen during salicylate intoxication.[54194] [54260]
Renal Effects: In addition to changes in sodium and fluid status secondary to acid/base changes, salicylates may decrease renal blood flow and glomerular filtration rate, which may be accompanied by water and potassium retention, in sodium-restricted patients and patients with impaired renal function or hypovolemic states. Changes in renal function are due to inhibition of renal prostaglandin synthesis, which increase renal blood flow and maintain normal renal function. Salicylate-induced renal effects are uncommon in patients with normal renal function.[54244]
Uricosuric Effects: Salicylates act on the renal tubules to affect uric acid excretion. Lower doses (e.g., 1 to 2 g/day) of salicylates inhibit the active secretion of uric acid into the urine via the proximal tubules. However, high doses (more than 3 g/day) of salicylates inhibit the tubular reabsorption of uric acid, resulting in a uricosuric effect. Uric acid secretion is not changed at intermediate dosages. While once used for their uricosuric properties, other agents have replaced salicylates for this purpose.[54248]
26402 - Awtry EH, Loscalzo J. Aspirin. Circulation 2000;101:1206-1218.54023 - Litalien C, Jacqz-Aigrain E. Risks and benefits of nonsteroidal anti-inflammatory drugs in children: a comparison with paracetamol. Paediatr Drugs 2001;3:817-858.54194 - Temple AR. Pathophysiology of aspirin overdosage toxicity, with implications for management. Pediatrics 1978;62:873-876.54244 - Mortensen ME, Rennebohm RM. Clinical pharmacology and use of nonsteroidal anti-inflammatory drugs. Pediatr Clin North Am 1989;36:1113-1139.54248 - Zhang Y, Neogi T, Chen C, et al. Low-dose aspirin and recurrent gout attacks. Ann Rheum Dis 2013;0:1-6.54260 - Yip L, Dart RC, Gabow PA. Concepts and controversies in salicylate toxicity. Emerg Med Clin North Am 1994;12:351-364.54310 - Snodgrass W, Rumack BH, Peterson RG, et al. Salicylate toxicity following therapeutic doses in young children. Clin Toxicol 1981;18:247-259.54315 - Eikelboom JW, Hirsch J, Spencer FA, et al. Antiplatelet drugs. Antithrombotic therapy and prevention of thrombosis. 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. CHEST 2012;142:e89S-e119S.
Aspirin is administered orally or rectally. Salicylic acid is widely distributed with high concentrations in the liver and kidney. During chronic administration, salicylate concentrations in the fetus may be higher than those in the mother. Aspirin is poorly protein-bound as compared to salicylic acid. However, aspirin may acetylate albumin, resulting in changes the ability of albumin to bind other drugs. Protein binding of salicylic acid to albumin varies with serum salicylate and albumin concentrations. At salicylate concentrations of 100 mcg/mL or less, salicylic acid is 90% to 95% protein-bound; approximately 70% to 85% protein-bound at 100 to 400 mcg/mL; and only 20% to 60% protein-bound at serum concentrations of more than 400 mcg/mL. Patients with low serum albumin have higher free salicylate concentrations.[54243][54244]
Aspirin has a half-life of 15 to 20 minutes in adults as it is rapidly hydrolyzed by the liver to salicylic acid. Salicylic acid is primarily metabolized in the liver. Metabolites include salicyluric acid (glycine conjugate), the ether or phenolic glucuronide, and the ester or acyl glucuronide. In addition, a small amount is metabolized to gentisic acid (2,5-dihydroxybenzoic acid) and 2,3-dihydroxybenzoic and 2,3,5-dihydroxybenzoic acids. Salicyluric acid and salicyl phenolic glucuronide are formed via saturable enzyme pathways, and therefore, exhibit non-linear pharmacokinetics. The elimination half-life of salicylic acid varies with dosage. After a single low dose, the serum half-life of salicylic acid is 2 to 3 hours, but can increase to 12 hours with anti-inflammatory doses and up to 15 to 30 hours after overdoses. Because of decreased serum protein binding, the effect of increasing doses is more pronounced on free salicylate concentrations than total salicylate concentrations. Approximately 80% to 100% of the salicylic acid from a single salicylate dose is excreted within 24 to 72 hours in the urine as free salicylic acid (10%), salicyluric acid (75%), salicylic phenolic (10%) and acyl (5%) glucuronides, and gentisic acid (less than 1%). The excretion of free salicylic acid is variable and depends upon the dose and the urinary pH. In alkaline urine, more than 30% of the dose may be eliminated as free salicylic acid, but in acidic urine only about 2% is eliminated as free salicylic acid.[54023][54243][54244]
Affected cytochrome P450 isoenzymes and drug transporters: none
Route-Specific Pharmacokinetics
Oral Route
Aspirin is absorbed orally via passive diffusion as unchanged drug and as hydrolyzed salicylic acid from the upper intestine and partly from the stomach. Approximately 70% of an aspirin dose reaches the circulation unchanged; the remaining 30% is hydrolyzed to salicylic acid during absorption by esterases in the GI tract, plasma, or liver. The rate of absorption is dependent upon many factors including oral formulation, gastric and intestinal pH, gastric emptying time, and the presence of food. Aspirin is rapidly absorbed after oral administration, and bioavailability of regular aspirin in adults is approximately 40% to 50%.[54315] Effervescent and soluble tablets are most rapidly absorbed, followed by uncoated or film-coated tablets, and then enteric-coated tablets and extended-release formulations. The absorption from enteric-coated tablets and sustained-release preparations is delayed and bioavailability is significantly lower compared with regular aspirin.[54023] [54243] [54315] Peak plasma salicylate concentrations occur in approximately 30 to 60 minutes for effervescent tablets, 45 to 120 minutes for film-coated tablets, 4 to 12 hours for extended-release tablets, and 8 to 14 hours for enteric-coated tablets. Food decreases the rate, but not the extent, of absorption. Salicylic acid is more ionized as the pH increases; however, a rise in pH increases the solubility of ionized salicylic acid and increases the dissolution of aspirin tablets. The overall effect of increased pH is an increase in absorption. Time to peak aspirin concentrations is 15 to 240 minutes depending upon the formulation. Plasma aspirin concentrations decrease as salicylic acid concentrations increase. Steady-state salicylate serum concentrations are similar after administration of plain, uncoated tablets and enteric-coated tablets.[23554]
Other Route(s)
Rectal Route
The bioavailability of aspirin after rectal administration in adults has been reported to be 20% to 40%.[54307] Peak concentrations are reached approximately 4 hours after rectal administration in adults.[54308] Limited pharmacokinetic data in 8 children (5 to 9 years) revealed that the absorption of aspirin was very slow after rectal administration and was highly dependent on retention time. In children that retained the suppository for 5 hours or less, urinary recovery was 54% to 64%. Therefore, aspirin given rectally may not attain effective serum concentrations.[54242]
Hepatic Impairment
Pharmacokinetic data are unavailable in patients with hepatic impairment; however, aspirin is extensively metabolized in the liver and patients with hepatic impairment may have decreased elimination.
Renal Impairment
Pharmacokinetic data are unavailable in patients with renal impairment. Aspirin is renally excreted and patients with renal impairment may have decreased elimination. Aspirin is 50% to 100% hemodialyzable.[32569]
Neonates would be expected to have a slower clearance of aspirin due to their immature hepatic function.[49232] Pharmacokinetic data are very limited in children. Data from 10 children (2 to 7 years) who received aspirin revealed a mean elimination half-life for salicylic acid of 3.4 hours. This is similar to what has been reported in adults.[54026]
The pharmacokinetics of aspirin are altered in children with Kawasaki disease. These patients have been shown to achieve lower salicylate concentrations compared with healthy children receiving the same aspirin dose due to a combination of impaired bioavailability and/or increased clearance.[54297]
23554 - Karahalios WJ, Sawyer WT, Rittase RA, et al. Comparative bioavailability of sustained-release and uncoated aspirin tablets. Am J Hosp Pharm 1981;38:1754-6.32569 - Aronoff GR, Bennett WM, Berns JS, et al. Drug prescribing in renal failure: dosing guidelines for adults and children, 5th ed. Philadelphia: American College of Physicians; 2007.49232 - Monagle P, Chan A, Goldenberg NA, et al. Antithrombotic therapy in neonates and children: American College of Physicians Evidence-Based Clinical Practice Guidelines (9th Edition). Chest 2012;141:e737S-801S.54023 - Litalien C, Jacqz-Aigrain E. Risks and benefits of nonsteroidal anti-inflammatory drugs in children: a comparison with paracetamol. Paediatr Drugs 2001;3:817-858.54026 - Wilson JT, Brown RD, Bocchini JA. Efficacy, disposition and pharmacodynamics of aspirin, acetaminophen and choline salicylate in young febrile children. Ther Drug Monit 1982;4:147-180.54242 - Nowak MM, Brundhofer B, Gibaldi M. Rectal absorption from aspirin suppositories in children and adults. Pediatrics 1974;54:23-26.54243 - Levy G. Clinical pharmacokinetics of aspirin. Pediatrics 1978;62:867-872.54244 - Mortensen ME, Rennebohm RM. Clinical pharmacology and use of nonsteroidal anti-inflammatory drugs. Pediatr Clin North Am 1989;36:1113-1139.54297 - Koren G. Salicylates in Kawasaki disease - a review of clinical pharmacokinetics and efficacy. Prog Clin Biol Res 1987;250:415-424.54307 - Gibaldi M, Grundhofer B. Bioavailability of aspirin from commercial suppositories. J Pharm Sci 1975;64:1064-1066.54308 - Dalvi SS, Gupta KC, Pohujani SM, et al. Bioavailability of aspirin after oral and rectal administration in volunteers and patients with fever. J Postgrad Med 1985;31:192-195.54315 - Eikelboom JW, Hirsch J, Spencer FA, et al. Antiplatelet drugs. Antithrombotic therapy and prevention of thrombosis. 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. CHEST 2012;142:e89S-e119S.
labor, obstetric delivery, pregnancy
27500 - American Academy of Pediatrics (AAP) Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001;108(3):776-789.49577 - Jamali F, Keshavarz E. Salicylate excretion in breast milk. Int J Pharm 1981;8:285-90.60438 - Durlaza (aspirin extended-release capsule) prescribing information. North Haven, CT; New Haven Pharmaceuticals: 2015 Sept.66040 - Food and Drug Administration MedWatch. Nonsteroidal anti-inflammatory drugs (NSAIDs): Drug safety communication - avoid use of NSAIDs in pregnancy at 20 weeks or later. Available at: https://www.fda.gov/safety/medical-product-safety-information/nonsteroidal-anti-inflammatory-drugs-nsaids-drug-safety-communication-avoid-use-nsaids-pregnancy-20. Accessed October 15, 2020.
