aspirin

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Pronunciation

Brand Names: US

Brand Names: Canada

Pharmacologic Category

Dosing: Adult

Dosing: Geriatric

Dosing: Pediatric

Dosing: Renal Impairment

Dosing: Hepatic Impairment

Calculations

Use: Labeled Indications

Use: Off-Label

Level of Evidence Definitions

Clinical Practice Guidelines

Administration: Oral

Administration: Rectal

Storage/Stability

Medication Patient Education with HCAHPS Considerations

Medication Safety Issues

Contraindications
 Warnings/Precautions

Geriatric Considerations

Pregnancy Considerations

Breast-Feeding Considerations

Briggs' Drugs in Pregnancy & Lactation

Adverse Reactions

Allergy and Idiosyncratic Reactions

Toxicology

Metabolism/Transport Effects

Drug Interactions

Food Interactions

Test Interactions

Genes of Interest

Reference Range

Nursing: Physical Assessment/Monitoring

Dosage Forms

Anatomic Therapeutic Chemical (ATC) Classification

Generic Available (US)

Pricing: US

Mechanism of Action

Pharmacodynamics/Kinetics

Dental Use

Local Anesthetic/Vasoconstrictor Precautions

Dental Health Professional Considerations

Effects on Dental Treatment

 Effects on Bleeding

Dental Usual Dosing

Related Information

Index Terms

References

International Brand Names

Pronunciation

(AS pir in)

Brand Names: US

Ascriptin Maximum Strength [OTC]

Ascriptin Regular Strength [OTC]

Aspercin [OTC]

Aspir-low [OTC]

Aspirtab [OTC]

Bayer Aspirin Extra Strength [OTC]

Bayer Aspirin Regimen Adult Low Strength [OTC]

Bayer Aspirin Regimen Children's [OTC]

Bayer Aspirin Regimen Regular Strength [OTC]

Bayer Genuine Aspirin [OTC]

Bayer Plus Extra Strength [OTC]

Bayer Women's Low Dose Aspirin [OTC]

Buffasal [OTC]

Bufferin Extra Strength [OTC]

Bufferin [OTC]

Buffinol [OTC]
 Durlaza

Ecotrin Arthritis Strength [OTC]

Ecotrin Low Strength [OTC]

Ecotrin [OTC]

Halfprin [OTC] [DSC]

St Joseph Adult Aspirin [OTC]

Tri-Buffered Aspirin [OTC]

Brand Names: Canada

Asaphen

Asaphen E.C.

Entrophen

Novasen

Praxis ASA EC 81 Mg Daily Dose

Pro-AAS EC-80

Pharmacologic Category

Analgesic, Nonopioid

Antiplatelet Agent

Nonsteroidal Anti-inflammatory Drug (NSAID), Oral

Salicylate

Dosing: Adult

Note: For most cardiovascular uses, typical maintenance dosing of aspirin is 81 mg once
daily. Manufacturer recommended dosing for some indications have been superseded by
more recent guideline recommended doses and therefore manufacturer recommended dosing
may not be represented; terminologies may also differ from manufacturers prescribing
information.

Acute coronary syndrome (ST-elevation myocardial infarction [STEMI], unstable

angina [UA]/non-ST-elevation myocardial infarction [NSTEMI]) (off-label dosing):
Immediate release: Oral: Initial: 162 to 325 mg given on presentation (patient should
 chew nonenteric-coated aspirin especially if not taking before presentation); for patients
unable to take oral, may use a rectal suppository dose of 600 mg (Maalouf, 2009).
Maintenance (secondary prevention): 81 mg once daily preferred. When aspirin is used
with ticagrelor, the recommended maintenance dose of aspirin is 81 mg/day
(ACCF/AHA [Anderson 2013]; ACCF/AHA [O'Gara 2013]).

UA/NSTEMI: Concomitant antiplatelet therapy (ACCF/AHA [Anderson 2013]):

If invasive strategy chosen: Aspirin is recommended in combination with either

clopidogrel, ticagrelor, (or prasugrel if at the time of PCI) or an IV GP IIb/IIIa
inhibitor (if given before PCI, eptifibatide and tirofiban are preferred agents).

If noninvasive strategy chosen: Aspirin is recommended in combination with

clopidogrel or ticagrelor and anticoagulant therapy.

Analgesic and antipyretic:

Oral: Immediate release: 325 to 650 mg as needed every 4 hours or 975 mg as needed
every 6 hours or 500 to 1,000 mg as needed every 4 to 6 hours for no more than 10
days or as directed by health care provider; maximum daily dose: 4 g/day.

Rectal: 300 to 600 mg every 4 hours for no more than 10 days or as directed by health
care provider

Anti-inflammatory (off-label dosing): Note: The use of non-aspirin NSAIDs has largely
supplanted the use of aspirin for osteoarthritis, rheumatoid arthritis, and other
inflammatory arthritides.

Immediate release: Oral: Usual maintenance dose: 2.1 to 7.3 g/day in divided doses
(individualize dose); monitor serum salicylate concentrations especially when
symptoms of salicylism (eg, tinnitus) appear; adjust dose accordingly (Csuka,
1989).

Aortic valve repair (off-label use): Immediate release: Oral: 50 to 100 mg once daily
(ACCP [Guyatt 2012])

Atrial fibrillation (to prevent thromboembolism in patients not candidates for oral
anticoagulation or at low risk of ischemic stroke [CHA 2DS2-VASc score of 1]) (off-
label use): Immediate release: Oral: 75 to 325 mg once daily (AHA/ACC/HRS [January
2014]; AHA/ASA [Furie 2011]). Note: Combination therapy with clopidogrel has been
suggested over aspirin alone for those patients who are unsuitable for or choose not to
take oral anticoagulant for reasons other than concerns for bleeding (ACCP [Guyatt
2012]).

As an alternative to adjusted-dose warfarin in patients with atrial fibrillation and mitral

stenosis: 75 to 325 mg once daily with (preferred) or without clopidogrel (ACCP
[Guyatt 2012])

Carotid artery stenosis (asymptomatic) (off-label use): Immediate release: Oral: 75 to 100
mg once daily (ACCP [Alonso-Coello, 2012]). Note: The addition of statin therapy has
 also been recommended for asymptomatic carotid stenosis (AHA/ASA [Meschia,
2014]). When symptomatic, the use of clopidogrel or aspirin/extended-release
dipyridamole has been suggested over aspirin alone (ACCP [Alonso-Coello 2012]).

Carotid endarterectomy (off-label dosing): Immediate release: Oral: 75 to 100 mg once

daily (ACCP [Alonso-Coello 2012]; AHA [Biller 1998]). The use of clopidogrel or
aspirin/extended-release dipyridamole has been suggested over aspirin alone (ACCP
[Alonso-Coello 2012]).

Colorectal cancer risk reduction (off-label use): Note: The optimal dose and duration of
therapy for colorectal cancer risk reduction are unknown. Consider risk versus benefit
ratio when initiating aspirin for this indication.

Primary/Secondary prevention: Immediate release: Oral: 75 to 325 mg once daily

(Rothwell, 2010; Sandler, 2003; Ye, 2013)

Hereditary nonpolyposis colon cancer (HNPCC; Lynch Syndrome) carriers: Immediate

release: Oral: 600 mg once daily for at least 2 years (ASCO [Stoffel 2014]; Burn,
2011)

Coronary artery disease (CAD), established or chronic:

Immediate release (off-label dosing): Oral: 75 to 100 mg once daily (ACCP [Guyatt
2012])

Extended release capsule: Oral: 162.5 mg once daily

Percutaneous coronary intervention (PCI) (off-label dosing): Immediate release: Oral:

Non-emergent PCI: Preprocedure: 81 to 325 mg (325 mg [nonenteric coated] in aspirin-

naive patients) starting at least 2 hours (preferably 24 hours) before procedure.
Postprocedure: 81 mg once daily continued indefinitely (in combination with a
P2Y12 inhibitor [eg, clopidogrel, prasugrel, ticagrelor] up to 12 months)
(ACCF/AHA/SCAI [Levine 2011])

Primary PCI: Preprocedure: 162 to 325 mg as early as possible prior to procedure; 325
mg preferred. Postprocedure: 81 mg once daily continued indefinitely (in
combination with a P2Y12 inhibitor [eg, clopidogrel] for at least 14 days and up to
12 months) (ACCF/AHA [O'Gara 2013]).

