Aspirin (Monograph)

Brand names: Ascriptin, Aspergum, Bayer, Bufferin, Easprin, ... show all 11 brands
Drug class: Salicylates
- Antithrombotic Agents
- Platelet-aggregation Inhibitors

Aspirin (Systemic) is also contained as an ingredient in the following combinations:
Acetaminophen and Aspirin
Acetaminophen, Aspirin, and Caffeine
Oxycodone and Aspirin
Pentazocine Hydrochloride and Aspirin
Propoxyphene Hydrochloride, Aspirin, and Caffeine

Medically reviewed by Drugs.com on Sep 10, 2024. Written by ASHP.

Introduction

NSAIA; salicylate ester of acetic acid.^a

Uses for Aspirin

Pain

Symptomatic relief of mild to moderate pain.^a

Self-medication in children for the temporary relief of minor aches and pains and headache.⁸⁴¹

Self-medication in adolescents and adults for the temporary relief of minor aches and pains associated with headache, common cold, toothache, muscular aches, backache, arthritis, menstrual cramps,⁸³⁶ and sore throat.⁸³⁷ ⁸⁴⁰

Self-medication in fixed combination with acetaminophen and caffeine for the temporary relief of mild to moderate pain associated with migraine headache;⁷⁰¹ ⁷⁰² ⁷⁰³ also can be used for the treatment of severe migraine headache if previous attacks have responded to similar non-opiate analgesics or NSAIAs.⁷⁰¹ ⁷⁰² ⁷⁰³ ⁷⁷⁸

Fever

Self-medication for reduction of fever associated with colds, sore throats, and teething.⁸³⁷ ⁸⁴¹ (See Contraindications and see Pediatric Use under Cautions.)

Inflammatory Diseases

Symptomatic treatment of rheumatoid arthritis, juvenile rheumatoid arthritis, osteoarthritis, spondyloarthropathies, and systemic lupus erythematosus (SLE).⁹⁰⁶ ⁹³⁸ ⁹⁴³ ^a

Rheumatic Fever

Symptomatic treatment of rheumatic fever^{† [off-label]}.^a A drug of choice in patients with mild carditis (without cardiomegaly or CHF, with or without polyarthritis) or with polyarthritis only.^h

Transient Ischemic Attacks and Ischemic Stroke

Reduction of the risk of recurrent TIAs or stroke or of death in patients with a history of TIAs or ischemic stroke (secondary prevention).⁶⁴⁶ ⁶⁸² ⁸⁴² ⁹⁰⁶ ⁹³⁸ ¹⁰⁰⁹

Also used in fixed combination with extended-release dipyridamole to reduce the risk of recurrent stroke, death from all vascular causes, or nonfatal MI in patients who have had TIAs or completed ischemic stroke caused by thrombosis.⁷³⁸ ⁷³⁹ ⁷⁴³ ¹⁰⁰⁹

The American College of Chest Physicians (ACCP), the American Stroke Association (ASA), and AHA consider aspirin or the combination of aspirin and extended-release dipyridamole acceptable antiplatelet regimens for secondary prevention of noncardioembolic ischemic stroke and TIAs; other options include cilostazol or clopidogrel.⁹⁹⁰ ¹⁰⁰⁹ When selecting an appropriate antiplatelet regimen, consider factors such as the patient's individual risk for recurrent stroke, tolerance, and cost of the different agents.⁹⁹⁰

Oral anticoagulation (e.g., dabigatran, warfarin) rather than antiplatelet therapy is recommended in patients with a history of ischemic stroke or TIA and concurrent atrial fibrillation; however, in patients who cannot take or choose not to take oral anticoagulants (e.g., those with difficulty maintaining stable INRs, compliance issues, dietary restrictions, or cost limitations), dual antiplatelet therapy with aspirin and clopidogrel is recommended.¹⁰⁰⁹

Also used for acute treatment of ischemic stroke in children^{† [off-label]}.¹⁰¹³

Coronary Artery Disease

Recommended by AHA and the American College of Cardiology Foundation (ACCF) for reduction of the risk of vascular events (e.g., stroke, recurrent MI) in all patients with CAD, unless contraindicated.⁹⁹²

Recommended by American Diabetes Association (ADA) for secondary prevention of cardiovascular events in patients with diabetes mellitus and a history of atherosclerotic cardiovascular disease (ASCVD).¹¹¹⁶

ST-Segment-Elevation MI (STEMI)

Reduction of the risk of stroke, recurrent infarction, and death in patients with STEMI.⁵²⁷ ⁵⁷⁹ ⁸⁴² ⁹⁹² ¹⁰¹⁰

Use in conjunction with a P2Y12 platelet adenosine diphosphate (ADP)-receptor antagonist (e.g., clopidogrel, prasugrel, ticagrelor).⁵²⁷ ⁹⁹² ⁹⁹³ ⁹⁹⁴ ¹⁰¹⁰

The addition of warfarin to antiplatelet therapy is recommended in patients with STEMI who have indications for anticoagulation (e.g., atrial fibrillation, left ventricular dysfunction, cerebral emboli, extensive wall-motion abnormality, mechanical heart valves).⁹⁹³ ⁹⁹⁶ ¹⁰⁰⁷ ¹⁰¹⁰

Primary Prevention of Ischemic Cardiac Events

Use of aspirin for primary prevention of cardiovascular disease remains controversial;¹¹¹² may reduce the risk of a first cardiac event (e.g., STEMI)^{† [off-label]} in certain patient populations (primary prevention).¹¹¹⁰ ¹¹¹⁷ ¹¹¹⁸ ¹¹¹⁹ Balance of risks and benefits is most favorable in patients at higher ASCVD risk who have a low risk of bleeding.¹¹¹⁰ ¹¹¹¹ ¹¹¹³ ¹¹¹⁴ ¹¹¹⁵

Some experts recommend reserving low-dose aspirin for primary prevention in adults 40–70 years of age who have a higher risk of cardiovascular disease without an increased risk of bleeding (e.g., history of previous GI bleed, peptic ulcer disease, thrombocytopenia, coagulopathy, chronic kidney disease, concomitant use of drugs that increase bleeding risk [e.g., NSAIAs, corticosteroids, direct oral anticoagulants, warfarin]).¹¹¹⁰ ¹¹¹¹

Consider totality of patient risk factors when determining risk for ASCVD, (e.g., strong family history of premature MI; inability to achieve lipid, BP, or blood glucose targets; substantial elevation in coronary artery calcium score) in conjunction with patient and clinician preferences.¹¹¹⁰ ¹¹¹⁸ ¹¹¹⁹ High-risk patients also include adults 40–70 years of age without diabetes mellitus who have a 10-year ASCVD risk ≥20% and those with diabetes mellitus who have a 10-year ASCVD risk ≥10%.¹¹¹¹

The US Preventive Services Task Force (USPSTF) states that the beneficial effects of aspirin for primary prevention of cardiovascular disease are modest and occur at daily dosages of ≤100 mg, with a potentially greater relative benefit for MI prevention in older adults.¹¹¹⁷

ADA states may be considered for primary prevention in patients with type 1 or type 2 diabetes mellitus who are at high risk for cardiovascular events (i.e., familial history of premature ASCVD, smoking, hypertension, chronic kidney disease/albuminuria, elevated blood cholesterol or triglyceride concentrations) after evaluating risks versus benefits.¹¹¹⁶

Not currently recommended for primary prevention in patients with a low risk of ASCVD.¹¹¹⁰ Not routinely recommended for primary prevention in individuals <40 or >70 years of age.¹¹¹⁰

Non-ST-Segment-Elevation Acute Coronary Syndromes (NSTE ACS)

Reduction of the risk of death and/or nonfatal MI in patients with NSTE ACS (unstable angina or non-ST-segment-elevation MI [NSTEMI]).⁵⁸¹ ⁶¹³ ⁶¹⁴ ⁶¹⁵ ⁶¹⁶ ⁶¹⁷ ⁶¹⁸ ⁶¹⁹ ⁶²⁰ ⁶²¹ ⁶⁸² ⁶⁸⁴ ⁷²⁸ ⁷³⁶ ⁹⁰⁶ ⁹³⁸ ¹¹⁰⁰

Dual-drug antiplatelet therapy with aspirin and a P2Y12-receptor antagonist (e.g., clopidogrel, ticagrelor) is considered part of the current standard of care for treatment and secondary prevention in patients with NSTE ACS.⁹⁹² ⁹⁹³ ⁹⁹⁴ ¹⁰¹⁰

Experts state that aspirin should be administered as soon as possible after presentation (and continued indefinitely) in all patients with NSTE ACS unless contraindicated; in addition, a P2Y12-receptor antagonist should be administered for up to 12 months.¹¹⁰⁰

Chronic Stable Angina

Reduction of the risk of MI and/or sudden death in patients with chronic stable angina.⁶⁴⁶ ⁶⁸⁰ ⁷²⁸ ⁷³⁶ ⁸²² ⁹⁰⁶ ⁹³⁸

Experts recommend that aspirin therapy (75–162 mg daily) be continued indefinitely in patients with stable ischemic heart disease who do not have contraindications.¹¹⁰¹

