Elsevier

English (United States)

Jul.16.2020

Elsevier Drug Monographs

Aspirin, ASA

Indications/Dosage

Labeled

  • acute myocardial infarction
  • arterial thromboembolism prophylaxis
  • arthralgia
  • dental pain
  • dysmenorrhea
  • fever
  • headache
  • mild pain
  • musculoskeletal pain
  • myocardial infarction prophylaxis
  • osteoarthritis
  • prosthetic heart valves
  • reduction of cardiovascular mortality
  • rheumatoid arthritis
  • stroke prophylaxis
  • unstable angina

Off-Label

  • claudication
  • colorectal cancer prophylaxis
  • ischemic stroke
  • Kawasaki disease
  • migraine prophylaxis
  • multisystem inflammatory syndrome in children (MIS-C)
  • percutaneous coronary intervention (PCI)
  • pericarditis
  • preeclampsia prophylaxis
  • thrombosis prophylaxis
  • vernal keratoconjunctivitis
† Off-label indication

For the treatment of rheumatoid arthritis

Oral dosage

Adults

Initially, 3 grams/day PO in divided doses. Target plasma salicylate concentrations range from 150 mcg/mL to 300 mcg/mL. The lowest effective dose should be used. Consider risks versus benefits in deciding optimal therapy, particularly in the older adult.[63923]

For the management of joint pain due to osteoarthritis

Oral dosage

Adults

3 grams/day PO or less in divided doses. The lowest effective dose should be used. Other agents, such as acetaminophen, are preferred per clinical guidelines for the treatment of osteoarthritis, particularly for geriatric adults.[60945] [63923]

For the temporary relief of fever and of mild pain and aches associated with minor arthritis pain (arthralgia), headache, muscular aches or backaches (musculoskeletal pain), toothache (dental pain), dysmenorrhea, and/or the common cold

Oral dosage

Adults

325 to 650 mg PO every 4 hours as needed. Alternatively, 1,000 mg PO every 6 hours, as needed. Self-medication Max: 4 grams/day PO. Do not take for more than 10 days for pain or more than 3 days for fever unless directed by a physician. Use the lowest effective dose.[49579] In the geriatric adult, consider preferred alternatives, such as acetaminophen.[63923]

Rectal dosage

Adults

300 to 600 mg PR every 4 to 6 hours, as needed. Self-medication Max: 6 doses/day PR. Do not take for more than 10 days for pain or more than 3 days for fever unless directed by a physician. Use the lowest effective dose. In the geriatric adult, consider preferred alternatives, such as acetaminophen.[63923]

For the treatment of acute ischemic stroke†

Oral dosage (immediate-release tablets)

Adults

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 the coronary artery thrombosis prophylaxis† in patients with acute coronary syndrome (ACS)

For long-term myocardial infarction prophylaxis

For arterial thromboembolism prophylaxis

For the treatment of Kawasaki disease†

Oral dosage

Infants, Children, and Adolescents

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 (2 grams/kg IV as a single dose) 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 the 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 ACCP and AHA 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†

Oral dosage

Adults

750 mg to 1000 mg PO 3 times per day, usually for 1 to 2 weeks for acute pericarditis, and usually a longer duration of 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). Indomethacin or ibuprofen are commonly used NSAIDs with similar levels of evidence.[60439] The concomitant use of colchicine 1 mg to 2 mg PO on the first day of therapy followed by 0.5 mg to 1 mg PO daily for 3 months significantly reduced the recurrence rate and symptom persistence at 72 hours compared to aspirin alone.[33628] [33629] [60440]

For colorectal cancer prophylaxis†

Oral dosage

Adults

The role of aspirin as chemoprevention for colorectal cancer has yet to be determined. Doses of 325 mg or 81 mg PO once daily have been studied. Although observational studies have suggested a trend toward reduced risk, one randomized trial did not show any benefit of aspirin chemoprevention in otherwise healthy males. In a long-term study, adult males were randomized to receive aspirin 325 mg PO every other day was performed. Over 12 years of follow-up, random assignment to aspirin was associated with a relative risk of colorectal cancer of 1.03 (95% confidence interval, 0.83 to 1.28).[27349] A cost-effectiveness analysis found that aspirin prophylaxis was generally not cost-effective for persons who follow appropriate colorectal cancer screening programs (NOTE: results of this analysis were very sensitive to changes in assumptions regarding aspirin's effects).[27350] Randomized trials in patients with a history of colorectal cancer or adenomas have suggested a possible decreased risk in development of colorectal cancer. In patients with previous colorectal cancer randomized to receive either aspirin 325 mg PO once daily or placebo, one or more adenomas was found in significantly less patients in the aspirin group vs. the placebo group (17% vs. 27%). Aspirin appeared to delay the development of adenomas; however, the mean size of the adenomas and the proportion of patients with advanced adenomas did not differ between the groups.[27351] In another trial, patients with a recent history of adenomas were randomized to receive placebo, aspirin 81 mg, or aspirin 325 mg PO once daily. After a mean duration of 33 months, the incidence of 1 or more adenomas was 47% in the placebo group, 38% in those given aspirin 81 mg, and 45% in those given aspirin 325 mg. The rate of recurrence was significantly lower in the low-dose aspirin group as compared to placebo, but the higher dose of aspirin did not significantly reduce the recurrence rate.[27352]

For preeclampsia prophylaxis†

For migraine prophylaxis†

Oral dosage

Adults

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 treatment of refractory vernal keratoconjunctivitis†

Oral dosage

Adults

Not a first line therapy. Limited data suggest that aspirin doses of 0.25 grams to 2 grams/day PO added to cromolyn have been useful in providing symptomatic relief in some refractory patients whose symptoms were not controlled by cromolyn or corticosteroids alone. The duration of therapy ranged from 2 to 8 weeks followed by gradual tapering.[33522] [33523] [33524]

For the management of multisystem inflammatory syndrome in children (MIS-C) post SARS-CoV-2 exposure†

Oral dosage

Infants, Children, and Adolescents

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]

Therapeutic Drug Monitoring

Most patients experience signs of acute salicylate toxicity when the total salicylate level is > 300 mcg/ml. In chronic salicylism, signs of toxicity may occur at lower concentrations (>= 150 mcg/ml).[54310]

 

Therapeutic monitoring must be taken in context of the ingestion details, such as the type of aspirin formulation ingested, the suspected quantity of ingestion, and other clinical factors, as delayed symptoms of toxicity have been reported. Enteric-coated aspirin formulations, pylorospasm, as well as structural abnormalities, such as pyloric stenosis, gastric outlet obstruction, and peptic ulcer disease, may increase the likelihood of delayed absorption of aspirin from the stomach and proximal small intestine, resulting in delayed toxicity following overdose.

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]

    † Off-label indication
    Revision Date: 07/16/2020, 03:44:46 PM

    References

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    Aspirin Chewable tablet

    Aspirin 81mg Chewable Tablet (63739-0025) (McKesson Packaging Inc) (off market)

    Aspirin Chewable tablet

    Aspirin 81mg Chewable Tablet (49614-0467) (Medicine Shoppe) null

    Aspirin Chewable tablet

    Aspirin 81mg Chewable Tablet (51079-0659) (Mylan Institutional LLC ) (off market)

    Aspirin Chewable tablet

    Aspirin 81mg Chewable Tablet (55966-0028) (PDK Labs Inc) null

    Aspirin Chewable tablet

    Aspirin 81mg Chewable Tablet (43063-0278) (PD-Rx Pharmaceuticals, Inc.) (off market)

    Aspirin Chewable tablet

    Aspirin 81mg Chewable Tablet (62107-0026) (Prime Marketing) null

    Aspirin Chewable tablet

    Aspirin 81mg Chewable Tablet (17236-0014) (R&S Northeast, LLC, formerly Dixon-Shane Drug Company) (off market)

    Aspirin Chewable tablet

    Aspirin 81mg Chewable Tablet (69618-0014) (Reliable 1 Laboratories LLC) null

    Aspirin Chewable tablet

    Aspirin 81mg Chewable Tablet (60814-0175) (Rexall Group) (off market)

    Aspirin Chewable tablet

    Aspirin 81mg Chewable Tablet (00536-1008) (Rugby Laboratories a Division of The Harvard Drug Group, LLC) null

    Aspirin Chewable tablet

    Aspirin 81mg Chewable Tablet (00677-1854) (Sun Pharmaceutical Industries, Inc.) (off market)

    Aspirin Chewable tablet

    Aspirin 81mg Chewable Tablet (00364-0023) (Teva/Actavis US) (off market)

    Aspirin Chewable tablet

    Aspirin Low Dose 81mg Chewable Tablet (16103-0366) (Pharbest Pharmaceuticals) null

    Aspirin Chewable tablet

    Aspirin Low Dose 81mg Chewable Tablet (68752-0003) (TriMarc Laboratories) null

    Aspirin Chewable tablet

    Aspirin Low Dose 81mg Chewable Tablet (Orange) (49483-0334) (Time Cap Laboratories Inc) null

    Aspirin Chewable tablet

    Bayer Aspirin 81mg Low Dose Chewable Tablet (Orange) (12843-0101) (Bayer Corp Consumer Care Div) null

    Aspirin Chewable tablet

    Bayer Aspirin 81mg Low Dose Chewable Tablet (Orange) (12843-0131) (Bayer Corp Consumer Care Div) (off market)

    Aspirin Chewable tablet

    Bayer Children's Aspirin 81mg Low Dose Chewable Tablet (Cherry) (12843-0132) (Bayer Corp Consumer Care Div) null

    Aspirin Chewable tablet

    Bayer Children's Aspirin 81mg Low Dose Chewable Tablet (Mint) (12843-0512) (Bayer Corp Consumer Care Div) (off market)

    Aspirin Chewable tablet

    Children's Aspirin 81mg Chewable Tablet (55154-6752) (Cardinal Health, Inc.) null

    Aspirin Chewable tablet

    Children's Aspirin 81mg Chewable Tablet (63739-0434) (McKesson Packaging Inc) null

    Aspirin Chewable tablet

    Children's Aspirin 81mg Chewable Tablet (00603-0024) (Par Pharmaceuticals, an Endo Company) (off market)

    Aspirin Chewable tablet

    Children's Aspirin 81mg Chewable Tablet (00536-3297) (Rugby Laboratories a Division of The Harvard Drug Group, LLC) (off market)

    Aspirin Chewable tablet

    Children's Aspirin 81mg Chewable Tablet (00536-3297) (Rugby Laboratories a Division of The Harvard Drug Group, LLC) (off market)

    Aspirin Chewable tablet

    Children's Aspirin 81mg Chewable Tablet (00677-1977) (Sun Pharmaceutical Industries, Inc.) (off market)

    Aspirin Chewable tablet

    Children's Aspirin 81mg Chewable Tablet (00182-1420) (Teva Pharmaceuticals USA) (off market)

    Aspirin Chewable tablet

    CVS Aspirin Low Dose 81mg Chewable Tablet (Cherry) (59779-0274) (CVS Health) nullCVS Aspirin Low Dose 81mg Chewable Tablet (Cherry) package photo

    Aspirin Chewable tablet

    CVS Aspirin Low Dose 81mg Chewable Tablet (Cherry) (59779-0274) (CVS Health) null

    Aspirin Chewable tablet

    CVS Aspirin Low Dose 81mg Chewable Tablet (Cherry) (59779-0274) (CVS Health) (off market)

    Aspirin Chewable tablet

    CVS Aspirin Low Dose 81mg Chewable Tablet (Cherry) (59779-0274) (CVS Health) (off market)CVS Aspirin Low Dose 81mg Chewable Tablet (Cherry) package photo

    Aspirin Chewable tablet

    CVS Aspirin Low Dose 81mg Chewable Tablet (Orange) (59779-0467) (CVS Health) (off market)

    Aspirin Chewable tablet

    CVS Aspirin Low Dose 81mg Chewable Tablet (Orange) (59779-0467) (CVS Health) null

    Aspirin Chewable tablet

    CVS Aspirin Low Dose 81mg Chewable Tablet (Orange) (59779-0467) (CVS Health) (off market)CVS Aspirin Low Dose 81mg Chewable Tablet (Orange) package photo

    Aspirin Chewable tablet

    CVS Aspirin Low Dose 81mg Chewable Tablet (Orange) (null) (CVS Health) (off market)

    Aspirin Chewable tablet

    CVS Aspirin Low Dose 81mg Chewable Tablet (Orange) (59779-0467) (CVS Health) nullCVS Aspirin Low Dose 81mg Chewable Tablet (Orange) package photo

    Aspirin Chewable tablet

    CVS Aspirin Low Strength 81mg Chewable Tablet (null) (CVS Health) nullCVS Aspirin Low Strength 81mg Chewable Tablet package photo

    Aspirin Chewable tablet

    Equaline Children's Aspirin 81mg Chewable Tablet (Cherry) (41163-0274) (Albertson's, Inc) (off market)

    Aspirin Chewable tablet

    Equaline Children's Aspirin 81mg Chewable Tablet (Orange) (41163-0467) (Albertson's, Inc) (off market)

    Aspirin Chewable tablet

    GNP Aspirin 81mg Chewable Tablet (Cherry) (24385-0278) (AmerisourceBergen Corporation) null

    Aspirin Chewable tablet

    GNP Aspirin 81mg Chewable Tablet (Orange) (24385-0028) (AmerisourceBergen Corporation) null

    Aspirin Chewable tablet

    GNP Aspirin 81mg Chewable Tablet (Orange) (24385-0364) (AmerisourceBergen Corporation) null

    Aspirin Chewable tablet

    GoodSense Aspirin 81mg Chewable Tablet (00113-0467) (Goodsense a Division of Perrigo) null

    Aspirin Chewable tablet

    GoodSense Aspirin 81mg Chewable Tablet (Cherry) (00113-0274) (Goodsense a Division of Perrigo) null

    Aspirin Chewable tablet

    Health Mart Aspirin Low Dose 81mg Chewable Tablet (Cherry) (62011-0212) (McKesson Corporation) null

    Aspirin Chewable tablet

    Health Mart Aspirin Low Dose 81mg Chewable Tablet (Orange) (62011-0028) (McKesson Corporation) null

    Aspirin Chewable tablet

    Health Mart Aspirin Low Dose 81mg Chewable Tablet (Orange) (62011-0021) (McKesson Corporation) null

    Aspirin Chewable tablet

    Leader Aspirin 81mg Chewable Tablet (Orange) (49781-0084) (Cardinal Health Inc.) null

    Aspirin Chewable tablet

    Leader Aspirin 81mg Chewable Tablet (Orange) (37205-0369) (Cardinal Health, Inc.) null

    Aspirin Chewable tablet

    Leader Aspirin Low Dose 81mg Chewable Tablet (Cherry) (37205-0708) (Cardinal Health, Inc.) null

    Aspirin Chewable tablet

    Leader Aspirin Low Dose 81mg Chewable Tablet (Cherry) (70000-0419) (Cardinal Health, Inc.) null

    Aspirin Chewable tablet

    Leader Aspirin Low Dose 81mg Chewable Tablet (Orange) (37205-0467) (Cardinal Health, Inc.) null

    Aspirin Chewable tablet

    Leader Aspirin Low Dose 81mg Chewable Tablet (Orange) (70000-0420) (Cardinal Health, Inc.) null

    Aspirin Chewable tablet

    Leader Aspirin Low Dose 81mg Chewable Tablet (Orange) (70000-0420) (Cardinal Health, Inc.) null

    Aspirin Chewable tablet

    Premier Value Aspirin 81mg Chewable Tablet (Cherry) (68016-0024) (Pharmacy Value Alliance LLC formerly Chain Drug Consortium , LLC) null

    Aspirin Chewable tablet

    Premier Value Aspirin 81mg Chewable Tablet (Cherry) (68016-0689) (Pharmacy Value Alliance LLC formerly Chain Drug Consortium , LLC) null

    Aspirin Chewable tablet

    Premier Value Aspirin 81mg Chewable Tablet (Orange) (68016-0690) (Pharmacy Value Alliance LLC formerly Chain Drug Consortium , LLC) null

    Aspirin Chewable tablet

    Premier Value Children's Aspirin 81mg Chewable Tablet (Orange) (68016-0013) (Pharmacy Value Alliance LLC formerly Chain Drug Consortium , LLC) null

    Aspirin Chewable tablet

    Premier Value Children's Aspirin 81mg Chewable Tablet (Orange) (68016-0024) (Pharmacy Value Alliance LLC formerly Chain Drug Consortium , LLC) null

    Aspirin Chewable tablet

    Publix Aspirin 81mg Low Dose Chewable Tablet (Orange) (56062-0467) (Publix Super Markets, Inc) null

    Aspirin Chewable tablet

    Quality Choice Aspirin Low Dose 81mg Chewable Tablet (Orange) (63868-0240) (Chain Drug Marketing Association) null

    Aspirin Chewable tablet

    RITE AID Aspirin Low Dose 81mg Chewable Tablet (Cherry) (null) (Rite Aid Corp) nullRITE AID Aspirin Low Dose 81mg Chewable Tablet (Cherry) package photo

    Aspirin Chewable tablet

    RITE AID Aspirin Low Dose 81mg Chewable Tablet (Orange) (null) (Rite Aid Corp) nullRITE AID Aspirin Low Dose 81mg Chewable Tablet (Orange) package photo

    Aspirin Chewable tablet

    RITE AID Low Dose Aspirin 81mg Chewable Tablet (null) (Rite Aid Corp) nullRITE AID Low Dose Aspirin 81mg Chewable Tablet package photo

    Aspirin Chewable tablet

    Select Brand Children's Aspirin 81mg Chewable Tablet (15127-0241) (Select Brand) nullSelect Brand Children's Aspirin 81mg Chewable Tablet package photo

    Aspirin Chewable tablet

    St. Joseph Adult Aspirin 81mg Chewable Tablet (69536-0281) (Foundation Consumer Healthcare, LLC) null

    Aspirin Chewable tablet

    St. Joseph Adult Aspirin 81mg Chewable Tablet (69536-0281) (Foundation Consumer Healthcare, LLC) null

    Aspirin Chewable tablet

    St. Joseph Adult Aspirin 81mg Chewable Tablet (00045-0173) (McNeil Consumer Healthcare Division of McNEIL-PPC, Inc.) (off market)

    Aspirin Chewable tablet

    Sunmark Aspirin Adult Low Strength 81mg Chewable Tablet (Orange) (49348-0498) (McKesson Corporation) null

    Aspirin Chewable tablet

    Sunmark Aspirin Low Dose 81mg Chewable Tablet (Cherry) (49348-0191) (McKesson Corporation) null

    Aspirin Chewable tablet

    Today's Health Aspirin 81mg Chewable Tablet (null) (Today's Health, Inc.) null

    Aspirin Chewable tablet

    Top Care Aspirin 81mg Chewable Tablet (36800-0259) (Topco Associates LLC) null

    Aspirin Chewable tablet

    Top Care Aspirin 81mg Chewable Tablet (36800-0467) (Topco Associates LLC) null

    Aspirin Chewable tablet

    Top Care Aspirin 81mg Chewable Tablet (Cherry) (36800-0274) (Topco Associates LLC) null

    Aspirin Chewable tablet

    Walgreens Aspirin Adult Low Strength 81mg Chewable Tablet (00363-0218) (Walgreens Co) nullWalgreens Aspirin Adult Low Strength 81mg Chewable Tablet package photo

    Aspirin Chewable tablet

    Walgreens Children's Aspirin 81mg Chewable Tablet (00363-0397) (Walgreens Co) nullWalgreens Children's Aspirin 81mg Chewable Tablet package photo

    Aspirin Chewing gum, medicated

    Aspergum 227mg Chewing Gum (Cherry) (null) (Medtech Products, Inc a Prestige Brands Company formerly Insight Pharmaceuticals) (off market)

    Aspirin Chewing gum, medicated

    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 tablet

    Aspirin 81mg Tablet (52297-0508) (Cardinal Health, Inc.) (off market)

    Aspirin Oral tablet

    Aspirin 81mg Tablet (52297-0507) (Cardinal Health, Inc.) (off market)