Alternatively, in patients who have undergone elective PCI with either bare metal or
drug-eluting stent placement: The American College of Chest Physicians
recommends the use of 75 to 325 mg once daily (in combination with clopidogrel)
for 1 month in patients receiving a bare metal stent or 3 to 6 months (dependent
upon drug eluting stent type) followed by 75 to 100 mg once daily (in combination
with clopidogrel) for up to 12 months. For patients who underwent PCI but did not
have stent placement, 75 to 325 mg once daily (in combination with clopidogrel)
for 1 month is recommended. In either case, single antiplatelet therapy (either
aspirin or clopidogrel) is recommended indefinitely (ACCP [Guyatt 2012]).
Pericarditis (off-label use): Immediate release: Oral: Initial: 2.4 to 3.6 g daily in 3 to 4
divided doses; usual maintenance: 3.6 to 5.4 g daily in divided doses; gradually taper
over 2- to 3-week period as appropriate (Imazio, 2004; Imazio, 2009).

Pericarditis in association with myocardial infarction (off-label use): Immediate release:

Oral: Initial: 650 mg 4 times daily; may increase after 24 hours to 975 mg 4 times daily
if necessary (ACCF/AHA [O'Gara 2013]; Berman, 1981).

Peripheral arterial disease (off-label use): Immediate release: Oral: 75 to 100 mg once
daily (ACCP [Guyatt 2012]) or 75 to 325 mg once daily; may use in conjunction with
clopidogrel in those who are not at an increased risk of bleeding but are of high
cardiovascular risk. Note: These recommendations also pertain to those with intermittent
claudication or critical limb ischemia, prior lower extremity revascularization, or prior
amputation for lower extremity ischemia (Rooke, 2011).

Peripheral artery percutaneous transluminal angioplasty (with or without stenting) or

peripheral artery bypass graft surgery, postprocedure (off-label use): Immediate
release: Oral: 75 to 100 mg once daily (ACCP [Guyatt 2012]). Note: For below-knee
bypass graft surgery with prosthetic grafts, combine with clopidogrel (ACCP [Guyatt
2012]).

Polycythemia vera (off-label use): Immediate release: Oral: 75 or 100 mg once daily. In
pregnant women, administer 75 mg once daily throughout pregnancy and for 6 weeks
after delivery (Barbui, 2006; McMullin, 2005).

Preeclampsia prevention (women at risk) (off-label use): Immediate release: Oral: 75 to

100 mg once daily starting in the second trimester (ACCP [Guyatt 2012]; USPSTF
[LeFevre 2014]) or 60 to 80 mg once daily beginning late in the first trimester (ACOG,
2013).

Prevention (primary) of cardiovascular disease (off-label use): Immediate release: Oral:

American College of Chest Physicians: Select individuals 50 years of age (without

symptomatic cardiovascular disease): 75 to 100 mg once daily (ACCP [Vandvik
2012])

American Diabetes Association: Individuals 50 years of age with diabetes type 1 or 2

who are increased cardiovascular risk (10-year risk >10%): 75 to 162 mg once
daily (ADA 2016)

Prevention (secondary) after coronary artery bypass graft (CABG) surgery (off-label
dosing): Immediate release: Oral: 81 to 325 mg once daily administered preoperatively
and within 6 hours postoperatively; continue indefinitely. Following off-pump CABG,
administer aspirin 81 to 162 mg in combination with clopidogrel for 12 months (AHA
[Kulik 2015]).

Prosthetic heart valve (thromboprophylaxis) (off-label use): Immediate release: Oral:

Bioprosthetic aortic valve (patient in normal sinus rhythm): 50 to 100 mg once daily
(ACCP [Guyatt 2012]).
 Bioprosthetic mitral valve: 50 to 100 mg once daily after 3 months of anticoagulation
with warfarin (ACCP [Guyatt 2012]).

Mechanical aortic or mitral valve:

Low risk of bleeding: 50 to 100 mg once daily (in combination with warfarin)
(ACCP [Guyatt 2012])

History of thromboembolism while receiving oral anticoagulants: 75 to 100 mg

once daily (in combination with warfarin) (Furie, 2011)

Transcatheter aortic bioprosthetic valve: 50 to 100 mg once daily (in combination with
clopidogrel) (ACCP [Guyatt 2012])

Pregnant women, mechanical or bioprosthetic: 75 to 100 mg once daily during the

second and third trimesters (when used for mechanical prosthetic valve, combine
with warfarin) (AHA/ACC [Nishimura 2014]).

Stroke/TIA: Oral:

Acute ischemic stroke/TIA:

Immediate release (off-label dosing): Initial: 160 to 325 mg within 48 hours of

stroke/TIA onset, followed by 75 to 100 mg once daily (ACCP [Guyatt 2012]).
The AHA/ASA recommends an initial dose of 325 mg within 24 to 48 hours
after stroke; do not administer aspirin within 24 hours after administration of
alteplase (Jauch, 2013).

Extended-release capsule: Maintenance (secondary prevention): 162.5 mg once

daily. Note: Not for initial dosing during acute ischemic stroke or TIA (use
immediate release)

Cardioembolic, secondary prevention (oral anticoagulation unsuitable) (off-label

dosing: Immediate release: 75 to 100 mg once daily (in combination with
clopidogrel) (ACCP [Guyatt 2012]; The ACTIVE Investigators [Connolly 2009])

Cryptogenic with patent foramen ovale (PFO) or atrial septal aneurysm (off-label use):
Immediate release: 50 to 100 mg once daily (ACCP [Guyatt 2012])

Noncardioembolic, secondary prevention (off-label use): Immediate release: 75 to 325

mg once daily (Smith, 2011) or 75 to 100 mg once daily (ACCP [Guyatt 2012]).
Note: Combination aspirin/extended release dipyridamole or clopidogrel is
preferred over aspirin alone (ACCP [Guyatt 2012]).

Women at high risk for first stroke, primary prevention: Immediate release: 81 mg once
daily or 100 mg every other day (AHA/ASA [Meschia 2014]).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Do not use aspirin in children <12 years (APS, 2008) and adolescents (per
manufacturer) who have or who are recovering from chickenpox or flu symptoms due to
the association with Reye's syndrome (APS, 2008).

Analgesic: Immediate release:

Infants, Children, and Adolescents weighing <50 kg (off-label use): Oral, rectal: 10 to
15 mg/kg/dose every 4 to 6 hours; maximum daily dose: The lesser value of either
90 mg/kg/day or 4 g/day (APS, 2008)

Children 12 years and Adolescents weighing 50 kg:

Oral: 325 to 650 mg as needed every 4 hours or 975 mg as needed every 6 hours or
500 to 1,000 mg as needed every 4 to 6 hours for no more than 10 days or as
directed by health care provider; maximum daily dose: 4 g/day

Rectal: 300 to 600 mg every 4 hours for no more than 10 days or as directed by
health care provider

Anti-inflammatory (off-label use): Immediate release: Oral: Initial: 60 to 90 mg/kg/day in

divided doses; usual maintenance: 80 to 100 mg/kg/day divided every 6 to 8 hours;
monitor serum concentrations

Antiplatelet effects (off-label use): Adequate pediatric studies have not been performed;
pediatric dosage is derived from adult studies and clinical experience and is not well
established. Doses are typically rounded to a convenient amount (eg, 1/2 of 81 mg tablet).