Percutaneous Coronary Intervention and Revascularization Procedures

Reduction of cardiovascular risks (e.g., early ischemic complications, graft closure) in patients with ACS undergoing PCI (e.g., coronary angioplasty, coronary artery stent implantation)⁶⁴⁶ ⁸⁶⁶ ⁸⁸⁷ ⁸⁸⁸ ⁸⁸⁹ ⁹⁹² ⁹⁹³ ⁹⁹⁴ ¹⁰¹⁰ or CABG.⁶⁴⁶ ⁶⁸³ ⁶⁸⁷ ⁷⁸¹ ⁷⁸²

Pretreatment with aspirin prior to PCI recommended by ACCF, AHA, and the Society for Cardiovascular Angiography and Interventions (SCAI).⁹⁹⁴ Adjunctive therapy with a P2Y12-receptor antagonist (e.g., clopidogrel, prasugrel, ticagrelor) also recommended in patients undergoing PCI with stent placement.⁹⁹⁴

Continue low-dose aspirin therapy indefinitely (as part of dual-drug antiplatelet therapy with a P2Y12-receptor antagonist for at least 12 months and possibly longer) as secondary prevention against cardiovascular events, including stent thrombosis, following PCI.⁹⁹³ ⁹⁹⁴ ¹⁰¹⁰ ¹⁰¹⁹ ¹⁰²⁰

Embolism Associated with Atrial Fibrillation

Used as an alternative or adjunct to warfarin therapy for reduction of the incidence of thromboembolism in selected patients with chronic atrial fibrillation^{† [off-label]}.⁷⁴⁹ ⁸⁸⁰ ⁹⁹⁹ ¹⁰⁰⁷

ACCP, ASA, ACC, AHA, and other experts currently recommend that antithrombotic therapy be given to all patients with nonvalvular atrial fibrillation (i.e., atrial fibrillation in the absence of rheumatic mitral stenosis, a prosthetic heart valve, or mitral valve repair) who are considered to be at increased risk of stroke, unless such therapy is contraindicated.⁹⁸⁹ ⁹⁹⁰ ⁹⁹⁹ ¹⁰⁰⁷ ¹⁰¹⁷ ¹⁰²¹ ¹⁰²² ¹⁰²³

Choice of antithrombotic therapy is based on patient's risk for stroke and bleeding.⁹⁹⁹ ¹⁰⁰⁷ ¹⁰²¹ ¹⁰²² ¹⁰²³ In general, oral anticoagulant therapy (traditionally warfarin) is recommended in patients with high risk for stroke and acceptably low risk of bleeding, while aspirin or no antithrombotic therapy may be considered in patients at low risk of stroke.⁹⁹⁹ ¹⁰⁰⁷ ¹⁰¹⁷ ¹⁰²¹ ¹⁰²² ¹⁰²³

In patients with atrial fibrillation at increased risk of stroke who cannot take or choose not to take oral anticoagulants for reasons other than concerns about major bleeding (e.g., those with difficulty maintaining stable INRs), combination therapy with clopidogrel and aspirin rather than aspirin alone is recommended.⁹⁹⁸ ¹⁰⁰⁷

Antithrombotic therapy in patients with atrial flutter generally managed in the same manner as in patients with atrial fibrillation.⁹⁹⁹ ¹⁰⁰⁷

Peripheral Arterial Disease

Has been used for primary and secondary prophylaxis of cardiovascular events in patients with peripheral arterial disease, including those with intermittent claudication or carotid stenosis and those undergoing revascularization procedures (peripheral artery percutaneous transluminal angioplasty or peripheral arterial bypass graft surgery).¹⁰¹¹

ACCP suggests the use of low-dose aspirin for primary prevention in patients with asymptomatic peripheral arterial disease.¹⁰¹¹

For patients with symptomatic peripheral arterial disease or those undergoing revascularization procedures, single-drug antiplatelet therapy with aspirin or clopidogrel generally is recommended.¹⁰¹¹

Valvular Heart Disease

Recommended by ACC and AHA for use in selected patients with mitral valve prolapse and atrial fibrillation, and also in symptomatic patients with mitral valve prolapse who experience TIAs.⁹⁹⁶

Prosthetic Heart Valves

Used for the prevention of thromboembolism in selected patients with prosthetic heart valves^{† [off-label]}.⁹⁹⁶ ¹⁰⁰⁸

ACCP and ACC/AHA suggest the use of low-dose aspirin for initial (i.e., first 3 months after valve insertion) and long-term antithrombotic therapy in patients with a bioprosthetic heart valve in the aortic position who are in sinus rhythm and have no other indications for warfarin.⁹⁹⁶ ¹⁰⁰⁸ Aspirin also may be considered after initial (3 months) warfarin therapy in patients with a bioprosthetic heart valve in the mitral position who are in sinus rhythm.¹⁰⁰⁸

Addition of an antiplatelet agent such as low-dose aspirin to warfarin therapy recommended in all patients with mechanical heart valves who are at low risk of bleeding.⁹⁹⁶ ¹⁰⁰⁸ Combination therapy with aspirin and warfarin also recommended in patients with bioprosthetic heart valves who have additional risk factors for thrombosis (e.g., atrial fibrillation, previous thromboembolism, left ventricular dysfunction, hypercoagulable condition).⁹⁹⁶

May be added to therapy with a low molecular weight heparin (LMWH) or heparin (referring throughout this monograph to unfractionated heparin) in pregnant women with prosthetic heart valves^† who are at high risk for thrombosis.¹⁰¹²

Thrombosis Associated with Fontan Procedure in Children

Has been used for prevention of thromboembolic complications following Fontan procedure^† (definitive palliative surgical treatment for most congenital univentricular heart lesions) in children.¹⁰¹³

Thromboprophylaxis in Orthopedic Surgery

Has been used for the prevention of venous thromboembolism in patients undergoing major orthopedic surgery (total-hip replacement, total-knee replacement, or hip-fracture surgery^†).¹⁰⁰³ Aspirin generally not considered the drug of choice for this use;¹⁰⁰³ however, some evidence suggests some benefit over placebo or no antithrombotic prophylaxis in patients undergoing major orthopedic surgery.⁹⁵³ ⁹⁵⁴ ¹⁰⁰³

ACCP considers aspirin an acceptable option for pharmacologic thromboprophylaxis in patients undergoing major orthopedic surgery.¹⁰⁰³

When selecting an appropriate thromboprophylaxis regimen, consider factors such as relative efficacy and bleeding risk in addition to other logistics and compliance issues.¹⁰⁰³

Thromboprophylaxis in General Surgery

Has been used for thromboprophylaxis in patients undergoing general (e.g., abdominal) surgery who are at high risk of venous thromboembolism;¹⁰⁰² however, generally recommended as an alternative to LMWHs and low-dose heparin.¹⁰⁰²

Pericarditis

Drug of choice for the management of pain associated with acute pericarditis^† following MI.⁵²⁷

Kawasaki Disease

Treatment of Kawasaki disease; used in conjunction with immune globulin IV (IGIV).⁶³⁶ ⁶³⁷ ⁶³⁸ ¹⁰¹³

Complications of Pregnancy

Has been used alone or in combination with other drugs (e.g., heparin, corticosteroids, immune globulin) for prevention of complications of pregnancy^† (e.g., preeclampsia, pregnancy loss in women with a history of antiphospholipid syndrome and recurrent fetal loss).⁵⁹⁴ ⁵⁹⁵ ⁵⁹⁶ ⁵⁹⁷ ⁵⁹⁹ ⁶⁰⁰ ⁶⁰¹ ⁶⁰⁵ ⁶²⁶ ⁶²⁷ ⁶²⁸ ⁶⁴⁸ ⁶⁵⁰ ⁶⁵¹ ⁶⁵² ⁶⁵³ ⁶⁵⁴ ⁷⁰⁵ ⁷⁰⁶ ⁷⁰⁷ ⁷⁰⁸ ⁷⁰⁹ ⁷¹⁰ ⁷¹¹ ⁷¹² ⁷¹³ ⁷¹⁴ ⁷¹⁵ ⁷²⁶ ⁸¹⁷ ⁸⁵⁷ ¹⁰¹²

Low-dose aspirin in combination with sub-Q heparin or an LMWH is recommended by ACCP in women with antiphospholipid antibody (APLA) syndrome^† and a history of multiple (≥3) pregnancy losses.¹⁰¹²

Routine use of aspirin prophylaxis to reduce the incidence and severity of preeclampsia (even in patients at increased risk of preeclampsia) generally not recommended; ⁷⁰⁵ ⁷⁰⁶ ⁷⁰⁷ ⁷¹² ⁷¹³ ⁷¹⁵ can consider prophylaxis in women with prior severe or early-onset preeclampsia, chronic hypertension, severe diabetes, or moderate to severe renal disease.⁸¹⁵ ⁸¹⁶ ⁸¹⁷ In women at high risk for preeclampsia, ACCP recommends low-dose aspirin during pregnancy, starting from the second trimester.¹⁰¹² (See Pregnancy under Cautions.)