    Aspirin Oral tablet

    Aspirin 81mg Tablet (52735-0761) (Family Pharmacy) (off market)

    Aspirin Oral tablet

    Aspirin 81mg Tablet (null) (Mason Vitamins) (off market)

    Aspirin Oral tablet

    Aspirin 81mg Tablet (51079-0845) (Mylan Institutional LLC ) (off market)

    Aspirin Oral tablet

    Aspirin 81mg Tablet (00084-0046) (Natural Nutritionals Company) (off market)

    Aspirin Oral tablet

    Aspirin 81mg Tablet (45802-0642) (Perrigo Pharmaceuticals Company) (off market)

    Aspirin Oral tablet

    Aspirin 81mg Tablet (60814-0172) (Rexall Group) (off market)

    Aspirin Oral tablet

    Aspirin Low Strength 81mg Tablet (58948-0535) (Goodsense a Division of Perrigo) (off market)

    Aspirin Oral tablet

    Bayer Women's Aspirin 81mg Plus Calcium Buffered Caplet (12843-0500) (Bayer Corp Consumer Care Div) null

    Aspirin Oral tablet

    Bayer Women's Aspirin 81mg Plus Calcium Buffered Caplet (12843-0555) (Bayer Corp Consumer Care Div) null

    Aspirin Oral tablet

    Aspirin 325mg Micro-Coated Tablet (00536-3305) (Rugby Laboratories a Division of The Harvard Drug Group, LLC) (off market)

    Aspirin Oral tablet

    Aspirin 325mg Micro-Coated Tablet (49483-0011) (Time Cap Laboratories Inc) null

    Aspirin Oral tablet

    Aspirin 325mg Tablet (65162-0378) (Akyma Pharmaceuticals, a subsidiary of Amneal Pharmaceuticals) (off market)

    Aspirin Oral tablet

    Aspirin 325mg Tablet (24385-0411) (AmerisourceBergen Corporation) (off market)

    Aspirin Oral tablet

    Aspirin 325mg Tablet (24385-0429) (AmerisourceBergen Corporation) (off market)

    Aspirin Oral tablet

    Aspirin 325mg Tablet (52297-0137) (Cardinal Health, Inc.) (off market)

    Aspirin Oral tablet

    Aspirin 325mg Tablet (52297-0429) (Cardinal Health, Inc.) (off market)

    Aspirin Oral tablet

    Aspirin 325mg Tablet (52297-0139) (Cardinal Health, Inc.) (off market)

    Aspirin Oral tablet

    Aspirin 325mg Tablet (52297-0292) (Cardinal Health, Inc.) (off market)

    Aspirin Oral tablet

    Aspirin 325mg Tablet (52297-0411) (Cardinal Health, Inc.) (off market)

    Aspirin Oral tablet

    Aspirin 325mg Tablet (52297-0133) (Cardinal Health, Inc.) (off market)

    Aspirin Oral tablet

    Aspirin 325mg Tablet (52297-0416) (Cardinal Health, Inc.) (off market)

    Aspirin Oral tablet

    Aspirin 325mg Tablet (00436-0416) (Century Pharmaceuticals Inc) (off market)

    Aspirin Oral tablet

    Aspirin 325mg Tablet (00295-1236) (Denison Pharmaceuticals Inc) null

    Aspirin Oral tablet

    Aspirin 325mg Tablet (52735-0703) (Family Pharmacy) (off market)

    Aspirin Oral tablet

    Aspirin 325mg Tablet (52735-0702) (Family Pharmacy) null

    Aspirin Oral tablet

    Aspirin 325mg Tablet (57896-0500) (Geri-Care Pharmaceuticals) (off market)

    Aspirin Oral tablet

    Aspirin 325mg Tablet (57896-0501) (Geri-Care Pharmaceuticals) (off market)

    Aspirin Oral tablet

    Aspirin 325mg Tablet (57896-0901) (Geri-Care Pharmaceuticals) null

    Aspirin Oral tablet

    Aspirin 325mg Tablet (60809-0108) (Glasgow Pharmaceutical Corporation) (off market)

    Aspirin Oral tablet

    Aspirin 325mg Tablet (59618-0099) (Global Source Management & Consulting) (off market)

    Aspirin Oral tablet

    Aspirin 325mg Tablet (00820-0134) (Logen Pharmaceuticals Inc.) (off market)

    Aspirin Oral tablet

    Aspirin 325mg Tablet (00820-0143) (Logen Pharmaceuticals Inc.) (off market)

    Aspirin Oral tablet

    Aspirin 325mg Tablet (00904-2009) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

    Aspirin Oral tablet

    Aspirin 325mg Tablet (00904-2009) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

    Aspirin Oral tablet

    Aspirin 325mg Tablet (00904-2019) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

    Aspirin Oral tablet

    Aspirin 325mg Tablet (00904-6811) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

    Aspirin Oral tablet

    Aspirin 325mg Tablet (00904-6809) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) null

    Aspirin Oral tablet

    Aspirin 325mg Tablet (00904-6744) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) null

    Aspirin Oral tablet

    Aspirin 325mg Tablet (10135-0150) (Marlex Pharmaceuticals) (off market)

    Aspirin Oral tablet

    Aspirin 325mg Tablet (null) (Mason Vitamins) null

    Aspirin Oral tablet

    Aspirin 325mg Tablet (null) (Mason Vitamins) null

    Aspirin Oral tablet

    Aspirin 325mg Tablet (null) (Mason Vitamins) null

    Aspirin Oral tablet

    Aspirin 325mg Tablet (49348-0001) (McKesson Corporation) null

    Aspirin Oral tablet

    Aspirin 325mg Tablet (49348-0034) (McKesson Corporation) null

    Aspirin Oral tablet

    Aspirin 325mg Tablet (63739-0024) (McKesson Packaging Inc) (off market)

    Aspirin Oral tablet

    Aspirin 325mg Tablet (57480-0104) (Medirex Inc) (off market)

    Aspirin Oral tablet

    Aspirin 325mg Tablet (51079-0018) (Mylan Institutional LLC ) (off market)

    Aspirin Oral tablet

    Aspirin 325mg Tablet (51079-0005) (Mylan Institutional LLC ) (off market)

    Aspirin Oral tablet

    Aspirin 325mg Tablet (54629-0803) (National Vitamin Company Inc) (off market)

    Aspirin Oral tablet

    Aspirin 325mg Tablet (54629-0801) (National Vitamin Company Inc) (off market)

    Aspirin Oral tablet

    Aspirin 325mg Tablet (00084-0408) (Natural Nutritionals Company) (off market)

    Aspirin Oral tablet

    Aspirin 325mg Tablet (00084-0057) (Natural Nutritionals Company) (off market)

    Aspirin Oral tablet

    Aspirin 325mg Tablet (00084-0073) (Natural Nutritionals Company) (off market)

    Aspirin Oral tablet

    Aspirin 325mg Tablet (10244-0562) (Otis Clapp and Son) (off market)

    Aspirin Oral tablet

    Aspirin 325mg Tablet (00603-0031) (Par Pharmaceuticals, an Endo Company) null

    Aspirin Oral tablet

    Aspirin 325mg Tablet (55966-0048) (PDK Labs Inc) null

    Aspirin Oral tablet

    Aspirin 325mg Tablet (55289-0743) (PD-Rx Pharmaceuticals, Inc.) null

    Aspirin Oral tablet

    Aspirin 325mg Tablet (16103-0365) (Pharbest Pharmaceuticals) null

    Aspirin Oral tablet

    Aspirin 325mg Tablet (17236-0378) (R&S Northeast, LLC, formerly Dixon-Shane Drug Company) (off market)

    Aspirin Oral tablet

    Aspirin 325mg Tablet (17236-0382) (R&S Northeast, LLC, formerly Dixon-Shane Drug Company) (off market)

    Aspirin Oral tablet

    Aspirin 325mg Tablet (69618-0016) (Reliable 1 Laboratories LLC) (off market)

    Aspirin Oral tablet

    Aspirin 325mg Tablet (00122-0821) (Rexall Group) (off market)

    Aspirin Oral tablet

    Aspirin 325mg Tablet (00122-0850) (Rexall Group) (off market)

    Aspirin Oral tablet

    Aspirin 325mg Tablet (60814-0109) (Rexall Group) (off market)

    Aspirin Oral tablet

    Aspirin 325mg Tablet (00122-0801) (Rexall Group) (off market)

    Aspirin Oral tablet

    Aspirin 325mg Tablet (00536-1053) (Rugby Laboratories a Division of The Harvard Drug Group, LLC) (off market)

    Aspirin Oral tablet

    Aspirin 325mg Tablet (00536-1054) (Rugby Laboratories a Division of The Harvard Drug Group, LLC) null

    Aspirin Oral tablet

    Aspirin 325mg Tablet (00182-0444) (Teva Pharmaceuticals USA) (off market)

    Aspirin Oral tablet

    Aspirin 325mg Tablet (00364-0835) (Teva/Actavis US) (off market)

    Aspirin Oral tablet

    Aspirin 325mg Tablet (47682-0805) (UniFirst First-Aid Corporation) null

    Aspirin Oral tablet

    Aspirin 325mg Tablet (47682-0116) (UniFirst First-Aid Corporation) null

    Aspirin Oral tablet

    Aspirin 325mg Tablet (11383-0050) (Weeks and Leo) null

    Aspirin Oral tablet

    Aspirin 325mg Tablet (11383-0148) (Weeks and Leo) null

    Aspirin Oral tablet

    Aspirtab 325mg Tablet (51469-0301) (Dover Pharmaceutical) (off market)

    Aspirin Oral tablet

    Aspir-Trin 325mg Tablet (null) (Mason Vitamins) (off market)

    Aspirin Oral tablet

    Bayer Advanced Aspirin 325mg Tablet (12843-0545) (Bayer Corp Consumer Care Div) null

    Aspirin Oral tablet

    Bayer Aspirin 325mg Caplet (12843-0102) (Bayer Corp Consumer Care Div) (off market)

    Aspirin Oral tablet

    Bayer Aspirin 325mg Tablet (12843-0101) (Bayer Corp Consumer Care Div) (off market)

    Aspirin Oral tablet

    Bayer Genuine Aspirin 325mg Tablet (12843-0536) (Bayer Corp Consumer Care Div) null

    Aspirin Oral tablet

    Bayer Genuine Aspirin 325mg Tablet (12843-0536) (Bayer Corp Consumer Care Div) null

    Aspirin Oral tablet

    Bayer Genuine Aspirin 325mg Tablet (12843-0555) (Bayer Corp Consumer Care Div) (off market)

    Aspirin Oral tablet

    Bayer Genuine Aspirin 325mg Tablet (12843-0545) (Bayer Corp Consumer Care Div) null

    Aspirin Oral tablet

    Bayer Genuine Aspirin 325mg Tablet (12843-0555) (Bayer Corp Consumer Care Div) (off market)

    Aspirin Oral tablet

    CVS Aspirin 325mg Coated Tablet (59779-0733) (CVS Health) null

    Aspirin Oral tablet

    CVS Aspirin 325mg Coated Tablet (null) (CVS Health) nullCVS Aspirin 325mg Coated Tablet package photo

    Aspirin Oral tablet

    CVS Aspirin 325mg Coated Tablet (null) (CVS Health) (off market)CVS Aspirin 325mg Coated Tablet package photo

    Aspirin Oral tablet

    CVS Aspirin 325mg Coated Tablet (null) (CVS Health) null

    Aspirin Oral tablet

    CVS Aspirin 325mg Tablet (null) (CVS Health) nullCVS Aspirin 325mg Tablet package photo

    Aspirin Oral tablet

    CVS Aspirin 325mg Tablet (null) (CVS Health) (off market)

    Aspirin Oral tablet

    CVS Aspirin 325mg Tablet (59779-0772) (CVS Health) null

    Aspirin Oral tablet

    CVS Genuine Aspirin 325mg Tablet (null) (CVS Health) null

    Aspirin Oral tablet

    Equaline Aspirin 325mg Buffered Tablet (41163-0642) (Albertson's, Inc) (off market)

    Aspirin Oral tablet

    Equaline Aspirin 325mg Tablet (41163-0416) (Albertson's, Inc) (off market)

    Aspirin Oral tablet

    GNP Aspirin 325mg Coated Tablet (46122-0292) (AmerisourceBergen Corporation) null

    Aspirin Oral tablet

    GNP Aspirin 325mg Coated Tablet (46122-0292) (AmerisourceBergen Corporation) null

    Aspirin Oral tablet

    GNP Aspirin 325mg Tablet (24385-0416) (AmerisourceBergen Corporation) null

    Aspirin Oral tablet

    GoodSense Aspirin 325mg Tablet (00113-0416) (Goodsense a Division of Perrigo) null

    Aspirin Oral tablet

    GoodSense Aspirin 325mg Tablet (00113-0411) (Goodsense a Division of Perrigo) null

    Aspirin Oral tablet

    GoodSense Aspirin 325mg Tablet (00113-0416) (Goodsense a Division of Perrigo) null

    Aspirin Oral tablet

    Health Mart Aspirin 325mg Tablet (62011-0020) (McKesson Corporation) null

    Aspirin Oral tablet

    Health Mart Aspirin 325mg Tablet (62011-0041) (McKesson Corporation) null

    Aspirin Oral tablet

    Health Mart Aspirin 325mg Tablet (62011-0020) (McKesson Corporation) null

    Aspirin Oral tablet

    Leader Aspirin 325mg Buffered Tablet (37205-0150) (Cardinal Health, Inc.) (off market)

    Aspirin Oral tablet

    Leader Aspirin 325mg Tablet (37205-0145) (Cardinal Health, Inc.) (off market)Leader Aspirin 325mg Tablet package photo

    Aspirin Oral tablet

    Leader Aspirin 325mg Tablet (70000-0253) (Cardinal Health, Inc.) (off market)

    Aspirin Oral tablet

    Leader Aspirin 325mg Tablet (37205-0668) (Cardinal Health, Inc.) null

    Aspirin Oral tablet

    Leader Aspirin 325mg Tablet (37205-0668) (Cardinal Health, Inc.) null

    Aspirin Oral tablet

    Leader Aspirin 325mg Tablet (70000-0253) (Cardinal Health, Inc.) null

    Aspirin Oral tablet

    Leader Aspirin 325mg Tablet (70000-0507) (Cardinal Health, Inc.) null

    Aspirin Oral tablet

    Leader Aspirin 325mg Tablet (70000-0507) (Cardinal Health, Inc.) null

    Aspirin Oral tablet

    Premier Value Aspirin 325mg Tablet (68016-0011) (Pharmacy Value Alliance LLC formerly Chain Drug Consortium , LLC) null

    Aspirin Oral tablet

    Publix Aspirin 325mg Coated Tablet (56062-0416) (Publix Super Markets, Inc) null

    Aspirin Oral tablet

    Publix Aspirin 325mg Coated Tablet (56062-0416) (Publix Super Markets, Inc) null

    Aspirin Oral tablet

    Quality Choice Aspirin 325mg Coated Tablet (63868-0352) (Chain Drug Marketing Association) null

    Aspirin Oral tablet

    Quality Choice Aspirin 325mg Coated Tablet (63868-0352) (Chain Drug Marketing Association) null

    Aspirin Oral tablet

    RITE AID Aspirin 325mg Coated Tablet (null) (Rite Aid Corp) nullRITE AID Aspirin 325mg Coated Tablet package photo

    Aspirin Oral tablet

    RITE AID Aspirin 325mg Coated Tablet (null) (Rite Aid Corp) nullRITE AID Aspirin 325mg Coated Tablet package photo

    Aspirin Oral tablet

    Select Brand Aspirin 325mg Tablet (15127-0738) (Select Brand) null

    Aspirin Oral tablet

    Today's Health Aspirin 325mg Tablet (null) (Today's Health, Inc.) null

    Aspirin Oral tablet

    Today's Health Aspirin 325mg Tablet (null) (Today's Health, Inc.) null

    Aspirin Oral tablet

    Today's Health Aspirin 325mg Tablet (null) (Today's Health, Inc.) null

    Aspirin Oral tablet

    Walgreens Aspirin 325mg Tablet (00363-0157) (Walgreens Co) nullWalgreens Aspirin 325mg Tablet package photo

    Aspirin Oral tablet

    Walgreens Aspirin 325mg Tablet (00363-0157) (Walgreens Co) null

    Aspirin Oral tablet

    Walgreens Aspirin 325mg Tablet (00363-0157) (Walgreens Co) null

    Aspirin Oral tablet

    Aspirin 500mg Tablet (24385-0545) (AmerisourceBergen Corporation) (off market)

    Aspirin Oral tablet

    Aspirin 500mg Tablet (12843-0005) (Bayer Corp Consumer Care Div) (off market)

    Aspirin Oral tablet

    Aspirin 500mg Tablet (52297-0260) (Cardinal Health, Inc.) (off market)

    Aspirin Oral tablet

    Aspirin 500mg Tablet (52297-0266) (Cardinal Health, Inc.) (off market)

    Aspirin Oral tablet

    Aspirin 500mg Tablet (52297-0448) (Cardinal Health, Inc.) (off market)

    Aspirin Oral tablet

    Aspirin 500mg Tablet (52735-0733) (Family Pharmacy) null

    Aspirin Oral tablet

    Aspirin 500mg Tablet (00904-2014) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

    Aspirin Oral tablet

    Aspirin 500mg Tablet (49348-0784) (McKesson Corporation) null

    Aspirin Oral tablet

    Bayer Advanced Aspirin 500mg Extra Strength Tablet (12843-0552) (Bayer Corp Consumer Care Div) (off market)

    Aspirin Oral tablet

    Bayer Aspirin 500mg Extra Strength Caplet (12843-0202) (Bayer Corp Consumer Care Div) (off market)

    Aspirin Oral tablet

    Bayer Aspirin 500mg Extra Strength Caplet (12843-0510) (Bayer Corp Consumer Care Div) (off market)

    Aspirin Oral tablet

    Bayer Aspirin 500mg Extra Strength Gelcap (12843-0363) (Bayer Corp Consumer Care Div) (off market)

    Aspirin Oral tablet

    Bayer Aspirin Extra Strength 500mg Gelcap (00280-2140) (Bayer Corp Consumer Care Div) (off market)

    Aspirin Oral tablet

    Bayer Aspirin Plus 500mg Extra Strength Caplet (12843-0124) (Bayer Corp Consumer Care Div) null

    Aspirin Oral tablet

    Bayer Extra Strength 500mg Caplet (12843-0555) (Bayer Corp Consumer Care Div) (off market)

    Aspirin Oral tablet

    Bayer Extra Strength Plus 500mg Caplet (12843-0555) (Bayer Corp Consumer Care Div) null

    Aspirin Oral tablet

    Aspirin 650mg Tablet (00084-0089) (Natural Nutritionals Company) (off market)

    Aspirin Oral tablet

    Aspirin 650mg Tablet (00536-3326) (Rugby Laboratories a Division of The Harvard Drug Group, LLC) (off market)

    Aspirin Oral tablet

    Aspirin 650mg Tablet (00677-0772) (Sun Pharmaceutical Industries, Inc.) (off market)

    Aspirin Oral tablet

    Aspirin 650mg Tablet (11383-0072) (Weeks and Leo) null

    Aspirin Oral tablet

    Aspir-Trin 650mg Tablet (null) (Mason Vitamins) null

    Aspirin Oral tablet

    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)

    Aspirin Oral tablet, extended release

    Zero Order Release Aspirin Controlled-Release 800mg Tablet (60258-0052) (Cypress Pharmaceutical Inc. a wholly-owned subsidiary of Currax Pharmaceuticals, LLC) (off market)

    Aspirin Oral tablet, extended release

    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) nullAdult Aspirin Low Dose 81mg Enteric Coated Tablet package photo

    Aspirin Oral tablet, gastro-resistant

    Adult Low Dose Aspirin 81mg Enteric Coated Tablet (57896-0981) (Geri-Care Pharmaceuticals) (off market)

    Aspirin Oral tablet, gastro-resistant

    Anacin Adult Low Strength 81mg Tablet (null) (Medtech Products, Inc a Prestige Brands Company formerly Insight Pharmaceuticals) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin 81mg Delayed-Release Enteric Coated Tablet (63739-0212) (McKesson Packaging) null