Acute ischemic stroke (AIS) (off-label use): Immediate release: Oral:

Noncardioembolic: 1 to 5 mg/kg/dose once daily for 2 years; patients with

recurrent AIS or TIAs should be transitioned to clopidogrel, LMWH, or
warfarin (ACCP [Monagle 2012])

Secondary to Moyamoya and non-Moyamoya vasculopathy: 1 to 5 mg/kg/dose

once daily. Note: In non-Moyamoya vasculopathy, continue aspirin for 3
months, with subsequent use guided by repeat cerebrovascular imaging
(ACCP [Monagle 2012]).

Norwood, Fontan surgery (postoperative) (primary prophylaxis) (off-label use):

Immediate release: Oral: 1 to 5 mg/kg/dose once daily (ACCP [Monagle 2011];
AHA [Giglia 2013])

Prosthetic heart valve (off-label use): Immediate release: Oral:

Bioprosthetic aortic valve (in normal sinus rhythm): 1 to 5 mg/kg/dose once daily
(ACCP [Guyatt 2012]; ACCP [Monagle 2012])
 Mechanical aortic and/or mitral valve: Low-dose aspirin (eg, 1 to 5 mg/kg/day)
combined with vitamin K antagonist (eg, warfarin) is recommended as first-
line antithrombotic therapy (ACCP [Guyatt 2012]). Alternative regimens: 6 to
20 mg/kg/dose once daily in combination with dipyridamole (Bradley 1985; El
Makhlouf 1987; LeBlanc 1993; Serra 1987; Solymar 1991)

Shunts: Blalock-Taussig or Glenn (primary prophylaxis) (off-label use): Immediate

release: Oral: 1 to 5 mg/kg/dose once daily (AHA [Giglia 2013]; ACCP [Monagle
2012])

Transcatheter Atrial Septal Defect (ASD) or Ventricular Septal Defect (VSD) devices
(postprocedure prophylaxis) (off-label use): Immediate release: Oral: 1 to 5
mg/kg/dose once daily starting one to several days prior to implantation and
continued for at least 6 months. For older children and adolescents, after device
closure of ASD, an additional anticoagulant may be given with aspirin for 3 to 6
months, but the aspirin should continue for at least 6 months (AHA [Giglia 2013]).

Ventricular assist device (VAD) placement (off-label use): Immediate release: Oral: 1 to
5 mg/kg/dose once daily initiated within 72 hours of VAD placement; should be
used with heparin (initiated between 8 to 48 hours following implantation) (ACCP
[Monagle 2012]).

Kawasaki disease (off-label use): Immediate release: Oral: 80 to 100 mg/kg/day divided
every 6 hours for up to 14 days (until fever resolves for at least 48 hours); then decrease
dose to 1 to 5 mg/kg/day once daily (AHA and AAP suggest 3 to 5 mg/kg/day).
Combine initial high-dose treatment with IV immune globulin within first 10 days of
symptom onset. In patients without coronary artery abnormalities, give lower dose for at
least 6 to 8 weeks. In patients with coronary artery abnormalities, low-dose aspirin
should be continued indefinitely (in combination with warfarin) (ACCP [Monagle
2012]; AHA [Giglia 2013]; Newburger, 2004; Red Book [AAP 2015]).

Rheumatic fever (off-label use): Limited data available: Infants, Children, and Adolescents:
Oral: Initial: 100 mg/kg/day divided into 4 to 5 doses; if response inadequate, may
increase dose to 125 mg/kg/day; continue for 2 weeks; then decrease dose to 60 to 70
mg/kg/day in divided doses for an additional 3 to 6 weeks (WHO Guidelines 2004)

Migratory polyarthritis, with carditis without cardiomegaly or congestive heart failure:

Initial: 100 mg/kg/day in 4 divided doses for 3 to 5 days, followed by 75 mg/kg/day
in 4 divided doses for 4 weeks (Kliegman 2011)

Carditis and cardiomegaly or congestive heart failure: At the beginning of the tapering
of the prednisone dose, aspirin should be started at 75 mg/kg/day in 4 divided doses
for 6 weeks (Kliegman 2011)

Dosing: Renal Impairment

Analgesia or anti-inflammatory uses: The manufacturer recommends avoiding in patients

with CrCl <10 mL/minute. However, may use with caution and monitor renal function
or consider the use of an alternative analgesic/anti-inflammatory agent (NKF [Henrich
1996], Whelton 2000).
Antiplatelet uses: The manufacturer recommends avoiding in patients with CrCl <10
mL/minute. However, in general, the benefit of low-dose aspirin outweighs any risk
associated with nephropathy or other adverse effects even in the setting of severe renal
impairment; the recommended aspirin dose should not be reduced in any patient with
suspected or documented ACS, other cardiovascular disease, or other antithrombotic
indication (Fernandez 2001, Harter 1979, Summaria 2015). In patients with diabetes and
chronic kidney disease or in dialysis patients, the National Kidney Foundation
recommends the use of antithrombotic doses of aspirin (ie, 75 to 162 mg daily) for
prevention and management of ischemic heart disease or primary prevention of
atherosclerotic disease (KDOQI 2005, KDOQI 2007).

Hemodialysis: Dialyzable (concentration dependent; higher salicylate concentrations are

more readily dialyzable: 50% to 60%) (Juurlink 2015; Rosenberg 1981); consider
administration after hemodialysis on dialysis days (Aronoff 2007).

Dosing: Hepatic Impairment

Avoid use in severe liver disease.

Calculations

Creatinine Clearance by Cockcroft-Gault

Creatinine Clearance by Cockcroft-Gault (SI units)

Creatinine Clearance by Cockcroft-Gault with IBW

Creatinine Clearance by Cockcroft-Gault with IBW (SI units)

Creatinine Clearance by Jelliffe

Creatinine Clearance by Sanaka

Glomerular Filtration Rate by Abbreviated MDRD

Glomerular Filtration Rate by Abbreviated MDRD (SI units)

Glomerular Filtration Rate by MDRD

Glomerular Filtration Rate by MDRD (IDMS-Traceable SCr)

Glomerular Filtration Rate by MDRD (SI units)

Glomerular Filtration Rate by Schwartz

Use: Labeled Indications

Immediate release:
 Analgesic/Antipyretic: For the temporary relief of headache, pain, and fever caused by
colds, muscle aches and pains, menstrual pain, toothache pain, and minor aches and
pains of arthritis.

Revascularization procedures: In patients who have undergone revascularization

procedures (ie, coronary artery bypass graft [CABG], percutaneous transluminal
coronary angioplasty, or carotid endarterectomy).

Rheumatoid disease: For the relief of the signs and symptoms of rheumatoid arthritis
(RA), juvenile idiopathic arthritis (formerly called juvenile RA), osteoarthritis,
spondyloarthropathies, and arthritis and pleurisy associated with systemic lupus
erythematosus.

Vascular indications (ischemic stroke, transient ischemic attack, acute myocardial

infarction, prevention of recurrent myocardial infarction, unstable angina, and
chronic stable angina): To reduce the combined risk of death and nonfatal stroke
in patients who have had ischemic stroke or transient ischemia of the brain due to
fibrin platelet emboli; to reduce the risk of vascular mortality in patients with a
suspected acute myocardial infarction (MI); to reduce the combined risk of death
and nonfatal MI in patients with a previous MI or unstable angina; to reduce the
combined risk of MI and sudden death in patients with chronic stable angina.

Extended-release capsules:

Chronic coronary artery disease: To reduce the risk of death and MI in patients with
chronic coronary artery disease (eg, history of MI, unstable angina, or chronic
stable angina).

History of ischemic stroke or transient ischemic attack: To reduce the risk of death
and recurrent stroke in patients who have had an ischemic stroke or transient
ischemic attack (TIA).