Prevention of Cancer

Limited data (observational studies) suggest that aspirin or other NSAIAs may reduce the risk of various cancers^† (e.g., colorectal, breast, gastric cancer);⁸⁶⁴ ⁸⁷⁰ ⁸⁷¹ ⁸⁷² ⁸⁷³ such results generally not confirmed in randomized controlled trials.⁸⁶⁴ ⁸⁷⁴ ⁸⁷⁵ ⁸⁷⁶

Regular use (e.g., daily) associated with a reduction in the risk of recurrent colorectal adenomas and colorectal cancer^† in some studies.⁷⁸⁹ ⁷⁹⁰ ⁷⁹¹ ⁷⁹² ⁷⁹³ ⁷⁹⁴ ⁷⁹⁵ ⁷⁹⁶ ⁷⁹⁷ ⁷⁹⁸ ⁷⁹⁹ ⁸⁰⁰ ⁸⁰¹ ⁸⁰² ⁸⁰³ ⁸⁰⁴ ⁸⁰⁵ ⁸⁰⁶ ⁸⁰⁷ ⁸⁰⁸ ⁸⁰⁹ ⁸¹⁰ ⁸¹¹ ⁸¹² ⁸¹³ ⁸¹⁴ ⁸¹⁵ Beneficial effects of NSAIAs in reducing colorectal cancer risk dissipate following discontinuance of such therapy.⁷⁹¹ ⁷⁹² ⁷⁹³ ⁷⁹⁴ ⁷⁹⁵ Preventive therapy with aspirin currently not recommended because aspirin does not completely eliminate adenomas; aspirin therapy should not be considered a replacement for colorectal cancer screening and surveillance.⁷⁹⁰ ⁷⁹³ ⁷⁹⁴ ⁷⁹⁵ ⁷⁹⁶ ⁸¹⁴

Aspirin Dosage and Administration

Administration

Administer orally; may administer rectally as suppositories in patients who cannot tolerate oral therapy.^a

Do not use aspirin preparation if strong vinegar-like odor is present.^a

Oral Administration

Usually administer orally with food or a full glass of water (240 mL).^a ⁸³⁶ ⁹⁰⁶

Film-coated, extended-release, or enteric-coated may be associated with less GI irritation and/or symptomatic GI disturbances than uncoated tablets.^a

Do not use delayed-release or extended-release tablets if rapid response is required.^a

Swallow delayed-release and extended-release tablets whole; do not crush or chew.^a

Prepare oral solution by dissolving 2 tablets for solution (Alka-Seltzer) in 120 mL of water; ingest the entire solution to ensure adequate dosing.⁸³⁸ ⁸⁴³ ⁸⁴⁴

Do not chew aspirin preparations for ≥7 days following tonsillectomy or oral surgery;⁸⁴¹ ⁸³⁷ do not place preparations directly on tooth or gum surface (possible tissue injury from prolonged contact).^a

Rectal Administration

Do not administer aspirin tablets rectally.^a

Dosage

When used for pain, fever, or inflammatory diseases, attempt to titrate to the lowest effective dosage.^a

When used in anti-inflammatory dosages, development of tinnitus can be used as a sign of elevated plasma salicylate concentrations (except in patients with high-frequency hearing impairment).^a

Pediatric Patients

Dosage in children should be guided by body weight or body surface area.^a ⁸⁴¹

Do not use in children and teenagers with varicella or influenza, unless directed by a clinician.⁸⁴¹ (See Contraindications under Cautions.)

Pain

Oral

Children 2–11 years of age: 1.5 g/m² daily administered in 4–6 divided doses (maximum 2.5 g/m² daily).^a

Dose may be given every 4 hours as necessary (up to 5 times in 24 hours).⁸⁴¹

Dosage for Self-medication of Pain in Children <12 Years of Age841
Age	Weight	Oral Dose
<3 years of age	<14.5 kg	Consult clinician
3–<4 years	14.5–16 kg	160 mg
4–<6 years	16–20.5 kg	240 mg
6–<9 years	20.5–30 kg	320 mg
9–<11 years	30–35 kg	320–400 mg
11 years	35–38 kg	320–480 mg

For self-medication in children ≥12 years of age, 325–650 mg every 4 hours (maximum 4 g daily) or 1 g every 6 hours as necessary.⁸³⁶ ⁹⁴⁰

For self-medication in children ≥12 years of age, 454 mg (as chewing gum pieces) every 4 hours as necessary (maximum 3.632 g daily).⁸³⁷

For self-medication in children ≥12 years of age, 650 mg (as highly buffered effervescent solution [Alka-Seltzer Original]) every 4 hours (maximum 2.6 g daily); alternatively, 1 g (Alka-Seltzer Extra Strength) every 6 hours (maximum 3.5 g daily).⁸⁴³ ⁸⁴⁴

Rectal

Children 2–11 years of age: 1.5 g/m² daily administered in 4–6 divided doses (maximum 2.5 g/m² daily).^a

Children ≥12 years of age: 325–650 mg every 4 hours as necessary (maximum 4 g daily).^a

Fever

Oral

Children 2–11 years of age: 1.5 g/m² daily administered in 4–6 divided doses (maximum 2.5 g/m² daily).^a

Dose may be given every 4 hours as necessary (up to 5 times in 24 hours).⁸⁴¹

Dosage for Self-medication of Fever in Children <12 Years of Age841
Age	Weight	Oral Dose
<3 years of age	<14.5 kg	Consult physician
3–<4 years	14.5–16 kg	160 mg
4–<6 years	16–20.5 kg	240 mg
6–<9 years	20.5–30 kg	320 mg
9–<11 years	30–35 kg	320–400 mg
11 years	35–38 kg	320–480 mg

Children ≥12 years of age: 325–650 mg every 4 hours as necessary (maximum 4 g daily).^a

For self-medication in children ≥12 years of age, 454 mg (as chewing gum pieces) every 4 hours as necessary (maximum 3.632 g daily).⁸³⁷

Rectal

Children 2–11 years of age: 1.5 g/m² daily administered in 4–6 divided doses (maximum 2.5 g/m² daily).^a

Children ≥12 years of age: 325–650 mg every 4 hours as necessary (maximum 4 g daily).^a

Inflammatory Diseases

Juvenile Rheumatoid Arthritis

Oral

Initially, 90–130 mg/kg daily in divided doses.⁹⁰⁶ ⁹³⁸ Increase dosage as necessary for anti-inflammatory efficacy; target plasma salicylate concentration is 150–300 mcg/mL.⁹⁰⁶ ⁹³⁸ Plasma concentrations >200 mcg/mL associated with an increased incidence of toxicity.⁹⁰⁶ ⁹³⁸

Rheumatic Fever†

Oral

Initially, 90–130 mg/kg daily given in divided doses every 4–6 hours for up to 1–2 weeks for maximal suppression of acute inflammation, followed by 60–70 mg/kg daily in divided doses for 1–6 weeks.^a Adjust dosage based on response, tolerance, and plasma salicylate concentrations.^a Gradually withdraw over 1–2 weeks.^a

Various regimens suggested depending on severity of initial manifestations.^a Consult published protocols for more information on specific dosages and schedules.^a

Thrombosis

Acute Arterial Ischemic Stroke†

Oral

ACCP recommends 1–5 mg/kg daily initially until cerebral arterial dissection and cardioembolic causes have been excluded; subsequently, continue same dosage for ≥2 years.¹⁰¹³

In children with acute arterial ischemic stroke secondary to non-Moyamoya vasculopathy, at least 3 months of therapy recommended; ongoing antithrombotic therapy should be guided by repeat cerebrovascular imaging.¹⁰¹³

Fontan Procedure†

Oral

1–5 mg/kg daily recommended by ACCP; optimal duration of therapy unknown.¹⁰¹³

Prosthetic Heart Valves (Mechanical or Biological)†

Oral

ACCP recommends that clinicians follow same recommendations as in adults.¹⁰¹³

Kawasaki Disease

Oral

Initially, 80–100 mg/kg daily given in 4 equally divided doses (in combination with IGIV) for up to 14 days; initiate within 10 days of onset of fever.⁶³⁶ ⁶³⁷ ⁶³⁸ ⁶³⁹ ⁶⁴⁰ ¹⁰¹³ When fever subsides, decrease dosage to 1–5 mg/kg once daily.⁶³⁶ ⁶³⁷ ⁶³⁸ ⁹⁵⁰ ¹⁰¹³

Continue indefinitely in those with coronary artery abnormalities;⁶³⁸ ⁹⁵⁰ ¹⁰¹³ in the absence of such abnormalities, continue low-dose aspirin for 6–8 weeks.⁶³⁸ ⁹⁵⁰ ¹⁰¹³

Adults

Pain

Oral

For self-medication, 325–650 mg every 4 hours (maximum 4 g daily) or 0.5–1 g every 6 hours as necessary.⁸³⁶ ⁹⁴⁰

For self-medication, 454 mg (as chewing gum pieces) every 4 hours as necessary (maximum 3.632 g daily).⁸³⁷

Adults <60 years of age for self-medication: 650 mg (as a highly buffered effervescent solution [Alka-Seltzer Lemon-Lime or Original]) every 4 hours (maximum 2.6 g daily); alternatively, 1 g (Alka-Seltzer Extra Strength) every 6 hours (maximum 3.5 g daily).⁸³⁸ ⁸⁴³ ⁸⁴⁴

Adults ≥60 years of age for self-medication: 650 mg (as a highly buffered effervescent solution [Alka-Seltzer Lemon-Lime or Original]) every 4 hours (maximum 1.3 g daily); alternatively, 1 g (Alka-Seltzer Extra Strength) every 6 hours (maximum 1.5 g daily).⁸³⁸ ⁸⁴³ ⁸⁴⁴

Rectal

325–650 mg every 4 hours as necessary (maximum 4 g daily).^a

Pain Associated with Migraine Headache

Oral

For self-medication, 500 mg (combined with acetaminophen 500 mg and caffeine 130 mg) as a single dose.⁷⁰¹