    Aspirin Oral tablet, gastro-resistant

    Aspirin 81mg Delayed-Release Tablet (10135-0173) (Marlex Pharmaceuticals) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin 81mg Delayed-Release Tablet (55966-0089) (PDK Labs Inc) null

    Aspirin Oral tablet, gastro-resistant

    Aspirin 81mg Delayed-Release Tablet (17236-0705) (R&S Northeast, LLC, formerly Dixon-Shane Drug Company) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin 81mg Enteric Coated Tablet (65162-0241) (Akyma Pharmaceuticals, a subsidiary of Amneal Pharmaceuticals) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin 81mg Enteric Coated Tablet (65162-0241) (Amneal Pharmaceuticals LLC) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin 81mg Enteric Coated Tablet (70882-0122) (Cambridge Therapeutics Technologies, LLC) null

    Aspirin Oral tablet, gastro-resistant

    Aspirin 81mg Enteric Coated Tablet (00904-6713) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin 81mg Enteric Coated Tablet (10135-0689) (Marlex Pharmaceuticals) null

    Aspirin Oral tablet, gastro-resistant

    Aspirin 81mg Enteric Coated Tablet (63739-0522) (McKesson Packaging) null

    Aspirin Oral tablet, gastro-resistant

    Aspirin 81mg Enteric Coated Tablet (63739-0272) (McKesson Packaging Inc) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin 81mg Enteric Coated Tablet (43063-0724) (PD-Rx Pharmaceuticals, Inc.) null

    Aspirin Oral tablet, gastro-resistant

    Aspirin 81mg Enteric Coated Tablet (69618-0046) (Reliable 1 Laboratories LLC) null

    Aspirin Oral tablet, gastro-resistant

    Aspirin 81mg Enteric Coated Tablet (69618-0017) (Reliable 1 Laboratories LLC) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin 81mg Enteric Coated Tablet (00536-3086) (Rugby Laboratories a Division of The Harvard Drug Group, LLC) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin 81mg Enteric Coated Tablet (00536-1004) (Rugby Laboratories a Division of The Harvard Drug Group, LLC) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin 81mg Enteric Coated Tablet (00536-3086) (Rugby Laboratories a Division of The Harvard Drug Group, LLC) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin 81mg Enteric Coated Tablet (00536-1149) (Rugby Laboratories a Division of The Harvard Drug Group, LLC ) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin 81mg Enteric Coated Tablet (00677-1855) (Sun Pharmaceutical Industries, Inc.) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin 81mg Enteric Coated Tablet (00677-1972) (Sun Pharmaceutical Industries, Inc.) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin 81mg Enteric Coated Tablet (00182-1061) (Teva Pharmaceuticals USA) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin 81mg Enteric Coated Tablet (00182-8217) (Teva Pharmaceuticals USA) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin 81mg Enteric Coated Tablet (49483-0387) (Time Cap Laboratories Inc) null

    Aspirin Oral tablet, gastro-resistant

    Aspirin 81mg Enteric Coated Tablet (49483-0481) (Time Cap Laboratories Inc) null

    Aspirin Oral tablet, gastro-resistant

    Aspirin Adult Low Dose 81mg Enteric Coated Tablet (43063-0862) (PD-Rx Pharmaceuticals, Inc.) null

    Aspirin Oral tablet, gastro-resistant

    Aspirin Adult Low Dose 81mg Enteric Coated Tablet (16103-0356) (Pharbest Pharmaceuticals) null

    Aspirin Oral tablet, gastro-resistant

    Aspirin Low Dose 81mg Enteric Coated Tablet (57896-0981) (Geri-Care Pharmaceuticals) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin Low Dose 81mg Enteric Coated Tablet (57896-0981) (Geri-Care Pharmaceuticals) null

    Aspirin Oral tablet, gastro-resistant

    Aspirin Low Dose 81mg Enteric Coated Tablet (00904-6751) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) nullAspirin Low Dose 81mg Enteric Coated Tablet package photo

    Aspirin Oral tablet, gastro-resistant

    Aspirin Low Dose 81mg Enteric Coated Tablet (00904-6783) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) null

    Aspirin Oral tablet, gastro-resistant

    Aspirin Low Dose 81mg Enteric Coated Tablet (00603-0025) (Par Pharmaceuticals, an Endo Company) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin Low Dose 81mg Enteric Coated Tablet (00603-0026) (Par Pharmaceuticals, an Endo Company) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin Low Dose 81mg Enteric Coated Tablet (00536-1234) (Rugby Laboratories a Division of The Harvard Drug Group, LLC) null

    Aspirin Oral tablet, gastro-resistant

    Aspirin Low Dose 81mg Safety Coated Tablet (72789-0039) (PD-Rx Pharmaceuticals, Inc.) null

    Aspirin Oral tablet, gastro-resistant

    Aspir-Low 81mg Enteric Coated Tablet (00904-7704) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

    Aspirin Oral tablet, gastro-resistant

    Bayer Low Dose Aspirin Regimen 81mg Tablet (00280-2100) (Bayer Corp Consumer Care Div) (off market)

    Aspirin Oral tablet, gastro-resistant

    Bayer Low Dose Aspirin Regimen 81mg Tablet (12843-0061) (Bayer Corp Consumer Care Div) null

    Aspirin Oral tablet, gastro-resistant

    Bayer Low Dose Aspirin Regimen 81mg Tablet (12843-0536) (Bayer Corp Consumer Care Div) null

    Aspirin Oral tablet, gastro-resistant

    Bayer Low Dose Aspirin Regimen 81mg Tablet (12843-0536) (Bayer Corp Consumer Care Div) null

    Aspirin Oral tablet, gastro-resistant

    Bayer Low Dose Aspirin Regimen 81mg Tablet (12843-0106) (Bayer Corp Consumer Care Div) (off market)

    Aspirin Oral tablet, gastro-resistant

    Bayer Low Dose Aspirin Regimen 81mg Tablet (12843-0536) (Bayer Corp Consumer Care Div) null

    Aspirin Oral tablet, gastro-resistant

    BeneHealth Aspirin 81mg Low Dose Enteric Coated Tablet (65155-0981) (BeneHealth) null

    Aspirin Oral tablet, gastro-resistant

    CVS Aspirin Adult Low Dose 81mg Enteric Coated Tablet (59779-0600) (CVS Health) null

    Aspirin Oral tablet, gastro-resistant

    CVS Aspirin Adult Low Strength 81mg Enteric Coated Tablet (null) (CVS Health) (off market)CVS Aspirin Adult Low Strength 81mg Enteric Coated Tablet package photo

    Aspirin Oral tablet, gastro-resistant

    CVS Aspirin Adult Low Strength 81mg Enteric Coated Tablet (null) (CVS Health) (off market)

    Aspirin Oral tablet, gastro-resistant

    CVS Aspirin Adult Low Strength 81mg Enteric Coated Tablet (null) (CVS Health) null

    Aspirin Oral tablet, gastro-resistant

    CVS Aspirin Adult Low Strength 81mg Enteric Coated Tablet (59779-0945) (CVS Health) null

    Aspirin Oral tablet, gastro-resistant

    CVS Aspirin Low Dose 81mg Enteric Coated Tablet (59779-0600) (CVS Health) null

    Aspirin Oral tablet, gastro-resistant

    CVS Aspirin Low Dose 81mg Enteric Coated Tablet (59779-0600) (CVS Health) null

    Aspirin Oral tablet, gastro-resistant

    CVS Aspirin Low Dose 81mg Enteric Coated Tablet (59779-0439) (CVS Health) (off market)

    Aspirin Oral tablet, gastro-resistant

    CVS Aspirin Low Dose 81mg Enteric Coated Tablet (null) (CVS Health) null

    Aspirin Oral tablet, gastro-resistant

    CVS Aspirin Low Dose 81mg Enteric Coated Tablet (null) (CVS Health) (off market)CVS Aspirin Low Dose 81mg Enteric Coated Tablet package photo

    Aspirin Oral tablet, gastro-resistant

    CVS Aspirin Low Dose 81mg Enteric Coated Tablet (59779-0600) (CVS Health) nullCVS Aspirin Low Dose 81mg Enteric Coated Tablet package photo

    Aspirin Oral tablet, gastro-resistant

    CVS Aspirin Low Dose 81mg Enteric Coated Tablet (59779-0727) (CVS Health) nullCVS Aspirin Low Dose 81mg Enteric Coated Tablet package photo

    Aspirin Oral tablet, gastro-resistant

    CVS Aspirin Low Dose 81mg Enteric Coated Tablet (59779-0600) (CVS Health) (off market)

    Aspirin Oral tablet, gastro-resistant

    CVS Aspirin Low Dose 81mg Enteric Coated Tablet (59779-0600) (CVS Health) null

    Aspirin Oral tablet, gastro-resistant

    CVS Aspirin Low Dose 81mg Enteric Coated Tablet (59779-0439) (CVS Health) nullCVS Aspirin Low Dose 81mg Enteric Coated Tablet package photo

    Aspirin Oral tablet, gastro-resistant

    CVS Aspirin Low Dose 81mg Enteric Coated Tablet (59779-0727) (CVS Health) (off market)

    Aspirin Oral tablet, gastro-resistant

    CVS Aspirin Low Dose Sugar Free 81mg Enteric Coated Tablet (null) (CVS Health) nullCVS Aspirin Low Dose Sugar Free 81mg Enteric Coated Tablet package photo

    Aspirin Oral tablet, gastro-resistant

    CVS Aspirin Low Strength 81mg Enteric Coated Tablet (null) (CVS Health) nullCVS Aspirin Low Strength 81mg Enteric Coated Tablet package photo

    Aspirin Oral tablet, gastro-resistant

    CVS Aspirin Low Strength 81mg Enteric Coated Tablet (59779-0945) (CVS Health) nullCVS Aspirin Low Strength 81mg Enteric Coated Tablet package photo

    Aspirin Oral tablet, gastro-resistant

    Ecotrin 81mg Low Strength Enteric Coated Tablet (00135-0117) (GlaxoSmithKline Consumer Healthcare) (off market)

    Aspirin Oral tablet, gastro-resistant

    Ecotrin 81mg Low Strength Enteric Coated Tablet (49692-0903) (Medtech Products, Inc a Prestige Brands Company) (off market)

    Aspirin Oral tablet, gastro-resistant

    Ecotrin 81mg Low Strength Enteric Coated Tablet (63029-0301) (Medtech Products, Inc a Prestige Brands Company) null

    Aspirin Oral tablet, gastro-resistant

    Ecotrin 81mg Low Strength Enteric Coated Tablet (63029-0301) (Medtech Products, Inc a Prestige Brands Company) null

    Aspirin Oral tablet, gastro-resistant

    Ecotrin 81mg Low Strength Enteric Coated Tablet (49692-0903) (Medtech Products, Inc a Prestige Brands Company) (off market)

    Aspirin Oral tablet, gastro-resistant

    Ecotrin 81mg Low Strength Enteric Coated Tablet (63029-0301) (Medtech Products, Inc a Prestige Brands Company) null

    Aspirin Oral tablet, gastro-resistant

    Ecotrin 81mg Low Strength Enteric Coated Tablet (49692-0903) (Medtech Products, Inc a Prestige Brands Company) (off market)

    Aspirin Oral tablet, gastro-resistant

    Ecotrin 81mg Low Strength Enteric Coated Tablet (63029-0311) (Medtech Products, Inc a Prestige Brands Company) null

    Aspirin Oral tablet, gastro-resistant

    Equaline Enteric Coated Aspirin 81mg Tablet (41163-0535) (Albertson's, Inc) (off market)

    Aspirin Oral tablet, gastro-resistant

    Equate Aspirin Adult Low Strength 81mg Enteric Coated Tablet (49035-0535) (Wal-Mart Stores, Inc.) (off market)

    Aspirin Oral tablet, gastro-resistant

    GNP Aspirin 81mg Enteric Coated Tablet (24385-0535) (AmerisourceBergen Corporation) null

    Aspirin Oral tablet, gastro-resistant

    GNP Aspirin 81mg Enteric Coated Tablet (24385-0541) (AmerisourceBergen Corporation) null

    Aspirin Oral tablet, gastro-resistant

    GNP Aspirin 81mg Enteric Coated Tablet (46122-0180) (AmerisourceBergen Corporation) (off market)

    Aspirin Oral tablet, gastro-resistant

    GoodSense Aspirin 81mg Enteric Coated Tablet (00113-0535) (Goodsense a Division of Perrigo) (off market)

    Aspirin Oral tablet, gastro-resistant

    GoodSense Aspirin 81mg Enteric Coated Tablet (00113-0277) (Goodsense a Division of Perrigo) (off market)

    Aspirin Oral tablet, gastro-resistant

    GoodSense Aspirin 81mg Safety Coated Tablet (50804-0227) (Geiss, Destin & Dunn, Inc.) (off market)

    Aspirin Oral tablet, gastro-resistant

    GoodSense Aspirin 81mg Safety Coated Tablet (50804-0880) (Perrigo Company) null

    Aspirin Oral tablet, gastro-resistant

    Halfprin 81mg Enteric Coated Tablet (null) (Kramer Laboratories) (off market)

    Aspirin Oral tablet, gastro-resistant

    Health Mart Aspirin Low Dose 81mg Enteric Coated Tablet (62011-0019) (McKesson Corporation) null

    Aspirin Oral tablet, gastro-resistant

    Health Mart Aspirin Low Dose 81mg Enteric Coated Tablet (62011-0019) (McKesson Corporation) null

    Aspirin Oral tablet, gastro-resistant

    Health Mart Safety Coated Aspirin 81mg Tablet (62011-0003) (McKesson Corporation) null

    Aspirin Oral tablet, gastro-resistant

    Leader Adult Aspirin Regimen 81mg Enteric Coated Tablet (70000-0178) (Cardinal Health Inc.) null

    Aspirin Oral tablet, gastro-resistant

    Leader Adult Aspirin Regimen 81mg Enteric Coated Tablet (70000-0218) (Cardinal Health, Inc.) null

    Aspirin Oral tablet, gastro-resistant

    Leader Aspirin Adult Low Strength 81mg Enteric Coated Tablet (37205-0510) (Cardinal Health, Inc.) null

    Aspirin Oral tablet, gastro-resistant

    Leader Aspirin Low Dose 81mg Enteric Coated Tablet (70000-0428) (Cardinal Health, Inc.) (off market)

    Aspirin Oral tablet, gastro-resistant

    MiniPrin 81mg Enteric Coated Tablet (49483-0054) (Time Cap Laboratories Inc) (off market)

    Aspirin Oral tablet, gastro-resistant

    MiniPrin Low Dose 81mg Enteric Coated Tablet (49483-0330) (Time Cap Laboratories Inc) null

    Aspirin Oral tablet, gastro-resistant

    Premier Value Aspirin 81mg Enteric Coated Tablet (68016-0089) (Pharmacy Value Alliance LLC formerly Chain Drug Consortium , LLC) null

    Aspirin Oral tablet, gastro-resistant

    Premier Value Low Dose Aspirin 81mg Enteric Coated Tablet (68016-0642) (Pharmacy Value Alliance LLC formerly Chain Drug Consortium , LLC) null

    Aspirin Oral tablet, gastro-resistant

    Premier Value Low Dose Aspirin 81mg Enteric Coated Tablet (68016-0642) (Pharmacy Value Alliance LLC formerly Chain Drug Consortium , LLC) null

    Aspirin Oral tablet, gastro-resistant

    Quality Choice Aspirin 81mg Enteric Coated Tablet (63868-0363) (Chain Drug Marketing Association) null

    Aspirin Oral tablet, gastro-resistant

    RITE AID Aspirin Low Dose 81mg Enteric Coated Tablet (null) (Rite Aid Corp) nullRITE AID Aspirin Low Dose 81mg Enteric Coated Tablet package photo

    Aspirin Oral tablet, gastro-resistant

    RITE AID Aspirin Low Dose 81mg Enteric Coated Tablet (null) (Rite Aid Corp) nullRITE AID Aspirin Low Dose 81mg Enteric Coated Tablet package photo

    Aspirin Oral tablet, gastro-resistant

    RITE AID Aspirin Low Dose 81mg Enteric Coated Tablet (null) (Rite Aid Corp) nullRITE AID Aspirin Low Dose 81mg Enteric Coated Tablet package photo

    Aspirin Oral tablet, gastro-resistant

    RITE AID Aspirin Low Dose 81mg Enteric Coated Tablet (null) (Rite Aid Corp) nullRITE AID Aspirin Low Dose 81mg Enteric Coated Tablet package photo

    Aspirin Oral tablet, gastro-resistant

    RITE AID Aspirin Low Dose 81mg Enteric Coated Tablet (null) (Rite Aid Corp) null

    Aspirin Oral tablet, gastro-resistant

    RITE AID Aspirin Low Strength 81mg Enteric Coated Tablet (null) (Rite Aid Corp) null

    Aspirin Oral tablet, gastro-resistant

    Select Brand Aspirin 81mg Enteric Coated Tablet (15127-0228) (Select Brand) nullSelect Brand Aspirin 81mg Enteric Coated Tablet package photo

    Aspirin Oral tablet, gastro-resistant

    St. Joseph Aspirin Adult Low Strength 81mg Safety Coated Tablet (69536-0181) (Foundation Consumer Healthcare, LLC) null

    Aspirin Oral tablet, gastro-resistant

    St. Joseph Aspirin Adult Low Strength 81mg Safety Coated Tablet (69536-0181) (Foundation Consumer Healthcare, LLC) null

    Aspirin Oral tablet, gastro-resistant

    St. Joseph Aspirin Adult Low Strength 81mg Safety Coated Tablet (69536-0181) (Foundation Consumer Healthcare, LLC) null

    Aspirin Oral tablet, gastro-resistant

    St. Joseph Aspirin Adult Low Strength 81mg Safety Coated Tablet (69536-0181) (Foundation Consumer Healthcare, LLC) null

    Aspirin Oral tablet, gastro-resistant

    St. Joseph Aspirin Adult Low Strength 81mg Safety Coated Tablet (00045-0126) (McNeil Consumer Healthcare Division of McNEIL-PPC, Inc.) (off market)

    Aspirin Oral tablet, gastro-resistant

    Sunmark Aspirin Adult Low Strength 81mg Enteric Coated Tablet (49348-0980) (McKesson Corporation) null

    Aspirin Oral tablet, gastro-resistant

    Sunmark Aspirin Adult Low Strength 81mg Enteric Coated Tablet (49348-0980) (McKesson Corporation) null

    Aspirin Oral tablet, gastro-resistant

    Sunmark Aspirin Adult Low Strength 81mg Safety Coated Tablet (49348-0981) (McKesson Corporation) null

    Aspirin Oral tablet, gastro-resistant

    Sunmark Aspirin Low Dose 81mg Enteric Coated Tablet (49348-0756) (McKesson Corporation) null

    Aspirin Oral tablet, gastro-resistant

    Today's Health Aspirin Low Dose 81mg Enteric Coated Tablet (null) (Today's Health, Inc.) null

    Aspirin Oral tablet, gastro-resistant

    Today's Health Aspirin Low Dose 81mg Enteric Coated Tablet (null) (Today's Health, Inc.) null

    Aspirin Oral tablet, gastro-resistant

    Top Care Aspirin 81mg Enteric Coated Tablet (36800-0277) (Topco Associates LLC) null

    Aspirin Oral tablet, gastro-resistant

    Walgreens Aspirin 81mg Enteric Coated Tablet (00363-0414) (Walgreens Co) nullWalgreens Aspirin 81mg Enteric Coated Tablet package photo

    Aspirin Oral tablet, gastro-resistant

    Walgreens Aspirin 81mg Enteric Coated Tablet (00363-0255) (Walgreens Co) null

    Aspirin Oral tablet, gastro-resistant

    Walgreens Aspirin 81mg Enteric Coated Tablet (00363-0414) (Walgreens Co) null

    Aspirin Oral tablet, gastro-resistant

    Walgreens Aspirin 81mg Enteric Coated Tablet (00363-0255) (Walgreens Co) nullWalgreens Aspirin 81mg Enteric Coated Tablet package photo