Limitations of use: Do not use extended-release capsules in situations for which a rapid
onset of action is required (such as acute treatment of MI or before percutaneous
coronary intervention); use immediate-release formulations instead.

Use: Off-Label

Acute coronary syndromes (ST-elevation MI, non-ST-elevation MI, unstable angina)

Based on the 2013 American College of Cardiology/American Heart Association

(ACCF/AHA) guidelines for the management of ST-elevation myocardial infarction
(STEMI) and the ACCF/AHA guidelines for the management of unstable angina/non-
ST-elevation myocardial infarction (UA/NSTEMI), the use of aspirin for the immediate
treatment of patients presenting with symptoms suggestive of STEMI or UA/NSTEMI is
recommended. Patients should be instructed to chew nonenteric-coated aspirin while
emergency medical services personnel are en route.

Acute ischemic stroke/transient ischemic attack

 Based on the American College of Chest Physicians (ACCP) guidelines for
antithrombotic therapy and prevention of thrombosis (9th edition) and the American
Heart Association/American Stroke Association Guidelines for the Early Management of
Patients with Acute Ischemic Stroke, the use of aspirin within 24 to 48 hours after acute
ischemic stroke or transient ischemic attack onset is recommended for the treatment of
most patients.

Atrial fibrillation (prevention of thromboembolism)

Based on the American Heart Association/American College of Cardiology/Heart

Rhythm Society (AHA/ACC/HRS) guidelines for the management of atrial fibrillation,
aspirin may be considered for use in patients with a CHA2DS2-VASc score of 1 as an
alternative to other oral anticoagulants (eg, warfarin) to prevent thromboembolism
associated with nonvalvular atrial fibrillation.

Based on the American Heart Association/American Stroke Association (AHA/ASA)

guidelines for the prevention of stroke in patients with stroke or transient ischemic
attack, aspirin is recommended for use in patients with paroxysmal or permanent atrial
fibrillation who have suffered ischemic stroke or transient ischemic attack and are
unable to take oral anticoagulants.

Carotid artery stenosis (asymptomatic)

Based on the American College of Chest Physicians (ACCP) guidelines for

antithrombotic therapy and prevention of thrombosis (9th edition), daily aspirin is
suggested over no aspirin therapy in patients with asymptomatic carotid artery stenosis
based on a slight reduction in total mortality observed when aspirin is taken over 10
years (regardless of cardiovascular risk profile). The American Heart
Association/American Stroke Association (AHA/ASA) guidelines for the primary
prevention of stroke recommend daily aspirin (in combination with a statin) for patients
with asymptomatic carotid stenosis to reduce the risk of a first stroke occurring.

Colorectal cancer risk reduction (primary/secondary prevention)

Data from a large randomized double-blind trial supports the use of aspirin for the
prevention of colorectal adenomas in patients previously diagnosed with colorectal
cancer (Sandler 2003). Two meta-analyses also support the use of aspirin for the primary
prevention of colorectal cancer (Rothwell 2010; Ye 2013).

Colorectal cancer risk reduction in hereditary nonpolyposis colon cancer carriers (Lynch
syndrome)

Data from a large randomized phase 3 trial (CAPP2) supports the use of high-dose
aspirin (600 mg daily) for the prevention of colorectal cancer in patients who are carriers
of hereditary nonpolyposis colon cancer (Burn 2011).

The American Society of Clinical Oncology Guideline (Endorsement) for Hereditary

Colorectal Cancer Syndromes states that although current data is based on a single trial,
 chemoprevention with aspirin may be used to reduce the incidence of colorectal cancer
among carriers of Lynch Syndrome.

Episodic Migraine Prevention (adults)

US and European guidelines on the prevention of migraine have issued conflicting

statements regarding the use of aspirin; US guidelines list aspirin as having inadequate
or conflicting data to support or refute its use, while European guidelines list aspirin as
probably effective for migraine prevention. Access Full Off-Label Monograph

Kawasaki disease

Use of aspirin in the management of Kawasaki disease is recommended in the American

Heart Association and American College of Chest Physicians guidelines. Access Full
Off-Label Monograph

Percutaneous coronary intervention

Based on the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention

(PCI), aspirin in conjunction with other antiplatelet agents (eg P2Y12 inhibitors and
glycoprotein IIb/IIIa inhibitors) is effective in reducing the frequency of ischemic
complications after PCI and recommended for use prior to the procedure and continued
indefinitely.

Pericarditis

Data from a prospective open-label clinical trial supports the use of high-dose aspirin
treatment in patients with acute low-risk pericarditis (Imazio 2004). Clinical experience
also suggests the utility of high-dose aspirin in managing patients with pericarditis
(Imazio 2009). Additional data may be necessary to further define the role of aspirin in
this condition.

Pericarditis associated with MI

Data from a small prospective, randomized, single-blinded study comparing aspirin to

indomethacin demonstrated that most patients achieve discomfort relief from pericarditis
after STEMI with aspirin (Berman 1981).

Based on the American College of Cardiology Foundation/American Heart Association

(ACCF/AHA) guidelines for the management of ST-elevation myocardial infarction,
aspirin is recommended for the treatment of pericarditis after STEMI.

Polycythemia vera

Aspirin 75 to 100 mg daily may be used in all patients with polycythemia vera without a
history of major bleeding or gastric intolerance. Aspirin has been studied in more than
1,000 patients and is recommended in multiple polycythemia vera guidelines. Unless
contraindicated, all pregnant women with polycythemia vera should take aspirin (75 mg
daily initially) during pregnancy and for 6 weeks after delivery. Clinicians must consider
 the potential risk for bleeding and monitor for signs and symptoms of bleeding. Access
Full Off-Label Monograph

Preeclampsia (prevention)

Based on the American College of Chest Physicians guidelines and the American
College of Obstetricians and Gynecologists (ACOG 2013), aspirin is effective and
recommended for use in patients at risk of preeclampsia.

Prevention (primary) of cardiovascular disease

Based on the American College of Chest Physicians guidelines and the American
Diabetes Association (ADA) Standards of Medical Care in Diabetes, aspirin is effective
and recommended for the primary prevention of cardiovascular disease. According to
ACCP, aspirin is recommended in select patients (individuals 50 years of age without
symptomatic cardiovascular disease). According to ADA, in patients with type 1 or 2
diabetes, aspirin should be considered in patients who have an increased cardiovascular
risk (10-year risk >10%), which includes most men and women 50 years of age with at
least one additional risk factor.

Prevention (secondary) after coronary artery bypass graft (CABG) surgery

Based on a scientific statement from the American Heart Association on secondary

prevention after coronary artery bypass graft surgery, the use of aspirin preoperatively
and within 6 hours after CABG is effective and recommended for use in patients
undergoing CABG. Aspirin should be continued indefinitely to reduce graft occlusion
and adverse cardiac events.

Prosthetic heart valve (thromboprophylaxis)

Based on the 2014 American Heart Association/American College of Cardiology

(AHA/ACC) guideline for the management of patients with valvular heart disease and
the American Heart Association/American Stroke Association (AHA/ASA) guidelines
for the primary prevention of stroke, aspirin in addition to a vitamin K antagonist (eg,
warfarin) is effective and recommended in patients with a mechanical prosthetic valve
(ie, aortic or mitral position) to reduce the risk of thromboembolism (eg, stroke) and
mortality. The use of aspirin is also reasonable in all patients with a bioprosthetic aortic
or mitral valve.