Fever

Oral

325–650 mg every 4 hours as necessary (maximum 4 g daily).^a

For self-medication, 454 mg (as chewing gum pieces) every 4 hours as necessary (maximum 3.632 g daily).⁸³⁷

Rectal

325–650 mg every 4 hours as necessary (maximum 4 g daily).^a

Inflammatory Diseases

Rheumatoid Arthritis and Arthritis and Pleurisy of SLE

Oral

Initially, 3 g daily in divided doses.⁹⁰⁶ ⁹³⁸ ⁹⁴³ Increase dosage as necessary for anti-inflammatory efficacy; target plasma salicylate concentration is 150–300 mcg/mL.⁹⁰⁶ ⁹³⁸ ⁹⁴³ Plasma concentrations >200 mcg/mL associated with an increased incidence of toxicity.⁹⁰⁶ ⁹³⁸ ⁹⁴³

Osteoarthritis

Oral

Up to 3 g daily in divided doses.⁹⁰⁶ ⁹³⁸

Spondyloarthropathies

Oral

Up to 4 g daily in divided doses.⁹⁰⁶ ⁹³⁸

Rheumatic Fever†

Oral

Initially, 4.9–7.8 g daily in divided doses given for maximal suppression of acute inflammation.^a Adjust dosage based on response, tolerance, and plasma salicylate concentrations.^a

Various regimens suggested depending on severity of initial manifestations.^a Consult published protocols for more information on specific dosages and schedules.^a

Transient Ischemic Attacks and Acute Ischemic Stroke

Secondary Prevention

Oral

50–325 mg daily;^a ⁶⁴⁶ ⁹⁰⁶ ⁹⁹⁰ some data suggest lower dosages (75–81 mg daily) may have similar benefits and possibly less bleeding risk.⁹⁰⁷

In patients with noncardioembolic ischemic stroke or TIA, 75–100 mg daily (or 25 mg twice daily, in combination with extended-release dipyridamole 200 mg twice daily) recommended; continue long term.⁷³⁸ ¹⁰⁰⁹

Acute Treatment†

Oral

ACCP recommends 160–325 mg daily, initiated ideally within 48 hours of stroke onset; may decrease dosage after 1–2 weeks to reduce bleeding risk. ¹⁰⁰⁹ (See Transient Ischemic Attacks and Acute Ischemic Stroke: Secondary Prevention, under Dosage.) ACCP states that initiation of aspirin therapy should be delayed for 24 hours following administration of recombinant tissue-type plasminogen activator (r-tPA, e.g., alteplase).¹⁰⁰⁹

Coronary Artery Disease and Myocardial Infarction

STEMI

Oral

162–325 mg as soon as acute STEMI is suspected, continued indefinitely at a dosage of 81–325 mg daily.⁵²⁷ ⁵⁷⁹ ⁶⁴⁶ ⁹⁰⁶ ⁹³⁸ Some experts prefer use of a maintenance dosage of 81 mg daily because of a decreased risk of bleeding and lack of definitive evidence demonstrating that higher dosages confer greater benefit.⁵²⁷

Use in conjunction with a P2Y12-receptor antagonist (e.g., clopidogrel, prasugrel, ticagrelor).⁹⁹² ⁹⁹³ ⁹⁹⁴ ¹⁰¹⁰ If used with ticagrelor, do not exceed aspirin maintenance dosage of 100 mg daily; possible reduced efficacy of ticagrelor with such aspirin dosages.⁹⁵⁵

Primary Prevention† of STEMI

Oral

Some experts recommend 75–162 mg once daily in carefully selected patients.¹¹¹⁰ ¹¹¹⁶ ¹¹¹⁸ ¹¹¹⁹ (See Primary Prevention of Ischemic Cardiac Events under Uses.)

Established Coronary Artery Disease

Oral

75–100 mg daily recommended by ACCP; continue indefinitely.¹⁰¹⁰ Some data suggest lower dosages (75–81 mg daily) may have similar benefits and possibly less bleeding risk.⁹⁰⁷

NSTE ACS

Oral

ACC and AHA recommend an initial dose of 162–325 mg as soon as possible after presentation, unless contraindicated.¹¹⁰⁰ Continue with maintenance dosage of 81–325 mg daily.¹¹⁰⁰

Use in conjunction with a P2Y12-receptor antagonist (e.g., clopidogrel, ticagrelor).⁹⁹¹ ⁹⁹² ⁹⁹³ ⁹⁹⁴ ¹⁰¹⁰ If used with ticagrelor, do not exceed aspirin maintenance dosage of 100 mg daily; possible reduced efficacy of ticagrelor with such aspirin dosages.⁹⁵⁵

Percutaneous Coronary Intervention and Coronary Artery Bypass Grafting Surgery

Oral

PCI in patients already receiving aspirin: 81–325 mg initiated ≥2 hours, and preferably 24 hours, before the procedure in conjunction with a P2Y12-receptor antagonist.⁹⁹⁴

PCI in patients not already receiving long-term aspirin therapy: 325 mg daily (as non-enteric-coated formulation), initiated ≥2 hours, preferably 24 hours, prior to PCI in conjunction with a P2Y12-receptor antagonist.⁹⁹⁴

Maintenance therapy following PCI and stent placement (drug-eluting or bare-metal): 75–162 mg daily in combination with a P2Y12-receptor antagonist.⁹⁹² ⁹⁹⁴ ¹⁰¹⁰ If used with ticagrelor, do not exceed aspirin maintenance dosage of 100 mg daily; possible reduced efficacy of ticagrelor with such aspirin dosages.⁹⁵⁵ Administer P2Y12-receptor antagonist for ≥12 months; continue aspirin indefinitely.⁹⁹⁴

CABG: Some manufacturers recommend 325 mg daily, initiated 6 hours after surgery.⁹⁰⁶ ⁹³⁸ AHA and ACCF recommend 100–325 mg daily, initiated within 6 hours after CABG and continued for up to 1 year.⁹⁹² For long-term therapy after 1 year, ACCP recommends aspirin 75–100 mg daily.¹⁰¹⁰

Embolism Associated with Atrial Fibrillation†

Oral

75–325 mg daily suggested for prevention of thromboembolism.¹⁰⁰⁷

Manage atrial flutter in the same manner as atrial fibrillation.⁹⁹⁹ ¹⁰⁰⁷

Mitral Valve Prolapse†

Oral

75–325 mg daily.⁹⁹⁶

Peripheral Arterial Disease

Oral

Primary prevention of cardiovascular events in patients with asymptomatic disease: 75–100 mg daily.¹⁰¹¹

Secondary prevention of cardiovascular events in patients with symptomatic disease: 75–100 mg daily; continue long term.¹⁰¹¹

Patients with refractory intermittent claudication: ACCP suggests the use of cilostazol in addition to aspirin therapy.¹⁰¹¹

Peripheral Artery Bypass Graft Surgery

Oral

To reduce graft occlusion: 75–100 mg daily recommended by ACCP; initiate preoperatively and continue long term.¹⁰¹¹

ACCP suggests addition of clopidogrel 75 mg daily to aspirin therapy in patients undergoing below-the-knee prosthetic graft bypass surgery.¹⁰¹¹

Prosthetic Heart Valves

Mechanical Prosthetic Heart Valves†

Oral

Aspirin 50–100 mg daily in addition to warfarin therapy recommended in all patients with a mechanical heart valve who have a low risk of bleeding.⁹⁹⁶ ¹⁰⁰⁸

Aspirin 75–325 mg once daily as monotherapy recommended as an alternative to warfarin in patients who are unable to take warfarin.⁹⁹⁶

Bioprosthetic Heart Valves†

Oral

Patients with bioprosthetic valves in the aortic position: 50–100 mg daily suggested by ACCP for initial (i.e., first 3 months after valve insertion) and long-term therapy.¹⁰⁰⁸

Patients with bioprosthetic heart valves in the mitral position: 50–100 mg daily may be used for long-term antithrombotic therapy after initial 3-month treatment with warfarin.¹⁰⁰⁸

Combination aspirin (75–100 mg daily) and warfarin therapy recommended by ACC/AHA for patients with bioprosthetic heart valves and additional risk factors for thromboembolism.⁹⁹⁶

Aspirin 75–325 mg once daily also recommended as an alternative to warfarin therapy in any patient who is unable to take warfarin.⁹⁹⁶

Complications of Pregnancy†

Oral

Antiphospholipid syndrome^† and a history of multiple (≥ 3) pregnancy losses: Antepartum prophylaxis with aspirin (75–100 mg daily) in combination with sub-Q heparin or an LMWH recommended by ACCP.¹⁰¹²

Patients at risk for preeclampsia: ACCP recommends low-dose aspirin during pregnancy (starting from the second trimester).¹⁰¹²

Prescribing Limits

Pediatric Patients

Pain

Oral

Children 2–11 years of age: Maximum 2.5 g/m² daily.^a

Children ≥12 years of age: Maximum 4 g daily.⁸³⁶ Maximum 2.6 g as highly buffered effervescent solution (Alka-Seltzer Original) or 3.5 g (Alka-Seltzer Extra Strength) in 24 hours.⁸⁴³ ⁸⁴⁴

For self-medication, do not exceed recommended daily dosage.⁸⁴¹ Treatment duration for self-medication for pain: ≤ 5 days.⁸⁴¹ (See Advice to Patients.) Treatment duration for self-medication of sore throat pain using chewing gum: ≤2 days.⁸³⁷

Rectal

Children 2–11 years of age: Maximum 2.5 g/m² daily.^a

Children ≥12 years of age: Maximum 4 g daily.^a

Fever

Oral

Children 2–11 years of age: Maximum 2.5 g/m² daily.^a

Children ≥12 years of age: Maximum 4 g daily.⁸³⁶

For self-medication, do not exceed recommended daily dosage.⁸⁴¹ Treatment duration for self-medication: <3 days.⁸⁴¹ (See Advice to Patients.)