    Aspirin Oral tablet, gastro-resistant

    Walgreens Aspirin 81mg Enteric Coated Tablet (00363-6450) (Walgreens Co) null

    Aspirin Oral tablet, gastro-resistant

    Walgreens Aspirin 81mg Enteric Coated Tablet (00363-0255) (Walgreens Co) null

    Aspirin Oral tablet, gastro-resistant

    Halfprin 162mg Enteric Coated Tablet (null) (Kramer Laboratories) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin 300mg Delayed-Release Tablet (00781-1603) (Sandoz Inc. a Novartis Company) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin 325mg Delayed-Release Tablet (52297-0918) (Cardinal Health, Inc.) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin 325mg Delayed-Release Tablet (00904-2011) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin 325mg Delayed-Release Tablet (10135-0126) (Marlex Pharmaceuticals) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin 325mg Delayed-Release Tablet (57480-0106) (Medirex Inc) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin 325mg Delayed-Release Tablet (55966-0045) (PDK Labs Inc) null

    Aspirin Oral tablet, gastro-resistant

    Aspirin 325mg Delayed-Release Tablet (00182-0448) (Teva Pharmaceuticals USA) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin 325mg Enteric Coated Tablet (65162-0382) (Akyma Pharmaceuticals, a subsidiary of Amneal Pharmaceuticals) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin 325mg Enteric Coated Tablet (62584-0127) (American Health Packaging) null

    Aspirin Oral tablet, gastro-resistant

    Aspirin 325mg Enteric Coated Tablet (68084-0848) (American Health Packaging) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin 325mg Enteric Coated Tablet (57896-0921) (Geri-Care Pharmaceuticals) nullAspirin 325mg Enteric Coated Tablet package photo

    Aspirin Oral tablet, gastro-resistant

    Aspirin 325mg Enteric Coated Tablet (57896-0921) (Geri-Care Pharmaceuticals) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin 325mg Enteric Coated Tablet (57896-0921) (Geri-Care Pharmaceuticals) null

    Aspirin Oral tablet, gastro-resistant

    Aspirin 325mg Enteric Coated Tablet (00904-2013) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin 325mg Enteric Coated Tablet (00904-6784) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) null

    Aspirin Oral tablet, gastro-resistant

    Aspirin 325mg Enteric Coated Tablet (63739-0523) (McKesson Packaging) null

    Aspirin Oral tablet, gastro-resistant

    Aspirin 325mg Enteric Coated Tablet (63739-0023) (McKesson Packaging Inc) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin 325mg Enteric Coated Tablet (00574-0002) (Paddock Laboratories Inc, a Perrigo Family) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin 325mg Enteric Coated Tablet (00603-0167) (Par Pharmaceuticals, an Endo Company) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin 325mg Enteric Coated Tablet (00603-0166) (Par Pharmaceuticals, an Endo Company) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin 325mg Enteric Coated Tablet (00603-0167) (Par Pharmaceuticals, an Endo Company) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin 325mg Enteric Coated Tablet (00603-0169) (Par Pharmaceuticals, an Endo Company) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin 325mg Enteric Coated Tablet (00603-0168) (Par Pharmaceuticals, an Endo Company) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin 325mg Enteric Coated Tablet (69618-0015) (Reliable 1 Laboratories LLC) null

    Aspirin Oral tablet, gastro-resistant

    Aspirin 325mg Enteric Coated Tablet (00536-3313) (Rugby Laboratories a Division of The Harvard Drug Group, LLC) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin 325mg Enteric Coated Tablet (00536-3318) (Rugby Laboratories a Division of The Harvard Drug Group, LLC) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin 325mg Enteric Coated Tablet (00536-1232) (Rugby Laboratories a Division of The Harvard Drug Group, LLC ) null

    Aspirin Oral tablet, gastro-resistant

    Aspirin 325mg Enteric Coated Tablet (00536-1148) (Rugby Laboratories a Division of The Harvard Drug Group, LLC ) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin 325mg Enteric Coated Tablet (00677-1971) (Sun Pharmaceutical Industries, Inc.) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin 325mg Enteric Coated Tablet (49483-0331) (Time Cap Laboratories Inc) null

    Aspirin Oral tablet, gastro-resistant

    Aspirin 325mg Safety Coated Tablet (00904-6712) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin 325mg Safety Coated Tablet (16103-0357) (Pharbest Pharmaceuticals) null

    Aspirin Oral tablet, gastro-resistant

    Aspirin 325mg Tablet (00677-0771) (Sun Pharmaceutical Industries, Inc.) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin Lite Coat 325mg Enteric Coated Tablet (57394-0286) (Apothecary Products) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin Lite Coat 325mg Enteric Coated Tablet (00677-1853) (Sun Pharmaceutical Industries, Inc.) (off market)

    Aspirin Oral tablet, gastro-resistant

    Bayer Aspirin Regimen 325mg Caplet (12843-0103) (Bayer Corp Consumer Care Div) null

    Aspirin Oral tablet, gastro-resistant

    Bayer Aspirin Regimen 325mg Caplet (12843-0555) (Bayer Corp Consumer Care Div) null

    Aspirin Oral tablet, gastro-resistant

    CVS Aspirin 325mg Enteric Coated Tablet (59779-0137) (CVS Health) null

    Aspirin Oral tablet, gastro-resistant

    CVS Aspirin 325mg Enteric Coated Tablet (59779-0137) (CVS Health) nullCVS Aspirin 325mg Enteric Coated Tablet package photo

    Aspirin Oral tablet, gastro-resistant

    CVS Aspirin 325mg Enteric Coated Tablet (null) (CVS Health) null

    Aspirin Oral tablet, gastro-resistant

    CVS Enteric Aspirin 325mg Tablet (59726-0370) (CVS Health) (off market)CVS Enteric Aspirin 325mg Tablet package photo

    Aspirin Oral tablet, gastro-resistant

    CVS Enteric Aspirin 325mg Tablet (59726-0370) (CVS Health) nullCVS Enteric Aspirin 325mg Tablet package photo

    Aspirin Oral tablet, gastro-resistant

    CVS Enteric Aspirin 325mg Tablet (59726-0370) (CVS Health) (off market)

    Aspirin Oral tablet, gastro-resistant

    Ecotrin 325mg Enteric Coated Tablet (00135-0014) (GlaxoSmithKline Consumer Healthcare) (off market)

    Aspirin Oral tablet, gastro-resistant

    Ecotrin 325mg Enteric Coated Tablet (49692-0903) (Medtech Products, Inc a Prestige Brands Company) (off market)

    Aspirin Oral tablet, gastro-resistant

    Ecotrin 325mg Enteric Coated Tablet (63029-0302) (Medtech Products, Inc a Prestige Brands Company) null

    Aspirin Oral tablet, gastro-resistant

    Ecotrin 325mg Enteric Coated Tablet (63029-0302) (Medtech Products, Inc a Prestige Brands Company) null

    Aspirin Oral tablet, gastro-resistant

    Ecotrin 325mg Enteric Coated Tablet (49692-0903) (Medtech Products, Inc a Prestige Brands Company) (off market)

    Aspirin Oral tablet, gastro-resistant

    Equaline Enteric Coated Aspirin 325mg Tablet (41163-0429) (Albertson's, Inc) (off market)

    Aspirin Oral tablet, gastro-resistant

    Equate Aspirin 325mg Safety-coated Tablet (49035-0370) (Sam's West/Wal-Mart Stores, Inc.) null

    Aspirin Oral tablet, gastro-resistant

    Genacote Aspirin 325mg Enteric Coated Tablet (00182-1415) (Teva Pharmaceuticals USA) (off market)

    Aspirin Oral tablet, gastro-resistant

    GNP Aspirin 325mg Enteric Coated Tablet (24385-0429) (AmerisourceBergen Corporation) null

    Aspirin Oral tablet, gastro-resistant

    GoodSense Aspirin 325mg Enteric Coated Tablet (00113-0429) (Goodsense a Division of Perrigo) (off market)

    Aspirin Oral tablet, gastro-resistant

    Health Mart Aspirin 325mg Enteric Coated Tablet (62011-0040) (McKesson Corporation) null

    Aspirin Oral tablet, gastro-resistant

    Leader Aspirin 325mg Enteric Coated Tablet (70000-0035) (Cardinal Health Inc.) null

    Aspirin Oral tablet, gastro-resistant

    Leader Aspirin 325mg Enteric Coated Tablet (70000-0359) (Cardinal Health Inc.) (off market)

    Aspirin Oral tablet, gastro-resistant

    Leader Aspirin 325mg Enteric Coated Tablet (37205-0429) (Cardinal Health, Inc.) (off market)Leader Aspirin 325mg Enteric Coated Tablet package photo

    Aspirin Oral tablet, gastro-resistant

    Leader Aspirin 325mg Enteric Coated Tablet (37205-0429) (Cardinal Health, Inc.) null

    Aspirin Oral tablet, gastro-resistant

    Leader Aspirin 325mg Enteric Coated Tablet (70000-0014) (Cardinal Health, Inc.) null

    Aspirin Oral tablet, gastro-resistant

    Leader Aspirin 325mg Enteric Coated Tablet (37205-0429) (Cardinal Health, Inc.) null

    Aspirin Oral tablet, gastro-resistant

    Premier Value Aspirin 325mg Enteric Coated Tablet (68016-0722) (Pharmacy Value Alliance LLC formerly Chain Drug Consortium , LLC) null

    Aspirin Oral tablet, gastro-resistant

    Premier Value Aspirin 325mg Enteric Coated Tablet (68016-0722) (Pharmacy Value Alliance LLC formerly Chain Drug Consortium , LLC) null

    Aspirin Oral tablet, gastro-resistant

    Publix Enteric Aspirin 325mg Tablet (56062-0429) (Publix Super Markets, Inc) null

    Aspirin Oral tablet, gastro-resistant

    Quality Choice Enteric Aspirin 325mg Tablet (63868-0898) (Chain Drug Marketing Association) null

    Aspirin Oral tablet, gastro-resistant

    RITE AID Pain Relief Aspirin 325mg Enteric Coated Tablet (null) (Rite Aid Corp) null

    Aspirin Oral tablet, gastro-resistant

    RITE AID Pain Relief Aspirin 325mg Enteric Coated Tablet (null) (Rite Aid Corp) nullRITE AID Pain Relief Aspirin 325mg Enteric Coated Tablet package photo

    Aspirin Oral tablet, gastro-resistant

    Select Brand Aspirin 325mg Enteric Coated Tablet (15127-0120) (Select Brand) null

    Aspirin Oral tablet, gastro-resistant

    Select Brand Aspirin 325mg Enteric Coated Tablet (15127-0011) (Select Brand) (off market)

    Aspirin Oral tablet, gastro-resistant

    Select Brand Aspirin 325mg Enteric Coated Tablet (15127-0760) (Select Brand) nullSelect Brand Aspirin 325mg Enteric Coated Tablet package photo

    Aspirin Oral tablet, gastro-resistant

    Sunmark Aspirin 325mg Enteric Coated Tablet (49348-0937) (McKesson Corporation) null

    Aspirin Oral tablet, gastro-resistant

    Today's Health Enteric Aspirin 325mg Tablet (null) (Today's Health, Inc.) null

    Aspirin Oral tablet, gastro-resistant

    Top Care Aspirin 325mg Enteric Coated Tablet (36800-0429) (Topco Associates LLC) null

    Aspirin Oral tablet, gastro-resistant

    Walgreens Aspirin 325mg Enteric Coated Caplet (00363-0691) (Walgreens Co) null

    Aspirin Oral tablet, gastro-resistant

    Walgreens Aspirin 325mg Enteric Coated Tablet (00363-0227) (Walgreens Co) nullWalgreens Aspirin 325mg Enteric Coated Tablet package photo

    Aspirin Oral tablet, gastro-resistant

    Walgreens Aspirin 325mg Enteric Coated Tablet (00363-0227) (Walgreens Co) null

    Aspirin Oral tablet, gastro-resistant

    Aspirin 500mg Delayed-Release Tablet (55966-0107) (PDK Labs Inc) null

    Aspirin Oral tablet, gastro-resistant

    Ecotrin 500mg Enteric Coated Tablet (49692-0903) (GlaxoSmithKline Consumer Healthcare) (off market)

    Aspirin Oral tablet, gastro-resistant

    Leader Aspirin 500mg Maximum Strength Enteric Coated Tablet (37205-0511) (Cardinal Health, Inc.) (off market)Leader Aspirin 500mg Maximum Strength Enteric Coated Tablet package photo

    Aspirin Oral tablet, gastro-resistant

    Aspirin 650mg Delayed-Release Tablet (00781-1610) (Sandoz Inc. a Novartis Company) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin 650mg Enteric Coated Tablet (00182-0449) (Teva Pharmaceuticals USA) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin 975mg Delayed-Release Tablet (00904-5212) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

    Aspirin Oral tablet, gastro-resistant

    Aspirin 975mg Delayed-Release Tablet (00677-1347) (Sun Pharmaceutical Industries, Inc.) (off market)

    Aspirin Oral tablet, gastro-resistant

    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 Rectal suppository

    Aspirin 125mg Rectal Suppository (51079-0551) (Mylan Institutional LLC ) (off market)

    Aspirin Rectal suppository

    Aspirin 125mg Rectal Suppository (45802-0702) (Perrigo Pharmaceuticals Company) (off market)

    Aspirin Rectal suppository

    Aspirin 125mg Rectal Suppository (00536-1330) (Rugby Laboratories a Division of The Harvard Drug Group, LLC) (off market)

    Aspirin Rectal suppository

    Aspirin 125mg Rectal Suppository (00182-0264) (Teva Pharmaceuticals USA) (off market)

    Aspirin Rectal suppository

    Aspirin 300mg Rectal Suppository (00839-5531) (HL Moore Drug Exchange) (off market)

    Aspirin Rectal suppository

    Aspirin 300mg Rectal Suppository (51079-0549) (Mylan Institutional LLC ) (off market)

    Aspirin Rectal suppository

    Aspirin 300mg Rectal Suppository (00574-7034) (Paddock Laboratories Inc, a Perrigo Family) null

    Aspirin Rectal suppository

    Aspirin 300mg Rectal Suppository (45802-0704) (Perrigo Pharmaceuticals Company) (off market)

    Aspirin Rectal suppository

    Aspirin 325mg Rectal Suppository (00536-1340) (Rugby Laboratories a Division of The Harvard Drug Group, LLC) (off market)

    Aspirin Rectal suppository

    Aspirin 325mg Rectal Suppository (00182-0266) (Teva Pharmaceuticals USA) (off market)

    Aspirin Rectal suppository

    Aspirin 600mg Rectal Suppository (00839-5532) (HL Moore Drug Exchange) (off market)

    Aspirin Rectal suppository

    Aspirin 600mg Rectal Suppository (51079-0483) (Mylan Institutional LLC ) (off market)

    Aspirin Rectal suppository

    Aspirin 600mg Rectal Suppository (00574-7036) (Paddock Laboratories Inc, a Perrigo Family) null

    Aspirin Rectal suppository

    Aspirin 600mg Rectal Suppository (45802-0705) (Perrigo Pharmaceuticals Company) (off market)

    Aspirin Rectal suppository

    Aspirin 600mg Rectal Suppository (00536-1350) (Rugby Laboratories a Division of The Harvard Drug Group, LLC) (off market)

    Aspirin Rectal suppository

    Aspirin 600mg Rectal Suppository (00182-0267) (Teva Pharmaceuticals USA) (off market)

    Aspirin Rectal suppository

    Aspirin 1200mg Rectal Suppository (45802-0706) (Perrigo Pharmaceuticals Company) (off market)

    Description/Classification

    Description

    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.

    Classifications

    • Blood and Blood Forming Organs
      • Antithrombotic Agents
        • Platelet Aggregation Inhibitors
          • Cyclo-oxygenase Inhibitor Platelet Aggregation Inhibitors
    • Central Nervous System
      • Analgesics
        • Analgesics with Antipyretic Activity
    Revision Date: 12/17/2019, 09:57:50 AM

    References

    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. Houston, TX: PLx Pharma Inc.; 2019 Dec.

    Administration Information

    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 GI 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.

    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
    • [object Object]
    Revision Date: 11/07/2019, 10:08:42 AMCopyright 2004-2020 by Lawrence A. Trissel. All Rights Reserved.

    References

    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.

    Adverse Reactions

    Mild

    • abdominal pain
    • diaphoresis
    • diarrhea
    • dizziness
    • drowsiness
    • dyspepsia
    • epistaxis
    • fever
    • headache
    • hyperventilation
    • leukocytosis
    • maculopapular rash
    • nausea
    • purpura
    • pyrosis (heartburn)
    • tinnitus
    • urticaria

    Moderate

    • bleeding
    • confusion
    • constipation
    • dehydration
    • dysphagia
    • elevated hepatic enzymes
    • esophagitis
    • gastritis
    • hallucinations
    • hematoma
    • hemorrhoids
    • hepatitis
    • hyperbilirubinemia
    • hyperglycemia
    • hypernatremia
    • hyperuricemia
    • hypoglycemia
    • hypokalemia
    • hypoprothrombinemia
    • jaundice
    • leukopenia
    • melena
    • metabolic acidosis
    • platelet dysfunction
    • prolonged bleeding time
    • respiratory depression
    • thrombocytopenia
    • wheezing
    • withdrawal

    Severe

    • acute generalized exanthematous pustulosis (AGEP)
    • agranulocytosis
    • anaphylactoid reactions
    • angioedema
    • aplastic anemia
    • azotemia
    • bronchospasm
    • disseminated intravascular coagulation (DIC)
    • erythema nodosum
    • esophageal stricture
    • esophageal ulceration
    • GI bleeding
    • GI perforation
    • hearing loss
    • hemolytic anemia
    • hepatic encephalopathy
    • hepatic necrosis
    • interstitial nephritis
    • intracranial bleeding
    • laryngeal edema
    • odynophagia
    • pancytopenia
    • peptic ulcer
    • pulmonary edema
    • renal failure (unspecified)
    • renal papillary necrosis
    • renal tubular necrosis
    • Reye's syndrome
    • seizures
    • Stevens-Johnson syndrome
    • toxic epidermal necrolysis
    • visual impairment

    Symptomatic GI disturbances occur in 2% to 10% of individuals receiving normal doses of aspirin for analgesia or pyrexia, 10% to 30% of individuals receiving doses more than 3.6 grams/day, and 30% to 90% of patients with preexisting GI disease. Nausea, dyspepsia, abdominal pain, pyrosis (heartburn), gastritis and other common symptoms of gastric distress can be reduced if aspirin is taken with food or a full glass of water. In patients receiving chronic aspirin therapy, preventative agents, such as proton pump inhibitors or H2-antagonists may be needed for protective effect on the gastric mucosa. Diarrhea or constipation may also occur. Melena, hemorrhoids, and rectal hemorrhage have occurred with aspirin therapy. Rare cases of esophagitis have been reported in patients receiving aspirin. Aspirin-induced esophagitis is characterized by sudden onset odynophagia, retrosternal pain, and dysphagia. Severe complications such as GI perforation, esophageal ulceration, esophageal stricture, and GI bleeding, have been reported rarely. Risk factors for aspirin-induced esophageal effects include taking the medication without water and at night. Symptoms usually resolve within days to weeks after stopping the medication. Penetration of the gastric or esophageal mucosal cell by unionized molecules is 1 mechanism by which aspirin causes mucosal damage.[23556] Raising the intragastric pH increases the amount of aspirin in the unionized form, and some data indicate that agents such as cimetidine or antacids can reduce mucosal injury from aspirin. Chronic aspirin therapy may induce peptic ulcer disease. Gastric or peptic ulcers up to 1 cm in diameter induced by salicylates may heal despite continued therapy when oral cimetidine or high dose antacids are used concomitantly. Duodenal mucosal damage appears to be less common when enteric-coated tablets are used when compared with buffered or uncoated tablets.[24456] GI bleeding or erosive gastritis can be minor or life-threatening and may result from a combination of direct irritant action on the stomach mucosa and an increased bleeding time. In general, the severity of GI bleeding with aspirin is dose-related. Occult GI bleeding occurs in many patients and is not necessarily correlated with GI distress. While the amount of blood lost is usually not significant, blood loss can result in iron deficiency anemia. Patients taking aspirin in large doses (more than 15 tablets per week) or regularly (4 days/week or more) are at increased risk of GI bleeding or gastric ulceration. GI bleeding is more common with aspirin than with other salicylates and is not reduced by administering aspirin with food.