Venous thromboembolism prevention after hip fracture surgery

According to ACCP guidelines, LMWH therapy is preferred over other drugs, including
aspirin, for thromboprophylaxis after hip fracture surgery. Aspirin plus an IPC device is
a possible option if an LMWH is unavailable or if the patient has a history of heparin-
induced thrombocytopenia. The primary concern regarding use of aspirin to prevent
VTE after hip fracture surgery is the potential for decreased efficacy compared with
LMWH therapy. Access Full Off-Label Monograph

Venous thromboembolism prevention after hip or knee arthroplasty

 ACCP guidelines recommend an LMWH over aspirin or other drugs for
thromboprophylaxis after hip or knee arthroplasty. Aspirin plus an IPC device is a
possible option if an LMWH is unavailable or if the patient has a history of heparin-
induced thrombocytopenia. The primary concern when using aspirin to prevent VTE
after hip or knee arthroplasty is the potential for decreased efficacy compared with
LMWH therapy. AAOS guidelines do not recommend one drug over another for the
prevention of VTE after hip or knee arthroplasty. Access Full Off-Label Monograph

Additional Off-Label Uses

Aortic valve repair (thromboprophylaxis); Blalock-Taussig or Glenn shunt placement

(primary prophylaxis); Fontan or Norwood surgery (primary prophylaxis); Peripheral
arterial occlusive disease; Peripheral artery percutaneous transluminal angioplasty;
Peripheral artery bypass graft surgery; Rheumatic fever; Transcatheter atrial septal
defect (ASD) or ventricular septal defect (VSD) devices (postprocedure prophylaxis);
Ventricular assist device (VAD) placement

Level of Evidence Definitions

Level of Evidence Scale

A - Consistent evidence from well-performed randomized, controlled trials or

overwhelming evidence of some other form (eg, results of the introduction of
penicillin treatment) to support the off-label use. Further research is unlikely to
change confidence in the estimate of benefit.

B - Evidence from randomized, controlled trials with important limitations (inconsistent

results, methodological flaws, indirect or imprecise), or very strong evidence of
some other research design. Further research (if performed) is likely to have an
impact on confidence in the estimate of benefit and risk and may change the
estimate.

C - Evidence from observational studies (eg, retrospective case series/reports providing

significant impact on patient care), unsystematic clinical experience, or from
potentially flawed randomized, controlled trials (eg, when limited options exist for
condition). Any estimate of effect is uncertain.

G - Use has been substantiated by inclusion in at least one evidence-based or consensus-

based clinical practice guideline.

Clinical Practice Guidelines

Atrial Fibrillation:

AAN, Prevention of Stroke in Nonvalvular Atrial Fibrillation, February 2014.

AHA/ACC/HRS, "2014 AHA/ACC/HRS Guideline for the Management of Patients

with Atrial Fibrillation," March 2014.
 Canadian Cardiovascular Society, "2014 Focused Update of the Canadian
Cardiovascular Society Guidelines for the Management of Atrial Fibrillation,"
August 2014

Coronary Artery Bypass Graft Surgery:

AHA Scientific Statement, Secondary Prevention After Coronary Artery Bypass Graft
Surgery, February 2015

Coronary Artery Stent Thrombosis Prevention:

AHA/ACC/SCAI/ACS/ADA Science Advisory, Prevention of Premature

Discontinuation of Dual Antiplatelet Therapy in Patients With Coronary Artery
Stents, February 2007

Ischemic Heart Disease:

ACC/AHA/AATS/PCNA/SCAI/STS, "2014 Focused Update of the Guideline for the

Diagnosis and Management of Patients with Stable Ischemic Heart Disease," July
2014

ACCF/AHA/ACP/AATS/PCNA/SCAI/STS, 2012 Guideline for the Diagnosis and

Management of Patients with Stable Ischemic Heart Disease, November 2012

Juvenile idiopathic arthritis:

American College of Rheumatology, 2013 Update of the 2011 American College of

Rheumatology Recommendations for the Treatment of Juvenile Idiopathic
Arthritis 2013

Percutaneous Coronary Intervention:

ACCF/AHA/SCAI, "2011 Guideline for Percutaneous Coronary Intervention,

November 2011

Peripheral Arterial Disease:

ACC/AHA, "2005 Guidelines for the Management of Patients with Peripheral Arterial
Disease, March 2006

ACCF/AHA, "2011 Focused Update of the Guideline for the Management of Patients
with Peripheral Artery Disease (Updating the 2005 Guideline), September 2011

Preeclampsia:
 Low-Dose Aspirin Use for the Prevention of Morbidity and Mortality From
Preeclampsia; U.S. Preventive Services Task Force Recommendation Statement,
September 2014

Prevention:

AHA/ACCF Secondary Prevention and Risk Reduction Therapy for Patients with
Coronary and Other Atherosclerotic Vascular Disease: 2011 Update, November
2011

American Diabetes Association, Standards of Medical Care in Diabetes - 2016,

January 2016

ASCO Hereditary Colorectal Cancer Syndromes Clinical Practice Guideline

[Endorsement], December 2014

Aspirin for the Prevention of Cardiovascular Disease: U.S. Preventive Services Task
Force Recommendation Statement, March 2009

ST-Elevation Myocardial Infarction:

ACCF/AHA, 2013 ACCF/AHA Guideline for the Management of ST-Elevation

Myocardial Infarction, December 2012

Stroke:

AHA/ASA , Guidelines for the Early Management of Patients With Acute Ischemic
Stroke, February 2013

AHA/ASA, Guidelines for the Prevention of Stroke in Women, 2014

AHA/ASA, Guidelines for Prevention of Stroke in Patients with Stroke and Transient
Ischemic Attack, May 2014 . Note: Information contained within this monograph
is pending revision based on these more recent guidelines.

AHA/ASA, Guidelines for the Primary Prevention of Stroke, December 2014

Surgery:

STS, 2012 Update to the Society of Thoracic Surgeons Guideline on Use of

Antiplatelet Drugs in Patients Having Cardiac and Noncardiac Operations,
November 2012

Unstable Angina/Non-ST-Elevation Myocardial Infarction:

 ACCF/AHA, "2012 ACCF/AHA Focused Update Incorporated Into the ACCF/AHA
2007 Guidelines for the Management of Patients With Unstable Angina/Non- ST-
Elevation Myocardial Infarction, April 2013

AHA/ACC, "2014 AHA/ACC Guideline for the Management of Patients with Non-ST-
Elevation Acute Coronary Syndromes, September 2014. Note: Information
contained within this monograph is pending revision based on these more recent
guidelines.

Valvular Heart Disease:

AHA/ACC, 2014 AHA/ACC Guideline for the Management of Patients with Valvular
Heart Disease, March 2014

Other:

ACC/AHA, 2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation

and Management of Patients Undergoing Noncardiac Surgery, August 2014. Note:
Information contained within this monograph is pending revision based on these
more recent guidelines.

AHA, Prevention and Treatment of Thrombosis in Pediatric and Congenital Heart

Disease, December 2013

American College of Chest Physicians Evidence-Based Clinical Practice

Guidelines (9th Edition), February 2012

American College of Chest Physicians (ACCP), Antithrombotic Therapy in

Peripheral Artery Disease: Antithrombotic Therapy and Prevention of
Thrombosis, 9th ed, February 2012

Canadian Cardiovascular Society, The Use of Antiplatelet Therapy in the Outpatient

Setting: Canadian Cardiovascular Society Guidelines, May 2011

Canadian Cardiovascular Society, Focused 2012 Update of the Canadian

Cardiovascular Society Guidelines for the Use of Antiplatelet Therapy, November
2013

Administration: Oral

Immediate-release tablets: Do not crush enteric-coated tablet. Administer with food or a full
glass of water to minimize GI distress. In situations for which a rapid onset of action is
required (eg, acute treatment of MI), have patient chew immediate-release tablet.

Extended-release capsules: Do not cut, crush, or chew. Administer with a full glass of water
at the same time each day. Do not administer 2 hours before or 1 hour after alcohol
consumption.
Administration: Rectal

Remove suppository from plastic packet and insert into rectum as far as possible.