Rectal

Children 2–11 years of age: Maximum 2.5 g/m² daily.^a

Children ≥12 years of age: Maximum 4 g daily.^a

Adults

Pain

Oral

Maximum 4 g daily.^a Treatment duration for self-medication for pain: ≤10 days.⁸⁴¹ Aspirin chewing gum should not be used for self-medication of sore throat pain for longer than 2 days.⁸³⁷ (See Advice to Patients.)

Adults <60 years of age taking highly buffered effervescent solutions: Maximum 2.6 g (Alka-SeltzerLemon-lime or Original) or 3.5 g (Alka-Seltzer Extra Strength) in 24 hours.⁸³⁸ ⁸⁴³ ⁸⁴⁴

Adults ≥60 years of age taking highly buffered effervescent solutions: Maximum 1.3 g (Alka-SeltzerLemon-lime or Original) or 1.5 g (Alka-Seltzer Extra Strength) in 24 hours.⁸³⁸ ⁸⁴³ ⁸⁴⁴

Rectal

Maximum 4 g daily.^a

Pain Associated with Migraine Headache

Oral

For self-medication, maximum 500 mg (in combination with acetaminophen 500 mg and caffeine 130 mg) in 24 hours.⁷⁰¹

Fever

Oral or Rectal

Maximum 4 g daily.^a

Special Populations

Geriatric Patients

Highly buffered effervescent solution: Maximum 1.3 g (Alka-SeltzerLemon-Lime or Original) or 1.5 g (Alka-Seltzer Extra Strength) in 24 hours.⁸³⁸ ⁸⁴³ ⁸⁴⁴

Cautions for Aspirin

Contraindications

Known hypersensitivity to aspirin or any ingredient in the formulation.⁹⁰⁶ ⁹³⁸
History of asthma, urticaria, or other sensitivity reaction precipitated by other NSAIAs.⁹⁰⁶ ⁹³⁸
Syndrome of asthma, rhinitis, and nasal polyps.⁹³⁸
Children or adolescents with viral infections (with or without fever) because of the possibility that the infection may be one associated with an increased risk of Reye’s syndrome.⁹⁰⁶ ⁹³⁸ (See Pediatric Use under Cautions.)

Warnings/Precautions

Warnings

Alcohol

Long-term heavy alcohol use (≥3 alcoholic beverages daily) associated with an increased risk of aspirin-induced bleeding.⁹⁰⁶ ⁹³⁸ ⁹⁴¹ (See Advice to Patients.)

Hematologic Effects

Inhibits platelet aggregation and may prolong bleeding time.⁹⁰⁶ ⁹³⁸ These effects may be particularly important in patients with inherited (e.g., hemophilia) or acquired (e.g., liver disease, vitamin K deficiency) bleeding disorders.⁹⁰⁶ ⁹³⁸

Because of the increased risk of bleeding, avoid aspirin-containing chewing gum tablets or gargles for ≥1 week after tonsillectomy or oral surgery.^h

GI Effects

Serious GI toxicity (e.g., bleeding, ulceration, perforation) can occur with or without warning symptoms.⁹³⁸ Increased risk in those with a history of GI bleeding or ulceration, geriatric patients, and those receiving an anticoagulant or corticosteroid, receiving excessive dosages or prolonged therapy, taking multiple NSAIAs concomitantly, or consuming ≥3 alcohol-containing beverages daily.⁹⁴¹ ¹⁰³⁵

Avoid in patients with active peptic ulcer disease; can cause gastric mucosal irritation and bleeding.⁹⁰⁶ ⁹³⁸

Despite current warnings on OTC product labels, serious bleeding events continue to occur in patients receiving aspirin in fixed combination with antacids for self-medication.¹⁰³⁵ FDA is evaluating whether additional actions are needed to address this safety concern.¹⁰³⁵

Thrombosis Associated with Drug-eluting Stents

Stent thrombosis with potentially fatal sequelae, particularly with drug-eluting stents (DES),⁸⁸⁶ ⁸⁹⁰ ⁸⁹¹ associated with premature discontinuance (<12 months) of dual-drug therapy with a thienopyridine derivative and aspirin.⁸⁸⁶ ⁸⁹⁰ ⁸⁹¹ ⁸⁹² ⁸⁹³ ⁸⁹⁴ ⁸⁹⁵ ⁸⁹⁶ ⁸⁹⁷ ⁸⁹⁸ ⁸⁹⁹ ⁹⁰⁰ (See Percutaneous Coronary Intervention and Revascularization Procedures under Uses.)

At least 12 months of dual-drug antiplatelet therapy is recommended in patients with any type of coronary artery stent (bare-metal or drug-eluting).⁹⁹³ ⁹⁹⁴ ¹⁰¹⁰ Preliminary evidence from a randomized controlled study suggests that an even longer duration (up to 30 months) of dual-drug antiplatelet therapy may be beneficial in reducing stent thrombosis and other cardiovascular events in patients with a drug-eluting stent; however, such prolonged therapy was associated with increased bleeding and an unexpected finding of increased all-cause mortality.¹⁰¹⁹ ¹⁰²⁰ FDA is continuing to evaluate these findings and will communicate final conclusions and recommendations once the analysis is complete.¹⁰¹⁹

For non-elective procedures that mandate premature discontinuance of thienopyridine-derivative therapy, continue aspirin therapy if at all possible.⁸⁸⁶ Restart thienopyridine therapy as soon as possible after the procedure.⁸⁸⁶ (See Advice to Patients.)

Sensitivity Reactions

Anaphylactoid reactions, severe urticaria, angioedema, or bronchospasm reported.⁸³⁶ ⁹⁰⁶ ⁹³⁸ ^h Immediate medical intervention and discontinuance for anaphylaxis.⁸³⁶

Potentially fatal or life-threatening syndrome of multi-organ hypersensitivity (i.e., drug reaction with eosinophilia and systemic symptoms [DRESS]) reported in patients receiving NSAIAs.¹²⁰² Clinical presentation is variable, but typically includes eosinophilia, fever, rash, lymphadenopathy, and/or facial swelling, possibly associated with other organ system involvement (e.g., hepatitis, nephritis, hematologic abnormalities, myocarditis, myositis).¹²⁰² Symptoms may resemble those of acute viral infection.¹²⁰² Early manifestations of hypersensitivity (e.g., fever, lymphadenopathy) may be present in the absence of rash.¹²⁰² If signs or symptoms of DRESS develop, discontinue the drug and immediately evaluate the patient.¹²⁰²

Contraindicated in patients with syndrome of asthma, rhinitis, and nasal polyps;⁹⁰⁶ ⁹³⁸ caution in patients with asthma.⁹³⁸

General Precautions

Sodium Content

Avoid highly buffered aspirin preparations in patients with CHF, renal failure, or other conditions in which high sodium content would be harmful.⁹⁰⁶ ⁹³⁸

Individuals with Phenylketonuria

Some preparations contain aspartame (NutraSweet), which is metabolized in the GI tract to phenylalanine.^a ⁸³⁸

Use of Fixed Combinations

When aspirin is used in fixed combination with other agents, consider the cautions, precautions, and contraindications associated with the other agent(s).^a

Specific Populations

Pregnancy

Use of NSAIAs during pregnancy at about ≥30 weeks’ gestation can cause premature closure of the fetal ductus arteriosus; use at about ≥20 weeks’ gestation associated with fetal renal dysfunction resulting in oligohydramnios and, in some cases, neonatal renal impairment.¹²⁰⁰ ¹²⁰²

Effects of NSAIAs on the human fetus during third trimester of pregnancy include prenatal constriction of the ductus arteriosus, tricuspid incompetence, and pulmonary hypertension; nonclosure of the ductus arteriosus during the postnatal period (which may be resistant to medical management); and myocardial degenerative changes, platelet dysfunction with resultant bleeding, intracranial bleeding, renal dysfunction or renal failure, renal injury or dysgenesis potentially resulting in prolonged or permanent renal failure, oligohydramnios, GI bleeding or perforation, and increased risk of necrotizing enterocolitis.¹²⁰²

Avoid use of NSAIAs in pregnant women at about ≥30 weeks’ gestation; if use required between about 20 and 30 weeks’ gestation, use lowest effective dosage and shortest possible duration of treatment, and consider monitoring amniotic fluid volume via ultrasound examination if treatment duration >48 hours; if oligohydramnios occurs, discontinue drug and follow up according to clinical practice.¹²⁰⁰ ¹²⁰² However, FDA states that these recommendations do not apply to low-dose aspirin therapy; low (e.g., 81-mg) doses of aspirin may be used under the direction of a clinician at any time during pregnancy for the treatment of certain pregnancy-related conditions.¹²⁰⁰ (See Advice to Patients.)