    Tinnitus (1% or less) and hearing loss may occur in patients receiving high-dose and/or long-term aspirin therapy.[28439] 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 male patients 40 to 74 years of age 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 less than 60 years of age 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] Counsel patients to report any symptoms of ototoxicity to a health care provider, as dosage adjustments may be needed.

    Anaphylactoid reactions, including angioedema, laryngeal edema, and acute bronchospasm, may occur with aspirin therapy. Most allergic reactions occur within minutes and almost always within an hour of ingestion, although delayed reactions have been noted. Aspirin hypersensitivity may manifest as a respiratory reaction including rhinitis and/or asthma or with urticaria and angioedema. Aspirin hypersensitivity, however, is uncommon and occurs in only 0.3% of the general population. Patients with chronic urticaria have the highest incidence (20%), followed by patients with asthma (4%) and patients with chronic rhinitis (1.5%). Sensitivity is manifested primarily as bronchospasm in asthmatic patients and is most commonly associated with nasal polyps. The correlation of aspirin hypersensitivity, asthma, and nasal polyps is known as the aspirin triad. Hypersensitivity reactions are more common with aspirin than other salicylates. Patients sensitive to aspirin may develop cross-sensitivity to other analgesics, NSAIDs, and azo dyes such as tartrazine. Acetaminophen and other salicylate salts are not cross-sensitive and may be used cautiously in patients with aspirin-induced asthma.

    Salicylates, such as aspirin, may cause reversible hepatotoxicity primarily manifested as mild focal hepatic necrosis and portal hypertension with elevated hepatic enzymes (usually transaminases) and hyperbilirubinemia. Transaminase elevations have been commonly reported in children with rheumatic diseases treated with aspirin.[44724] [54244] Jaundice has been reported in some patients. Rarely, salicylates are associated with hypoprothrombinemia resulting in a prolonged prothrombin time and chronic hepatitis. Usually salicylate-induced hepatotoxicity is mild, but in some cases fatalities or hepatic encephalopathy have occurred. The occurrence of these events appears to be dose and duration related.[54267] [44724]

    Reye's syndrome, a potentially fatal disease, has been associated with aspirin use in children after active varicella infection or other viral illnesses.[54240] [54281] [54282] 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 of age.[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]

    Dermatologic reactions are uncommon; usually reported in patients who receive salicylate therapy for more than 1 week continually or with overdosage. These reactions include acneiform rash, erythema nodosum, maculopapular rash, pruritus, purpura, and urticaria. Rarely, aspirin has been associated with Stevens-Johnson syndrome and toxic epidermal necrolysis.[54287] Aspirin (acetylsalicylic acid) has been associated with acute generalized exanthematous pustulosis (AGEP). The nonfollicular, pustular, erythematous rash starts suddenly and is associated with fever above 38 degrees C. Drugs are the main cause of AGEP. A period of 2 to 3 weeks after an inciting drug exposure appears necessary for a first episode of AGEP; unintentional reexposure may cause a second episode within 2 days.[27736]

    Aspirin therapy causes platelet dysfunction by inhibiting platelet aggregation resulting in a prolonged bleeding time; this effect is a common and expected pharmacologic effect of the drug leading to drug efficacy.[26402] [54294] Infrequently this effect on platelet aggregation may result in minor bleeding episodes such as epistaxis (3% or less) or hematoma or gingival bleeding (1% or less) in clinical use, either alone or in combination with other medications.[28439] Leukopenia, pancytopenia, thrombocytopenia, agranulocytosis, aplastic anemia, and disseminated intravascular coagulation (DIC) have been reported rarely with salicylates. Leukocytosis has occurred in patients with salicylate overdose. If hemolytic anemia occurs in patients receiving aspirin, it almost always occurs in G6PD-deficient individuals. It appears that aspirin can induce hemolysis at therapeutic concentrations if other oxidative stressors are present. Otherwise, hemolysis only occurs at much higher concentrations.[24682]

    With chronic, high-dose aspirin use, analgesic abuse, or salicylate overdose, a marked reduction in creatinine clearance, renal papillary necrosis, interstitial nephritis, or renal tubular necrosis with renal failure (unspecified) may be seen; however, in usual doses, salicylates rarely cause clinically significant renal effects in patients with normal renal function. Salicylates may cause transient urinary excretion of renal tubular epithelial cells, azotemia, albuminuria, and proteinuria.[44725]

    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 large doses of salicylates (more than 3 g/day) induce uricosuria and lower plasma uric acid concentrations.[54248] Small doses of salicylates can block the effects of probenecid and other uricosuric agents that decrease the tubular reabsorption of uric acid.

    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 levels, 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 loss, 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), 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]

    Moderate-to-severe noncardiogenic pulmonary edema may occur during aspirin associated acute or chronic salicylic acid toxicity.[54194] [54260]

    Intracranial bleeding may occur in patients at risk who are taking aspirin. Intracranial bleeding is rarely observed when aspirin is used in lower doses for prophylactic purposes. One trial reported an incidence of 0.4% in patients treated with 50 mg/day aspirin vs. 0.4% for placebo in patients being evaluated for stroke prophylaxis.[24493] The risk is significantly increased with concomitant use of other antithrombotics, anticoagulants, or thrombolytics.

    Overuse of drugs for treating acute migraines, including aspirin, ASA, may lead to headache exacerbation (medication overuse headache). Patients may experience migraine-like daily headaches or a significant increase in migraine attack frequency. Withdrawal of the overused drug and treatment of withdrawal symptoms (e.g., transient worsening of headache) may be necessary. Patients should be informed of the risks of medication overuse (e.g., use of a single agent or a combination of drugs for at least 10 days per month) and encouraged to keep a written record of headache frequency and drug use.[57799]

    Dizziness, drowsiness, headache, lightheadedness, and lethargy may be signs of salicylism, mild salicylate toxicity. Other symptoms of salicylism include uncontrollable flapping movements of the hands, increased thirst, and visual impairment. In severe aspirin overdose, seizures, hallucinations, severe nervousness, excitement, confusion, wheezing or shortness of breath, and unexplained fever may occur. In young children, the only signs of overdose may be behavioral changes.[54194] [54244] [54260]

    Revision Date: 11/07/2019, 10:37:23 AM

    References

    23556 - Graham DY, Smith JL. Aspirin and the stomach. Ann Intern Med 1986;104:390-8.24456 - Savon JJ, et al. Gastrointestinal blood loss with low dose (325 mg) plain and enteric coated aspirin administration. Am J Gastroenterol 1995;90:581-5.24493 - Diener HC, Cunha L, Forbes C, Sivenius J, Smets P, Lowenthal A. European Stroke Prevention Study. 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci. 1996;143:1-1324682 - Sanford-Driscoll M, Knodel LC. Induction of hemolytic anemia by nonsteroidal antiinflammatory drugs. Drug Intell Clin Pharm 1986:20:925-34.26402 - Awtry EH, Loscalzo J. Aspirin. Circulation 2000;101:1206-1218.27736 - Beylot C, Doutre M, Beylot-Barry M. Acute generalized exanthematous pustulosis. Semin Cutan Med Surg 1996;15(4):244-249.28439 - Aggrenox (aspirin/dipyridamole extended release) package insert. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; 2018 Nov.44724 - Rich RR, Johnson JS. Salicylate hepatotoxicity in patients with juvenile rheumatoid arthritis. Arthritis Rheum 1973;16:1-9.44725 - Burry H, Dieppe P, Bresnihan F, et al. Salicylates and renal function in rheumatoid arthritis. BMJ 1976;1:613-615.53719 - 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;9:195-204.54244 - 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;0:1-6.54259 - 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;12:351-364.54267 - Prescott LF. Hepatotoxicity of mild analgesics. Br J Clin Pharmac 1980;10:373s-379s.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;41:303-304.54287 - Kowalski ML, Makowska JS, Blanca M, et al. Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs)-classification, diagnosis, and management: review of the EAACI/ENDA and GA2LEN/HANNA. Allergy 2011;66:818-829.54294 - Pochedly C, Ente G. Adverse hematologic effects of drugs. Ped Clin N Am 1972;19:1095-1111.54310 - Snodgrass W, Rumack BH, Peterson RG, et al. Salicylate toxicity following therapeutic doses in young children. Clin Toxicol 1981;18:247-259.57799 - American Headache Society. Silberstein SD. Medication Overuse Headache. Retrieved from the World Wide Web August 19, 2014. http://www.americanheadachesociety.org/assets/1/7/Stephen_Silberstein_-_Medication_Overuse_Headache.pdf

    Contraindications/Precautions

    Absolute contraindications are italicized.

    • salicylate hypersensitivity
    • abrupt discontinuation
    • acid/base imbalance
    • acute bronchospasm
    • agranulocytosis
    • alcoholism
    • aneurysm
    • anticoagulant therapy
    • ascites
    • asthma
    • bone marrow suppression
    • breast-feeding
    • coagulopathy
    • dehydration
    • esophagitis
    • G6PD deficiency
    • gastritis
    • geriatric
    • GI bleeding
    • GI disease
    • gout
    • head trauma
    • heart failure
    • hemophilia
    • hepatic disease
    • hypertension
    • hypoprothrombinemia
    • hypovolemia
    • immunosuppression
    • increased intracranial pressure
    • influenza
    • intracranial bleeding
    • intramuscular injections
    • iron-deficiency anemia
    • labor
    • metabolic acidosis
    • metabolic alkalosis
    • nasal polyps
    • neonates
    • neutropenia
    • NSAID hypersensitivity
    • obstetric delivery
    • peptic ulcer disease
    • pregnancy
    • renal disease
    • renal failure
    • renal impairment
    • respiratory acidosis
    • respiratory alkalosis
    • Reye's syndrome
    • surgery
    • systemic lupus erythematosus (SLE)
    • thrombocytopenia
    • thrombolytic therapy
    • thrombotic thrombocytopenic purpura (TTP)
    • tobacco smoking
    • urticaria
    • varicella
    • viral infection
    • vitamin K deficiency

    Aspirin use is contraindicated in patients with hypersensitivity to other medications for pain or fever, including those with salicylate hypersensitivity or NSAID hypersensitivity. The risk of cross-sensitivity with other nonsteroidal antiinflammatory drugs is significantly greater with aspirin than other salicylates. Patients with nasal polyps or with allergic reactions (e.g. urticaria) to aspirin are at risk of developing bronchoconstriction or anaphylaxis and should not receive aspirin. Patients with asthma are at risk of developing severe and potentially fatal exacerbations of asthma after taking aspirin. Aspirin should be avoided in asthmatics with a history of aspirin-induced acute bronchospasm.

    In patients with gout, salicylates such as aspirin may increase serum uric acid levels, resulting in hyperuricemia, and interfere with the efficacy of uricosuric agents.

    Aspirin has been associated with the occurrence of Reye's syndrome when given to children with varicella (i.e., chickenpox) or influenza. Although a causal relationship has not been confirmed, most authorities advise against the use of aspirin in children with varicella, influenza, or other viral infection. 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.

    Aspirin can induce gastric or intestinal ulceration that can occasionally be accompanied by iron-deficiency anemia or other anemia from the resultant blood loss. Aspirin should be used cautiously, if at all, in patients with a history of or active GI disease including erosive gastritis, esophagitis, GI bleeding, peptic ulcer disease, or previous NSAID-induced bleeding. Such patients should be monitored closely, with special caution in tobacco smoking patients or in patients with alcoholism. All patients receiving chronic treatment should be routinely monitored for potential GI ulceration and bleeding. In patients who develop gastric or duodenal ulcers during aspirin treatment, the drug should be discontinued due to an increased risk of bleeding and/or perforation. In addition, patients should not self-medicate with aspirin if they consume 3 or more alcoholic beverages per day because of the potential increased risk for GI bleeding. In patients with anemia, this condition may be exacerbated during aspirin therapy due to GI blood loss. Hematocrit should be monitored periodically in patients receiving prolonged or high-dose aspirin therapy since iron deficiency anemia may occur. Traditionally, aspirin has been recommended to be discontinued for a time interval (e.g., 1 week) prior to surgery to minimize postoperative bleeding. However, data presented at the 2003 meeting of the American College of Chest Physicians indicates a risk of increased coronary events with abrupt discontinuation of aspirin in patients with pre-existing coronary artery disease.[27715] Patients with stable coronary disease developed acute coronary events within one week of stopping aspirin therapy; these events included unstable angina and myocardial infarction. Until the results of this trial are published and/or consensus recommendations are available, the decision whether to discontinue aspirin therapy abruptly should include a careful evaluation of the overall risks and benefits given the patient's coexisting conditions and the type of surgery or procedure. The use of aspirin is generally not recommended in patients expected to require CNS surgery due to the increased risk of perioperative bleeding.

    Since even low doses of aspirin inhibit platelet aggregation and increase bleeding time, aspirin should be used cautiously in patients with coagulopathy, hemophilia, pre-existing thrombocytopenia, thrombotic thrombocytopenic purpura (TTP), or in patients receiving anticoagulant therapy or thrombolytic therapy. Medical evaluation of the potential risks versus benefits of aspirin therapy is needed in patients with aplastic anemia, agranulocytosis, or pancytopenia. Aspirin should be used with caution in patients with immunosuppression or neutropenia following myelosuppressive chemotherapy. Aspirin may mask signs of infection, such as fever and pain, in patients with bone marrow suppression.

    Avoid aspirin in patients with potential for intracranial bleeding (e.g., subarachnoid aneurysm, head trauma, increased intracranial pressure) because of the possibility of interference with platelet function.[26402]

    Because salicylates may cause or aggravate hemolysis in patients with G6PD deficiency, some reference texts state that aspirin should be used cautiously in these patients. If hemolytic anemia occurs in patients receiving aspirin, it almost always occurs in G6PD-deficient individuals. Otherwise, hemolysis only occurs at high concentrations.[24682]

    Intramuscular injections should be administered cautiously to patients receiving aspirin. IM injections may cause bleeding, bruising, or hematomas due to aspirin-induced inhibition of platelet aggregation.

    Liver function should be monitored in patients receiving large doses of aspirin (e.g., for treatment of Kawasaki disease, rheumatoid arthritis) or in patients with preexisting hepatic disease or impairment in order to prevent reversible, dose-dependent hepatotoxicity. Large doses also can cause hypoprothrombinemia, which can be reversed by vitamin K.[54310] Patients with vitamin K deficiency should be closely monitored if taking large doses of aspirin.

    Salicylates should be used with caution in patients with renal impairment; regular-dose aspirin should be avoided in patients with advanced, chronic renal failure since salicylic acid and its metabolites are excreted in the urine.[32569] [54023] Although data are limited in patients with chronic kidney disease, use of low-dose aspirin for primary and secondary prevention of atherosclerotic events in patients with concomitant cardiovascular disease is recommended.[60881] Observational data of dialysis patients who received aspirin following myocardial infarction (MI) indicate that, similar to the general population, aspirin use is associated with a reduction in post-MI mortality.[60883] [60885] Even though cardiovascular disease is prevalent among patients with chronic kidney disease, data indicate aspirin for the primary and secondary prevention of atherosclerotic events is underutilized in hemodialysis patients.[60882] Salicylates should be used cautiously in patients with renal disease or systemic lupus erythematosus (SLE) due to the risk of decreased glomerular filtration rate in these patients. In addition, patients with renal impairment may be at increased risk of developing salicylate-induced nephrotoxicity. In a case-controlled study of patients with early renal failure, the regular use of aspirin (without acetaminophen) was associated with a risk of chronic renal failure that was 2.5-times as high as that for non-aspirin users.[27368] The risk increased significantly with increasing cumulative lifetime dose and increasing average dose during periods of regular use; duration of therapy was not associated with increased risk. When aspirin was given regularly in analgesic doses (more than 500 g per year during periods of regular use) the odds ratio for chronic renal failure was 3.5 (95% confidence interval 1.4 to 8). Low-dose aspirin use for cardiovascular prophylaxis was not significantly associated with the development of renal failure. In this study, it appears that pre-existing renal disease or systemic disease is a required precursor to the development of analgesic-induced renal failure; patients without preexisting renal disease who used analgesics had only a small risk of developing end-stage renal disease. Renal function should be monitored periodically in patients receiving prolonged or high-dose salicylate therapy.

    Aspirin, ASA should be used with caution in the geriatric patient. Care should be taken in dose selection and the lowest effective dose should be used. Elderly patients should be monitored for the development of pedal edema, rales, blood pressure elevation, or changes in creatinine or BUN levels. Monitoring of stool for occult blood, serum potassium levels, and a complete blood count should be considered at baseline and periodically during chronic use of aspirin, ASA. 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]

    Caution is advised with aspirin use in sodium-restricted patients or patients with hypovolemic states (e.g., ascites, dehydration, heart failure, hypertension, or hypovolemia) as they may be more susceptible to adverse renal effects of salicylate therapy.[54023] Patients with sodium-retaining states, such as congestive heart failure or renal failure, should avoid sodium-containing buffered aspirin preparations because of their high sodium content.

    Salicylates primarily alter acid-base balance by causing metabolic acidosis and respiratory alkalosis, either alone or mixed.[54194] The respiratory effects of salicylates, such as aspirin, may contribute to serious acid/base imbalance in patients with underlying acid/base disorders (e.g., metabolic acidosis, metabolic alkalosis, respiratory acidosis, or respiratory alkalosis) or in overdose situations. Patients who are unable to compensate for salicylate-induced metabolic acidosis (i.e., respiratory response to CO2 is depressed) may develop respiratory acidosis and increased levels of plasma CO2.

    Avoid aspirin use especially during the third trimester of pregnancy due to the risk of constriction or premature closure of the fetal ductus arteriosus.[49579] Fetal and newborn effects from aspirin exposure in utero may include increased perinatal mortality, intrauterine growth retardation, congenital salicylate intoxication, or depressed albumin-binding capacity. However, a large prospective study involving over 40,000 patients, 64% of whom used aspirin sometime during gestation, failed to show that aspirin was a cause of stillbirths, neonatal deaths, or reduced birth weight.[25400] The lack of adverse effects of aspirin therapy in this study may have been related to the use of relatively low aspirin doses. Several groups have evaluated low-dose aspirin (60 to 150 mg/day) administered during the second and third trimesters of pregnancy as an agent to prevent preeclampsia. One group found that the efficacy in preventing preeclampsia was only marginal, and a higher risk of abruptio placentae was seen. Another group concluded that aspirin appears to be safe for the mother and the fetus.[24348] [25401] The safety of higher doses and/or administration during the first trimester, however, is uncertain. Full doses of aspirin administered to pregnant women near term have been associated with toxicities such as hemorrhage, premature closure of the ductus arteriosus, and pulmonary hypertension. In a study of 40 babies born with persistent pulmonary hypertension of the newborn (PPHN), 87.5% had the presence of an NSAID in their meconium vs. 24.6% of 61 babies born without PPHN; the presence of only 4 NSAIDs was examined. In addition to meconium aspiration, asphyxia, respiratory distress syndrome, and group B streptococcal pneumonia, ductus arteriosus constriction by an NSAID appears to be another predisposing factor for PPHN development, as a patent ductus arteriosus was absent in 18 of the 40 babies.[27563] Some NSAIDs have been shown to prolong pregnancy and inhibit labor if taken during the third trimester.[45816] [45818] Also, the antiplatelet effects of aspirin may increase the risk of bleeding during obstetric delivery.