Storage/Stability

Store oral dosage forms (caplets, tablets, capsules) at room temperature; protect from
moisture; see product-specific labeling for details. Keep suppositories in refrigerator; do not
freeze. Hydrolysis of aspirin occurs upon exposure to water or moist air, resulting in
salicylate and acetate, which possess a vinegar-like odor. Do not use if a strong odor is
present.

Medication Patient Education with HCAHPS Considerations

Discuss specific use of drug and side effects with patient as it relates to treatment.
(HCAHPS: During this hospital stay, were you given any medicine that you had not
taken before? Before giving you any new medicine, how often did hospital staff tell you
what the medicine was for? How often did hospital staff describe possible side effects in
a way you could understand?)

Patient may experience heartburn, vomiting, or nausea. Have patient report immediately to
prescriber signs of abdominal ulcers (very bad stomach or back pain; black, tarry, or
bloody stools; vomiting blood or vomit that looks like coffee grounds; or weight gain or
swelling that is not normal), signs of bleeding (vomiting blood or vomit that looks like
coffee grounds, coughing up blood, blood in the urine, black, red, or tarry stools,
bleeding from the gums, abnormal vaginal bleeding, bruises without a reason or that get
bigger, or any bleeding that is very bad or that will not stop), signs of kidney problems
(urinary retention, blood in urine, change in amount of urine passed, or weight gain),
signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal
pain, light-colored stools, vomiting, or yellow skin or eyes), severe dizziness, passing
out, confusion, severe headache, tinnitus, hearing impairment, severe abdominal pain,
agitation, seizures, severe rectal pain or irritation, or rectal bleeding (HCAHPS).

Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever;
itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat).
Note: This is not a comprehensive list of all side effects. Patient should consult
prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information
is intended to serve as a concise initial reference for health care professionals to use when
discussing medications with a patient.You must ultimately rely on your own discretion,
experience, and judgment in diagnosing, treating, and advising patients.

Medication Safety Issues

Sound-alike/look-alike issues:

Aspirin may be confused with Afrin

 Ascriptin may be confused with Aricept

Ecotrin may be confused with Edecrin, Epogen

Halfprin may be confused with Haltran

ZORprin may be confused with Zyloprim

International issues:

Cartia [multiple international markets] may be confused with Cartia XT brand name for
diltiazem [US]

Geriatric Patients: High-Risk Medication:

Beers Criteria: Aspirin, when used chronically at doses more than 325 mg, is identified
in the Beers Criteria as a potentially inappropriate medication to be avoided in
patients 65 years and older (unless alternative agents ineffective and patient can
receive concomitant gastroprotective agent) due to increased risk of GI bleeding
and peptic ulcer disease in older adults in high risk category (eg, older than 75
years of age or receiving concomitant oral/parenteral corticosteroids,
anticoagulants, or antiplatelet agents). In addition, when aspirin is used for the
primary prevention of cardiac events, it should be used with caution in older adults
80 years and older due to a lack of evidence of benefit versus risk (Beers Criteria
[AGS 2015]).

Contraindications

Hypersensitivity to NSAIDs; patients with asthma, rhinitis, and nasal polyps; use in children
or teenagers for viral infections, with or without fever.

Documentation of allergenic cross-reactivity for salicylates is limited. However, because of

similarities in chemical structure and/or pharmacologic actions, the possibility of cross-
sensitivity cannot be ruled out with certainty.

Warnings/Precautions

Concerns related to adverse effects:

Salicylate sensitivity: Patients with sensitivity to tartrazine dyes, nasal polyps, and
asthma may have an increased risk of salicylate sensitivity.

Tinnitus: Discontinue use if tinnitus or impaired hearing occurs.

Upper gastrointestinal (UGI) events (eg, symptomatic or complicated ulcers): Low-

dose aspirin for cardioprotective effects is associated with a two- to fourfold
increase in UGI events. The risks of these events increase with increasing aspirin
dose; during the chronic phase of aspirin dosing, doses >81 mg are not
recommended unless indicated (Bhatt, 2008).
Disease-related concerns:

Bleeding disorders: Use with caution in patients with platelet and bleeding disorders.

Dehydration: Use with caution in patients with dehydration.

Ethanol use: Heavy ethanol use (>3 drinks/day) can increase bleeding risks and may
enhance gastric mucosal damage.

Gastrointestinal disease: Use with caution in patients with erosive gastritis. Avoid use
in patients with active peptic ulcer disease.

Hepatic impairment: Avoid use in severe hepatic failure.

Renal impairment: When using high dosages (eg, analgesic or anti-inflammatory uses),
use with caution and monitor renal function or consider the use of an alternative
analgesic/anti-inflammatory agent (NKF [Henrich 1996], Whelton 2000). Low-
dose aspirin (eg, 75 to 162 mg daily) may be safely used in patients with any
degree of renal impairment (KDOQI 2005, KDOQI 2007).

Concurrent drug therapy issues:

Alteplase: In the treatment of acute ischemic stroke, avoid aspirin for 24 hours
following administration of alteplase; administration within 24 hours increases the
risk of hemorrhagic transformation (Jauch, 2013).

Clopidogrel: Concurrent use of aspirin and clopidogrel is not recommended for

secondary prevention of ischemic stroke or TIA in patients unable to take oral
anticoagulants due to hemorrhagic risk (Furie, 2011).

COX-2 inhibitors/NSAIDs: When used concomitantly with 325 mg of aspirin,

NSAIDs (including selective COX-2 inhibitors) substantially increase the risk of
gastrointestinal complications (eg, ulcer); concomitant gastroprotective therapy (eg,
proton pump inhibitors) is recommended (Bhatt, 2008).

Drug-drug interactions: Potentially significant interactions may exist, requiring dose or

frequency adjustment, additional monitoring, and/or selection of alternative
therapy. Consult drug interactions database for more detailed information.

Special populations:

Pediatric: When used for self-medication (OTC labeling): Children and teenagers who
have or are recovering from chickenpox or flu-like symptoms should not use this
product. Changes in behavior (along with nausea and vomiting) may be an early
sign of Reye's syndrome; patients should be instructed to contact their healthcare
provider if these occur.

Pregnancy: In general, low doses during pregnancy needed for the treatment of certain
medical conditions have not been shown to cause fetal harm; however,
discontinuing therapy prior to delivery is recommended. Use of safer agents for
 routine management of pain or headache throughout pregnancy should be
considered. If possible, avoid use during the third trimester of pregnancy.

Surgical patients: ASA should be avoided (if possible) in surgical patients for 1 to 2
weeks prior to surgery, to reduce the risk of excessive bleeding (except in patients
with cardiac stents that have not completed their full course of dual antiplatelet
therapy [aspirin, clopidogrel]; patient specific situations need to be discussed with
cardiologist; AHA/ACC/SCAI/ACS/ADA Science Advisory provides
recommendations).

Dosage form specific issues:

Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as
Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported
following exposure to pharmaceutical products containing polysorbate 80 in certain
individuals (Isaksson, 2002; Lucente 2000; Shelley, 1995). Thrombocytopenia,
ascites, pulmonary deterioration, and renal and hepatic failure have been reported
in premature neonates after receiving parenteral products containing polysorbate 80
(Alade, 1986; CDC, 1984). See manufacturers labeling.

Other warnings/precautions:

Resistance: Aspirin resistance is defined as measurable, persistent platelet activation

that occurs in patients prescribed a therapeutic dose of aspirin. Clinical aspirin
resistance, the recurrence of some vascular event despite a regular therapeutic dose
of aspirin, is considered aspirin treatment failure. Proposed mechanisms of aspirin
resistance include poor adherence with therapy, poor absorption, inadequate
dosage, drug interactions, increased isoprostane activity, platelet hypersensitivity to
agonists, increased COX-2 activity, COX-1 polymorphism, and platelet alloantigen
2 polymorphism of platelet glycoprotein IIIa. Estimates of biochemical aspirin
resistance range from 5.5% to 60% depending on the population studied and the
assays used (Gasparyan, 2008). Patients with aspirin resistance may have a higher
risk of cardiovascular events compared to those who are aspirin sensitive (Gum,
2003). Aspirin resistance is likely dose-related but may be influenced by dynamic
factors yet to be identified; further research is required.