Fetal renal dysfunction resulting in oligohydramnios and, in some cases, neonatal renal impairment observed, on average, following days to weeks of maternal NSAIA use; infrequently, oligohydramnios observed as early as 48 hours after initiation of NSAIAs.¹²⁰⁰ ¹²⁰² Oligohydramnios is often, but not always, reversible (generally within 3–6 days) following NSAIA discontinuance.¹²⁰⁰ ¹²⁰² Complications of prolonged oligohydramnios may include limb contracture and delayed lung maturation.¹²⁰⁰ ¹²⁰² In limited number of cases, neonatal renal dysfunction (sometimes irreversible) occurred without oligohydramnios.¹²⁰⁰ ¹²⁰² Some neonates have required invasive procedures (e.g., exchange transfusion, dialysis).¹²⁰⁰ ¹²⁰² Deaths associated with neonatal renal failure also reported.¹²⁰⁰ Limitations of available data (lack of control group; limited information regarding dosage, duration, and timing of drug exposure; concomitant use of other drugs) preclude a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal NSAIA use.¹²⁰² Available data on neonatal outcomes generally involved preterm infants; extent to which risks can be generalized to full-term infants is uncertain.¹²⁰²

Animal data indicate important roles for prostaglandins in kidney development and endometrial vascular permeability, blastocyst implantation, and decidualization.¹²⁰² In animal studies, inhibitors of prostaglandin synthesis increased pre- and post-implantation losses; also impaired kidney development at clinically relevant doses.¹²⁰²

Maternal and fetal hemorrhagic complications observed with maternal ingestion of large doses (e.g., 12–15 g daily) of aspirin⁵⁹⁴ ⁵⁹⁵ ⁵⁹⁷ ⁶¹¹ ⁶¹² generally have not been observed in studies in which low doses (60–150 mg daily) of the drug were used for prevention of complications of pregnancy^†.⁵⁹⁴ ⁵⁹⁵ ⁵⁹⁶ ⁵⁹⁷ ⁵⁹⁸ ⁵⁹⁹ ⁶⁰⁰ ⁶⁰¹ ⁶⁰⁵ ⁶²⁶ ⁶²⁷ ⁶²⁹ ⁶³⁰ ⁶³¹ ⁶³²

Lactation

Distributed into milk; use not recommended.⁹⁰⁶ ⁹³⁸ High doses may result in adverse effects (rash, platelet abnormalities, bleeding) in nursing infants.⁹⁰⁶ ⁹³⁸

Pediatric Use

Dosing recommendations for juvenile rheumatoid arthritis based on well controlled clinical studies.⁹⁰⁶ ⁹³⁸ High dosages that result in plasma concentrations >200 mcg/mL associated with an increased incidence of toxicity.⁹⁰⁶ ⁹³⁸

Use in children with varicella infection or influenza-like illnesses reportedly is associated with an increased risk of developing Reye’s syndrome.¹⁶⁶ ¹⁶⁷ ¹⁶⁸ ¹⁶⁹ ⁴⁶⁸ ⁵³⁸ ⁵⁴⁹ ⁶³⁸ US Surgeon General, AAP Committee on Infectious Diseases, FDA, and other authorities advise that salicylates not be used in children and teenagers with varicella or influenza, unless directed by a clinician.⁴⁶⁶ ⁴⁶⁷ ⁵⁵⁴ ⁶³⁸ Generally avoid salicylates in children and teenagers with suspected varicella or influenza and during presumed outbreaks of influenza, since accurate diagnosis of these diseases may be impossible during the prodromal period;⁴⁶⁶ use of salicylates in the management of viral infections in children or adolescents is contraindicated, since the infection may be one associated with an increased risk of Reye’s syndrome.⁶⁴⁶ ⁹⁰⁶

Use with caution in pediatric patients who are dehydrated (increased susceptibility to salicylate intoxication).^h

Safety and efficacy of aspirin in fixed combination with extended-release dipyridamole not established.⁷³⁸

Risk of overdosage and toxicity (including death) in children <2 years of age receiving preparations containing antihistamines, cough suppressants, expectorants, and nasal decongestants alone or in combination for relief of symptoms of upper respiratory tract infection.⁹³⁷ ⁹³⁹ Limited evidence of efficacy for these preparations in this age group; appropriate dosages not established.⁹³⁷ Use such preparations in children <2 years of age with caution and only as directed by clinician.⁹³⁷ ⁹³⁹ Clinicians should ask caregivers about use of OTC cough/cold preparations to avoid overdosage.⁹³⁷

Hepatic Impairment

Avoid in patients with severe hepatic impairment.⁹⁰⁶ ⁹³⁸

Renal Impairment

Avoid in patients with GFR <10 mL/minute.⁹⁰⁶ ⁹³⁸

Common Adverse Effects

Minor upper GI symptoms (dyspepsia).⁹³⁸

Drug Interactions

Protein-bound Drugs

Potential for salicylate to be displaced from binding sites by, or to displace from binding sites, other protein-bound drugs.⁹⁰⁶ ^h Aspirin acetylates serum albumin, which may alter binding of other drugs to the protein.^a

Specific Drugs

Drug	Interaction	Comments
ACE inhibitors	Reduced BP response to ACE inhibitors⁹³⁸ Possible attenuation of hemodynamic actions of ACE inhibitors in patients with CHF^h Reduced hyponatremic effect of ACE inhibitors⁹⁰⁶ ⁹³⁸	Monitor BP⁹³⁸
Acidifying agents	Drugs that decrease urine pH may decrease salicylate excretion^h
Alcohol	Increased risk of bleeding⁹⁰⁶ ⁹³⁸ (see Advice to Patients)
Alkalinizing agents	Drugs that increase urine pH may increase salicylate excretion^h	Monitor plasma salicylate concentrations in patients receiving high-dose aspirin therapy if antacids are initiated or discontinued^h
Anticoagulants (warfarin, heparin)	Increased risk of bleeding⁹⁰⁶ ⁹³⁸ May displace warfarin from protein-binding sites, leading to prolongation of PT and bleeding time⁹⁰⁶ ⁹³⁸	Use with caution^h
Anticonvulsants	May displace phenytoin from binding sites; possible decrease in total plasma phenytoin concentrations, with increased free fraction⁹⁰⁶ ⁹³⁸ May displace valproic acid from binding sites; possible increase in free plasma valproic acid concentrations;⁹⁰⁶ ⁹³⁸ ^h possible increased risk of bleeding^h	Monitor patients receiving aspirin with valproic acid^h
Antidiabetic drugs (sulfonylureas)	Potential for increased hypoglycemic effect⁹⁰⁶ ⁹³⁸	Monitor closely^h
β-adrenergic blocking agents	Reduced BP response to β-adrenergic blocking agents ⁹⁰⁶ ⁹³⁸ Potential for salt and fluid retention⁹⁰⁶	Monitor BP⁹³⁸
Carbonic anhydrase inhibitors (acetazolamide)	Increased risk of salicylate toxicity^h Increased plasma acetazolamide concentrations; increased risk of acetazolamide toxicity⁹⁰⁶ ⁹³⁸	Avoid concomitant use in patients receiving high-dose aspirin^h
Corticosteroids	Decreased plasma salicylate concentrations^h	Monitor for adverse effects of either drug^h
Diuretics	Possible reduced natriuretic effect⁹³⁸
Methotrexate	Increased plasma methotrexate concentrations^h Inhibition of renal clearance of methotrexate leading to bone marrow toxicity, especially in geriatric patients or patients with renal impairment⁹⁰⁶	Monitor for methotrexate toxicity^h
NSAIAs	Increased risk of bleeding, GI ulceration, decreased renal function, or other complications⁸⁶¹ ⁹⁰⁶ ⁹⁴⁶ ⁹⁴⁷ ⁹⁴⁸ No consistent evidence that low-dose aspirin mitigates increased risk of serious cardiovascular events associated with NSAIAs⁸⁶¹ ⁹⁴⁸ Pharmacokinetic interactions with many NSAIAs^h Antagonism (ibuprofen, naproxen) of the irreversible platelet-aggregation inhibitory effect of aspirin; may limit the cardioprotective effects of aspirin⁷⁸⁸ ⁸⁵⁸ ⁸⁵⁹ ⁸⁶⁰ Minimal risk of attenuating effects of low-dose aspirin with occasional use of ibuprofen⁸⁵⁸ Not known whether ketoprofen interferes with the antiplatelet effect of aspirin⁸⁵⁸ ⁸⁵⁹ Decreased peak plasma concentration and AUC of diclofenac;⁹⁴⁶ ⁹⁴⁷ limited data indicate that diclofenac does not inhibit antiplatelet effect of aspirin⁷⁸⁸	Concomitant use not recommended⁹⁰⁶ ⁹³⁸ ⁹⁴⁶ ⁹⁴⁷ ⁹⁴⁸ Pharmacokinetic interactions unlikely to be clinically important^h Immediate-release aspirin: Administer a single dose of ibuprofen 400 mg for self-medication≥8 hours before or ≥30 minutes after administration of aspirin⁸⁵⁸ ⁸⁵⁹ Enteric-coated low-dose aspirin: No recommendations regarding timing of administration with single dose of ibuprofen⁸⁵⁸ ⁸⁵⁹ Consider use of alternative analgesics that do not interfere with antiplatelet effect of low-dose aspirin (e.g., acetaminophen, opiates) for patients at high risk of cardiovascular events⁸⁵⁸ ⁸⁵⁹ Concomitant use with prescription NSAIAs not recommended because of potential for increased adverse effects⁸⁶¹
Pyrazinamide	Possible prevention or reduction of hyperuricemia associated with pyrazinamide^h
Tetracycline	Decreased oral absorption of tetracyclines when administered with aspirin preparations containing divalent or trivalent cations (Bufferin)^h	Administer preparations containing divalent or trivalent cations (Bufferin) 1 hr before or after tetracycline^h
Thrombolytic agents	Additive reduction in mortality reported in patients with AMI receiving aspirin in low dosages and thrombolytic agents (streptokinase, alteplase)⁵⁷⁹ ⁵⁸⁰ ⁵⁸¹ ⁵⁸² ⁵⁸³ ⁵⁸⁴ ⁵⁸⁵ ⁵⁸⁶ ⁵⁸⁷ ⁵⁸⁸ ⁵⁸⁹ ⁵⁹⁰	Used for therapeutic effect⁵⁷⁹ ⁵⁸⁰ ⁵⁸¹ ⁵⁸² ⁵⁸³ ⁵⁸⁴ ⁵⁸⁵ ⁵⁸⁶ ⁵⁸⁷ ⁵⁸⁸ ⁵⁸⁹ ⁵⁹⁰
Uricosuric agents (probenecid, sulfinpyrazone)	Reduced uricosuric effect of uricosuric agents⁹⁰⁶ ⁹³⁸
Varicella virus vaccine live	Theoretical possibility of Reye’s syndrome⁶³⁸	Manufacturer of varicella virus vaccine live recommends that individuals who receive the vaccine avoid use of salicylates for 6 weeks following vaccination⁷⁵⁶ For children who are receiving long-term salicylate therapy, AAP suggests weighing theoretical risks of vaccination against known risks of wild-type virus;⁶³⁸ ACIP states that children who have rheumatoid arthritis or other conditions requiring therapeutic salicylate therapy probably should receive varicella virus vaccine live in conjunction with subsequent close monitoring⁷⁵⁷