    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]

    Clearance of aspirin is slower in neonates, potentially placing them at risk for bleeding for longer periods of time. If a neonate is also receiving indomethacin, then additive antiplatelet effects should be considered.[49232]

    Revision Date: 11/07/2019, 10:21:39 AM

    References

    24348 - Sibai BM, Caritis SN, Thom E, et al. Prevention of preeclampsia with low-dose aspirin in healthy, nulliparous pregnant women. N Engl J Med 1993;329:1213-8.24682 - Sanford-Driscoll M, Knodel LC. Induction of hemolytic anemia by nonsteroidal antiinflammatory drugs. Drug Intell Clin Pharm 1986:20:925-34.25400 - Collins E. Maternal and fetal effects of acetaminophen and salicylates in pregnancy. Obstet Gynecol 1981;58(Suppl):57S-62S.25401 - CLASP Collaborative Group. CLASP: a randomised trial of low-dose aspirin for the prevention and treatment of pre-eclampsia among 9364 pregnant women. Lancet 1994;343:619-29.26402 - Awtry EH, Loscalzo J. Aspirin. Circulation 2000;101:1206-1218.27368 - Fored CM, Ejerblad E, Lindblad P, et al. Acetaminophen, aspirin, and chronic renal failure. N Engl J Med 2001;345:1801-8.27500 - American Academy of Pediatrics (AAP) Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001;108(3):776-789.27563 - Alano MA, Ngougmna E, Ostrea EM, et al. Analysis of nonsteroidal antiinflammatory drugs in meconium and its relation to persistent pulmonary hypertension of the newborn. Pediatrics 2001;107:519-23.27715 - Ferrari E, Benhamou M, Cerboni P, et al. Coronary syndromes following aspirin withdrawal. Chest 2003;124:148S-b (abstract).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; 2007.45816 - Lewis RB, Schulman JD. Influence of acetylsalicylic acid, an inhibitor of prostaglandin synthesis, on the duration of human gestation and labour. Lancet 1973;2:1159-61.45818 - Zuckerman HK, Reiss U, Rubinstein I. Inhibition of human premature labor by indomethacin. Obstet Gynecol 1974;44:787-92.49232 - 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;8:285-90.49579 - Aspirin regular strength package insert. Morristown, NJ: Bayer Healthcare; 2011 Mar.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;62:873-876.54310 - Snodgrass W, Rumack BH, Peterson RG, et al. Salicylate toxicity following therapeutic doses in young children. Clin Toxicol 1981;18:247-259.60742 - Health Care Financing Administration. Interpretive Guidelines for Long-term Care Facilities. Title 42 CFR 483.25(l) F329: Unnecessary Drugs. Revised 2015.60881 - KDOQI Work Group. KDOQI clinical practice guidelines for cardiovascular disease in dialysis patients. Am J Kidney Dis 2005;45:S1-S15360882 - Dempster DW, Rosenstock JL, Schwimmer G, et al. Underutilization of aspirin in hemodialysis patients for primary and secondary prevention of cardiovascular disease. Clin Nephrol 2005;5:371-77.60883 - McCullough PA, Sandberg BS, Borzak S, et al. Benefits of aspirin and beta-blocker blockade after myocardial infarction in patients with chronic kidney disease. Am Heart J 2002;144:226-32.60885 - Berger AK, Duval S, Krumholz HM. Aspirin, beta blocker, and angiotensin converting enzyme inhibitor therapy in patients with end-stage renal disease and an acute myocardial infarction. J Am Coll Cardiol 2003;42:201-8.63923 - 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.

    Mechanism of Action

    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]

    Revision Date: 11/29/2019, 02:20:45 PM

    References

    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.

    Pharmacokinetics

    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]

    Special Populations

    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]

    Pediatrics

    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]

    Revision Date: 11/29/2019, 02:38:40 PM

    References

    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.

    Pregnancy/Breast-feeding

    labor, obstetric delivery, pregnancy

    Avoid aspirin use especially during the third trimester of pregnancy due to the risk of constriction or premature closure of the fetal ductus arteriosus.[49579] Fetal and newborn effects from aspirin exposure in utero may include increased perinatal mortality, intrauterine growth retardation, congenital salicylate intoxication, or depressed albumin-binding capacity. However, a large prospective study involving over 40,000 patients, 64% of whom used aspirin sometime during gestation, failed to show that aspirin was a cause of stillbirths, neonatal deaths, or reduced birth weight.[25400] The lack of adverse effects of aspirin therapy in this study may have been related to the use of relatively low aspirin doses. Several groups have evaluated low-dose aspirin (60 to 150 mg/day) administered during the second and third trimesters of pregnancy as an agent to prevent preeclampsia. One group found that the efficacy in preventing preeclampsia was only marginal, and a higher risk of abruptio placentae was seen. Another group concluded that aspirin appears to be safe for the mother and the fetus.[24348] [25401] The safety of higher doses and/or administration during the first trimester, however, is uncertain. Full doses of aspirin administered to pregnant women near term have been associated with toxicities such as hemorrhage, premature closure of the ductus arteriosus, and pulmonary hypertension. In a study of 40 babies born with persistent pulmonary hypertension of the newborn (PPHN), 87.5% had the presence of an NSAID in their meconium vs. 24.6% of 61 babies born without PPHN; the presence of only 4 NSAIDs was examined. In addition to meconium aspiration, asphyxia, respiratory distress syndrome, and group B streptococcal pneumonia, ductus arteriosus constriction by an NSAID appears to be another predisposing factor for PPHN development, as a patent ductus arteriosus was absent in 18 of the 40 babies.[27563] Some NSAIDs have been shown to prolong pregnancy and inhibit labor if taken during the third trimester.[45816] [45818] Also, the antiplatelet effects of aspirin may increase the risk of bleeding during obstetric delivery.

    breast-feeding

    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]

    Revision Date: 11/07/2019, 10:21:39 AM

    References

    24348 - Sibai BM, Caritis SN, Thom E, et al. Prevention of preeclampsia with low-dose aspirin in healthy, nulliparous pregnant women. N Engl J Med 1993;329:1213-8.25400 - Collins E. Maternal and fetal effects of acetaminophen and salicylates in pregnancy. Obstet Gynecol 1981;58(Suppl):57S-62S.25401 - CLASP Collaborative Group. CLASP: a randomised trial of low-dose aspirin for the prevention and treatment of pre-eclampsia among 9364 pregnant women. Lancet 1994;343:619-29.27500 - American Academy of Pediatrics (AAP) Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001;108(3):776-789.27563 - Alano MA, Ngougmna E, Ostrea EM, et al. Analysis of nonsteroidal antiinflammatory drugs in meconium and its relation to persistent pulmonary hypertension of the newborn. Pediatrics 2001;107:519-23.45816 - Lewis RB, Schulman JD. Influence of acetylsalicylic acid, an inhibitor of prostaglandin synthesis, on the duration of human gestation and labour. Lancet 1973;2:1159-61.45818 - Zuckerman HK, Reiss U, Rubinstein I. Inhibition of human premature labor by indomethacin. Obstet Gynecol 1974;44:787-92.49577 - Jamali F, Keshavarz E. Salicylate excretion in breast milk. Int J Pharm 1981;8:285-90.49579 - Aspirin regular strength package insert. Morristown, NJ: Bayer Healthcare; 2011 Mar.

    Interactions

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    Level 3 (Moderate)

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    • Acetaminophen; Butalbital
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    • Sodium Bicarbonate
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    • Triamterene
    • Tromethamine
    • Valproic Acid, Divalproex Sodium
    • Verteporfin
    • Vilazodone
    • Vorapaxar
    • Vortioxetine

    Level 4 (Minor)

    • Aminoglycosides
    • Amoxicillin
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    • Amoxicillin; Clavulanic Acid
    • Amphotericin B
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    • Ticarcillin; Clavulanic Acid
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    • Vancomycin
    • Verapamil
    • 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] Acetaminophen; Butalbital: (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; Butalbital; 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] Acetaminophen; Butalbital; 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] 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] 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] 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] 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] 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; 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; 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; 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] Acetaminophen; Tramadol: (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; Hydrochlorothiazide, HCTZ; Olmesartan: (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] Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: (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; Lansoprazole: (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] Antithymocyte Globulin: (Moderate) An increased risk of bleeding may occur when salicylates are used with agents that cause clinically significant thrombocytopenia due to decreases in platelet aggregation, such as anti-thymocyte immune globulin. [30110] [30137] 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; 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] 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] Calcium Carbonate: (Minor) By increasing urinary pH, calcium carbonate can increase the urinary excretion of salicylates. [7648] Calcium Carbonate; Magnesium Hydroxide: (Minor) By increasing urinary pH, calcium carbonate can increase the urinary excretion of salicylates. [7648] Calcium Carbonate; Risedronate: (Minor) By increasing urinary pH, calcium carbonate can increase the urinary excretion of salicylates. [7648] Calcium Carbonate; Simethicone: (Minor) By increasing urinary pH, calcium carbonate can increase the urinary excretion of salicylates. [7648] 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] 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: (Severe) 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: (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] 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] Citric Acid; 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] 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] Colchicine; Probenecid: (Severe) 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] 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] 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: (Severe) 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] 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] Efalizumab: (Minor) Due to aspirin's effect on platelet aggregation and GI mucosa, aspirin should be used cautiously in patients with thrombocytopenia following treatment with antineoplastic agents due to an increased risk of bleeding. [5717] 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] 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] Esomeprazole; 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] 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 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] Fluoxetine; Olanzapine: (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; Pioglitazone: (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] 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; Irbesartan: (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; 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] (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; Losartan: (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; Metoprolol: (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] Hydrochlorothiazide, HCTZ; Olmesartan: (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; Propranolol: (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; 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] (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; 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] (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; Telmisartan: (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; 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] (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; Valsartan: (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] 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: (Severe) Increased adverse gastrointestinal and other effects are possible if ketorolac is used with salicylates. In addition, concomitant administration of salicylates and ketorolac has resulted in a reduction in protein binding and a two-fold increase in unbound plasma concentrations of ketorolac. As a result, concomitant use of ketorolac and aspirin or any other NSAID is contraindicated. Because ketorolac can cause GI bleeding, inhibit platelet aggregation, and may prolong bleeding time, additive effects may be seen in patients receiving platelet inhibitors (e.g., aspirin), anticoagulants, or thrombolytic agents. [5060] 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; 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] 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] 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; Pioglitazone: (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; 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: (Severe) Caution should be exercised when salicylates are given in combination with methotrexate. Since both are weak acids, salicylates can impair the renal secretion of methotrexate and increase the risk of methotrexate toxicity. Salicylates can also displace methotrexate from protein-binding sites. Although the risk for drug interactions with methotrexate is greatest during high-dose methotrexate therapy, it has been recommended that any of these drugs be used cautiously with methotrexate even when methotrexate is used in low doses for the treatment of rheumatoid arthritis. A significantly higher incidence of leukopenia has been reported in patients taking aspirin during methotrexate therapy. In addition, large doses of salicylates (>= 3 to 4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. [28440] 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] 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] Muromonab-CD3: (Minor) Due to aspirin's effect on platelet aggregation and GI mucosa, aspirin should be used cautiously in patients with thrombocytopenia following treatment with antineoplastic agents due to an increased risk of bleeding. [5717] 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; 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] Naproxen; Sumatriptan: (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] 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] 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] 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] Polymyxins: (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] 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 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: (Severe) 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] 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] 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 Hyaluronate, Hyaluronic Acid: (Moderate) Increased bruising or bleeding at the injection site may occur when using hyaluronate sodium with salicylates, especially if used within the 3 weeks prior to the procedure. [45808] [45809] [45810] [45811] [45813] [45814] [45817] [45819] [45926] 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] 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] 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] 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] 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] 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] 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]
    Revision Date: 05/05/2020, 02:36:00 AM

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Foster City, CA: Gilead Sciences, Inc.; 2019 Dec.61360 - Levine GN, Bates ER, Bittl JA, et al. 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease. J Am Coll Cardiol 2016;68(10):1082-1115.61487 - Dentali F, Douketis JD, Lim W, et al. Combined aspirin-oral anticoagulant therapy compared with oral anticoagulation therapy alone among patients at risk for cardiovascular disease. Arch Intern Med 2007;167:117-124.61488 - Hansen ML, Sorensen R, Clausen MT, et al. Risk of bleeding with single, dual, or triple therapy with warfarin, aspirin, and clopidogrel in patients with atrial fibrillation. Arch Intern Med 2010;170:1433-41.61489 - Andreotti F, Testa L, Biondi-Zoccai G, et al. Aspirin plus warfarin compared to aspirin alone after acute coronary syndromes: an updated and comprehensive meta-analysis of 25, 307 patients. Eur Heart J 2006;27:519-26.61490 - Zhang P, Li J, Wu C, et al. Efficacy and safety of aspirin combined with warfarin after acute coronary syndrome: a meta-analysis Herz 2016 Oct 26 [Epub ahead of print]62037 - Bevyxxa (betrixaban) capsules package insert. South San Francisco, Ca: Portola Pharmaceuticals, Inc.; 2019 Jul.62723 - Macrilen (macimorelin) package insert. Frankfurt am Main, Germany: Aeterna Zentaris GmbH; 2018 Jan.63043 - Tattelman E. Health effects of garlic. Am Fam Physician. 2005;72:103-106. Review.63624 - Tegsedi (inotersen) injection package insert. Boston, MA: Akcea Therapeutics, Inc.; 2020 Jul.

    Monitoring Parameters

    • LFTs
    • serum creatinine/BUN
    • serum salicylate concentrations
    • stool guaiac

    US Drug Names

    • 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
    • DURLAZA
    • Easprin
    • Ecotrin
    • Genacote
    • Halfprin
    • MiniPrin
    • St. Joseph Adult Low Strength
    • St. Joseph Aspirin
    • Zero Order Release Aspirin
    • ZORprin

    Global Drug names

    Argentina

    • Adiro - (Bayer)
    • Alikal - (GSK)
    • Alka-Seltzer Doble Accion - (Bayer Consumer)
    • Aspimed - (Cassara)
    • Aspirina - (Bayer Consumer)
    • Aspirinetas - (Bayer Consumer)
    • Ball - (Argenfarma)
    • Bayaspirina - (Bayer Consumer)
    • Bayaspirina C - (Bayer Consumer)
    • Bio Grip C - (Sanofi-Aventis)
    • Blastop Prevent - (TRB)
    • Bufferin - (BMS)
    • Cardiax - (Sidus)
    • Cardio Vent3 - (Vent-3)
    • Cardioaspirina - (Bayer)
    • Desenfriolito - (Schering-Plough)
    • Dristan Analgesico - (Wyeth-Whitehall)
    • Ecotrin - (Schering-Plough)
    • Geniol AP - (GSK)
    • Geniol Prevencion - (GSK)
    • Geniol SC sin Cafeina - (GSK)
    • Geniolito - (GSK)
    • Isaspirina - (ISA)
    • Lacefal - (Lacefa)
    • Lafeaspirina - (Lafedar)
    • Mudagrip - (Lafedar)
    • Nefazan Compuesto - (Phoenix)
    • Nuevapina - (Fabop)
    • Nulagrip C - (Medical)
    • Pirinace - (Sidus)
    • Thrombo ASS - (Lafedar)
    • Trastocir Duo - (Ivax)
    • Tromasin con Aspirina - (Parke, Davis)
    • Vipirina Ginsex Corazon - (Benitol)

    Australia

    • Alka-Seltzer - (Bayer Consumer)
    • Aspro - (Bayer Consumer)
    • Aspro Protect - (Bayer)
    • Astrix - (Mayne)
    • Bex - (Roche Consumer)
    • Bufferin - (Bristol-Myers)
    • Cardiprin - (Reckitt Benckiser)
    • Cartia - (Aspen)
    • Codox - (Boots Healthcare)
    • Disprin - (Reckitt Benckiser)
    • Disprin Direct - (Reckitt Benckiser)
    • Doloxene Co - (Lilly)
    • Ecotrin - (Link)
    • Morphalgin - (Fawns & McAllan)
    • Orthoxicol - (Upjohn)
    • Percodan - (Boots)
    • Solprin - (Reckitt Benckiser)
    • Solvin - (Reckitt & Colman)
    • Spren - (Arrow)
    • SRA - (Boots)
    • Vincent's Powders - (Roche Consumer)
    • Winsprin - (SmithKline Beecham Consumer)

    Austria

    • Acekapton - (Strallhofer)
    • Acimetten - (Pharmonta)
    • Adolorin ASS/Vit C - (Kwizda)
    • Adoquick Vit C - (Kwizda)
    • Adovit C - (Kwizda)
    • Algobene - (Ratiopharm)
    • Algofina - (Sanamed)
    • Alka-Seltzer - (Bayer)
    • Ascorbisal - (GL Pharma)
    • Aspiricor - (Bayer)
    • Aspirin + C - (Bayer)
    • Aspirin Complex - (Bayer)
    • Aspirin Protect - (Bayer)
    • Aspro - (Klosterfrau)
    • Aspro mit Vitamin C - (Klosterfrau)
    • ASS - (Genericon)
    • ASS + C - (1A)
    • ASS plus Vit C - (1A)
    • ASSbene - (Ratiopharm)
    • Axanum - (AstraZeneca)
    • Colfarit - (Bayer)
    • CorProtect - (Ratiopharm)
    • Dolenso - (Kwizda)
    • Dolocod - (Astellas)
    • Dolomo Nacht - (Klinge)
    • Dolopharm - (Interpharm)
    • Duaneo mit Codein - (Klosterfrau)
    • Duokapton - (Strallhofer)
    • Grippinon - (Nycomed)
    • Herz ASS - (GL Pharma)
    • Herzschutz ASS - (Ratiopharm)
    • RheumaASS - (Ratiopharm)
    • Rilfit - (Apomedica)
    • Salimont - (Pharmonta)
    • Thomapyrin mit Vitamin C - (Boehringer Ingelheim)
    • Thrombo ASS - (GL Pharma)
    • Thrombostad - (Stada)
    • Togal - (Sanova)
    • Togal Mono - (Sanova)
    • Veganin - (Parke, Davis)

    Belgium

    • Acenterine - (Nycomed)
    • Afebryl - (SMB)
    • Algo-Nevriton - (Rhone-Poulenc Rorer)
    • Alka-Seltzer - (Bayer)
    • Asa - (Eurogenerics)
    • Asaflow - (Takeda)
    • Asamed - (Takeda)
    • Asarid - (Boehringer Ingelheim)
    • Aspaxa - (AstraZeneca)
    • Aspirine - (Bayer)
    • Aspirine C - (Bayer)
    • Aspro - (Bayer)
    • Aspro + C - (Roche)
    • Assur - (Delagrange)
    • Cardioaspirine - (Bayer)
    • Cardiphar - (Teva)
    • Catalgix - (Rhone-Poulenc Rorer)
    • Catalgix C - (Rhone-Poulenc Rorer)
    • Chymalgyl - (Rhone-Poulenc Rorer)
    • Coldrex - (Sterling Health)
    • Dispril - (Reckitt Benckiser)
    • Dolean - (3M)
    • Dolviran - (Bayer)
    • Efferbalgine - (Pharmethic)
    • Gripalgine - (Pharmethic)
    • Neomeritine - (Janssen-Cilag)
    • Nogrimine - (Eurogenerics)
    • Perdolan Compositum - (Janssen-Cilag)
    • Rhodine - (Rhone-Poulenc Rorer)
    • Rhonal - (Rhone-Poulenc Rorer)
    • Sedergine - (BMS)
    • Sedergine C - (BMS)
    • Therasa - (Pharmachemie)
    • Troc - (Melisana)
    • Veganine - (Warner-Lambert Consumer)