Geriatric Considerations

Elderly are a high-risk population for adverse effects from nonsteroidal anti-inflammatory
agents. As much as 60% of elderly with GI complications to NSAIDs can develop peptic
ulceration and/or hemorrhage asymptomatically. The concomitant use of H2 blockers and
sucralfate is not effective as prophylaxis with the exception of NSAID-induced duodenal
ulcers which may be prevented by the use of ranitidine. Misoprostol and proton pump
inhibitors are the only prophylactic agents proven to help prevent the development of
NSAID-induced ulcers. Also, concomitant disease and drug use contribute to the risk for GI
adverse effects. Use lowest effective dose for shortest period possible. Consider renal
function decline with age. Use of NSAIDs can compromise existing renal function especially
when CrCl is 30 mL/minute. Tinnitus may be a difficult and unreliable indication of toxicity
due to age-related hearing loss or eighth cranial nerve damage. CNS adverse effects such as
confusion, agitation, and hallucination are generally seen in overdose or high dose situations,
but elderly may demonstrate these adverse effects at lower doses than younger adults.

Pregnancy Considerations

Salicylates have been noted to cross the placenta and enter fetal circulation. Adverse effects
reported in the fetus include mortality, intrauterine growth retardation, salicylate intoxication,
bleeding abnormalities, and neonatal acidosis. Use of aspirin close to delivery may cause
premature closure of the ductus arteriosus. Adverse effects reported in the mother include
anemia, hemorrhage, prolonged gestation, and prolonged labor (stensen, 1998). Low-dose
aspirin may be used to prevent preeclampsia in women with a history of early-onset
preeclampsia and preterm delivery (<34 0/7 weeks), or preeclampsia in 1 prior pregnancy
(ACOG, 2013). Low-dose aspirin is used to treat complications resulting from
antiphospholipid syndrome in pregnancy (either primary or secondary to SLE) (ACCP
[Guyatt, 2012]; Carp, 2004; Tincani, 2003). Low-dose aspirin to prevent thrombosis may also
be used during the second and third trimesters in women with prosthetic valves (mechanical
or bioprosthetic). The use of warfarin is recommended, along with low dose aspirin, in those
with mechanical prosthetic valves (Nishimura, 2014). In general, low doses during pregnancy
needed for the treatment of certain medical conditions have not been shown to cause fetal
harm; however, discontinuing therapy prior to delivery is recommended (stensen, 2006).
Use of safer agents for routine management of pain or headache should be considered.

Breast-Feeding Considerations

Low amounts of aspirin can be found in breast milk. Milk/plasma ratios ranging from 0.03 to
0.3 have been reported. Peak levels in breast milk are reported to be at ~9 hours after a dose.
Metabolic acidosis was reported in one infant following an aspirin dose of 3.9 g/day in the
mother. The WHO considers occasional doses of aspirin to be compatible with breast-
feeding, but to avoid long-term therapy and consider monitoring the infant for adverse effects
(WHO, 2002). Other sources suggest avoiding aspirin while breast-feeding due to the
theoretical risk of Reye's syndrome (Bar-Oz, 2003; Spigset, 2000). When used for vascular
indications, breast-feeding may be continued during low-dose aspirin therapy (ACCP
[Guyatt, 2012]).

Briggs' Drugs in Pregnancy & Lactation

Aspirin

Adverse Reactions

As with all drugs which may affect hemostasis, bleeding is associated with aspirin.
Hemorrhage may occur at virtually any site. Risk is dependent on multiple variables
including dosage, concurrent use of multiple agents which alter hemostasis, and patient
susceptibility. Many adverse effects of aspirin are dose related, and are rare at low dosages.
Other serious reactions are idiosyncratic, related to allergy or individual sensitivity. Accurate
estimation of frequencies is not possible. The reactions listed below have been reported for
aspirin.

Cardiovascular: Cardiac arrhythmia, edema, hypotension, tachycardia

Central nervous system: Agitation, cerebral edema, coma, confusion, dizziness, fatigue,
headache, hyperthermia, insomnia, lethargy, nervousness, Reye's syndrome

Dermatologic: Skin rash, urticaria

Endocrine & metabolic: Acidosis, dehydration, hyperglycemia, hyperkalemia, hypernatremia

(buffered forms), hypoglycemia (children)

Gastrointestinal: Gastrointestinal ulcer (6% to 31%), duodenal ulcer, dyspepsia, epigastric

distress, gastritis, gastrointestinal erosion, heartburn, nausea, stomach pain, vomiting

Genitourinary: Postpartum hemorrhage, prolonged gestation, prolonged labor, proteinuria,

stillborn infant

Hematologic & oncologic: Anemia, blood coagulation disorder, disseminated intravascular

coagulation, hemolytic anemia, hemorrhage, iron deficiency anemia, prolonged
prothrombin time, thrombocytopenia

Hepatic: Hepatitis (reversible), hepatotoxicity, increased serum transaminases

Hypersensitivity: Anaphylaxis, angioedema

Neuromuscular & skeletal: Acetabular bone destruction, rhabdomyolysis, weakness

Otic: Hearing loss, tinnitus

Renal: Increased blood urea nitrogen, increased serum creatinine, interstitial nephritis, renal
failure (including cases caused by rhabdomyolysis), renal insufficiency, renal papillary
necrosis

Respiratory: Asthma, bronchospasm, dyspnea, hyperventilation, laryngeal edema,

noncardiogenic pulmonary edema, respiratory alkalosis, tachypnea

Miscellaneous: Low birth weight

Postmarketing and/or case reports: Anorectal stenosis (suppository), atrial fibrillation

(toxicity), cardiac conduction disturbance (toxicity), cerebral infarction (ischemic),
cholestatic jaundice, colitis, colonic ulceration, coronary artery vasospasm, delirium,
esophageal obstruction, esophagitis (with esophageal ulcer), hematoma (esophageal),
macular degeneration (age-related) (Li 2014), periorbital edema, rhinosinusitis

Allergy and Idiosyncratic Reactions

Salicylate Allergy/Sensitivity

Toxicology

Salicylates

Metabolism/Transport Effects
Substrate of CYP2C9 (minor); Note: Assignment of Major/Minor substrate status based on
clinically relevant drug interaction potential; Induces CYP2C19 (weak/moderate)

Drug Interactions

ACE Inhibitors: Salicylates may enhance the nephrotoxic effect of ACE Inhibitors.
Salicylates may diminish the therapeutic effect of ACE Inhibitors. Risk C: Monitor
therapy

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May
enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result.
Risk C: Monitor therapy

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May
enhance the antiplatelet effect of other Agents with Antiplatelet Properties. Risk C:
Monitor therapy

Ajmaline: Salicylates may enhance the adverse/toxic effect of Ajmaline. Specifically, the risk
for cholestasis may be increased. Risk C: Monitor therapy

Alcohol (Ethyl): May enhance the adverse/toxic effect of Aspirin. Specifically, alcohol may
increase the bleeding risk of aspirin. Alcohol (Ethyl) may diminish the therapeutic effect
of Aspirin. Specifically, alcohol may interfere with the controlled release mechanism of
extended release aspirin. Management: Monitor patients who drink 3 or more alcoholic
drinks a day for increased bleeding while taking aspirin. Counsel patients about the risk
of bleeding and discourage such consumption. Give extended release aspirin 2 hours
before, or 1 hour after, alcohol. Risk D: Consider therapy modification