Aspirin Pharmacokinetics

Absorption

Bioavailability

Well absorbed following oral administration.⁹⁰⁶ ^h Rapidly metabolized to salicylic acid; plasma aspirin concentrations are undetectable 1–2 hours after administration.⁹⁰⁶ Peak plasma salicylic acid concentrations attained within 1–2 hours following administration of uncoated tablets.⁹⁰⁶

Slowly and variably absorbed following rectal administration.^h

Onset

Single oral doses of rapidly absorbed preparations: 30 minutes for analgesic and antipyretic effects.^h

Rectal suppositories: 1–2 hours for antipyretic effects.^h

Continuous oral therapy: 1–4 days for anti-inflammatory effect.^h

Food

Food decreases rate but not extent of absorption; peak plasma concentrations of aspirin and salicylate may be decreased.^h

Plasma Concentrations

Plasma salicylate concentrations of 30–100 mcg/mL produce analgesia and antipyresis; the concentration required for anti-inflammatory effect is 150–300 mcg/mL; toxicity noted at 300–350 mcg/mL.^h

Steady-state plasma salicylate concentrations increase more than proportionally with increasing doses as a result of capacity-limiting processes.^h

Special Populations

During the febrile phase of Kawasaki disease, oral absorption may be impaired or highly variable.^h

Distribution

Extent

Widely distributed; aspirin and salicylate distribute into synovial fluid.⁹⁰⁶ ^a ^h Crosses placenta and distributed into milk.⁹⁰⁶

Plasma Protein Binding

Aspirin: 33%.^a

Salicylate: 90–95% bound at plasma salicylate concentrations <100 mcg/mL; 70–85% bound at concentrations of 100–400 mcg/mL; 25–60% bound at concentrations >400 mcg/mL.⁹⁰⁶ ^h

Elimination

Metabolism

Partially hydrolyzed to salicylate by esterases in the GI mucosa.^a Unhydrolyzed aspirin subsequently undergoes hydrolysis by esterases mainly in the liver but also in plasma, erythrocytes, and synovial fluid.^a

Salicylate is metabolized in the liver by the microsomal enzyme system.^h

Elimination Route

Excreted in urine via glomerular filtration and renal tubular reabsorption as salicylate and its metabolites.^h Urinary excretion of salicylate is pH dependent; as urine pH increases from 5 to 8, urinary excretion of salicylate is greatly increased.^h

Half-life

Aspirin: 15–20 minutes.^a

Half-life of salicylate increases with increasing plasma salicylate concentrations.⁹⁰⁶ ^h

Salicylate: 2–3 hours when aspirin administered in low doses (325 mg).^h

Salicylate: 15–30 hours when aspirin administered in higher dosages.^h

Special Populations

Salicylate and its metabolites readily removed by hemodialysis and, to a lesser extent, by peritoneal dialysis.^h

Stability

Storage

Oral

Capsules

Aspirin in fixed-combination with extended-release dipyridamole: 25°C (may be exposed to 15–30°C).⁷³⁸ Protect from excessive moisture.⁷³⁸

Gum

15–25°C; protect from excessive moisture.⁸³⁷

Tablets

Room temperature (Bayer products, excluding Alka-Seltzer products);⁸³⁹ ⁸⁴⁰ ⁸⁴¹ ⁸⁴² ⁹⁰⁶ avoid high humidity and excessive heat (40°C).⁸⁴⁰

15–30°C (Easprin).⁹⁴³

20–25°C (Anacin Extra Strength); protect from moisture.⁸³⁶

Protect from excessive heat (Alka-Seltzer products).⁸³⁸ ⁸⁴³ ⁸⁴⁴

Rectal

Suppositories

2–15°C.^a

Actions

Inhibits COX-1 and COX-2 activity.¹⁰¹⁶
Pharmacologic actions similar to those of prototypical NSAIAs; exhibits anti-inflammatory, analgesic, and antipyretic activity.⁹³⁸
Irreversibly acetylates and inactivates COX-1 in platelets.¹⁰¹⁶
The existence of 2 COX isoenzymes with different aspirin sensitivities and extremely different recovery rates of their COX activity following inactivation by aspirin at least partially explains the different dosage requirements and durations of aspirin effects on platelet function versus the drug’s analgesic and anti-inflammatory effects.¹⁰¹⁶
Effects on urinary excretion of uric acid are dose related; large dosages (e.g., 1.3 g 4 times daily) enhance urinary excretion and decrease serum concentrations of uric acid , intermediate dosages (e.g., 650 mg to 1 g 3 times daily) usually do not alter uric acid excretion, and low dosages (e.g., <325 mg 3 times daily) inhibit excretion and may increase serum uric acid concentrations.^h

Advice to Patients

When used for self-medication, importance of reading the product labeling.⁸³⁶ ⁸⁴¹ ⁸³⁷ ⁸³⁸ ⁸⁴³ ⁸⁴⁴ ⁹⁴⁰
When used for self-medication, importance of asking clinician whether to use aspirin or another analgesic if alcohol consumption is ≥3 alcohol-containing drinks per day.⁸³⁶ ⁸³⁷ ⁸³⁸ ⁸⁴¹ ⁸⁴³ ⁸⁴⁴ ⁹⁴⁰
Importance of informing patients about risk of bleeding associated with chronic, heavy alcohol use while taking aspirin.⁹⁰⁶ ⁹⁴¹
When used for self-medication in children, importance of basing the dose on the child’s weight or body surface area.⁸⁴¹
In patients with drug-eluting stents (DES) receiving aspirin in combination with clopidogrel or ticlopidine, importance of not discontinuing antiplatelet therapy without consulting cardiologist, even if instructed to do so by other health-care professional (e.g., dentist).⁸⁸⁶
Importance of not using aspirin for chicken pox or flu symptoms in children or adolescents without consulting a clinician.⁸³⁶ ⁸³⁷ ⁸³⁸ ⁸⁴¹ ⁸⁴³ ⁸⁴⁴ ⁹⁴⁰
Patients receiving anticoagulants and those with asthma, gout, diabetes, arthritis, peptic ulcers, bleeding problems, or stomach problems that persist or recur should consult a clinician before using aspirin for self-medication.⁸³⁶ ⁸³⁷ ⁸³⁸ ⁸⁴¹ ⁸⁴³ ⁸⁴⁴ ⁹⁴⁰
Discontinue and consult clinician if pain or fever persists or progresses, new symptoms occur, redness or swelling is present in a painful area, or ringing in the ears or loss of hearing occurs.⁸³⁶ ⁸³⁷ ⁸³⁸ ⁸⁴¹ ⁸⁴³ ⁸⁴⁴ ⁹⁴⁰
Risk of GI bleeding or ulceration, particularly with prolonged therapy,⁹⁰⁶ ⁹³⁸ ⁹⁴¹ and concomitant therapy with another NSAIA.⁹⁴¹
Risk of anaphylactoid and other sensitivity reactions.⁹³⁸
Importance of notifying clinician if signs and symptoms of GI ulceration or bleeding or rash develop.⁹³⁸
Importance of seeking immediate medical attention if an anaphylactic reaction occurs.⁹³⁸
Importance of women informing clinicians if they are or plan to become pregnant or to breast-feed.⁹³⁸
Importance of avoiding NSAIA use beginning at 20 weeks’ gestation unless otherwise advised by a clinician; importance of avoiding NSAIAs beginning at 30 weeks’ gestation because of risk of premature closure of the fetal ductus arteriosus; monitoring for oligohydramnios may be necessary if NSAIA therapy required for >48 hours’ duration between about 20 and 30 weeks’ gestation.¹²⁰⁰ ¹²⁰²
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.⁹³⁸
Importance of informing patients of other important precautionary information.⁹³⁸ (See Cautions.)