    Brazil

    • AAS - (Sanofi-Aventis)
    • Aasedatil - (Vitapan)
    • Aceticil - (Cazi)
    • Acetin - (Millet Roux)
    • Alidor - (Aventis)
    • Alka-Seltzer - (Bayer)
    • Analgesin - (Teuto)
    • Antifebrin - (Royton)
    • Ascedor - (Globo)
    • Asetisin - (Pharlab)
    • As-Med - (Medquimica)
    • Aspi-C - (Eurofarma)
    • Aspirina - (Bayer)
    • Aspirina C - (Bayer)
    • Aspisin - (Farmasa)
    • Aspylin - (QIF)
    • Atagripe - (Windson)
    • Atroveran Composto - (Cosmed)
    • Besaprin - (Sanofi Winthrop)
    • Bufferin - (Novartis)
    • Caas - (EMS)
    • Cardio AAS - (EMS)
    • Cefunk - (Apsen)
    • Cimaas - (Cimed)
    • Dermafree - (Delta)
    • Doloxene-A - (ABL)
    • Doraine - (Labortecne)
    • Ecasil - (Avert)
    • Endosalil - (Elofar)
    • Engov - (Cosmed)
    • Enjoy - (HB)
    • Griptol - (Brasmedica)
    • Hipotermal - (Sanval)
    • Melhoral Infantil - (Cosmed)
    • Melhoral Vit C - (Cosmed)
    • Navasprin - (Ache)
    • Orosprevent - (Bayer)
    • Posdrink - (Catarinense)
    • Prevencor - (Medley)
    • Ronal - (Aventis)
    • Salicetil - (Brasterapica)
    • Salicil - (Ducto)
    • Salicin - (Greenpharma)
    • Salipirin - (Geolab)
    • Salisvit C - (Cifarma)
    • Salitil - (Cifarma)
    • Sedalive - (Vitamedic)
    • Sifaas - (Sinterapico)
    • Somalgin - (Sigma)
    • Sonrisal - (GSK)
    • Superhist - (Supera)
    • Vasclin - (Libbs)

    Canada

    • 217 - (Frosst)
    • 217 Strong - (Frosst)
    • 222 - (McNeil Consumer)
    • 282 - (Pendopharm)
    • 282 MEP - (Pendopharm)
    • 292 - (Pendopharm)
    • 293 - (Frosst)
    • AC & C - (Pharmascience)
    • Alka-Seltzer - (Bayer Consumer)
    • Anacin with Codeine - (Whitehall-Robins)
    • Ancasal - (Sandoz)
    • APF - (Whitehall)
    • Apo-Asa - (Apotex)
    • Arco Pain - (Romilo)
    • Arthrisin - (Sandoz)
    • Artria - (Sandoz)
    • ASA - (Apotex)
    • ASA with codeine - (Stanley)
    • Asadol - (Pendopharm)
    • Asadrine - (Sabex)
    • Asaphen - (Pharmascience)
    • Asatab - (Odan)
    • Aspergum - (Heritage)
    • Aspirin Stomach Guard - (Bayer Consumer)
    • Bufferin - (Novartis Consumer)
    • C2 with Codeine - (Wampole)
    • Coricidin Non-Drowsy - (Schering)
    • Coryphen - (Rougier)
    • Darvon-N with ASA - (Lilly)
    • Dristan Formula P - (Whitehall-Robins)
    • Ecotrin - (SmithKline Beecham Consumer)
    • Entrophen - (Pendopharm)
    • Equate Daily Low-Dose - (Pharmascience)
    • Euro-ASA - (Euro-Pharm)
    • Headache Tablets - (Romilo)
    • Herbopyrine - (Herbes Universelles)
    • Life Brand Daily Low Dose ASA - (Pharmascience)
    • Lowprin - (Euro-Pharm)
    • Methoxisal-C - (Teva)
    • Novasen - (Novopharm)
    • Novo AC and C - (Novopharm)
    • Phenaphen with Codeine - (Wyeth-Ayerst)
    • PMS-ASA - (Pharmascience)
    • Pro-AAS - (Pro Doc)
    • Relief ASA - (Pendopharm)
    • Rivasa - (Riva)
    • Robaxisal-C - (Pfizer Consumer)
    • Sal - (Beecham)
    • Spasmhalt-ASA - (Pendopharm)
    • Supasa - (Nordic)
    • Tri-Buffered ASA - (Zee)

    Chile

    • Aspirina - (Bayer)
    • Aspirina C - (Bayer)
    • Cardioaspirina - (Bayer)
    • Corvasol - (Medipharm)
    • Disgren - (Pasteur)
    • Ecotrin - (GSK)
    • Fluicor - (Maver)
    • Hassapirin - (Mintlab)
    • Thrombo AS - (Merck)
    • Yasta - (Bayer)

    China

    • An Ni Tuo - (Zheng An)
    • Bamyl - (AstraZeneca)
    • Bayaspirin - (Bayer Schering)
    • Bo Ji - (Yung Shin)
    • Jie Ning - (Xinhua)
    • Niu Ke Te - (Wanze)
    • Sai Ning - (Gelalei)
    • Shi Tai Le - (Jutai)
    • Si Er Li - (Gui Long)
    • Tai Lin - (Taiji)
    • Xie Mei Da - (Beijing Union)
    • Xin Dong - (Meng Xin)
    • Yixinxue - (Lisheng)

    Czech Republic

    • Acygal - (Galmed)
    • Acylpyrin - (Herbacos)
    • Acylpyrin + C - (Herbacos)
    • Algirin - (Max Pharma)
    • Alka-Seltzer - (Bayer)
    • Alnagon - (Zentiva)
    • Anopyrin - (Zentiva)
    • Apo-Asa - (Apotex)
    • Asateva - (Teva)
    • Aspirin C - (Bayer)
    • Aspirin Complex - (Bayer)
    • Aspirin Protect - (Bayer)
    • Aspro - (Roche Nicholas)
    • Aspro C - (Roche Nicholas)
    • Axanum - (AstraZeneca)
    • Cardioral - (IBSA)
    • Dynalgic - (Bride)
    • Godasal - (ProMed)
    • Manoass - (GL Pharma)
    • Oltrola - (Pfizer)
    • Ring N - (Mack)
    • Stacyl - (Stada)
    • Tomapyrin C - (Boehringer Ingelheim)
    • Upsarin - (UPSA)
    • Upsarin C - (BMS)
    • Vasopirin - (PharmaSwiss)

    Denmark

    • Acetard - (Nycomed)
    • Albyl - (Leo)
    • Carnyl - (Nycomed)
    • Hjercatyl - (Orifarm)
    • Hjerdyl - (Sandoz)
    • Hjertealbyl - (Actavis)
    • Hjertemagnyl - (Takeda)
    • Hjertemin - (Meda)
    • Idotyl - (Ferrosan)
    • Iskaemyl - (Astra)
    • Magnyl - (Takeda)

    Finland

    • Alka-Seltzer - (Bayer)
    • ASA - (Ratiopharm)
    • Aspirin C - (Bayer)
    • Aspirin Cardio - (Bayer)
    • Aspirin Zipp - (Bayer)
    • Bartal - (KRKA)
    • Coldrex - (GSK Consumer)
    • Disperin - (Orion)
    • Finrexin - (Takeda)
    • Paraflex comp - (AstraZeneca)
    • Posinova - (Orion)
    • Posivil - (Orion)
    • Primaspan - (Orion)
    • Seloken ZOC/ASA - (AstraZeneca)
    • Thrombo ASA - (GL Pharma)

    France

    • Actispirine - (Millot-Solac)
    • Afebryl - (SMB)
    • Algimax - (Martinet)
    • Algispir - (Soekami)
    • Algocratine - (Soekami)
    • Algo-Névriton - (Sciencex)
    • Alka-Seltzer - (Bayer Consumer)
    • Antigrippine à l'Aspirine - (Omega)
    • Antigrippine Midy à la Vitamine C - (Sterling Midy)
    • Ascriptine - (Rorer)
    • Aspirange - (Schwarz)
    • Aspirine - (Bayer)
    • Aspirine pH8 - (Meda)
    • Aspirine vitamine C - (UPSA)
    • Aspirisucre - (Arkomedika)
    • Aspro - (Bayer Consumer)
    • Aspro vitamine C - (Bayer Consumer)
    • Assur - (Delagrange)
    • Broncho-Tulisan Eucalyptol - (Logeais)
    • Catalgine - (Aerocid)
    • Catalgine Vitamine C - (Medipha)
    • Chymalgyl - (Martinet)
    • Chymogrip - (Martinet)
    • Claragine - (Bayer)
    • Detoxalgine - (Organon)
    • Diaflexol - (Paillusseau)
    • DuoPlavin - (BMS)
    • Eucalyptine Aspirine Quinine - (Janssen)
    • Eucalyptospirine - (Doms-Adrian)
    • Eucalyptospirine bébé - (Doms-Adrian)
    • Garaspirine - (IPRAD)
    • Isofebril Vitamine C - (Ratiopharm)
    • Juvepirine - (Asta Medica)
    • Juvepirine à la Promethazine - (Sarget)
    • Nevral Vitamine B1-B6 - (Biodica)
    • Novacétol - (Pharmastra)
    • Occigrip - (Soekami)
    • Polypirine - (Lehning)
    • Prenoxan au phénobarbital - (Schering-Plough)
    • Protéosulfan - (Gallier)
    • Resitune - (Pfizer)
    • Rhonal - (Theraplix)
    • Sargepirine - (Asta Medica)
    • Sédaspir - (Bride)
    • Solucetyl - (Arrow)
    • Trancogesic - (Sterling Winthrop)
    • Vegadeine - (Warner-Lambert)

    Germany

    • Acesal - (Kade)
    • Acesal Calcium - (OPW)
    • Acetylin - (BMS)
    • Alka-Seltzer - (Bayer)
    • Apernyl - (Bayer)
    • Aspalox - (Rorer)
    • Aspirin Complex - (Bayer)
    • Aspirin plus C - (Bayer)
    • Aspro - (Bayer)
    • ASS - (Worwag)
    • ASS + C - (Ratiopharm)
    • ASS OPT - (Optimed)
    • ASS-Kombi - (Ratiopharm)
    • Axanum - (AstraZeneca)
    • Bersicaran N - (Janssen-Cilag)
    • Bonakiddi - (Weimer)
    • Bonfal - (Worwag)
    • Boxazin plus C - (Boehringer Ingelheim)
    • Cebion Erkältungs - (Merck)
    • Chinaspin - (Bayer)
    • Colfarit - (Bayer)
    • Contradol - (Merz)
    • Contraneural N - (Pfleger)
    • Contrheuma - (Spitzner)
    • Deskoval N - (Sanol)
    • DoloVisano - (Kade)
    • DoloVisano Suppositorien - (Kade)
    • Dolviran - (Bayer)
    • Fensum N - (Merckle)
    • Fibrex Hot Drink - (Berlin-Chemie)
    • Fibrex Tabletten - (Berlin-Chemie)
    • Fonal N - (Merckle)
    • Gelonida NA - (Godecke)
    • Gepan - (Pohl)
    • Gepan CN - (Pohl)
    • Godamed - (Pfleger)
    • Grippal + C - (Ratiopharm)
    • Hermes ASS - (Hermes)
    • HerzASS - (Ratiopharm)
    • Ilvico - (Merck)
    • Klar - (Hermes)
    • Malinert - (Strathmann)
    • Mandros - (Henk)
    • Mega-Dolor - (Lorenz)
    • Melabon - (Oramon)
    • Melabon plus C - (Rentschler)
    • Mentopin Vitamin C + ASS - (Hermes)
    • Micristin - (OPW)
    • Miniasal - (Nycomed)
    • Miophen - (Robugen)
    • Monacant - (Rorer)
    • monobeltin - (Schwarz)
    • Neo-Gepan C - (Pohl)
    • Neuralgin ASS - (Pfleger)
    • Praecimed N - (Molimin)
    • Protectin-OPT - (Truw)
    • ratioGrippal + C - (Ratiopharm)
    • Ring N - (Pfizer Consumer)
    • Romigal - (Romigal)
    • Sanocapt - (Sanol)
    • Santasal N - (Merckle)
    • Solpyron - (Beecham)
    • Spalt - (Much)
    • Spalt Schmerztabletten - (Whitehall-Much)
    • Temagin ASS - (Beiersdorf)
    • Tempil N - (Temmler)
    • Thomapyrin akut - (Boehringer Ingelheim)
    • Thomapyrin Brausetabletten - (Boehringer Ingelheim)
    • Thomapyrin C - (Boehringer Ingelheim)
    • Togal ASS - (Togal)
    • Togal Classic - (Togal)
    • Togal Kopfschmerzbrause + Vitamin C - (Togal)
    • Trineral - (Bayer)
    • Veralgit - (Krewel)

    Greece

    • Alka-Seltzer N - (Bayer)
    • Anadin Extra - (Wyeth)
    • Apyr - (Gerolymatos)
    • Ascriptin - (Sanofi-Aventis)
    • Aspirin C - (Bayer)
    • Bufferin - (GSK)
    • Cardioral - (IBSA)
    • Cespire - (Neiadas (Νειαδας))
    • Junior Algon - (Elvipe)
    • Measurin - (GSK)
    • Neospir - (Elvipe)
    • Salospir - (Unipharma)
    • Salospir C-500 - (Unipharma)
    • Upsalgin-N - (BMS)
    • Vasopirin - (PharmaSwiss)

    Hong Kong

    • Aceprin - (Hovid)
    • Alka-Seltzer - (Bayer)
    • Ascot - (Natural Health)
    • Ascriptin - (Rhone-Poulenc Rorer)
    • ASP - (CNW)
    • Aspi-Cor - (Julius Chen)
    • Aspilets - (United American)
    • Aspro - (Roche)
    • Astrix - (Hospira)
    • Bokey - (Yung Shin)
    • Cardiprin - (Reckitt Benckiser)
    • Cartia - (GSK)
    • Disprin - (Reckitt Benckiser)
    • Ecotrin - (Goldshield)
    • Fusen - (Hitpharm)
    • Glyprin - (CCM)
    • LAsprin - (Cipla)
    • Propirin - (Christo)
    • Qualitea - (Quality)
    • Repisprin - (Leamyk)
    • Uni-Acetil - (Universal)
    • Veganin - (Warner-Lambert)

    Hungary

    • AcizalEP - (Extractum)
    • Alka-Seltzer - (Bayer)
    • ASA - (PharmaSwiss)
    • Asactal - (Actavis)
    • Asatrin - (Teva)
    • Aspaxa - (AstraZeneca)
    • Aspirin plus C - (Bayer)
    • Aspirin Protect - (Bayer)
    • Aspro C - (Bayer)
    • ASS + C - (BMS)
    • Astrix - (Teva)
    • Colfarit - (Bayer)
    • Dynalgic - (Bride)
    • Istopirin - (Biogal-Teva)
    • Kalmopyrin - (Gedeon Richter)
    • Upsarin C - (BMS)

    India

    • Alpyrin - (Lincoln)
    • ASA - (Zydus)
    • Ascad - (Micro)
    • Asicom - (Comed)
    • Asicom Plus - (Comed)
    • Aspent - (Ranbaxy)
    • Aspicot - (Concept)
    • Aspin - (Cipla)
    • Aspisol - (Shreya)
    • Aspitrate - (Aristo)
    • Caplor-AS - (Ind-Swift)
    • Cenoza A - (Aamorb)
    • Ceruvin-A - (Ranbaxy)
    • C-Grel Plus - (Triton)
    • Cidogrel-A - (Karnataka)
    • Clasprin - (Biocon)
    • Clavix-AS - (Intas)
    • Clodrel Forte - (Unichem)
    • Clodrel Plus - (Unichem)
    • Clofre AS - (East West)
    • Clopact A - (Ipca)
    • Clopid-AS - (Hetero)
    • Clopirad-A - (Indoco)
    • Clopisa - (Skymax)
    • Clopitab-A - (Lupin)
    • Clopivas AP - (Cipla)
    • Clopizide-A - (Essweil)
    • Clopod-A - (Biochem)
    • Cloprez-A - (RPG)
    • Clouds - (Bestochem)
    • Colsprin - (Reckitt Benckiser)
    • Complatt - (Grandix)
    • Cotasprin - (Natco)
    • CV-Sprin - (Cadila)
    • Delisprin - (Aristo)
    • Deplatt-A - (Torrent)
    • Disprin - (Reckitt Benckiser)
    • Dospin - (Ajanta)
    • Ecosprin - (USV)
    • E-Prin - (Elder)
    • Equagesic - (Wyeth)
    • Gra - (East West)
    • Insprin-ER - (Avinash)
    • Kabitrol - (Kamakshi)
    • LDA - (AstraZeneca)
    • Linzi - (Neon)
    • Loprin - (Unichem)
    • Manospirin - (Orchid)
    • Mazoral - (Cosme)
    • Mono-A - (Troikaa)
    • Myogrel-AP - (Macleods)
    • Noklot Plus - (Zydus)
    • Nugrel Plus - (Micro)
    • Nusprin - (Emcure)
    • Od-Prin - (Ordain)
    • Optaz - (Shreya)
    • Otaspirin - (Natco)
    • Solosprin - (Cadila)

    Indonesia

    • Aptor - (Nicholas)
    • Ascardia - (Pharos)
    • Aspilets - (Darya-Varia)
    • Aspitrom - (Interbat)
    • Astika - (Ikapharmindo)
    • Bodrexin - (Bode)
    • Cardio Aspirin - (Bayer)
    • Contrexyn - (Supra Ferbindo)
    • Farmasal - (Fahrenheit)
    • Frosit - (Promed)
    • Glocar - (Global Health)
    • Inzana - (Konimex)
    • Miniaspi - (Mersifarma)
    • Minigrip - (Kalbe)
    • Naspro - (Nicholas)
    • Norspirinal - (Novell)
    • Procardin - (Medikon)
    • Proxime - (Sanbe)
    • Restor - (Sandoz)
    • Rheumapill - (Supra Ferbindo)
    • Thrombo Aspilets - (Darya-Varia)

    Ireland

    • Alka-Seltzer - (Bayer)
    • Anadin Analgesic - (Pfizer)
    • Asacard - (Flamel)
    • Ascriptin - (Rhone-Poulenc Rorer)
    • Aspro - (Bayer)
    • Caprin - (Pinewood)
    • Claradin - (Nicholas)
    • Clonteric - (Clonmel)
    • Disprin - (Reckitt Benckiser)
    • Disprin Direct - (Reckitt Benckiser)
    • Disprin Extra - (Reckitts)
    • Disprin Extra Strength - (Reckitt Benckiser)
    • Lowasa - (Mayne)
    • Nuasa - (Uniphar)
    • Nuprin - (Actavis)
    • Nu-Seals - (Alliance)
    • Resprin - (Rice Steele)
    • Veganin - (Pfizer Consumer)

    Israel

    • Acetosal - (Rekah)
    • Alka-Seltzer - (Bayer)
    • Ascriptin - (Aventis)
    • Aspirin C - (Bayer)
    • Aspirin Cardio - (Bayer)
    • Buffered Pirin - (Gramse)
    • Cardiopirin - (Dexcel)
    • Cartia - (Perrigo)
    • Ecoprin - (Sam-On)
    • Godamed - (Pfleger)
    • Gramse Pirin - (Gramse)
    • Micropirin - (Dexcel)
    • Rhonal - (Rhone-Poulenc Rorer)
    • Rogaan - (Teva)
    • Rokal - (Taro)
    • Rokal Plus - (Taro)
    • Tevapirin - (Teva)

    Italy

    • Acesal - (Geymonat)
    • Algopirina - (Pielle)
    • Alka-Seltzer - (Bayer)
    • Alsogil - (Also)
    • Antinevralgico Penegal - (FAMA)
    • Apernyl - (Bayer)
    • Asapiuci - (Mylan)
    • ASA-ratio - (Ratiopharm)
    • Ascriptin - (Sanofi-Aventis)
    • Aspergum - (Farmades)
    • Aspiglicina - (Antonetto)
    • Aspirina - (Bayer)
    • Aspirina 03 - (Bayer)
    • Aspirina 05 - (Bayer)
    • Aspirina C - (Bayer)
    • Aspirinetta - (Bayer)
    • Aspirinetta C - (Bayer)
    • Aspro - (Bayer)
    • Aspro C - (Bayer)
    • Bufferin - (BMS)
    • Cardioaspirin - (Bayer)
    • Carin - (Federfarma)
    • Carin 300 all'Arancia - (Corvi)
    • Carin all'Arancia - (Corvi)
    • Cebiopirina - (Bracco)
    • Cemirit - (Bayer)
    • Contralgen - (Pietrasanta)
    • Doloflex - (Altana)
    • Domupirina - (Medici Domus)
    • Dreimal - (Rhone-Poulenc)
    • Endydol - (Guidotti)
    • Femidol - (Lepetit)
    • Istantal - (Farmakopea)
    • Kilios - (Pharmacia)
    • Kynosina - (IRBI)
    • Neo Nisidina C-Fher - (Boehringer Ingelheim)
    • Neo Uniplus - (Angelini)
    • Neo Uniplus C - (Angelini)
    • Rectosalyl - (Bouty)
    • Salicina - (Ratiopharm)
    • Upsalgina - (Upsamedica)
    • Vivin C - (Menarini)