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Repaglinide
Rosiglitazone
Saxagliptin
Serotonin norepinephrine reuptake inhibitors
Sibutramine
Simvastatin; Sitagliptin
Sitagliptin
Sodium Citrate; Citric Acid
Sodium Thiosulfate; Salicylic Acid
Spironolactone
Spironolactone; Hydrochlorothiazide, HCTZ
Telmisartan; Hydrochlorothiazide, HCTZ
Tenofovir Alafenamide
Thiazide diuretics
Thrombin Inhibitors
Thrombolytic Agents
Ticagrelor
Tinzaparin
Tipranavir
Tirofiban
Tolazamide
Tolbutamide
Tramadol; Acetaminophen
Trandolapril
Trandolapril; Verapamil
Treprostinil
Triamterene; Hydrochlorothiazide, HCTZ
Tromethamine
Valproic Acid, Divalproex Sodium
Valsartan; Hydrochlorothiazide, HCTZ
Vilazodone
Vorapaxar
Vortioxetine
Level 4 (Minor)
Aminoglycosides
Amoxicillin; Clarithromycin; Omeprazole
Amoxicillin; Clavulanic Acid
Amphotericin B cholesteryl sulfate complex (ABCD)
Amphotericin B lipid complex (ABLC)
Amphotericin B liposomal (LAmB)
Ampicillin; Sulbactam
Ascorbic Acid, Vitamin C
Aspirin, ASA; Butalbital; Caffeine
Aspirin, ASA; Butalbital; Caffeine; Codeine
Aspirin, ASA; Caffeine
Aspirin, ASA; Caffeine; Dihydrocodeine
Aspirin, ASA; Caffeine; Orphenadrine
Bacitracin
Bromocriptine
Caffeine; Sodium Benzoate
Carbenicillin
Cefotetan
Daratumumab; Hyaluronidase
Dicloxacillin
Ergotamine; Caffeine
Ethotoin
Foscarnet
Fosphenytoin
Lansoprazole; Amoxicillin; Clarithromycin
Omeprazole; Amoxicillin; Rifabutin
Oxacillin
Penicillin G
Penicillin G Benzathine
Penicillin G Benzathine; Penicillin G Procaine
Penicillin V
Penicillins
Pertuzumab; Trastuzumab; Hyaluronidase
Photosensitizing agents (topical)
Piperacillin
Piperacillin; Tazobactam
Rituximab; Hyaluronidase
Sulfonamides
Telavancin
Ticarcillin
Ticarcillin; Clavulanic Acid
Trastuzumab; Hyaluronidase
Vancomycin
Zafirlukast
Abciximab: (Moderate) Unless contraindicated, aspirin is used in combination with abciximab. However, both drugs are associated with bleeding. Monitor for bleeding during concomitant therapy. [29816] Acetaminophen: (Moderate) Prolonged concurrent use of acetaminophen and salicylates is not recommended. High-dose, chronic administration of the combined analgesics significantly increases the risk of analgesic nephropathy, renal papillary necrosis, and end-stage renal disease. Do not exceed the recommended individual maximum doses when these agents are given concurrently for short-term therapy. [4064] Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Prolonged concurrent use of acetaminophen and salicylates is not recommended. High-dose, chronic administration of the combined analgesics significantly increases the risk of analgesic nephropathy, renal papillary necrosis, and end-stage renal disease. Do not exceed the recommended individual maximum doses when these agents are given concurrently for short-term therapy. [4064] (Minor) Caffeine has been reported to increase the metabolism of aspirin. [66338] Acetaminophen; Caffeine: (Moderate) Prolonged concurrent use of acetaminophen and salicylates is not recommended. High-dose, chronic administration of the combined analgesics significantly increases the risk of analgesic nephropathy, renal papillary necrosis, and end-stage renal disease. Do not exceed the recommended individual maximum doses when these agents are given concurrently for short-term therapy. [4064] (Minor) Caffeine has been reported to increase the metabolism of aspirin. [66338] Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Prolonged concurrent use of acetaminophen and salicylates is not recommended. High-dose, chronic administration of the combined analgesics significantly increases the risk of analgesic nephropathy, renal papillary necrosis, and end-stage renal disease. Do not exceed the recommended individual maximum doses when these agents are given concurrently for short-term therapy. [4064] (Minor) Caffeine has been reported to increase the metabolism of aspirin. [66338] Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Moderate) Prolonged concurrent use of acetaminophen and salicylates is not recommended. High-dose, chronic administration of the combined analgesics significantly increases the risk of analgesic nephropathy, renal papillary necrosis, and end-stage renal disease. Do not exceed the recommended individual maximum doses when these agents are given concurrently for short-term therapy. [4064] (Minor) Caffeine has been reported to increase the metabolism of aspirin. [66338] Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Moderate) Prolonged concurrent use of acetaminophen and salicylates is not recommended. High-dose, chronic administration of the combined analgesics significantly increases the risk of analgesic nephropathy, renal papillary necrosis, and end-stage renal disease. Do not exceed the recommended individual maximum doses when these agents are given concurrently for short-term therapy. [4064] (Minor) Caffeine has been reported to increase the metabolism of aspirin. [66338] Acetaminophen; Chlorpheniramine: (Moderate) Prolonged concurrent use of acetaminophen and salicylates is not recommended. High-dose, chronic administration of the combined analgesics significantly increases the risk of analgesic nephropathy, renal papillary necrosis, and end-stage renal disease. Do not exceed the recommended individual maximum doses when these agents are given concurrently for short-term therapy. [4064] Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Prolonged concurrent use of acetaminophen and salicylates is not recommended. High-dose, chronic administration of the combined analgesics significantly increases the risk of analgesic nephropathy, renal papillary necrosis, and end-stage renal disease. Do not exceed the recommended individual maximum doses when these agents are given concurrently for short-term therapy. [4064] Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Prolonged concurrent use of acetaminophen and salicylates is not recommended. High-dose, chronic administration of the combined analgesics significantly increases the risk of analgesic nephropathy, renal papillary necrosis, and end-stage renal disease. Do not exceed the recommended individual maximum doses when these agents are given concurrently for short-term therapy. [4064] Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Prolonged concurrent use of acetaminophen and salicylates is not recommended. High-dose, chronic administration of the combined analgesics significantly increases the risk of analgesic nephropathy, renal papillary necrosis, and end-stage renal disease. Do not exceed the recommended individual maximum doses when these agents are given concurrently for short-term therapy. [4064] Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Prolonged concurrent use of acetaminophen and salicylates is not recommended. High-dose, chronic administration of the combined analgesics significantly increases the risk of analgesic nephropathy, renal papillary necrosis, and end-stage renal disease. Do not exceed the recommended individual maximum doses when these agents are given concurrently for short-term therapy. [4064] Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Moderate) Prolonged concurrent use of acetaminophen and salicylates is not recommended. High-dose, chronic administration of the combined analgesics significantly increases the risk of analgesic nephropathy, renal papillary necrosis, and end-stage renal disease. Do not exceed the recommended individual maximum doses when these agents are given concurrently for short-term therapy. [4064] Acetaminophen; Codeine: (Moderate) Prolonged concurrent use of acetaminophen and salicylates is not recommended. High-dose, chronic administration of the combined analgesics significantly increases the risk of analgesic nephropathy, renal papillary necrosis, and end-stage renal disease. Do not exceed the recommended individual maximum doses when these agents are given concurrently for short-term therapy. [4064] Acetaminophen; Dextromethorphan: (Moderate) Prolonged concurrent use of acetaminophen and salicylates is not recommended. High-dose, chronic administration of the combined analgesics significantly increases the risk of analgesic nephropathy, renal papillary necrosis, and end-stage renal disease. Do not exceed the recommended individual maximum doses when these agents are given concurrently for short-term therapy. [4064] Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Prolonged concurrent use of acetaminophen and salicylates is not recommended. High-dose, chronic administration of the combined analgesics significantly increases the risk of analgesic nephropathy, renal papillary necrosis, and end-stage renal disease. Do not exceed the recommended individual maximum doses when these agents are given concurrently for short-term therapy. [4064] Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Prolonged concurrent use of acetaminophen and salicylates is not recommended. High-dose, chronic administration of the combined analgesics significantly increases the risk of analgesic nephropathy, renal papillary necrosis, and end-stage renal disease. Do not exceed the recommended individual maximum doses when these agents are given concurrently for short-term therapy. [4064] Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Prolonged concurrent use of acetaminophen and salicylates is not recommended. High-dose, chronic administration of the combined analgesics significantly increases the risk of analgesic nephropathy, renal papillary necrosis, and end-stage renal disease. Do not exceed the recommended individual maximum doses when these agents are given concurrently for short-term therapy. [4064] Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Prolonged concurrent use of acetaminophen and salicylates is not recommended. High-dose, chronic administration of the combined analgesics significantly increases the risk of analgesic nephropathy, renal papillary necrosis, and end-stage renal disease. Do not exceed the recommended individual maximum doses when these agents are given concurrently for short-term therapy. [4064] Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Prolonged concurrent use of acetaminophen and salicylates is not recommended. High-dose, chronic administration of the combined analgesics significantly increases the risk of analgesic nephropathy, renal papillary necrosis, and end-stage renal disease. Do not exceed the recommended individual maximum doses when these agents are given concurrently for short-term therapy. [4064] Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) Prolonged concurrent use of acetaminophen and salicylates is not recommended. High-dose, chronic administration of the combined analgesics significantly increases the risk of analgesic nephropathy, renal papillary necrosis, and end-stage renal disease. Do not exceed the recommended individual maximum doses when these agents are given concurrently for short-term therapy. [4064] Acetaminophen; Diphenhydramine: (Moderate) Prolonged concurrent use of acetaminophen and salicylates is not recommended. High-dose, chronic administration of the combined analgesics significantly increases the risk of analgesic nephropathy, renal papillary necrosis, and end-stage renal disease. Do not exceed the recommended individual maximum doses when these agents are given concurrently for short-term therapy. [4064] Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) Prolonged concurrent use of acetaminophen and salicylates is not recommended. High-dose, chronic administration of the combined analgesics significantly increases the risk of analgesic nephropathy, renal papillary necrosis, and end-stage renal disease. Do not exceed the recommended individual maximum doses when these agents are given concurrently for short-term therapy. [4064] Acetaminophen; Hydrocodone: (Moderate) Prolonged concurrent use of acetaminophen and salicylates is not recommended. High-dose, chronic administration of the combined analgesics significantly increases the risk of analgesic nephropathy, renal papillary necrosis, and end-stage renal disease. Do not exceed the recommended individual maximum doses when these agents are given concurrently for short-term therapy. [4064] Acetaminophen; Oxycodone: (Moderate) Prolonged concurrent use of acetaminophen and salicylates is not recommended. High-dose, chronic administration of the combined analgesics significantly increases the risk of analgesic nephropathy, renal papillary necrosis, and end-stage renal disease. Do not exceed the recommended individual maximum doses when these agents are given concurrently for short-term therapy. [4064] Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Prolonged concurrent use of acetaminophen and salicylates is not recommended. High-dose, chronic administration of the combined analgesics significantly increases the risk of analgesic nephropathy, renal papillary necrosis, and end-stage renal disease. Do not exceed the recommended individual maximum doses when these agents are given concurrently for short-term therapy. [4064] Acetaminophen; Pentazocine: (Moderate) Prolonged concurrent use of acetaminophen and salicylates is not recommended. High-dose, chronic administration of the combined analgesics significantly increases the risk of analgesic nephropathy, renal papillary necrosis, and end-stage renal disease. Do not exceed the recommended individual maximum doses when these agents are given concurrently for short-term therapy. [4064] Acetaminophen; Propoxyphene: (Moderate) Prolonged concurrent use of acetaminophen and salicylates is not recommended. High-dose, chronic administration of the combined analgesics significantly increases the risk of analgesic nephropathy, renal papillary necrosis, and end-stage renal disease. Do not exceed the recommended individual maximum doses when these agents are given concurrently for short-term therapy. [4064] Acetaminophen; Pseudoephedrine: (Moderate) Prolonged concurrent use of acetaminophen and salicylates is not recommended. High-dose, chronic administration of the combined analgesics significantly increases the risk of analgesic nephropathy, renal papillary necrosis, and end-stage renal disease. Do not exceed the recommended individual maximum doses when these agents are given concurrently for short-term therapy. [4064] Acetazolamide: (Major) Avoid the coadministration of high-dose salicylates and carbonic anhydrase inhibitors whenever possible. There were reports of anorexia, tachypnea, lethargy, metabolic acidosis, coma, and death with high-dose aspirin and acetazolamide. Two mechanisms could cause increased acetazolamide concentrations, resulting in CNS depression and metabolic acidosis: first, competition with aspirin for renal tubular secretion and, second, displacement by salicylates from plasma protein binding sites. Additionally, carbonic anhydrase inhibitors alkalinize urine and increase the excretion of normal doses of salicylates; decreased plasma salicylate concentrations may or may not be clinically significant. [26584] [28267] [28294] [31254] Acetohexamide: (Moderate) If salicylates and sulfonylureas are to be administered together, patients should be monitored for changes in glycemic control. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of other antidiabetic agents. This mechanism may explain how salicylates can potentiate the clinical effects of sulfonylureas; however, displacement of sulfonylureas from protein binding sites has also been reported. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. [24711] [29403] Acidifying Agents: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic. [6675] [6676] Ado-Trastuzumab emtansine: (Moderate) Use caution if coadministration of aspirin with ado-trastuzumab emtansine is necessary due to reports of severe and sometimes fatal hemorrhage, including intracranial bleeding, with ado-trastuzumab emtansine therapy. Consider additional monitoring when concomitant use is medically necessary. While some patients who experienced bleeding during ado-trastuzumab therapy were also receiving anticoagulation therapy, others had no known additional risk factors [53295] Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide. [29398] Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide. [29398] Alkalinizing Agents: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid. [7468] Alogliptin: (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents. [6141] Alogliptin; Metformin: (Moderate) Large doses of salicylates may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis. If these agents are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. [29403] (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents. [6141] Alogliptin; Pioglitazone: (Moderate) Salicylates can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar. In large doses, salicylates can cause hyperglycemia and glycosuria. [29403] (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents. [6141] Alpha-glucosidase Inhibitors: (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents. [1310] [6141] [6859] Amiloride: (Moderate) Salicylates can increase the risk of renal insufficiency in patients receiving diuretics, secondary to effects on renal blood flow. Salicylates inhibit renal prostaglandin production, which causes salt and water retention and decreased renal blood flow. Coadministration may cause hyperkalemia. [58798] Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Salicylates can increase the risk of renal insufficiency in patients receiving diuretics, secondary to effects on renal blood flow. Salicylates inhibit renal prostaglandin production, which causes salt and water retention and decreased renal blood flow. Coadministration may cause hyperkalemia. [58798] (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide. [29398] Aminoglycosides: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity. [7823] Amlodipine; Benazepril: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation. [28983] [29322] Amlodipine; Celecoxib: (Major) Concomitant use of analgesic doses of aspirin and celecoxib is generally not recommended due to the increased risks of bleeding and nephrotoxicity. Concurrent use of aspirin with NSAIDs does not produce a greater analgesic effect compared to the use of NSAIDs alone. Celecoxib (200 to 400 mg daily) did not interfere with the cardioprotective antiplatelet effect of aspirin (100 to 325 mg) in 2 studies in healthy volunteers and in patients with osteoarthritis and established heart disease. Concurrent use does not produce greater therapeutic effect. [56268] Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide. [29398] Amoxicillin: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects. [30110] [31209] Amoxicillin; Clarithromycin; Omeprazole: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects. [30110] [31209] Amoxicillin; Clavulanic Acid: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects. [30110] [31209] Amphotericin B cholesteryl sulfate complex (ABCD): (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity. [5068] [7823] Amphotericin B lipid complex (ABLC): (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity. [5068] [7823] Amphotericin B liposomal (LAmB): (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity. [5068] [7823] Amphotericin B: (Minor) Concurrent use of amphotericin B and other potentially nephrotoxic medications, like the salicylates, may enhance the potential for drug-induced renal toxicity. [5068] [7823] Ampicillin: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects. [30110] [31209] Ampicillin; Sulbactam: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects. [30110] [31209] Anagrelide: (Moderate) Use caution with the coadministration of aspirin and anagrelide. The coadministration of single or repeated doses of anagrelide and aspirin resulted in greater ex vivo anti-platelet aggregation effects than administration of aspirin alone. In an observational study, the concomitant use of anagrelide and aspirin increased the rate of major hemorrhagic events compared to patients receiving other cytoreductive therapy. Assess the risks and benefits of concomitant aspirin and anagrelide use, particularly in patients at high risk for hemorrhage. Monitor for bleeding during concomitant therapy. [30163] Angiotensin-converting enzyme inhibitors: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation. [28983] [29322] Antithrombin III: (Moderate) Large doses of salicylates (more than 3 to 4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Patients taking large doses of salicylates and antithrombin III should be monitored closely for bleeding. [28440] Apixaban: (Major) Large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Patients taking large doses of salicylates and apixaban should be monitored closely for bleeding. [28440] Ardeparin: (Moderate) An additive risk of bleeding may be seen in patients receiving a low molecular weight heparin in combination with other agents known to increase the risk of bleeding such as salicylates. Monitor clinical and laboratory response closely during concurrent use. [28440] [29732] [40621] [49946] Ascorbic Acid, Vitamin C: (Minor) Agents that acidify the urine should be avoided in patients receiving high-dose salicylates. Urinary pH changes can decrease salicylate excretion. However, if the urine is acidic prior to administration of an acidifying agent, the increase in salicylic acid concentrations should be minimal. [5449] [6859] Aspirin, ASA; Butalbital; Caffeine: (Minor) Caffeine has been reported to increase the metabolism of aspirin. [66338] Aspirin, ASA; Butalbital; Caffeine; Codeine: (Minor) Caffeine has been reported to increase the metabolism of aspirin. [66338] Aspirin, ASA; Caffeine: (Minor) Caffeine has been reported to increase the metabolism of aspirin. [66338] Aspirin, ASA; Caffeine; Dihydrocodeine: (Minor) Caffeine has been reported to increase the metabolism of aspirin. [66338] Aspirin, ASA; Caffeine; Orphenadrine: (Minor) Caffeine has been reported to increase the metabolism of aspirin. [66338] Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid. [7468] Aspirin, ASA; Dipyridamole: (Moderate) Although aspirin may be used in combination with dipyridamole, both drugs are associated with bleeding. Monitor for bleeding during concomitant therapy. [28439] [42296] Atenolol; Chlorthalidone: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide. [29398] Azilsartan; Chlorthalidone: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide. [29398] Bacitracin: (Minor) Additive nephrotoxicity may occur with concurrent use of systemic bacitracin and other nephrotoxic agents, including salicylates. Topical administration of any preparation containing bacitracin, especially when applied to large surface areas, also should not be given with other drugs that have a nephrotoxic potential. [7020] [7818] [7819] Barbiturates: (Moderate) Due to high protein binding, salicylates could be displaced from binding sites, or could displace other highly protein-bound drugs such as barbiturates. An enhanced effect of the displaced drug may occur. [7823] Benazepril: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation. [28983] [29322] Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation. [28983] [29322] (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide. [29398] Bendroflumethiazide; Nadolol: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide. [29398] Benzhydrocodone; Acetaminophen: (Moderate) Prolonged concurrent use of acetaminophen and salicylates is not recommended. High-dose, chronic administration of the combined analgesics significantly increases the risk of analgesic nephropathy, renal papillary necrosis, and end-stage renal disease. Do not exceed the recommended individual maximum doses when these agents are given concurrently for short-term therapy. [4064] Beta-blockers: (Moderate) Concurrent use of beta-blockers with aspirin and other salicylates may result in loss of antihypertensive activity due to inhibition of renal prostaglandins and thus, salt and water retention and decreased renal blood flow. [28982] Betrixaban: (Major) Monitor patients closely and promptly evaluate any signs or symptoms of bleeding if betrixaban and aspirin are used concomitantly. Coadministration of betrixaban and aspirin may increase the risk of bleeding. [62037] Bismuth Subsalicylate: (Major) Concomitant use of aspirin with repeated or maximum doses of bismuth subsalicylate-containing preparations may contribute to elevated serum salicylate levels and should be avoided. Consider replacing aspirin therapy with an alternative non-steroidal anti-inflammatory agent that is not salicylate based where appropriate. [26498] [28982] Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Concomitant use of aspirin with repeated or maximum doses of bismuth subsalicylate-containing preparations may contribute to elevated serum salicylate levels and should be avoided. Consider replacing aspirin therapy with an alternative non-steroidal anti-inflammatory agent that is not salicylate based where appropriate. [26498] [28982] Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide. [29398] Bisphosphonates: (Moderate) Aspirin, ASA use is associated with esophageal and/or gastric irritation, and GI ulceration. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. In clinical trials, aspirin use along with bisphosphonates increased the risk of GI events in some patients; however, some clinical trials of bisphosphonates have not reported increased rates of GI adverse events with aspirin co-use. Exercise caution when administering aspirin with a bisphosphonate. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, and monitor renal function during combined use. [28644] [29352] [29558] [31027] [31826] [40021] [40288] Bromocriptine: (Minor) Bromocriptine is highly bound (more than 90%) to serum proteins. Therefore, it may increase the unbound fraction of other highly protein-bound medications (e.g., aspirin and other salicylates), which may alter their effectiveness and risk for side effects. [35591] Bumetanide: (Moderate) Salicylates may decrease the diuretic, natriuretic, and antihypertensive actions of diuretics, possibly through inhibition of renal prostaglandin synthesis. Patients receiving loop diuretics and salicylates should be monitored for changes in the effectiveness of their diuretic therapy. [28429] [29398] Bupivacaine; Meloxicam: (Major) Additive adverse gastrointestinal (GI) effects are possible if meloxicam is used with salicylates (e.g., aspirin). The concurrent use of aspirin and a nonsteroidal anti-inflammatory drug (NSAID) does increase the risk of serious gastrointestinal events. Concomitant administration of aspirin, ASA (3000 mg/day) to healthy volunteers increased the meloxicam AUC by 10% and increased the meloxicam peak plasma concentrations by 24%. Because of its lack of platelet effects, meloxicam is not a substitute for aspirin for cardiovascular prophylaxis. [28502] [29611] Buspirone: (Minor) In vitro studies showed that therapeutic levels of aspirin, ASA increased the plasma concentrations of free buspirone by 23% through plasma protein binding displacement. In vivo interaction studies with these drugs have not been performed. [5231] Butalbital; Acetaminophen: (Moderate) Prolonged concurrent use of acetaminophen and salicylates is not recommended. High-dose, chronic administration of the combined analgesics significantly increases the risk of analgesic nephropathy, renal papillary necrosis, and end-stage renal disease. Do not exceed the recommended individual maximum doses when these agents are given concurrently for short-term therapy. [4064] Butalbital; Acetaminophen; Caffeine: (Moderate) Prolonged concurrent use of acetaminophen and salicylates is not recommended. High-dose, chronic administration of the combined analgesics significantly increases the risk of analgesic nephropathy, renal papillary necrosis, and end-stage renal disease. Do not exceed the recommended individual maximum doses when these agents are given concurrently for short-term therapy. [4064] (Minor) Caffeine has been reported to increase the metabolism of aspirin. [66338] Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Prolonged concurrent use of acetaminophen and salicylates is not recommended. High-dose, chronic administration of the combined analgesics significantly increases the risk of analgesic nephropathy, renal papillary necrosis, and end-stage renal disease. Do not exceed the recommended individual maximum doses when these agents are given concurrently for short-term therapy. [4064] (Minor) Caffeine has been reported to increase the metabolism of aspirin. [66338] Caffeine: (Minor) Caffeine has been reported to increase the metabolism of aspirin. [66338] Caffeine; Sodium Benzoate: (Minor) Caffeine has been reported to increase the metabolism of aspirin. [66338] Canagliflozin: (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents. [6141] Canagliflozin; Metformin: (Moderate) Large doses of salicylates may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis. If these agents are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. [29403] (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents. [6141] Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide. [29398] Capreomycin: (Major) Since capreomycin is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including salicylates, may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered. [44155] [6859] Captopril: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation. [28983] [29322] Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation. [28983] [29322] (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide. [29398] Carbenicillin: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects. [30110] [31209] Cefixime: (Minor) In vitro, salicylates have displaced cefixime from its protein-binding sites, resulting in a 50% increase in free cefixime levels. The clinical significance of this effect is unclear at this time. [7817] Cefotetan: (Minor) Cefotetan has been associated with hypoprothrombinemia and may cause additive effects when given concurrently with salicylates. [6814] Celecoxib: (Major) Concomitant use of analgesic doses of aspirin and celecoxib is generally not recommended due to the increased risks of bleeding and nephrotoxicity. Concurrent use of aspirin with NSAIDs does not produce a greater analgesic effect compared to the use of NSAIDs alone. Celecoxib (200 to 400 mg daily) did not interfere with the cardioprotective antiplatelet effect of aspirin (100 to 325 mg) in 2 studies in healthy volunteers and in patients with osteoarthritis and established heart disease. Concurrent use does not produce greater therapeutic effect. [56268] Chlorothiazide: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide. [29398] Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Major) Concomitant use of analgesic doses of aspirin with ibuprofen is generally not recommended due to the increased risk of bleeding, including GI bleeding. Concurrent use of aspirin with NSAIDs may significantly increase the incidence of GI adverse reactions and does not produce greater therapeutic effect compared to the use of NSAIDs alone. The use of ibuprofen with other salicylates can also lead to additive GI toxicity. For patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider the use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or a non-NSAID analgesic. After discontinuation of ibuprofen in patients taking low-dose aspirin, there may be an increased risk of cardiovascular events due to ibuprofen interference with the antiplatelet effect of aspirin. A decrease in antiplatelet activity (53%) was observed at 24 hours after 6 days of ibuprofen 400 mg/day given 2 hours before immediate-release aspirin 81 mg/day. An interaction was still observed, but minimized, when ibuprofen 400 mg/day was given as early as 8 hours before immediate-release aspirin (90.7%). There was no interaction when ibuprofen 400 mg/day was given 2 hours after the immediate-release aspirin dose (99.2%). In a study with enteric-coated aspirin, subjects given aspirin 81 mg/day with ibuprofen 400 mg 3 times daily (2, 7, and 12 hours after aspirin dose) for 6 days, there was an interaction with antiplatelet activity at 24 hours after the day 6 aspirin dose (67%). An in vitro study has shown that the antagonism of aspirin platelet inhibition probably involves competition at platelet-derived COX-1 and is related to the NSAIDs' ability to inhibit COX-1 mediated thromboxane B2 production in platelets. Clinically, the interaction may be more dramatic with routine as compared with intermittent ibuprofen usage. Quantification of the risk was determined by the analysis of retrospective data, which may be inaccurate and incomplete. However, a trend towards a greater risk of a second myocardial infarction in the year after the initial event among adults taking daily aspirin was associated with a greater length of ibuprofen exposure. [27367] [28502] [28982] [32213] [35893] Chlorpropamide: (Moderate) If salicylates and sulfonylureas are to be administered together, patients should be monitored for changes in glycemic control. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of other antidiabetic agents. This mechanism may explain how salicylates can potentiate the clinical effects of sulfonylureas; however, displacement of sulfonylureas from protein binding sites has also been reported. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. [24711] [29403] Chlorthalidone: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide. [29398] Chlorthalidone; Clonidine: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide. [29398] Cidofovir: (Contraindicated) The concomitant administration of cidofovir and NSAIDs, such as aspirin, is contraindicated due to the potential for increased nephrotoxicity. Aspirin should be discontinued 7 days prior to beginning cidofovir. [28388] Cilostazol: (Moderate) Use caution with the coadministration of aspirin and cilostazol. Although the short-term (<= 4 days) coadministration of aspirin and cilostazol increased the inhibition of ADP-induced platelet aggregation by 22% to 37% compared to aspirin or cilostazol use alone, no clinically significant effect on PT, aPTT, or bleeding time was observed compared to aspirin alone. In clinical trials, there was no apparent increase in hemorrhagic adverse effects in patients taking cilostazol and aspirin compared to aspirin alone. The effects of long-term coadministration are unknown. Monitor for bleeding during concomitant therapy. [48620] Citalopram: (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation. [28343] Citric Acid; Potassium Citrate; Sodium Citrate: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid. [7468] (Moderate) Urinary alkalinizing agents, like potassium citrate, increase the excretion of salicylates by increasing renal clearance. [7648] Clomipramine: (Moderate) Clomipramine may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. This may increase the risk for an upper GI bleed. [27414] Clopidogrel: (Moderate) Although aspirin may be used in combination with clopidogrel, both drugs are associated with bleeding. In clinical trials, bleeding rates with concomitant use of aspirin and clopidogrel vs. placebo vary from similar to increased bleeding with coadministration. Monitor for bleeding during concomitant therapy. [28435] [61360] Colistimethate, Colistin, Polymyxin E: (Major) Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered. Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including salicylates, may increase serum concentrations of either drug. [30110] [33636] Colistin: (Major) Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered. Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including salicylates, may increase serum concentrations of either drug. [30110] [33636] Collagenase: (Moderate) Cautious use of injectable collagenase by patients taking more than 150 mg/day of aspirin is advised. The efficacy and safety of administering injectable collagenase to a patient taking more than 150 mg/day of aspirin within 7 days before the injection are unknown. Receipt of injectable collagenase may cause an ecchymosis or bleeding at the injection site. [38955] Corticosteroids: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Cyclosporine: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like cyclosporine may lead to additive nephrotoxicity. [7020] Dabigatran: (Major) Educate patients about the signs of increased bleeding and the need to report these signs to a healthcare provider immediately if coadministration of dabigatran and aspirin or another salicylate is necessary. Dabigatran can cause significant and, sometimes, fatal bleeding. This risk may be increased by concurrent use of chronic salicylate therapy. [42121] Dalteparin: (Moderate) An additive risk of bleeding may be seen in patients receiving a low molecular weight heparin in combination with other agents known to increase the risk of bleeding such as salicylates. Monitor clinical and laboratory response closely during concurrent use. [28440] [29732] [40621] [49946] Danazol: (Moderate) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with platelet inhibitors. [3946] Dapagliflozin: (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents. [6141] Dapagliflozin; Metformin: (Moderate) Large doses of salicylates may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis. If these agents are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. [29403] (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents. [6141] Dapagliflozin; Saxagliptin: (Moderate) Salicylates can indirectly increase insulin secretion, decreasing blood glucose concentrations. In large doses, salicylates may cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving saxagliptin. [6141] (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents. [6141] Daratumumab; Hyaluronidase: (Minor) Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect. [28946] [41365] [41366] Deferasirox: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including salicylates. [31807] Defibrotide: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like aspirin is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue antithrombotic agents prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated. [60681] Dextrin: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid. [7468] Dichlorphenamide: (Major) Dichlorphenamide is contraindicated with the concomitant use of high dose aspirin, ASA and should be used cautiously in patients receiving low dose aspirin. Dichlorphenamide may cause an elevation in salicylate concentrations in patients receiving aspirin. Adverse reactions including anorexia, tachypnea, lethargy, and coma have been reported with the concomitant use of dichlorphenamide and high dose aspirin. [60122] Diclofenac: (Major) Increased adverse gastrointestinal effects, including gastric ulceration or blood loss, are possible if diclofenac is used with salicylates. The concurrent use of aspirin with other NSAIDs should be avoided because this may increase bleeding or lead to decreased renal function. [1162] [5717] Diclofenac; Misoprostol: (Major) Increased adverse gastrointestinal effects, including gastric ulceration or blood loss, are possible if diclofenac is used with salicylates. The concurrent use of aspirin with other NSAIDs should be avoided because this may increase bleeding or lead to decreased renal function. [1162] [5717] Dicloxacillin: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects. [30110] [31209] Diflunisal: (Major) The concurrent use of diflunisal and salicylates is not recommended due to the increased risk of gastrointestinal toxicity with little or no increase in anti-inflammatory efficacy. [49143] Diphenhydramine; Ibuprofen: (Major) Concomitant use of analgesic doses of aspirin with ibuprofen is generally not recommended due to the increased risk of bleeding, including GI bleeding. Concurrent use of aspirin with NSAIDs may significantly increase the incidence of GI adverse reactions and does not produce greater therapeutic effect compared to the use of NSAIDs alone. The use of ibuprofen with other salicylates can also lead to additive GI toxicity. For patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider the use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or a non-NSAID analgesic. After discontinuation of ibuprofen in patients taking low-dose aspirin, there may be an increased risk of cardiovascular events due to ibuprofen interference with the antiplatelet effect of aspirin. A decrease in antiplatelet activity (53%) was observed at 24 hours after 6 days of ibuprofen 400 mg/day given 2 hours before immediate-release aspirin 81 mg/day. An interaction was still observed, but minimized, when ibuprofen 400 mg/day was given as early as 8 hours before immediate-release aspirin (90.7%). There was no interaction when ibuprofen 400 mg/day was given 2 hours after the immediate-release aspirin dose (99.2%). In a study with enteric-coated aspirin, subjects given aspirin 81 mg/day with ibuprofen 400 mg 3 times daily (2, 7, and 12 hours after aspirin dose) for 6 days, there was an interaction with antiplatelet activity at 24 hours after the day 6 aspirin dose (67%). An in vitro study has shown that the antagonism of aspirin platelet inhibition probably involves competition at platelet-derived COX-1 and is related to the NSAIDs' ability to inhibit COX-1 mediated thromboxane B2 production in platelets. Clinically, the interaction may be more dramatic with routine as compared with intermittent ibuprofen usage. Quantification of the risk was determined by the analysis of retrospective data, which may be inaccurate and incomplete. However, a trend towards a greater risk of a second myocardial infarction in the year after the initial event among adults taking daily aspirin was associated with a greater length of ibuprofen exposure. [27367] [28502] [28982] [32213] [35893] Diphenhydramine; Naproxen: (Major) Concomitant use of analgesic doses of aspirin with naproxen is generally not recommended due to the increased risk of bleeding, including GI bleeding. Concurrent use of aspirin with NSAIDs may significantly increase the incidence of GI adverse reactions and does not produce greater therapeutic effect compared to the use of NSAIDs alone. The use of naproxen with other salicylates can also lead to additive GI toxicity. For patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider the use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or a non-NSAID analgesic. After discontinuation of naproxen in patients taking low-dose aspirin, there may be an increased risk of cardiovascular events due to naproxen interference with the antiplatelet effect of aspirin during the washout period. A decrease in antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with immediate-release aspirin 81 mg/day vs. aspirin alone [(93.1% (naproxen and aspirin) vs. 98.7% (aspirin alone)]. The interaction was observed even after discontinuation of naproxen on day 11 while aspirin therapy continued but normalized by day 13. The interaction was greater when naproxen was given 30 minutes before aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes before naproxen (95.4% vs. 98.7%). The interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was given 30 minutes before low-dose immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11 after naproxen discontinuation (84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). The interaction may also be present with the use of prescription doses of naproxen or with enteric-coated, low-dose aspirin; however, peak interference with aspirin function may occur later due to a longer washout period. [32122] Dipyridamole: (Moderate) Although aspirin may be used in combination with dipyridamole, both drugs are associated with bleeding. Monitor for bleeding during concomitant therapy. [28439] [42296] Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus. [28193] [28197] Drotrecogin Alfa: (Major) Treatment with drotrecogin alfa should be carefully considered in patients who are receiving or have received salicylates within 7 days. These patients are at increased risk of bleeding during drotrecogin alfa therapy. Caution should be used when drotrecogin alfa is used with any other drugs that affect hemostasis. [28475] Edoxaban: (Major) Monitor for bleeding in patients who require chronic treatment with aspirin. Concomitant use of edoxaban with drugs that affect hemostasis, such as aspirin, may increase the risk of bleeding. The coadministration of aspirin (100 mg or 325 mg) and edoxaban increased bleeding time relative to that seen with either drug alone. [58685] Efavirenz; Emtricitabine; Tenofovir: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus. [28193] [28197] Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus. [28193] [28197] Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus. [28193] [28197] Empagliflozin: (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents. [6141] Empagliflozin; Linagliptin: (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents, such as linagliptin. [6141] (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents. [6141] Empagliflozin; Linagliptin; Metformin: (Moderate) Large doses of salicylates may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis. If these agents are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. [29403] (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents, such as linagliptin. [6141] (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents. [6141] Empagliflozin; Metformin: (Moderate) Large doses of salicylates may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis. If these agents are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. [29403] (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents. [6141] Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus. [28193] [28197] Emtricitabine; Tenofovir disoproxil fumarate: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus. [28193] [28197] Enalapril, Enalaprilat: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation. [28983] [29322] Enalapril; Felodipine: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation. [28983] [29322] Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation. [28983] [29322] (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide. [29398] Enoxaparin: (Moderate) An additive risk of bleeding may be seen in patients receiving a low molecular weight heparin in combination with other agents known to increase the risk of bleeding such as salicylates. Monitor clinical and laboratory response closely during concurrent use. [28440] [29732] [40621] [49946] Epoprostenol: (Moderate) When used concurrently with platelet inhibitors, epoprostenol may increase the risk of bleeding. [4892] Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide. [29398] Eptifibatide: (Moderate) Unless contraindicated, aspirin is used in combination with eptifibatide. However, both drugs are associated with bleeding. Monitor for bleeding during concomitant therapy. [30141] Ergotamine; Caffeine: (Minor) Caffeine has been reported to increase the metabolism of aspirin. [66338] Ertugliflozin; Metformin: (Moderate) Large doses of salicylates may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis. If these agents are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. [29403] Ertugliflozin; Sitagliptin: (Moderate) Salicylates can indirectly increase insulin secretion, decreasing blood glucose concentrations. In large doses, salicylates may cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents. [29403] Escitalopram: (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation. [28343] Ethacrynic Acid: (Moderate) Salicylates may decrease the diuretic, natriuretic, and antihypertensive actions of diuretics, possibly through inhibition of renal prostaglandin synthesis. Patients receiving loop diuretics and salicylates should be monitored for changes in the effectiveness of their diuretic therapy. [28429] [29398] Ethanol: (Major) Concomitant ingestion of alcohol with salicylates, especially aspirin, ASA, increases the risk of developing gastric irritation and GI mucosal bleeding. Alcohol and salicylates are mucosal irritants and aspirin decreases platelet aggregation. Routine ingestion of alcohol and aspirin can cause significant GI bleeding, which may or may not be overt. Even occasional concomitant use of salicylates and alcohol should be avoided. Chronic ingestion of alcohol is often associated with hypoprothrombinemia and this condition increases the risk of salicylate-induced bleeding. Patients should be warned regarding the potential for increased risk of GI bleeding if alcohol-containing beverages are taken concurrently with salicylates. [30427] (Major) Concomitant ingestion of ethanol with salicylates, especially aspirin, ASA, increases the risk of developing gastric irritation and GI mucosal bleeding. Ethanol and salicylates are mucosal irritants and aspirin decreases platelet aggregation. Routine ingestion of ethanol and aspirin can cause significant GI bleeding, which may or may not be overt. Even occasional concomitant use of salicylates and ethanol should be avoided. Chronic alcoholism is often associated with hypoprothrombinemia and this condition increases the risk of salicylate-induced bleeding. Patients should be warned regarding the potential for increased risk of GI bleeding if alcohol-containing beverages are taken concurrently with salicylates. [30427] Ethotoin: (Minor) Large doses of salicylates can displace hydantoins from plasma protein-binding sites. Although increased serum concentrations of unbound phenytoin may lead to phenytoin toxicity, the liver may also more rapidly clear unbound drug. [5503] Etodolac: (Major) The concurrent use of aspirin with other NSAIDs should be avoided because this may increase bleeding or lead to decreased renal function. The use of salicylates together with NSAIDs can also lead to additive GI toxicity. [5232] [5717] Famotidine; Ibuprofen: (Major) Concomitant use of analgesic doses of aspirin with ibuprofen is generally not recommended due to the increased risk of bleeding, including GI bleeding. Concurrent use of aspirin with NSAIDs may significantly increase the incidence of GI adverse reactions and does not produce greater therapeutic effect compared to the use of NSAIDs alone. The use of ibuprofen with other salicylates can also lead to additive GI toxicity. For patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider the use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or a non-NSAID analgesic. After discontinuation of ibuprofen in patients taking low-dose aspirin, there may be an increased risk of cardiovascular events due to ibuprofen interference with the antiplatelet effect of aspirin. A decrease in antiplatelet activity (53%) was observed at 24 hours after 6 days of ibuprofen 400 mg/day given 2 hours before immediate-release aspirin 81 mg/day. An interaction was still observed, but minimized, when ibuprofen 400 mg/day was given as early as 8 hours before immediate-release aspirin (90.7%). There was no interaction when ibuprofen 400 mg/day was given 2 hours after the immediate-release aspirin dose (99.2%). In a study with enteric-coated aspirin, subjects given aspirin 81 mg/day with ibuprofen 400 mg 3 times daily (2, 7, and 12 hours after aspirin dose) for 6 days, there was an interaction with antiplatelet activity at 24 hours after the day 6 aspirin dose (67%). An in vitro study has shown that the antagonism of aspirin platelet inhibition probably involves competition at platelet-derived COX-1 and is related to the NSAIDs' ability to inhibit COX-1 mediated thromboxane B2 production in platelets. Clinically, the interaction may be more dramatic with routine as compared with intermittent ibuprofen usage. Quantification of the risk was determined by the analysis of retrospective data, which may be inaccurate and incomplete. However, a trend towards a greater risk of a second myocardial infarction in the year after the initial event among adults taking daily aspirin was associated with a greater length of ibuprofen exposure. [27367] [28502] [28982] [32213] [35893] Fenoprofen: (Major) The concurrent use of aspirin with other NSAIDs should be avoided because this may increase bleeding or lead to decreased renal function. The use of salicylates together with NSAIDs can also lead to additive GI toxicity. [5232] [5717] Fish Oil, Omega-3 Fatty Acids (Dietary Supplements): (Moderate) Because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with aspirin. Theoretically, the risk of bleeding may be increased. [3535] [6320] Flavocoxid, Flavocoxid; Citrated Zinc Bisglycinate: (Major) Because flavocoxid has been associated with isolated cases of occult GI bleeding, additive pharmacodynamic effects may be seen in patients receiving salicylates. Avoid the concurrent use of flavocoxid with salicylates until further data are available. [32141] Fluoxetine: (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation. [28343] Flurbiprofen: (Major) The concurrent use of aspirin with other NSAIDs should be avoided because this may increase bleeding or lead to decreased renal function. The use of salicylates together with NSAIDs can also lead to additive GI toxicity. [5232] [5717] Fluvoxamine: (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation. [28343] Fondaparinux: (Moderate) An additive risk of bleeding may be seen in patients receiving platelet inhibitors (e.g. aspirin, ASA) in combination with fondaparinux. Data on the concomitant use of fondaparinux with aspirin are lacking; however, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [28440] [40227] Foscarnet: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents, such as foscarnet, may lead to additive nephrotoxicity. [7020] Fosinopril: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation. [28983] [29322] Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation. [28983] [29322] (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide. [29398] Fosphenytoin: (Minor) Large doses of salicylates can displace phenytoin from plasma protein-binding sites. Although increased serum concentrations of unbound phenytoin may lead to phenytoin toxicity, the liver may also more rapidly clear unbound drug. Fosphenytoin is converted to phenytoin in vivo, so this interaction may also occur with fosphenytoin. [5265] [5503] Furosemide: (Moderate) Salicylates may decrease the diuretic, natriuretic, and antihypertensive actions of diuretics, possibly through inhibition of renal prostaglandin synthesis. Patients receiving loop diuretics and salicylates should be monitored for changes in the effectiveness of their diuretic therapy. [28429] [29398] Gallium Ga 68 Dotatate: (Major) In general, avoid use of mannitol and salicylates. Concomitant administration of nephrotoxic drugs, such as the salicylates, increases the risk of renal failure after administration of mannitol. However, mannitol promotes the urinary excretion of salicylates, and may be used as an adjunct in salicylate intoxication. [29398] [30110] [31139] [31946] [33007] Garlic, Allium sativum: (Moderate) Garlic, Allium sativum may produce clinically-significant antiplatelet effects; until more data are available, garlic should be used cautiously in patients receiving drugs with a potential risk for bleeding such as aspirin, ASA. [25588] [63043] Ginger, Zingiber officinale: (Moderate) There may be an increased risk of bleeding in patients on aspirin therapy who take ginger as a supplement (i.e., usual dietary intake is not expected to pose a risk). Several pungent constituents of ginger, Zingiber officinale are reported to inhibit arachidonic acid induced platelet activation in human whole blood. Ginger-associated platelet inhibition may be related to a decrease in COX-1/Thromboxane synthase enzymatic activity. The increased risk of bleeding is theoretical; clinical data of an interaction are not available. [28470] [29960] [58798] Ginkgo, Ginkgo biloba: (Major) Avoid Ginkgo biloba in patients on aspirin therapy, as there is an increased risk of bleeding. Ginkgo biloba inhibits platelet aggregation; several case reports describe bleeding complications, with or without concomitant drug therapy. [25273] [28470] Glimepiride: (Moderate) If salicylates and sulfonylureas are to be administered together, patients should be monitored for changes in glycemic control. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of other antidiabetic agents. This mechanism may explain how salicylates can potentiate the clinical effects of sulfonylureas; however, displacement of sulfonylureas from protein binding sites has also been reported. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. [24711] [29403] Glimepiride; Rosiglitazone: (Moderate) If salicylates and sulfonylureas are to be administered together, patients should be monitored for changes in glycemic control. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of other antidiabetic agents. This mechanism may explain how salicylates can potentiate the clinical effects of sulfonylureas; however, displacement of sulfonylureas from protein binding sites has also been reported. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. [24711] [29403] (Moderate) Salicylates can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar. In large doses, salicylates can cause hyperglycemia and glycosuria. [29403] Glipizide: (Moderate) If salicylates and sulfonylureas are to be administered together, patients should be monitored for changes in glycemic control. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of other antidiabetic agents. This mechanism may explain how salicylates can potentiate the clinical effects of sulfonylureas; however, displacement of sulfonylureas from protein binding sites has also been reported. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. [24711] [29403] Glipizide; Metformin: (Moderate) If salicylates and sulfonylureas are to be administered together, patients should be monitored for changes in glycemic control. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of other antidiabetic agents. This mechanism may explain how salicylates can potentiate the clinical effects of sulfonylureas; however, displacement of sulfonylureas from protein binding sites has also been reported. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. [24711] [29403] (Moderate) Large doses of salicylates may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis. If these agents are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. [29403] Glyburide: (Moderate) If salicylates and sulfonylureas are to be administered together, patients should be monitored for changes in glycemic control. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of other antidiabetic agents. This mechanism may explain how salicylates can potentiate the clinical effects of sulfonylureas; however, displacement of sulfonylureas from protein binding sites has also been reported. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. [24711] [29403] Glyburide; Metformin: (Moderate) If salicylates and sulfonylureas are to be administered together, patients should be monitored for changes in glycemic control. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of other antidiabetic agents. This mechanism may explain how salicylates can potentiate the clinical effects of sulfonylureas; however, displacement of sulfonylureas from protein binding sites has also been reported. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. [24711] [29403] (Moderate) Large doses of salicylates may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis. If these agents are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. [29403] Green Tea: (Moderate) Green tea should be used cautiously in patients taking aspirin; there may be an increased risk of bleeding. Monitoring clinical and/or laboratory parameters is warranted. Green tea has demonstrated antiplatelet and fibrinolytic actions in animals. [29691] [29697] Griseofulvin: (Moderate) Concurrent administration of griseofulvin with salicylates may result in decreased salicylate serum concentrations. Caution and close monitoring for changes in the effectiveness of the salicylate are recommended. [45723] Heparin: (Moderate) An additive risk of bleeding may be seen in patients receiving platelet inhibitors (e.g. aspirin, ASA). Despite the potential drug-drug interaction between aspirin and heparin, heparin is frequently administered in combination with low-dose aspirin therapy to patients who have had an acute myocardial infarction and in other disease states. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [28440] [41347] Hyaluronidase, Recombinant; Immune Globulin: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function. [6859] [7020] [7823] (Minor) Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect. [28946] [41365] [41366] Hyaluronidase: (Minor) Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect. [28946] [41365] [41366] Hydralazine; Hydrochlorothiazide, HCTZ: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide. [29398] Hydrochlorothiazide, HCTZ: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide. [29398] Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide. [29398] Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation. [28983] [29322] (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide. [29398] Hydrocodone; Ibuprofen: (Major) Concomitant use of analgesic doses of aspirin with ibuprofen is generally not recommended due to the increased risk of bleeding, including GI bleeding. Concurrent use of aspirin with NSAIDs may significantly increase the incidence of GI adverse reactions and does not produce greater therapeutic effect compared to the use of NSAIDs alone. The use of ibuprofen with other salicylates can also lead to additive GI toxicity. For patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider the use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or a non-NSAID analgesic. After discontinuation of ibuprofen in patients taking low-dose aspirin, there may be an increased risk of cardiovascular events due to ibuprofen interference with the antiplatelet effect of aspirin. A decrease in antiplatelet activity (53%) was observed at 24 hours after 6 days of ibuprofen 400 mg/day given 2 hours before immediate-release aspirin 81 mg/day. An interaction was still observed, but minimized, when ibuprofen 400 mg/day was given as early as 8 hours before immediate-release aspirin (90.7%). There was no interaction when ibuprofen 400 mg/day was given 2 hours after the immediate-release aspirin dose (99.2%). In a study with enteric-coated aspirin, subjects given aspirin 81 mg/day with ibuprofen 400 mg 3 times daily (2, 7, and 12 hours after aspirin dose) for 6 days, there was an interaction with antiplatelet activity at 24 hours after the day 6 aspirin dose (67%). An in vitro study has shown that the antagonism of aspirin platelet inhibition probably involves competition at platelet-derived COX-1 and is related to the NSAIDs' ability to inhibit COX-1 mediated thromboxane B2 production in platelets. Clinically, the interaction may be more dramatic with routine as compared with intermittent ibuprofen usage. Quantification of the risk was determined by the analysis of retrospective data, which may be inaccurate and incomplete. However, a trend towards a greater risk of a second myocardial infarction in the year after the initial event among adults taking daily aspirin was associated with a greater length of ibuprofen exposure. [27367] [28502] [28982] [32213] [35893] Ibritumomab Tiuxetan: (Major) During and after therapy, avoid the concomitant use of Yttrium (Y)-90 ibrutumomab tiuxetan with drugs that interfere with platelet function such as aspirin; the risk of bleeding may be increased. If coadministration with asprin is necessary, monitor platelet counts more frequently for evidence of thrombocytopenia. [41826] (Moderate) Agents that acidify the urine, like phosphate salts, should be avoided in patients receiving high-dose salicylates. Urine acidifying agents may increase renal tubular reabsorption of salicylic acid and possibly increase salicylic acid levels. [6859] (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid. [7468] Ibrutinib: (Moderate) The concomitant use of ibrutinib and antiplatelet agents such as aspirin may increase the risk of bleeding; monitor patients for signs of bleeding. Severe bleeding events have occurred with ibrutinib therapy including intracranial hemorrhage, GI bleeding, hematuria, and post procedural hemorrhage; some events were fatal. The mechanism for bleeding with ibrutinib therapy is not well understood. Also, aspirin may mask signs of infection such as fever and in patients following treatment with antineoplastic agents or immunosuppressives. [56410] [6859] Ibuprofen: (Major) Concomitant use of analgesic doses of aspirin with ibuprofen is generally not recommended due to the increased risk of bleeding, including GI bleeding. Concurrent use of aspirin with NSAIDs may significantly increase the incidence of GI adverse reactions and does not produce greater therapeutic effect compared to the use of NSAIDs alone. The use of ibuprofen with other salicylates can also lead to additive GI toxicity. For patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider the use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or a non-NSAID analgesic. After discontinuation of ibuprofen in patients taking low-dose aspirin, there may be an increased risk of cardiovascular events due to ibuprofen interference with the antiplatelet effect of aspirin. A decrease in antiplatelet activity (53%) was observed at 24 hours after 6 days of ibuprofen 400 mg/day given 2 hours before immediate-release aspirin 81 mg/day. An interaction was still observed, but minimized, when ibuprofen 400 mg/day was given as early as 8 hours before immediate-release aspirin (90.7%). There was no interaction when ibuprofen 400 mg/day was given 2 hours after the immediate-release aspirin dose (99.2%). In a study with enteric-coated aspirin, subjects given aspirin 81 mg/day with ibuprofen 400 mg 3 times daily (2, 7, and 12 hours after aspirin dose) for 6 days, there was an interaction with antiplatelet activity at 24 hours after the day 6 aspirin dose (67%). An in vitro study has shown that the antagonism of aspirin platelet inhibition probably involves competition at platelet-derived COX-1 and is related to the NSAIDs' ability to inhibit COX-1 mediated thromboxane B2 production in platelets. Clinically, the interaction may be more dramatic with routine as compared with intermittent ibuprofen usage. Quantification of the risk was determined by the analysis of retrospective data, which may be inaccurate and incomplete. However, a trend towards a greater risk of a second myocardial infarction in the year after the initial event among adults taking daily aspirin was associated with a greater length of ibuprofen exposure. [27367] [28502] [28982] [32213] [35893] Ibuprofen; Oxycodone: (Major) Concomitant use of analgesic doses of aspirin with ibuprofen is generally not recommended due to the increased risk of bleeding, including GI bleeding. Concurrent use of aspirin with NSAIDs may significantly increase the incidence of GI adverse reactions and does not produce greater therapeutic effect compared to the use of NSAIDs alone. The use of ibuprofen with other salicylates can also lead to additive GI toxicity. For patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider the use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or a non-NSAID analgesic. After discontinuation of ibuprofen in patients taking low-dose aspirin, there may be an increased risk of cardiovascular events due to ibuprofen interference with the antiplatelet effect of aspirin. A decrease in antiplatelet activity (53%) was observed at 24 hours after 6 days of ibuprofen 400 mg/day given 2 hours before immediate-release aspirin 81 mg/day. An interaction was still observed, but minimized, when ibuprofen 400 mg/day was given as early as 8 hours before immediate-release aspirin (90.7%). There was no interaction when ibuprofen 400 mg/day was given 2 hours after the immediate-release aspirin dose (99.2%). In a study with enteric-coated aspirin, subjects given aspirin 81 mg/day with ibuprofen 400 mg 3 times daily (2, 7, and 12 hours after aspirin dose) for 6 days, there was an interaction with antiplatelet activity at 24 hours after the day 6 aspirin dose (67%). An in vitro study has shown that the antagonism of aspirin platelet inhibition probably involves competition at platelet-derived COX-1 and is related to the NSAIDs' ability to inhibit COX-1 mediated thromboxane B2 production in platelets. Clinically, the interaction may be more dramatic with routine as compared with intermittent ibuprofen usage. Quantification of the risk was determined by the analysis of retrospective data, which may be inaccurate and incomplete. However, a trend towards a greater risk of a second myocardial infarction in the year after the initial event among adults taking daily aspirin was associated with a greater length of ibuprofen exposure. [27367] [28502] [28982] [32213] [35893] Ibuprofen; Pseudoephedrine: (Major) Concomitant use of analgesic doses of aspirin with ibuprofen is generally not recommended due to the increased risk of bleeding, including GI bleeding. Concurrent use of aspirin with NSAIDs may significantly increase the incidence of GI adverse reactions and does not produce greater therapeutic effect compared to the use of NSAIDs alone. The use of ibuprofen with other salicylates can also lead to additive GI toxicity. For patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider the use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or a non-NSAID analgesic. After discontinuation of ibuprofen in patients taking low-dose aspirin, there may be an increased risk of cardiovascular events due to ibuprofen interference with the antiplatelet effect of aspirin. A decrease in antiplatelet activity (53%) was observed at 24 hours after 6 days of ibuprofen 400 mg/day given 2 hours before immediate-release aspirin 81 mg/day. An interaction was still observed, but minimized, when ibuprofen 400 mg/day was given as early as 8 hours before immediate-release aspirin (90.7%). There was no interaction when ibuprofen 400 mg/day was given 2 hours after the immediate-release aspirin dose (99.2%). In a study with enteric-coated aspirin, subjects given aspirin 81 mg/day with ibuprofen 400 mg 3 times daily (2, 7, and 12 hours after aspirin dose) for 6 days, there was an interaction with antiplatelet activity at 24 hours after the day 6 aspirin dose (67%). An in vitro study has shown that the antagonism of aspirin platelet inhibition probably involves competition at platelet-derived COX-1 and is related to the NSAIDs' ability to inhibit COX-1 mediated thromboxane B2 production in platelets. Clinically, the interaction may be more dramatic with routine as compared with intermittent ibuprofen usage. Quantification of the risk was determined by the analysis of retrospective data, which may be inaccurate and incomplete. However, a trend towards a greater risk of a second myocardial infarction in the year after the initial event among adults taking daily aspirin was associated with a greater length of ibuprofen exposure. [27367] [28502] [28982] [32213] [35893] Iloprost: (Moderate) When used concurrently with platelet inhibitors, inhaled iloprost may increase the risk of bleeding. [7537] Immune Globulin IV, IVIG, IGIV: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and salicylates. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function. [6859] [7020] [7823] Incretin Mimetics: (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents. Monitor blood glucose closely during coadministration. [29403] Indapamide: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics because salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. [6136] Indomethacin: (Major) The concurrent use of salicylates and indomethacin is not recommended. Combined use does not produce any greater therapeutic effect than indomethacin monotherapy. Also, a significantly greater incidence of gastrointestinal adverse effects with concurrent use has been observed. Because NSAIDs can cause GI bleeding, inhibit platelet aggregation, and prolong bleeding time, additive effects may be seen in patients receiving platelet inhibitors (e.g., aspirin), anticoagulants, or thrombolytic agents. [7305] Inotersen: (Moderate) Use caution with concomitant use of inotersen and salicylates due to the risk of glomerulonephritis and nephrotoxicity as well as the potential risk of bleeding from thrombocytopenia. Consider discontinuation of salicylates in a patient taking inotersen with a platelet count of less than 50,000 per microliter. [63624] Insulins: (Moderate) Use large doses of aspirin cautiously in patients receiving insulin. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. [29403] [60172] Intravenous Lipid Emulsions: (Moderate) Because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with aspirin. Theoretically, the risk of bleeding may be increased. [3535] [6320] Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide. [29398] Iron Sucrose, Sucroferric Oxyhydroxide: (Moderate) Administer aspirin at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide. Oral iron salts may reduce the bioavailability of aspirin, leading to decreased absorption. [56601] Ketoprofen: (Major) The concurrent use of aspirin with other NSAIDs should be avoided because this may increase bleeding or lead to decreased renal function. The use of salicylates together with NSAIDs can also lead to additive GI toxicity. [5232] [5717] Ketorolac: (Contraindicated) Ketorolac is contraindicated in patients currently receiving salicylates due to increased risk of serious NSAID-related adverse events, including gastrointestinal bleeding, ulceration, and perforation. Concomitant administration of salicylates and ketorolac reduces ketorolac protein binding, although the clearance of free ketorolac is not altered. The clinical significance of this interaction is not known. [28331] [32018] Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus. [28193] [28197] Lansoprazole; Amoxicillin; Clarithromycin: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects. [30110] [31209] Lansoprazole; Naproxen: (Major) Concomitant use of analgesic doses of aspirin with naproxen is generally not recommended due to the increased risk of bleeding, including GI bleeding. Concurrent use of aspirin with NSAIDs may significantly increase the incidence of GI adverse reactions and does not produce greater therapeutic effect compared to the use of NSAIDs alone. The use of naproxen with other salicylates can also lead to additive GI toxicity. For patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider the use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or a non-NSAID analgesic. After discontinuation of naproxen in patients taking low-dose aspirin, there may be an increased risk of cardiovascular events due to naproxen interference with the antiplatelet effect of aspirin during the washout period. A decrease in antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with immediate-release aspirin 81 mg/day vs. aspirin alone [(93.1% (naproxen and aspirin) vs. 98.7% (aspirin alone)]. The interaction was observed even after discontinuation of naproxen on day 11 while aspirin therapy continued but normalized by day 13. The interaction was greater when naproxen was given 30 minutes before aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes before naproxen (95.4% vs. 98.7%). The interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was given 30 minutes before low-dose immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11 after naproxen discontinuation (84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). The interaction may also be present with the use of prescription doses of naproxen or with enteric-coated, low-dose aspirin; however, peak interference with aspirin function may occur later due to a longer washout period. [32122] Lesinurad: (Moderate) Aspirin, ASA at doses higher than 325 mg per day may decrease the efficacy of lesinurad in combination with allopurinol. Aspirin at doses of 325 mg or less per day (i.e., for cardiovascular protection) does not decrease the efficacy of lesinurad and can be coadministered with lesinurad. [60473] Lesinurad; Allopurinol: (Moderate) Aspirin, ASA at doses higher than 325 mg per day may decrease the efficacy of lesinurad in combination with allopurinol. Aspirin at doses of 325 mg or less per day (i.e., for cardiovascular protection) does not decrease the efficacy of lesinurad and can be coadministered with lesinurad. [60473] Linagliptin: (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents, such as linagliptin. [6141] Linagliptin; Metformin: (Moderate) Large doses of salicylates may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis. If these agents are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. [29403] (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents, such as linagliptin. [6141] Lisinopril: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation. [28983] [29322] Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation. [28983] [29322] (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide. [29398] Loop diuretics: (Moderate) Salicylates may decrease the diuretic, natriuretic, and antihypertensive actions of diuretics, possibly through inhibition of renal prostaglandin synthesis. Patients receiving loop diuretics and salicylates should be monitored for changes in the effectiveness of their diuretic therapy. [28429] [29398] Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide. [29398] Low Molecular Weight Heparins: (Moderate) An additive risk of bleeding may be seen in patients receiving a low molecular weight heparin in combination with other agents known to increase the risk of bleeding such as salicylates. Monitor clinical and laboratory response closely during concurrent use. [28440] [29732] [40621] [49946] Macimorelin: (Major) Avoid use of macimorelin with drugs that directly affect pituitary growth hormone secretion, such as salicylates. Healthcare providers are advised to discontinue salicylate therapy and observe a sufficient washout period before administering macimorelin. Use of these medications together may impact the accuracy of the macimorelin growth hormone test. [62723] Mannitol: (Major) In general, avoid use of mannitol and salicylates. Concomitant administration of nephrotoxic drugs, such as the salicylates, increases the risk of renal failure after administration of mannitol. However, mannitol promotes the urinary excretion of salicylates, and may be used as an adjunct in salicylate intoxication. [29398] [30110] [31139] [31946] [33007] Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Major) No adverse events associated with the use of salicylates after varicella vaccination have been reported. However, the manufacturer of varicella virus vaccine live recommends the avoidance of salicylates or aspirin, ASA use for 6 weeks after vaccination. Reye's syndrome, which exclusively affects children under 15 years old, has been associated with aspirin use following active varicella infection. Vaccination with close clinical monitoring is recommended for children who require therapeutic aspirin, ASA therapy; according to the CDC the use of attenuated, live varicella virus vaccine is thought to present less risk than natural varicella disease to such children. [28336] Meclofenamate Sodium: (Major) The concurrent use of aspirin with other NSAIDs should be avoided because this may increase bleeding or lead to decreased renal function. The use of salicylates together with NSAIDs can also lead to additive GI toxicity. [5232] [5717] Mefenamic Acid: (Major) Increased adverse gastrointestinal (GI) effects are possible if mefenamic acid is used with salicylates. In addition, concomitant administration of salicylates and mefenamic acid may result in an increase in unbound plasma concentrations of either drug, which could result in greater adverse effects. In general, concomitant use of aspirin and mefenamic acid is not recommended. [7254] Meglitinides: (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of antidiabetic agents. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose or use of greater than maximum recommended daily dosages, salicylates can cause either hypoglycemia or hyperglycemia. Large doses of aspirin should be used cautiously in patients who receive antidiabetic agents. [5232] [6141] Meloxicam: (Major) Additive adverse gastrointestinal (GI) effects are possible if meloxicam is used with salicylates (e.g., aspirin). The concurrent use of aspirin and a nonsteroidal anti-inflammatory drug (NSAID) does increase the risk of serious gastrointestinal events. Concomitant administration of aspirin, ASA (3000 mg/day) to healthy volunteers increased the meloxicam AUC by 10% and increased the meloxicam peak plasma concentrations by 24%. Because of its lack of platelet effects, meloxicam is not a substitute for aspirin for cardiovascular prophylaxis. [28502] [29611] Metformin: (Moderate) Large doses of salicylates may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis. If these agents are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. [29403] Metformin; Repaglinide: (Moderate) Large doses of salicylates may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis. If these agents are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. [29403] (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of antidiabetic agents. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose or use of greater than maximum recommended daily dosages, salicylates can cause either hypoglycemia or hyperglycemia. Large doses of aspirin should be used cautiously in patients who receive antidiabetic agents. [5232] [6141] Metformin; Rosiglitazone: (Moderate) Large doses of salicylates may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis. If these agents are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. [29403] (Moderate) Salicylates can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar. In large doses, salicylates can cause hyperglycemia and glycosuria. [29403] Metformin; Saxagliptin: (Moderate) Large doses of salicylates may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis. If these agents are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. [29403] (Moderate) Salicylates can indirectly increase insulin secretion, decreasing blood glucose concentrations. In large doses, salicylates may cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving saxagliptin. [6141] Metformin; Sitagliptin: (Moderate) Large doses of salicylates may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis. If these agents are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. [29403] (Moderate) Salicylates can indirectly increase insulin secretion, decreasing blood glucose concentrations. In large doses, salicylates may cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents. [29403] Methazolamide: (Major) Avoid the coadministration of high-dose salicylates and carbonic anhydrase inhibitors, like methazolamide, whenever possible. The combination yielded reports of anorexia, tachypnea, lethargy, metabolic acidosis, coma, and death. The mechanism appears to be accumulation of the carbonic anhydrase inhibitor, resulting in increased CNS depression and metabolic acidosis. The acidosis may allow greater CNS penetration of the salicylate. [26584] [28267] [28294] [31254] Methotrexate: (Major) Do not administer salicylates before or concomitantly with high doses of methotrexate, such as used in the treatment of osteosarcoma. Concomitant administration of some NSAIDs with high dose methotrexate therapy has been reported to elevate and prolong serum methotrexate concentrations, resulting in deaths from severe hematologic and gastrointestinal toxicity. Use caution when salicylates are administered concomitantly with lower doses of methotrexate. Salicylates have been reported to reduce the tubular secretion of methotrexate in an animal model and may enhance its toxicity. Methotrexate is partially bound to serum albumin, and toxicity may be increased because of displacement by salicylates. [54012] [56263] [57771] [61900] Methyclothiazide: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide. [29398] Methylsulfonylmethane, MSM: (Moderate) It would be prudent for patients who take aspirin to avoid methylsulfonylmethane, MSM. Monitor patients who choose to take MSM while on aspirin therapy for bleeding. Patients taking MSM and anticoagulant drugs have reported increased anticoagulant effects such as increased bruising or blood in the stool. [32984] [32986] Metoclopramide: (Minor) Metoclopramide can increase the rate or extent of absorption of aspirin because of accelerated gastric emptying, which increases the contact time with the small bowel where this drug is absorbed. [6107] Metolazone: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide. [29398] Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide. [29398] Moexipril: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation. [28983] [29322] Mycophenolate: (Moderate) Mycophenolic acid is more than 98% bound to albumin. Concurrent use of mycophenolate with salicylates can decrease the protein binding of mycophenolic acid resulting in an increase in the free fraction of MPA. Patients should be observed for increased clinical effects from mycophenolate as well as additive adverse effects. [4873] Nabumetone: (Major) The concurrent use of aspirin with other NSAIDs should be avoided because this may increase bleeding or lead to decreased renal function. The use of salicylates together with NSAIDs can also lead to additive GI toxicity. [5232] [5717] Nafcillin: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects. [30110] [31209] Naproxen: (Major) Concomitant use of analgesic doses of aspirin with naproxen is generally not recommended due to the increased risk of bleeding, including GI bleeding. Concurrent use of aspirin with NSAIDs may significantly increase the incidence of GI adverse reactions and does not produce greater therapeutic effect compared to the use of NSAIDs alone. The use of naproxen with other salicylates can also lead to additive GI toxicity. For patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider the use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or a non-NSAID analgesic. After discontinuation of naproxen in patients taking low-dose aspirin, there may be an increased risk of cardiovascular events due to naproxen interference with the antiplatelet effect of aspirin during the washout period. A decrease in antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with immediate-release aspirin 81 mg/day vs. aspirin alone [(93.1% (naproxen and aspirin) vs. 98.7% (aspirin alone)]. The interaction was observed even after discontinuation of naproxen on day 11 while aspirin therapy continued but normalized by day 13. The interaction was greater when naproxen was given 30 minutes before aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes before naproxen (95.4% vs. 98.7%). The interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was given 30 minutes before low-dose immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11 after naproxen discontinuation (84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). The interaction may also be present with the use of prescription doses of naproxen or with enteric-coated, low-dose aspirin; however, peak interference with aspirin function may occur later due to a longer washout period. [32122] Naproxen; Esomeprazole: (Major) Concomitant use of analgesic doses of aspirin with naproxen is generally not recommended due to the increased risk of bleeding, including GI bleeding. Concurrent use of aspirin with NSAIDs may significantly increase the incidence of GI adverse reactions and does not produce greater therapeutic effect compared to the use of NSAIDs alone. The use of naproxen with other salicylates can also lead to additive GI toxicity. For patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider the use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or a non-NSAID analgesic. After discontinuation of naproxen in patients taking low-dose aspirin, there may be an increased risk of cardiovascular events due to naproxen interference with the antiplatelet effect of aspirin during the washout period. A decrease in antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with immediate-release aspirin 81 mg/day vs. aspirin alone [(93.1% (naproxen and aspirin) vs. 98.7% (aspirin alone)]. The interaction was observed even after discontinuation of naproxen on day 11 while aspirin therapy continued but normalized by day 13. The interaction was greater when naproxen was given 30 minutes before aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes before naproxen (95.4% vs. 98.7%). The interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was given 30 minutes before low-dose immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11 after naproxen discontinuation (84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). The interaction may also be present with the use of prescription doses of naproxen or with enteric-coated, low-dose aspirin; however, peak interference with aspirin function may occur later due to a longer washout period. [32122] Naproxen; Pseudoephedrine: (Major) Concomitant use of analgesic doses of aspirin with naproxen is generally not recommended due to the increased risk of bleeding, including GI bleeding. Concurrent use of aspirin with NSAIDs may significantly increase the incidence of GI adverse reactions and does not produce greater therapeutic effect compared to the use of NSAIDs alone. The use of naproxen with other salicylates can also lead to additive GI toxicity. For patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider the use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or a non-NSAID analgesic. After discontinuation of naproxen in patients taking low-dose aspirin, there may be an increased risk of cardiovascular events due to naproxen interference with the antiplatelet effect of aspirin during the washout period. A decrease in antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with immediate-release aspirin 81 mg/day vs. aspirin alone [(93.1% (naproxen and aspirin) vs. 98.7% (aspirin alone)]. The interaction was observed even after discontinuation of naproxen on day 11 while aspirin therapy continued but normalized by day 13. The interaction was greater when naproxen was given 30 minutes before aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes before naproxen (95.4% vs. 98.7%). The interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was given 30 minutes before low-dose immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11 after naproxen discontinuation (84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). The interaction may also be present with the use of prescription doses of naproxen or with enteric-coated, low-dose aspirin; however, peak interference with aspirin function may occur later due to a longer washout period. [32122] Nateglinide: (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of antidiabetic agents. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose or use of greater than maximum recommended daily dosages, salicylates can cause either hypoglycemia or hyperglycemia. Large doses of aspirin should be used cautiously in patients who receive antidiabetic agents. [5232] [6141] Nitazoxanide: (Moderate) The active metabolite of nitazoxanide, tizoxanide, is highly bound to plasma proteins. Caution should be exercised when administering nitazoxanide concurrently with other highly plasma protein-bound drugs with narrow therapeutic indices because competition for binding sites may occur. [7756] Nitroglycerin: (Moderate) When coadministered with aspirin, ASA (doses between 500 mg and 1000 mg), the maximum plasma concentration (Cmax) and exposure (AUC) of a single nitroglycerin dose is increased by 67% and 73%, respectively. Additionally, limited data suggest that patients receiving aspirin, ASA in high doses can exhibit an exaggerated response to sublingual nitroglycerin. Although hypotension and tachycardia were more significant during concomitant therapy, no special precautions appear necessary. The pharmacologic effects of 0.4% nitroglycerin rectal ointment may also be enhanced when administered concomitantly with aspirin, ASA; therefore, close clinical monitoring is advised. [45135] Olanzapine; Fluoxetine: (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation. [28343] Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide. [29398] Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide. [29398] Omacetaxine: (Major) Avoid the concomitant use of omacetaxine and aspirin, ASA when the platelet count is less than 50,000 cells/microliter due to an increased risk of bleeding. Also, aspirin may mask signs of infection such as fever and pain in patients following treatment with antineoplastic agents or immunosuppressives. Aspirin, ASA should be used with caution in patients receiving immunosuppressive therapy. Special consideration should be given to myelosuppressed patients prior to receiving aspirin. [52213] [5717] [6859] Omeprazole; Amoxicillin; Rifabutin: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects. [30110] [31209] Omeprazole; Sodium Bicarbonate: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid. [7468] Oxacillin: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects. [30110] [31209] Oxaprozin: (Major) The concurrent use of aspirin with other NSAIDs should be avoided because this may increase bleeding or lead to decreased renal function. The use of salicylates together with NSAIDs can also lead to additive GI toxicity. [5232] [5717] Paroxetine: (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation. [28343] Penicillin G Benzathine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects. [30110] [31209] Penicillin G Benzathine; Penicillin G Procaine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects. [30110] [31209] Penicillin G Procaine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects. [30110] [31209] Penicillin G: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects. [30110] [31209] Penicillin V: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects. [30110] [31209] Penicillins: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects. [30110] [31209] Pentosan: (Moderate) Pentosan is a weak anticoagulant. Pentosan has 1/15 the anticoagulant activity of heparin. An additive risk of bleeding may be seen in patients receiving other platelet inhibitors (e.g. aspirin, ASA) in combination with pentosan. Also, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [28440] [40043] Pentoxifylline: (Moderate) The concomitant administration of platelet inhibitor with pentoxifylline in the treatment of intermittent claudication has not been evaluated and should be approached with caution, due to the potential for synergistic effects. [6316] Perindopril: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation. [28983] [29322] Perindopril; Amlodipine: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation. [28983] [29322] Pertuzumab; Trastuzumab; Hyaluronidase: (Minor) Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect. [28946] [41365] [41366] Phentermine; Topiramate: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as aspirin, ASA and other salicylates may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Phenytoin: (Minor) Large doses of salicylates can displace phenytoin from plasma protein-binding sites. Although increased serum concentrations of unbound phenytoin may lead to phenytoin toxicity, the liver may also more rapidly clear unbound drug. Displacement of phenytoin from binding sites can lead to a decrease in the total phenytoin serum concentration. Close monitoring for excessive phenytoin toxicity or decreased phenytoin efficacy is recommended. [5503] Phosphorated Carbohydrate Solution: (Moderate) Agents that acidify the urine, like phosphate salts, should be avoided in patients receiving high-dose salicylates. Urine acidifying agents may increase renal tubular reabsorption of salicylic acid and possibly increase salicylic acid levels. [6859] Phosphorus: (Moderate) Agents that acidify the urine, like phosphate salts, should be avoided in patients receiving high-dose salicylates. Urine acidifying agents may increase renal tubular reabsorption of salicylic acid and possibly increase salicylic acid levels. [6859] Photosensitizing agents (topical): (Minor) Preclinical data suggest that agents that affect platelet function and inhibit prostaglandin synthesis could decrease the efficacy of photosensitizing agents used during photodynamic therapy. [6359] Pioglitazone: (Moderate) Salicylates can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar. In large doses, salicylates can cause hyperglycemia and glycosuria. [29403] Pioglitazone; Glimepiride: (Moderate) If salicylates and sulfonylureas are to be administered together, patients should be monitored for changes in glycemic control. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of other antidiabetic agents. This mechanism may explain how salicylates can potentiate the clinical effects of sulfonylureas; however, displacement of sulfonylureas from protein binding sites has also been reported. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. [24711] [29403] (Moderate) Salicylates can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar. In large doses, salicylates can cause hyperglycemia and glycosuria. [29403] Pioglitazone; Metformin: (Moderate) Large doses of salicylates may enhance hypoglycemia in diabetic patients via inhibition of prostaglandin synthesis. If these agents are administered or discontinued in patients receiving oral antidiabetic agents, patients should be monitored for hypoglycemia or loss of blood glucose control. [29403] (Moderate) Salicylates can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar. In large doses, salicylates can cause hyperglycemia and glycosuria. [29403] Piperacillin: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects. [30110] [31209] Piperacillin; Tazobactam: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects. [30110] [31209] Piroxicam: (Major) The concurrent use of aspirin with other NSAIDs should be avoided because this may increase bleeding or lead to decreased renal function. The use of salicylates together with NSAIDs can also lead to additive GI toxicity. [5232] [5717] Pneumococcal Vaccine, Polyvalent: (Moderate) Concomitant administration of antipyretics, such as aspirin, ASA, may decrease an individual's immunological response to the pneumococcal vaccine. A post-marketing study conducted in Poland using a non-US vaccination schedule (2, 3, 4, and 12 months of age) evaluated the impact of prophylactic oral acetaminophen on antibody responses to Prevnar 13. Data show that acetaminophen, given at the time of vaccination and then dosed at 6 to 8 hour intervals for 3 doses on a scheduled basis, reduced the antibody response to some serotypes after the third dose of Prevnar 13 when compared to the antibody responses of infants who only received antipyretics 'as needed' for treatment. However, reduced antibody responses were not observed after the fourth dose of Prevnar 13 with prophylactic acetaminophen. [39165] Potassium Bicarbonate: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid. [7468] (Moderate) Urinary alkalinizing agents, like potassium citrate, increase the excretion of salicylates by increasing renal clearance. [7648] Potassium Chloride: (Moderate) Urinary alkalinizing agents, like potassium citrate, increase the excretion of salicylates by increasing renal clearance. [7648] Potassium Citrate: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid. [7468] (Moderate) Urinary alkalinizing agents, like potassium citrate, increase the excretion of salicylates by increasing renal clearance. [7648] Potassium Citrate; Citric Acid: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid. [7468] (Moderate) Urinary alkalinizing agents, like potassium citrate, increase the excretion of salicylates by increasing renal clearance. [7648] Potassium Phosphate: (Moderate) Agents that acidify the urine, like phosphate salts, should be avoided in patients receiving high-dose salicylates. Urine acidifying agents may increase renal tubular reabsorption of salicylic acid and possibly increase salicylic acid levels. [6859] Potassium Phosphate; Sodium Phosphate: (Moderate) Agents that acidify the urine, like phosphate salts, should be avoided in patients receiving high-dose salicylates. Urine acidifying agents may increase renal tubular reabsorption of salicylic acid and possibly increase salicylic acid levels. [6859] Pramlintide: (Moderate) Salicylates can indirectly increase insulin secretion, and thus decrease blood glucose concentrations. In large doses, salicylates may cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents. [6141] Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements): (Moderate) Prasterone, dehydroepiandrosterone, DHEA appears to have antiplatelet effects, which may prolong bleeding times. Because of these potential, varied effects on coagulation, patients receiving DHEA concurrently with aspirin, should be monitored for side effects or the need for dosage adjustments. [2459] Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved): (Moderate) Prasterone, dehydroepiandrosterone, DHEA appears to have antiplatelet effects, which may prolong bleeding times. Because of these potential, varied effects on coagulation, patients receiving DHEA concurrently with aspirin, should be monitored for side effects or the need for dosage adjustments. [2459] Prasugrel: (Moderate) Although indicated for concomitant use, both prasugrel and aspirin are associated with bleeding. Aspirin 150 mg did not alter prasugrel-mediated inhibition of platelet aggregation; however, bleeding time was increased compared to either drug alone. Monitor for bleeding during concomitant therapy. [36055] [61360] Probenecid: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates. [5035] Probenecid; Colchicine: (Contraindicated) Concurrent use of probenecid and salicylates is contraindicated. The uricosuric actions of probenecid are inhibited by salicylates. When probenecid is used to treat hyperuricemia or gout, do not administer with salicylates. [5035] Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide. [29398] Psyllium: (Moderate) Psyllium can interfere with the absorption of certain oral drugs if administered concomitantly. For example, psyllium fiber can adsorb salicylates. Per the psyllium manufacturers, administration of other prescribed oral drugs should be separated from the administration of psyllium by at least 2 hours. [6107] Quinapril: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation. [28983] [29322] Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation. [28983] [29322] (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide. [29398] Ramipril: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation. [28983] [29322] Repaglinide: (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of antidiabetic agents. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose or use of greater than maximum recommended daily dosages, salicylates can cause either hypoglycemia or hyperglycemia. Large doses of aspirin should be used cautiously in patients who receive antidiabetic agents. [5232] [6141] Rituximab; Hyaluronidase: (Minor) Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect. [28946] [41365] [41366] Rivaroxaban: (Major) Salicylates such as aspirin are known to increase bleeding, and bleeding risk may be increased when these drugs are used concomitantly with rivaroxaban. The safety of long-term concomitant use of these drugs has not been studied. Promptly evaluate any signs or symptoms of bleeding or blood loss if patients are treated concomitantly with salicylates. In a single-dose drug interaction study, no pharmacokinetic interactions were observed after concomitant administration of acetylsalicylic acid (aspirin, ASA) with rivaroxaban. [44854] Rosiglitazone: (Moderate) Salicylates can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar. In large doses, salicylates can cause hyperglycemia and glycosuria. [29403] Salicylic Acid: (Moderate) Concomitant use of salicylic acid with other drugs which may contribute to elevated serum salicylate levels (e.g., oral aspirin or other oral salicylates and other salicylate containing medications, such as sports injury creams) should be avoided. Concurrent use may result in excessive exposure to salicylic acid. Consider replacing aspirin therapy with an alternative non-steroidal anti-inflammatory agent that is not salicylate based where appropriate. [57016] Saxagliptin: (Moderate) Salicylates can indirectly increase insulin secretion, decreasing blood glucose concentrations. In large doses, salicylates may cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving saxagliptin. [6141] Selective serotonin reuptake inhibitors: (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation. [28343] Serotonin norepinephrine reuptake inhibitors: (Moderate) Platelet aggregation may be impaired by serotonin norepinephrine reuptake inhibitors (SNRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving aspirin, ASA or other salicylates which affect hemostasis. Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SNRI with medications which impair platelet function and to promptly report any bleeding events to the practitioner. [23431] [28275] [29934] Sertraline: (Moderate) The combined use of selective serotonin reuptake inhibitors and aspirin, ASA may elevate the risk for an upper GI bleed. SSRIs may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of aspirin. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation. [28343] Sibutramine: (Moderate) Bleeding events have occurred in patients receiving sibutramine. Serotonin reuptake inhibitors, like sibutramine, may inhibit serotonin uptake by platelets, impairing platelet function. Aspirin has antiplatelet effects that may be additive. Additionally, aspirin impairs the gastric mucosa defenses by inhibiting prostaglandin formation. [40133] Simvastatin; Sitagliptin: (Moderate) Salicylates can indirectly increase insulin secretion, decreasing blood glucose concentrations. In large doses, salicylates may cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents. [29403] Sitagliptin: (Moderate) Salicylates can indirectly increase insulin secretion, decreasing blood glucose concentrations. In large doses, salicylates may cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents. [29403] Sodium Bicarbonate: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid. [7468] Sodium Citrate; Citric Acid: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid. [7468] Sodium Lactate: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid. [7468] Sodium Thiosulfate; Salicylic Acid: (Moderate) Concomitant use of salicylic acid with other drugs which may contribute to elevated serum salicylate levels (e.g., oral aspirin or other oral salicylates and other salicylate containing medications, such as sports injury creams) should be avoided. Concurrent use may result in excessive exposure to salicylic acid. Consider replacing aspirin therapy with an alternative non-steroidal anti-inflammatory agent that is not salicylate based where appropriate. [57016] Spironolactone: (Moderate) Concomitant use of aspirin and spironolactone may decrease the efficacy of spironolactone due to possible inhibition of tubular secretion of canrenone. Monitor patient closely during coadministration for desired effect; a higher maintenance dose may be necessary. In drug interaction studies, a single dose of 600 mg of aspirin inhibited the natriuretic effect of spironolactone. Salicylates can also increase the risk of renal insufficiency in patients receiving diuretics, secondary to effects on renal blood flow. Salicylates inhibit renal prostaglandin production, which causes salt and water retention and decreased renal blood flow. This combination may cause hyperkalemia. [45984] [58798] Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of aspirin and spironolactone may decrease the efficacy of spironolactone due to possible inhibition of tubular secretion of canrenone. Monitor patient closely during coadministration for desired effect; a higher maintenance dose may be necessary. In drug interaction studies, a single dose of 600 mg of aspirin inhibited the natriuretic effect of spironolactone. Salicylates can also increase the risk of renal insufficiency in patients receiving diuretics, secondary to effects on renal blood flow. Salicylates inhibit renal prostaglandin production, which causes salt and water retention and decreased renal blood flow. This combination may cause hyperkalemia. [45984] [58798] (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide. [29398] Sulfinpyrazone: (Major) Salicylates should not be used concurrently with probenecid or sulfinpyrazone when these are used to treat hyperuricemia or gout because the uricosuric effect can be decreased. In addition, probenecid and sulfinpyrazone can decrease salicylic acid excretion leading to increased plasma concentration. [5035] Sulfonamides: (Minor) Due to high protein binding, salicylates could be displaced from binding sites, or could displace other highly protein-bound drugs such as sulfonamides. An enhanced effect of the displaced drug may occur. [6859] [7109] Sulfonylureas: (Moderate) If salicylates and sulfonylureas are to be administered together, patients should be monitored for changes in glycemic control. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of other antidiabetic agents. This mechanism may explain how salicylates can potentiate the clinical effects of sulfonylureas; however, displacement of sulfonylureas from protein binding sites has also been reported. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. [24711] [29403] Sulindac: (Major) The concurrent use of aspirin with other NSAIDs should be avoided because this may increase bleeding or lead to decreased renal function. The use of salicylates together with NSAIDs can also lead to additive GI toxicity. [5232] [5717] Sumatriptan; Naproxen: (Major) Concomitant use of analgesic doses of aspirin with naproxen is generally not recommended due to the increased risk of bleeding, including GI bleeding. Concurrent use of aspirin with NSAIDs may significantly increase the incidence of GI adverse reactions and does not produce greater therapeutic effect compared to the use of NSAIDs alone. The use of naproxen with other salicylates can also lead to additive GI toxicity. For patients taking low-dose aspirin for cardioprotection who require intermittent analgesics, consider the use of an NSAID that does not interfere with the antiplatelet effect of aspirin, or a non-NSAID analgesic. After discontinuation of naproxen in patients taking low-dose aspirin, there may be an increased risk of cardiovascular events due to naproxen interference with the antiplatelet effect of aspirin during the washout period. A decrease in antiplatelet activity was observed at 24 hours after 10 days of naproxen 220 mg/day with immediate-release aspirin 81 mg/day vs. aspirin alone [(93.1% (naproxen and aspirin) vs. 98.7% (aspirin alone)]. The interaction was observed even after discontinuation of naproxen on day 11 while aspirin therapy continued but normalized by day 13. The interaction was greater when naproxen was given 30 minutes before aspirin (87.7% vs. 98.7%) and minimal when aspirin was administered 30 minutes before naproxen (95.4% vs. 98.7%). The interaction was minimal at 24 hours after day 10 when naproxen 220 mg twice daily was given 30 minutes before low-dose immediate-release aspirin (95.7% vs. 98.7%); however, the interaction was greater on day 11 after naproxen discontinuation (84.3% vs. 98.7%) and did not normalize by day 13 (90.7% vs. 98.5%). The interaction may also be present with the use of prescription doses of naproxen or with enteric-coated, low-dose aspirin; however, peak interference with aspirin function may occur later due to a longer washout period. [32122] Tacrolimus: (Moderate) Tacrolimus, in the absence of overt renal impairment, may adversely affect renal function. Care should be taken in using tacrolimus with other nephrotoxic drugs, such as salicylates. [5342] Telavancin: (Minor) Concurrent or sequential use of telavancin with drugs that inhibit renal prostaglandins such as salicylates may lead to additive nephrotoxicity. Closely monitor renal function and adjust telavancin doses based on calculated creatinine clearance. [36615] [7823] Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide. [29398] Tenofovir Alafenamide: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of a nephrotoxic agent, such as salicylates. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus, and urine glucose and protein. [30110] [60269] [60688] Tenofovir, PMPA: (Major) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir disoproxil fumarate with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents, like salicylates should be carefully monitored for changes in serum creatinine and phosphorus. [28193] [28197] Thiazide diuretics: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide. [29398] Thiazolidinediones: (Moderate) Salicylates can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar. In large doses, salicylates can cause hyperglycemia and glycosuria. [29403] Thrombin Inhibitors: (Moderate) An additive risk of bleeding may be seen in patients receiving salicylates (e.g. aspirin, ASA) in combination with thrombin inhibitors. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Nonsteroidal antiinflammatory drugs (NSAIDs) may also increase bleeding risk when given with argatroban because of their potential to cause GI bleeding or inhibit platelet aggregation. [28440] [28723] [29402] Thrombolytic Agents: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding. [5199] Ticagrelor: (Moderate) Avoid aspirin maintenance doses of more than 100 mg with concomitant ticagrelor. Maintenance doses of aspirin above 100 mg decreased ticagrelor effectiveness in a clinical trial. After the typical aspirin loading dose of 325 mg, use ticagrelor with an aspirin maintenance dose of 75 to 100 mg. Additionally, both drugs are associated with bleeding. Monitor for bleeding. [44951] [61360] Ticarcillin: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects. [30110] [31209] Ticarcillin; Clavulanic Acid: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects. [30110] [31209] Ticlopidine: (Moderate) Use caution with coadministration of ticlopidine and aspirin. Ticlopidine potentiates the effect of aspirin on platelet aggregation. Safety of concomitant use of ticlopidine and aspirin has not been established beyond 30 days. Monitor for bleeding during concomitant therapy. [28436] Tinzaparin: (Moderate) An additive risk of bleeding may be seen in patients receiving a low molecular weight heparin in combination with other agents known to increase the risk of bleeding such as salicylates. Monitor clinical and laboratory response closely during concurrent use. [28440] [29732] [40621] [49946] Tipranavir: (Moderate) Caution should be used when administering tipranavir to patients receiving platelet inhibitors. In clinical trials, there have been reports of intracranial bleeding, including fatalities, in HIV infected patients receiving tipranavir as part of combination antiretroviral therapy. In many of these reports, the patients had other medical conditions (CNS lesions, head trauma, recent neurosurgery, coagulopathy, hypertension, or alcoholism/alcohol abuse) or were receiving concomitant medications, including platelet inhibitors, that may have caused or contributed to these events. [8102] Tirofiban: (Moderate) Unless contraindicated, aspirin is used in combination with tirofiban. However, both drugs are associated with bleeding. Monitor for bleeding during concomitant therapy. [30142] Tolazamide: (Moderate) If salicylates and sulfonylureas are to be administered together, patients should be monitored for changes in glycemic control. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of other antidiabetic agents. This mechanism may explain how salicylates can potentiate the clinical effects of sulfonylureas; however, displacement of sulfonylureas from protein binding sites has also been reported. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. [24711] [29403] Tolbutamide: (Moderate) If salicylates and sulfonylureas are to be administered together, patients should be monitored for changes in glycemic control. Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood sugar and may potentiate the effects of other antidiabetic agents. This mechanism may explain how salicylates can potentiate the clinical effects of sulfonylureas; however, displacement of sulfonylureas from protein binding sites has also been reported. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. [24711] [29403] Tolmetin: (Major) The concurrent use of aspirin with other NSAIDs should be avoided because this may increase bleeding or lead to decreased renal function. The use of salicylates together with NSAIDs can also lead to additive GI toxicity. [5232] [5717] Topiramate: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as aspirin, ASA and other salicylates may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Torsemide: (Moderate) Salicylates may decrease the diuretic, natriuretic, and antihypertensive actions of diuretics, possibly through inhibition of renal prostaglandin synthesis. Patients receiving loop diuretics and salicylates should be monitored for changes in the effectiveness of their diuretic therapy. [28429] [29398] Tramadol; Acetaminophen: (Moderate) Prolonged concurrent use of acetaminophen and salicylates is not recommended. High-dose, chronic administration of the combined analgesics significantly increases the risk of analgesic nephropathy, renal papillary necrosis, and end-stage renal disease. Do not exceed the recommended individual maximum doses when these agents are given concurrently for short-term therapy. [4064] Trandolapril: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation. [28983] [29322] Trandolapril; Verapamil: (Moderate) Aspirin, ASA may reduce the vasodilatory efficacy of ACE inhibitors by inhibiting the synthesis of vasodilatory prostaglandins. This interaction has been documented primarily in heart failure patients. However, the established benefits of using aspirin in combination with an ACE inhibitor in patients with ischemic heart disease and left ventricular dysfunction generally outweigh this concern. Patients receiving concurrent salicylates and ACE inhibitor therapy should be monitored for antihypertensive or vasodilatory efficacy; the dose of the ACE inhibitor can be adjusted if indicated based on clinical evaluation. [28983] [29322] (Minor) In a few reported cases, coadministration of verapamil with aspirin, ASA has led to increased bleeding times greater than observed with aspirin alone. The exact mechanism and clinical significance of this interaction is unknown. [6446] Trastuzumab; Hyaluronidase: (Minor) Salicylates, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect. [28946] [41365] [41366] Trazodone: (Moderate) The combined use of trazodone and salicylates that affect hemostasis may elevate the risk for an upper GI bleed. Trazodone may inhibit serotonin uptake by platelets, augmenting the antiplatelet effects of salicylates. Additionally, salicylates impair the gastric mucosa defenses by inhibiting prostaglandin formation. It would be prudent for clinicians to monitor the patient's clinical status closely if trazodone is added to or removed from the regimen of a patient stabilized on salicylate therapy. [38831] Treprostinil: (Moderate) When used concurrently with anticoagulants or platelet inhibitors, treprostinil may increase the risk of bleeding. [6960] Triamterene: (Moderate) Salicylates can increase the risk of renal insufficiency in patients receiving diuretics, secondary to effects on renal blood flow. Salicylates inhibit renal prostaglandin production, which causes salt and water retention and decreased renal blood flow. Coadministration may cause hyperkalemia. [58798] Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Salicylates can increase the risk of renal insufficiency in patients receiving diuretics, secondary to effects on renal blood flow. Salicylates inhibit renal prostaglandin production, which causes salt and water retention and decreased renal blood flow. Coadministration may cause hyperkalemia. [58798] (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide. [29398] Tromethamine: (Moderate) Concurrent administration of high doses of alkalinizing agents may increase urine pH and decrease serum salicylate levels by decreasing renal tubular reabsorption of salicylic acid. [7468] Valproic Acid, Divalproex Sodium: (Moderate) Concurrent salicylate therapy can increase the free-fraction of valproic acid, causing possible valproic acid toxicity. Valproic acid levels should be monitored when these agents are used concomitantly. [28982] Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Salicylates can increase the risk of renal toxicity in patients receiving diuretics. Salicylates inhibit renal prostaglandin synthesis, which can lead to fluid retention and increased peripheral vascular resistance. Salicylates may decrease the hyperuricemic effect of hydrochlorothiazide. [29398] Vancomycin: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents, such as vancomycin, may lead to additive nephrotoxicity. [5198] [6767] Varicella-Zoster Virus Vaccine, Live: (Major) No adverse events associated with the use of salicylates after varicella vaccination have been reported. However, the manufacturer of varicella virus vaccine live recommends the avoidance of salicylates or aspirin, ASA use for 6 weeks after vaccination. Reye's syndrome, which exclusively affects children under 15 years old, has been associated with aspirin use following active varicella infection. Vaccination with close clinical monitoring is recommended for children who require therapeutic aspirin, ASA therapy; according to the CDC the use of attenuated, live varicella virus vaccine is thought to present less risk than natural varicella disease to such children. [28336] Verapamil: (Minor) In a few reported cases, coadministration of verapamil with aspirin, ASA has led to increased bleeding times greater than observed with aspirin alone. The exact mechanism and clinical significance of this interaction is unknown. [6446] Verteporfin: (Moderate) Use caution if coadministration of verteporfin with aspirin is necessary due to the risk of decreased verteporfin efficacy. Verteporfin is a light-activated drug. Once activated, local damage to neovascular endothelium results in a release of procoagulant and vasoactive factors resulting in platelet aggregation, fibrin clot formation, and vasoconstriction. Concomitant use of drugs that decrease platelet aggregation like aspirin could decrease the efficacy of verteporfin therapy. [30003] Vilazodone: (Moderate) Patients should be instructed to monitor for signs and symptoms of bleeding while taking vilazodone concurrently with salicylates or other platelet inhibitors and to promptly report any bleeding events to the practitioner. Platelet aggregation may be impaired by vilazodone due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors (e.g., aspirin, cilostazol, clopidogrel, dipyridamole, ticlopidine, platelet glycoprotein IIb/IIIa inhibitors). [43177] Vorapaxar: (Moderate) Although indicated for concomitant use, both vorapaxar and aspirin are associated with bleeding. Monitor for bleeding during concomitant therapy. [57151] Vortioxetine: (Moderate) Platelet aggregation may be impaired by vortioxetine due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving aspirin, ASA or other salicylates. Bleeding events related to drugs that inhibit serotonin reuptake have ranged from ecchymosis to life-threatening hemorrhages. Patients should be instructed to monitor for signs and symptoms of bleeding while taking vortioxetine concurrently with aspirin products and to promptly report any bleeding events to the practitioner. [56041] Warfarin: (Major) Co-administration of aspirin and warfarin is associated with an increased risk of bleeding. Consider alternate therapy for aspirin for analgesic or antipyretic uses. If aspirin and warfarin are coadministered, monitor the patient for signs or symptoms of bleeding. Gastrointestinal irritation and impaired hemostasis secondary to platelet inhibition have been observed with relatively small doses of aspirin. In addition, aspirin may displace warfarin from protein binding sites leading to increased anticoagulation effects. Large doses (more than 3 to 4 g/day) of aspirin can cause hypoprothrombinemia, an additional risk factor for bleeding; hypoprothrombinemia has also been reported with aspirin doses less than 2 g/day. Lower doses (less than 100 mg) of aspirin are recommended for use in combination with aspirin for the prevention of cardiovascular events in specific cases, including in patients with mechanical mitral or aortic valve or atrial fibrillation after percutaneous coronary intervention or revascularization. The addition of warfarin to aspirin and a P2Y12 inhibitor in patients after ST-elevation myocardial infarction should be limited to situations where the risk of systemic or venous thromboembolism or stent thrombosis is considered to exceed that of bleeding. Data regarding the benefit vs. risk of combination therapy for other cardiovascular conditions remains unclear. [28440] [55688] [61487] [61488] [61489] [61490] Zafirlukast: (Minor) Coadministration of aspirin may increase plasma concentrations of zafirlukast. The potential clinical sequelae of increased zafirlukast concentrations are not known. [4948]
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LFTs
serum creatinine/BUN
serum salicylate concentrations
Anacin Adult Low Strength
Aspergum
Aspir-Low
Aspirtab
Aspir-Trin
Bayer Advanced Aspirin
Bayer Aspirin
Bayer Aspirin Extra Strength
Bayer Aspirin Plus
Bayer Aspirin Regimen
Bayer Children's Aspirin
Bayer Extra Strength
Bayer Extra Strength Plus
Bayer Genuine Aspirin
Bayer Low Dose Aspirin Regimen
Bayer Womens Aspirin
BeneHealth Aspirin
Bufferin
Bufferin Extra Strength
Bufferin Low Dose
DURLAZA
Easprin
Ecotrin
Genacote
Halfprin
MiniPrin
St. Joseph Adult Low Strength
St. Joseph Aspirin
VAZALORE
Zero Order Release Aspirin
ZORprin
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