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Aspirin
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Pieces, chewing gum	227 mg	Aspergum	Heritage
	Tablets	81 mg*	Aspirin Tablets
		325 mg*	Aspirin Tablets
			Norwich Aspirin	Chattem
		500 mg*	Aspirin Tablets
			Norwich Aspirin Maximum Strength	Chattem
		650 mg*	Aspirin Tablets
	Tablets, chewable	81 mg*	Aspirin Chewable Tablets
			Bayer Aspirin Children’s	Bayer
			St. Joseph Aspirin Low Strength Adult Chewable	McNeil
	Tablets, delayed-release (enteric-coated)	81 mg*	Aspirin Delayed-release (Enteric-coated) Tablets
			Bayer Aspirin Regimen Adult Low Strength	Bayer
			Ecotrin Adult Low Strength	GlaxoSmithKline
			Halfprin	Kramer
			St. Joseph Pain Reliever Adult	McNeil
		162 mg	Halfprin	Kramer
		325 mg*	Aspirin Delayed-release (Enteric-coated) Tablets
			Bayer Aspirin Regimen Regular Strength Caplets	Bayer
			Ecotrin Regular Strength	GlaxoSmithKline
			Genacote	Ivax
		500 mg*	Aspirin Delayed-release (Enteric-coated) Tablets
			Ecotrin Maximum Strength	GlaxoSmithKline
		650 mg*	Aspirin Delayed-release (Enteric-coated) Tablets
		975 mg*	Aspirin Delayed-release (Enteric-coated) Tablets
			Easprin	Rosedale
	Tablets, extended-release	800 mg	ZORprin	Par
	Tablets, film-coated	325 mg*	Aspirin Tablets
			Genuine Bayer Aspirin Tablets	Bayer
		500 mg	Bayer Extra Strength Aspirin Caplets	Bayer
Rectal	Suppositories	60 mg*	Aspirin Suppositories
		120 mg*	Aspirin Suppositories
		200 mg*	Aspirin Suppositories
		300 mg*	Aspirin Suppositories
		600 mg*	Aspirin Suppositories

Aspirin with Buffers
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets, enteric-coated	325 mg with buffers	Ascriptin Enteric Regular Strength	Novartis
	Tablets, film-coated	81 mg with buffers	Women’s Bayer Aspirin Plus Calcium Caplets	Bayer
		325 mg with buffers	Ascriptin Arthritis Pain Caplets	Novartis
			Ascriptin Regular Strength	Novartis
			Bufferin Tablets	Novartis
		500 mg with buffers	Ascriptin Maximum Strength Caplets	Novartis
			Bayer Plus Extra Strength Caplets	Bayer
			Bufferin Extra Strength Caplets	Novartis
			Bufferin Extra Strength	Novartis
	Tablets, for solution	325 mg	Alka-Seltzer Effervescent Pain Reliever and Antacid	Bayer
			Alka-Seltzer Lemon Lime Effervescent Pain Reliever and Antacid	Bayer
		500 mg	Alka-Seltzer Extra Strength Effervescent Pain Reliever and Antacid	Bayer

Acetaminophen and Aspirin
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	For solution	325 mg/packet Acetaminophen and Aspirin 500 mg/packet	Goody’s Back & Body Pain Powder	Prestige
	Tablets, film-coated	250 mg Acetaminophen, Aspirin 250 mg, and buffer	Excedrin Back and Body Caplets	Novartis

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Acetaminophen, Aspirin, and Caffeine
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Capsules, gel-coated	250 mg Acetaminophen, Aspirin 250 mg, and Caffeine 65 mg*	Acetaminophen, Aspirin, and Caffeine Gelcaps
			Excedrin Menstrual Complete Gelcaps	Novartis
	For solution	260 mg/packet Acetaminophen, Aspirin 520 mg/packet, and Caffeine 32.5 mg/packet	Goody’s Extra Strength Headache Powder	Prestige
		325 mg/packet Acetaminophen, Aspirin 500 mg/packet, and Caffeine 65 mg/packet	Goody’s Cool Orange Extra Strength Powder	Prestige
	Tablets, film-coated	194 mg Acetaminophen, Aspirin 227 mg, Caffeine 33 mg, and buffers	Vanquish Caplets	Moberg
		250 mg Acetaminophen, Aspirin 250 mg, and Caffeine 65 mg	Excedrin Extra Strength Caplets	Novartis
			Excedrin Migraine Caplets	Novartis
			Goody's Extra Strength Caplets	Prestige
			Pamprin Max	Chattem

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Oxycodone and Aspirin
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	4.8355 mg Oxycodone Hydrochloride and Aspirin 325 mg*	Endodan ( C-II )	Qualitest
			Oxycodone Hydrochloride and Aspirin Tablets ( C-II )
			Percodan ( C-II; scored)	Endo

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Other Aspirin Combinations
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Capsules	325 mg with Butalbital 50 mg and Caffeine 40 mg*	Butalbital, Aspirin, and Caffeine Capsules ( C-III )
			Fiorinal ( C-III )	Actavis
		325 mg with Butalbital 50 mg, Caffeine 40 mg, and Codeine Phosphate 30 mg*	Butalbital, Aspirin, Caffeine, and Codeine Phosphate Capsules ( C-III )
			Fiorinal with Codeine ( C-III )	Actavis
		356.4 mg with Caffeine 30 mg and Dihydrocodeine Bitartrate 16 mg	Synalgos-DC ( C-III )	Leitner
	Capsules, extended-release core (dipyridamole only)	25 mg with Dipyridamole 200 mg	Aggrenox	Boehringer Ingelheim
	For solution	845 mg/packet with Caffeine 65 mg/packet	BC Powder	Prestige
			Stanback Powder	Prestige
		1000 mg/packet with Caffeine 65 mg/packet	BC Powder Arthritis Strength	Prestige
	Tablets	325 mg with Butalbital 50 mg and Caffeine 40 mg*	Butalbital, Aspirin, and Caffeine Tablets ( C-III )
			Fortabs ( C-III )	United Research
		325 mg with Carisoprodol 200 mg*	Carisoprodol and Aspirin Tablets ( C-IV )
			Soma Compound ( C-IV )	Meda
		325 mg with Carisoprodol 200 mg and Codeine Phosphate 16 mg*	Carisoprodol, Aspirin, and Codeine Phosphate Tablets ( C-III )
			Soma Compound with Codeine ( C-III )	Meda
		325 mg with Meprobamate 200 mg	Equagesic ( C-IV; scored)	Leitner
			Micrainin ( C-IV )	Wallace
		385 mg with Caffeine 30 mg and Orphenadrine Citrate 25 mg*	Norgesic	3M
			Orphenadrine Citrate, Aspirin, and Caffeine Tablets	Sandoz
		400 mg with Caffeine 32 mg	P-A-C Analgesic	Lee
		770 mg with Caffeine 60 mg, and Orphenadrine Citrate 50 mg*	Norgesic Forte (scored)	3M
			Orphenadrine Citrate, Aspirin, and Caffeine Tablets	Sandoz
	Tablets, film-coated	400 mg with Caffeine 32 mg	Anacin Caplets	Wyeth
			Anacin Tablets	Wyeth
		421 mg with Caffeine 32 mg and buffers	Cope	Lee
		500 mg with Caffeine 32 mg	Anacin Maximum Strength	Wyeth
		500 mg with Caffeine 32.5 mg	Extra Strength Bayer Back and Body Pain (with propylene glycol)	Bayer
	Tablets, for solution	500 mg with Caffeine 65 mg	Alka Seltzer Morning Relief	Bayer

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

Only references cited for selected revisions after 1984 are available electronically.

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168. Partin JS, Schubert WK, Partin JC et al. Serum salicylate concentrations in Reye’s disease: a study of 130 biopsy-proven cases. Lancet. 1982; 1:191-4. https://pubmed.ncbi.nlm.nih.gov/6119559

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620. Waters D, Lam J, Theroux P. Newer concepts in the treatment of unstable angina pectoris. Am J Cardiol. 1991; 68:34C-41C. https://pubmed.ncbi.nlm.nih.gov/1951101

621. Theroux P. Antiplatelet and antithrombotic therapy in unstable angina. Am J Cardiol. 1991; 68:92-8B.

622. Hyers TM. Heparin therapy. Regimens and treatment considerations. Drugs. 1992; 44:738-49. https://pubmed.ncbi.nlm.nih.gov/1280566

623. Schreiber TL, Rizik D, White C et al. Randomized trial of thrombolysis versus heparin in unstable angina. Circulation. 1992; 86:1407-14. https://pubmed.ncbi.nlm.nih.gov/1423953

624. Qui S, Theroux P, McCans J et al. Heparin prevents myocardial infarction better than aspirin in the acute phase of unstable angina. Circulation. 1991; 84(Suppl II):II-345.

625. Theroux P, Waters D, Lam J et al. Reactivation of unstable angina after the discontinuation of heparin. N Engl J Med. 1992; 327:141-5. https://pubmed.ncbi.nlm.nih.gov/1608405

626. Cowchock FS, Reece EA, Balaban D et al. Repeated fetal losses associated with antiphospholipid antibodies: a collaborative randomized trial comparing prednisone with low-dose heparin treatment. Am J Obstet Gynecol. 1992; 166:1318-23. https://pubmed.ncbi.nlm.nih.gov/1595785

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