    Japan

    • Asphanate - (Nakakita)
    • Bassamin - (Teva)
    • Bayaspirin - (Bayer)
    • Bufferin - (Lion)
    • Famoter - (Tsuruhara)
    • Iskia - (Shiono)
    • Nitogis - (Shiono)
    • Takelda - (Takeda)
    • Zenaspirin - (Zensei)

    Malaysia

    • Aceprin - (Hovid)
    • Alka-Seltzer - (Bayer)
    • Asaphen - (Pharmascience)
    • Aspirin Cardio - (Bayer)
    • Bufferin Low Dose - (BMS)
    • Cardiprin - (Reckitt Benckiser)
    • Casprin - (YSP)
    • Disprin - (Reckitt Benckiser)
    • Dusil - (Alpharma)
    • Glyprin - (CCM)

    Mexico

    • Acetil-A - (Precimex)
    • Acetin - (IQFA)
    • Aciben - (Mavi)
    • Acitab - (Mavi)
    • Adiro - (Bayer)
    • Agin - (Nordin)
    • Antacsal - (Alpharma)
    • ASA - (Liomont)
    • Asawin - (Sanofi Winthrop)
    • Ascriptin - (Sanofi-Aventis)
    • Aspirina Protect - (Bayer)
    • Axal - (Randall)
    • Axanum - (AstraZeneca)
    • Barigesic - (Degorts)
    • Captral ASA - (Silanes)
    • Cardioprotect - (Janssen-Cilag)
    • Disprina - (Sanofi-Aventis)
    • Dolmex - (Ofimex)
    • Doloquim - (Quimica y Farmacia)
    • Ecotrin - (GSK)
    • Labysal - (Arlex)
    • Midolen - (Degorts)
    • Rhonal - (Rhone-Poulenc Rorer)
    • Vastecel - (Medix)
    • Zolidime - (Collins)

    Netherlands

    • Alka-Seltzer - (Bayer)
    • Asacard - (Flamel)
    • Aspirine C - (Bayer)
    • Aspirine Protect - (Bayer)
    • Aspro - (Bayer)
    • Axanum - (AstraZeneca)
    • Bisolgripin - (Boehringer Ingelheim)
    • Cardioral - (IBSA)
    • Chefarine - (Chefaro)
    • Coldrex - (Sterling)
    • Coldrex C - (SmithKline Beecham Consumer)
    • Darosal - (Heca)
    • Dolviran N - (Bayer)
    • DuoCover - (Sanofi-Aventis)
    • DuoPlavin - (Sanofi-Aventis)
    • Rhonal - (Nattermann)
    • Sinaspril - (Nicholas)
    • Togal - (Togal)

    New Zealand

    • Alka-Seltzer - (Bayer)
    • Aspec - (PSM)
    • Aspro - (Bayer)
    • Cardiprin - (Reckitt Benckiser)
    • Cartia - (Healthcare Logistics)
    • Disprin - (Reckitt Benckiser)
    • Ecotrin - (Link)
    • Pharmacare Aspec - (PSM)
    • Pirophen - (Pfizer)
    • Solprin - (Reckitt Benckiser)
    • Spren - (Healthcare Logistics)

    Norway

    • Acetyratio - (Ratiopharm)
    • Albyl-E - (Takeda)
    • Axanum - (AstraZeneca)
    • Bamycor - (AstraZeneca)
    • Dispril - (Reckitt Benckiser)
    • Globentyl - (Nycomed)
    • Globoid - (Takeda)
    • Magnyl-E - (Nycomed)
    • Novid - (Nycomed)

    Philippines

    • Aceprin - (Hovid)
    • Alka-Seltzer - (Bayer)
    • Anthrom - (Yung Shin)
    • Asaprim - (Primera)
    • Aspec - (Pharmaspec)
    • Aspen - (Lloyd)
    • Aspilets - (Imperial)
    • Aspitor - (Concept)
    • Asthromed - (Medhaus)
    • Astrix - (Mayne)
    • Bayprin - (Bayer)
    • Besprin - (Lloyd)
    • Cor-30 - (Pascual)
    • Cortal - (Pharma-Rex)
    • Daspirin - (Yung Shin)
    • Enteroprin - (Metro)
    • Tromcor - (Integrated Pharmaceutical)

    Poland

    • Abrea - (KRKA)
    • Acard - (Polfa Warszawa)
    • Acesan - (Sun-Farm)
    • Acoren - (Wooller)
    • Acticard - (Medicofarma)
    • Alepton - (GL Pharma)
    • Alka-Prim - (Polpharma)
    • Alka-Seltzer - (Bayer)
    • Antygrypin - (Natur Produkt)
    • ASA - (Curtis)
    • Asaltec - (Polfa Warszawa)
    • Asapirine - (Wooller)
    • Ascalcin - (Bio-Profil)
    • Ascalcin Plus - (Bio-Profil)
    • Aspicont - (Medicofarma)
    • Aspifox - (Actavis)
    • Aspimag - (Espefa)
    • Aspirin C - (Bayer)
    • Aspirin Complex - (Bayer)
    • Aspirin Protect - (Bayer)
    • Asprocard - (Arrow)
    • Asprocol - (PharmaSwiss)
    • Bestpirin - (Teva)
    • Bonacard - (Eubioco)
    • Bonapiryna - (Eubioco)
    • Calcipiryna - (Polpharma)
    • Cardioas - (Esculap)
    • Cardiofil - (Filofarm)
    • Cardiopirin - (Colfarm)
    • DuoCover - (BMS)
    • DuoPlavin - (BMS)
    • Encopirin - (Medicofarma)
    • Etopiryna Max - (Polpharma)
    • Eubiocard - (Eubioco)
    • Eupirin - (Eubioco)
    • Galocard - (Galenus)
    • Gripblocker - (Hasco-Lek)
    • Grypostop Control - (Medicofarma)
    • Hascopiryn Cardio - (Hasco-Lek)
    • Lecardi - (Espefa)
    • Maxipirin - (Max Pharma)
    • Neuroas - (Esculap)
    • Nipas - (Galena)
    • Polocard - (Polpharma)
    • Polopiryna - (Polpharma)
    • Polopiryna C - (Polpharma)
    • Polopiryna C Plus - (Polpharma)
    • Polopiryna S - (Polpharma)
    • Proficar - (Adamed)
    • Pyramidon Fast - (Adamed)
    • Salpirin - (Sun-Farm)
    • Thromboass - (GL Pharma)
    • Upsarin - (BMS)
    • Upsarin C - (BMS)
    • Vasopirin - (ICN)
    • V-piryna - (Natur Produkt)

    Portugal

    • AAS - (Omega)
    • Actipiril - (Confar)
    • Afebryl - (Azevedos)
    • Alka-Seltzer - (Bayer)
    • Asacard - (Flamel)
    • ASP - (Medinfar)
    • Aspirina - (Bayer)
    • Aspirina C - (Bayer)
    • Aspro - (Roche)
    • Cartia - (Lusofarmaco)
    • Casfen - (Menarini)
    • Codiasp - (Codilab)
    • Cofena - (Sanobia)
    • Cordilon - (IBSA)
    • Cortigripe - (Generis)
    • Dolviran - (Bayer)
    • DuoCover - (Sanofi-Aventis)
    • DuoPlavin - (BMS)
    • Gripetral - (Atral)
    • Gripidor - (Gestafarma)
    • Higigripe - (CPH)
    • Melhoral Infantil - (GSK Consumer)
    • Migraspirina - (Bayer)
    • Salycilina - (Upsifarma)
    • Sedergine - (BMS)
    • Toldex - (Bial)
    • Tromalyt - (Neo-Farmaceutica)
    • Veganine - (Warner-Lambert Consumer)

    Russian Federation

    • Acecardol - (Sintez)
    • Alka-Prim - (Polpharma)
    • Alka-Seltzer - (Bayer Consumer)
    • Antigrippin-ANVI - (Antiviral)
    • Asa-Cardio - (Medisorb)
    • Aspikard - (Borisov)
    • Aspikor - (Vertex)
    • Aspinat - (Valenta)
    • Aspinat C - (Valenta)
    • Aspinat Cardio - (Valenta)
    • Aspirin C - (Bayer)
    • Aspirin Cardio - (Bayer)
    • CardiASK - (Kanonfarma)
    • Cardiomagnyl - (Takeda)
    • Cardiopyrin - (Roche)
    • Midol C - (Hemofarm)
    • Nextrim Fast - (Polpharma)
    • Taspir - (Tatkhimfarm)
    • Thrombo ASS - (Valeant)
    • Trombogard - (Adipharm)
    • Trombopol - (Polpharma)
    • Upsarin - (BMS)
    • Upsarin with Vitamin C - (BMS)
    • Zorex Utro - (Valenta)

    Singapore

    • Alka-Seltzer - (Bayer)
    • Aspirin Protect - (Bayer)
    • Aspro - (Bayer)
    • Astrix - (Faulding)
    • Bokey - (Yung Shin)
    • Bufferin - (BMS)
    • Cardiprin - (Reckitt Benckiser)
    • CoPlavix - (Sanofi-Aventis)
    • Disprin - (Reckitt Benckiser)
    • Dusil - (Alpharma)
    • Glyprin - (Upha)
    • Platet - (Nicholas)

    South Africa

    • Acetapon - (Pharmagen)
    • Analgen - (Aventis)
    • ASAtard - (Boehringer Ingelheim)
    • Aspro - (Roche)
    • Borstol Cold and Flu Powders with Vitamin C - (Group)
    • Coprin - (Smart)
    • Disprin - (Reckitt Benckiser)
    • Ecotrin - (Litha)
    • Excedrin - (Novartis Consumer)
    • Gertges Pain Powders - (Technikon)
    • KPP - (Novartis Consumer)
    • Med-Lemon Hot Medication with Vitamin C - (Group)
    • Med-Lemon Hot Medication-Lemon Menthol - (Group)
    • Myoprin - (iPharma)
    • Paincod - (Crown)
    • Soluspirin CV - (Resmed)
    • Specific Nerve Pain Remedy - (Group)
    • Tenston - (Adcock Ingram)
    • Veganin - (Aspen)

    Spain

    • AAS - (Sanofi-Aventis)
    • AB FE - (Camps)
    • Acyflox - (Arafarma)
    • Adiro - (Bayer)
    • Alegrina - (Madariaga)
    • Algho - (Rhone-Poulenc Rorer)
    • Asboi - (BOI)
    • Aspidolce - (Alonga)
    • Aspinfantil - (Diviser Aquilea)
    • Aspirina - (Bayer)
    • Aspirina C - (Bayer)
    • Aspro - (Roche Nicholas)
    • Bartal - (KRKA)
    • Biontop - (Merck)
    • Bioplak - (Ern)
    • Calmante Vitaminado Infant - (Perez Gimenez)
    • Calmante Vitaminado PG - (Perez Gimenez)
    • Calmante Vitaminado PG Efervescente - (Perez Gimenez)
    • Calmante Vitaminado Rinver - (Monik)
    • Calmantina - (Inexfa)
    • Casprium Retard - (Liade)
    • Codalgina Retard - (Faes)
    • Dolmen - (Ern)
    • Doloana - (Quimifar)
    • Dolosarto - (Biosarto)
    • Dolviran - (Kern)
    • Dulcipirina - (SmithKline Beecham)
    • Eucalyptospirine - (Pfizer Consumer)
    • Eucalyptospirine Lact - (Rovi)
    • Fiorinal Codeina - (Novartis)
    • Frialgina - (Prodes)
    • Helver Sal - (Bauxili)
    • Lafena - (Cinfa)
    • Mejoral - (SmithKline Beecham)
    • Okal - (Puerto Galiano)
    • Okaldol - (Puerto Galiano)
    • Orravina - (Diviser Aquilea)
    • Rhonal - (Sanofi-Aventis)
    • Salicilina - (Faes)
    • Saspryl - (Inibsa)
    • Sedergine - (Uriach Aquilea OTC)
    • Sedergine C - (Uriach Aquilea OTC)
    • Superaspidin - (Landerlan)
    • Tromalyt - (Rottapharm)
    • Upsalgina - (Upsamedica)
    • Veganin - (Warner-Lambert)
    • Vivin C - (Alter)
    • Yafin - (Normon)

    Sweden

    • Acetard - (Benzon)
    • Albyl minor - (Recip)
    • Alka-Seltzer - (Bayer)
    • Asaferm - (Merckle)
    • Asalite - (Kabi)
    • Bamycor - (Hassle)
    • Bamyl - (Meda)
    • Bamyl S - (Ellem)
    • Dispril - (Meda)
    • Doleron - (AstraZeneca)
    • Emotpin - (Meda)
    • Magnecyl - (Meda)
    • Paraflex comp - (AstraZeneca)
    • Reumyl - (Hassle)
    • Seloken ZOC/ASA - (Hassle)
    • Treo comp - (Meda)
    • Trombyl - (Pfizer)
    • Zocord/ASA - (MSD)

    Switzerland

    • Acide acetylsalicylique comp. "Radix" - (Streuli)
    • Alca-Direct - (Melisana)
    • Algo-Nevriton - (Rhone-Poulenc Rorer)
    • Alka-Seltzer - (Bayer)
    • ASA - (Streuli)
    • Ascosal - (Grossmann)
    • Asperivo - (Rivopharm)
    • Aspirine C - (Bayer)
    • Aspirine Cardio - (Bayer)
    • Aspirine Complex - (Bayer)
    • Aspirine S - (Bayer)
    • Aspro - (Bayer)
    • Aspro C - (Roche)
    • ASS - (Mepha)
    • ASS + C - (Sandoz)
    • ASS Cardio - (Spirig)
    • Axanum - (AstraZeneca)
    • Cardiax-ASS - (Drossapharm)
    • Cardioral - (IBSA)
    • Colfarit - (Bayer)
    • Contre-Douleurs C - (Wild)
    • Demoprin nouvelle formule - (Democal)
    • Dolean pH 8 - (3M)
    • Dolopirin - (Amavita)
    • Enterosarine - (Synthelabo)
    • Febradolor sans codeine - (Demopharm)
    • Fortalidon - (Sandoz)
    • Fribagyl - (Vifor)
    • Gelonida - (Warner-Lambert)
    • Instacyl - (Streuli)
    • Juridin - (Togal)
    • Radix - (Streuli)
    • Rhonal - (Rhone-Poulenc Rorer)
    • Silentan - (Lubapharm)
    • Silix - (Tentan)
    • Tagol - (Ars Vitae)
    • Thrombace Neo - (Drossapharm)
    • Tiatral 100 SR - (Novartis)
    • Togal ASS - (Ars Vitae)
    • Togal ASS + C - (Togal)
    • Treupel - (Asta Medica)
    • Treupel Grippe - (Meda)
    • Treupel sans codeine - (Asta Medica)
    • Treupel simplex - (Viatris)
    • Triplex - (Streuli)
    • Triplex sans codeine - (Streuli)
    • Upsalgin C - (Upsamedica)
    • Va-t'en - (Melisana)

    Thailand

    • Actorin - (Hua)
    • Alka-Seltzer - (Bayer Consumer)
    • Anassa - (TO-Chemicals)
    • Arpisine - (PP Lab)
    • ASA - (SSP)
    • Asatab - (TO-Chemicals)
    • Ascot - (Polipharm)
    • Aspaco - (Burapha)
    • Aspent - (Daiichi Sankyo)
    • Aspilets - (Great Eastern)
    • Aspipac - (Inpac)
    • Aspirine - (SSP)
    • Asrina - (Central)
    • B-Aspirin - (Osoth)
    • Buntaopoad-Bura - (Burapha)
    • Caparin - (Osotspa)
    • Cardiprin - (Reckitt Benckiser)
    • Comoprin - (British Dispensary)
    • Empirin - (Chew)
    • Entrarin - (Asian Pharm)
    • Pirin - (Patar)
    • Seferin - (General Drugs)
    • SP - (SSP)
    • V-AS - (Medicine Products)

    Turkey

    • Afebryl - (Galepharma)
    • Algo - (Lokman)
    • Algo Bebe - (Frik)
    • Alka-Seltzer - (Bayer)
    • Asabrin - (Biokem)
    • Asinpirine - (Ulagay)
    • Aspapirine - (ICE)
    • Aspimirin - (Er-Em)
    • Aspinal - (Munir)
    • Aspirin Complexoral - (Bayer)
    • Aspirin plus-C - (Bayer)
    • Ataspin - (Atabay)
    • Babyprin - (Pfizer)
    • Coraspin - (Bayer)
    • Dispril - (Reckitt Benckiser)
    • Dolviran - (Bayer)
    • Ecopirin - (Abdi)
    • Isaspin - (SSK)
    • Nötras - (Liba)
    • Opon - (Gripin)
    • Pharmaspirin - (Sodhan)
    • Sedergine Vit-C - (Abdi)

    Ukraine

    • Acard - (Polpharma)
    • Acecardin - (Phytopharm)
    • Acecor Cardio - (Microkhim)
    • Alka-Prim - (Polpharma)
    • Alka-Seltzer - (Bayer)
    • Asaphen - (Pharmascience)
    • Aspecard - (Stirol)
    • Aspenorm - (Pharmex)
    • Aspeter - (Stirol)
    • Aspicard Cardio - (Vertex)
    • Aspigrel - (Mili)
    • Aspirin C - (Bayer)
    • Aspirin Cardio - (Bayer)
    • Cardiomagnyl - (Takeda)
    • Cardiseve - (Farmak)
    • Citramon Forte - (Darnitsa)
    • Clopix Forte - (Cipla)
    • Combi-ASA - (Pharma Start)
    • Ecorin - (USV)
    • Godasal - (Pfleger)
    • Lowspirin - (Kusum)
    • Magnikor - (KVZ)
    • Polocard - (Polpharma)

    United Arab Emirates

    • Jusprin - (Julphar)

    United Kingdom

    • Alka - (Bayer Consumer)
    • Alka-Seltzer - (Bayer Consumer)
    • Alka-Seltzer XS - (Bayer Consumer)
    • Anadin Soluble - (Whitehall)
    • Angettes - (BMS)
    • Antoin - (Cox)
    • Askit - (Askit)
    • Aspav - (Alpharma)
    • Aspergum - (Plough)
    • Aspro - (Roche Consumer)
    • Banimax - (SmithKline Beecham)
    • Beechams Lemon Tablets - (SmithKline Beecham Consumer)
    • Caprin - (Wockhardt)
    • Claradin - (Nicholas)
    • Cojene - (Roche Consumer)
    • Danamep - (Ecogen)
    • Disprin - (Reckitt Benckiser)
    • Disprin CV - (Reckitt & Colman)
    • Disprin Direct - (Reckitt Benckiser)
    • Disprin Extra - (Reckitt Benckiser)
    • Enprin - (Galpharm)
    • Femigraine - (Roche Consumer)
    • Flamasacard - (Abbey)
    • Fynnon Calcium Aspirin - (Seton)
    • Gencardia - (Genus)
    • Hypon - (Calmic)
    • Imazin - (Napp)
    • Micropirin - (Ratiopharm)
    • Migravess - (Bayer Consumer)
    • Nu-Seals - (Alliance)
    • Paynocil - (Beecham Research)
    • Phensic Soluble - (SmithKline Beecham Consumer)
    • Platet - (Nicholas)
    • PostMI - (Focus)
    • Pure Health - (Lexon)
    • Resprin - (Martindale Pharmaceuticals)
    • Solprin - (Reckitt & Colman)

    Venezuela

    • Alka-Seltzer - (Bayer)
    • Asaprol - (Leti)
    • Ascriptin - (Vargas)
    • Aspicor - (SM)
    • Aspiretina - (Andromaco)
    • Azacard - (Oftalmi)
    • Cardipirina - (Zuoz)
    • Coraspirina - (Bayer)
    • Dolviran - (Bayer)