Alendronate: Aspirin may enhance the adverse/toxic effect of Alendronate. Specifically, the
incidence of upper gastrointestinal adverse events may be increased Risk C: Monitor
therapy

Ammonium Chloride: May increase the serum concentration of Salicylates. Risk C: Monitor
therapy

Anticoagulants: Agents with Antiplatelet Properties may enhance the anticoagulant effect of
Anticoagulants. Risk C: Monitor therapy

Anticoagulants: Salicylates may enhance the anticoagulant effect of Anticoagulants. Risk C:

Monitor therapy

Antidepressants (Tricyclic, Tertiary Amine): May enhance the antiplatelet effect of Aspirin.
Risk C: Monitor therapy

Apixaban: Aspirin may enhance the adverse/toxic effect of Apixaban. Specifically, the risk
for bleeding may be increased. Management: Carefully consider risks and benefits of
this combination and monitor closely. Risk D: Consider therapy modification

Benzbromarone: Salicylates may diminish the therapeutic effect of Benzbromarone. Risk C:

Monitor therapy
Blood Glucose Lowering Agents: Salicylates may enhance the hypoglycemic effect of Blood
Glucose Lowering Agents. Risk C: Monitor therapy

Calcium Channel Blockers (Nondihydropyridine): May enhance the anticoagulant effect of

Salicylates. Exceptions: Bepridil. Risk C: Monitor therapy

Carbonic Anhydrase Inhibitors: Salicylates may enhance the adverse/toxic effect of Carbonic
Anhydrase Inhibitors. Salicylate toxicity might be enhanced by this same combination.
Management: Avoid these combinations when possible.Dichlorphenamide use with
high-dose aspirin as contraindicated. If another combination is used, monitor patients
closely for adverse effects. Tachypnea, anorexia, lethargy, and coma have been reported.
Exceptions: Brinzolamide; Dorzolamide. Risk D: Consider therapy modification

Carisoprodol: Aspirin may increase serum concentrations of the active metabolite(s) of

Carisoprodol. Specifically, Meprobamate concentrations may be increased. Aspirin may
decrease the serum concentration of Carisoprodol. Risk C: Monitor therapy

Cephalothin: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of
Cephalothin. Specifically, the risk for bleeding may be increased. Risk C: Monitor
therapy

Collagenase (Systemic): Agents with Antiplatelet Properties may enhance the adverse/toxic
effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or
bleeding may be increased. Risk C: Monitor therapy

Corticosteroids (Systemic): Salicylates may enhance the adverse/toxic effect of

Corticosteroids (Systemic). These specifically include gastrointestinal ulceration and
bleeding. Corticosteroids (Systemic) may decrease the serum concentration of
Salicylates. Withdrawal of corticosteroids may result in salicylate toxicity. Risk C:
Monitor therapy

Dabigatran Etexilate: Aspirin may enhance the adverse/toxic effect of Dabigatran Etexilate.
Specifically, the risk for bleeding may be increased. Management: Carefully consider
risks and benefits of this combination and monitor closely; Canadian labeling states that
low dose aspirin could be considered, but the use of antiplatelets are not recommended
for stroke prevention in patients with atrial fibrillation. Risk D: Consider therapy
modification

Dasatinib: May enhance the anticoagulant effect of Agents with Antiplatelet Properties. Risk
C: Monitor therapy

Deoxycholic Acid: Agents with Antiplatelet Properties may enhance the adverse/toxic effect
of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area
may be increased. Risk C: Monitor therapy

Dexketoprofen: Salicylates may enhance the adverse/toxic effect of Dexketoprofen.

Dexketoprofen may diminish the therapeutic effect of Salicylates. Salicylates may
decrease the serum concentration of Dexketoprofen. Management: The use of high-dose
salicylates (3 g/day or more in adults) together with dexketoprofen is inadvisable.
Consider administering dexketoprofen 30-120 min after or at least 8 hrs before
 cardioprotective doses of aspirin to minimize any possible interaction. Risk X: Avoid
combination

Edoxaban: Aspirin may enhance the adverse/toxic effect of Edoxaban. Specifically, the risk
of bleeding may be increased. Aspirin may increase the serum concentration of
Edoxaban. Management: Carefully consider the anticipated risks and benefits of this
combination. If combined, increased monitoring for bleeding is recommended. Risk D:
Consider therapy modification

Floctafenine: May enhance the adverse/toxic effect of Aspirin. An increased risk of bleeding
may be associated with use of this combination. Floctafenine may diminish the
cardioprotective effect of Aspirin. Risk X: Avoid combination

Ginkgo Biloba: May enhance the anticoagulant effect of Salicylates. Management: Consider
alternatives to this combination of agents. Monitor for signs and symptoms of bleeding
(especially intracranial bleeding) if salicylates are used in combination with ginkgo
biloba. Risk D: Consider therapy modification

Glucosamine: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk
C: Monitor therapy

Heparin: Aspirin may enhance the anticoagulant effect of Heparin. Risk C: Monitor therapy

Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the
adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Risk D:
Consider therapy modification

Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the
adverse/toxic effect of Salicylates. Bleeding may occur. Risk D: Consider therapy
modification

Hyaluronidase: Salicylates may diminish the therapeutic effect of Hyaluronidase.

Management: Patients receiving salicylates (particularly at larger doses) may not
experience the desired clinical response to standard doses of hyaluronidase. Larger doses
of hyaluronidase may be required. Risk D: Consider therapy modification

Ibritumomab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of
Ibritumomab. Both agents may contribute to impaired platelet function and an increased
risk of bleeding. Risk C: Monitor therapy

Ibrutinib: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk
C: Monitor therapy

Influenza Virus Vaccine (Live/Attenuated): May enhance the adverse/toxic effect of

Salicylates. Specifically, Reye's syndrome may develop. Risk X: Avoid combination

Ketorolac (Nasal): May enhance the adverse/toxic effect of Aspirin. An increased risk of
bleeding may be associated with use of this combination. Ketorolac (Nasal) may
diminish the cardioprotective effect of Aspirin. Risk X: Avoid combination
Ketorolac (Systemic): May enhance the adverse/toxic effect of Aspirin. An increased risk of
bleeding may be associated with use of this combination. Ketorolac (Systemic) may
diminish the cardioprotective effect of Aspirin. Risk X: Avoid combination

Lesinurad: Aspirin may diminish the therapeutic effect of Lesinurad. Risk C: Monitor therapy

Limaprost: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C:
Monitor therapy

Loop Diuretics: Salicylates may diminish the diuretic effect of Loop Diuretics. Loop
Diuretics may increase the serum concentration of Salicylates. Risk C: Monitor therapy

Methotrexate: Salicylates may increase the serum concentration of Methotrexate. Salicylate

doses used for prophylaxis of cardiovascular events are not likely to be of concern. Risk
D: Consider therapy modification

Multivitamins/Fluoride (with ADE): May enhance the antiplatelet effect of Aspirin. Aspirin
may decrease the serum concentration of Multivitamins/Fluoride (with ADE).
Specifically, aspirin may decrease the absorption of ascorbic acid. Risk C: Monitor
therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the antiplatelet effect of
Aspirin. Aspirin may decrease the serum concentration of Multivitamins/Minerals (with
ADEK, Folate, Iron). Specifically, aspirin may decrease absorption of ascorbic acid.
Risk C: Monitor therapy

Multivitamins/Minerals (with AE, No Iron): May enhance the antiplatelet effect of Aspirin.
Aspirin may decrease the serum concentration of Multivitamins/Minerals (with AE, No
Iron). Specifically, aspirin may decrease the absorption of ascorbic acid. Risk C:
Monitor therapy

Nicorandil: Aspirin may enhance the adverse/toxic effect of Nicorandil. Specifically, the risk
of gastrointestinal ulceration and hemorrhage may be increased. Risk C: Monitor
therapy

NSAID (COX-2 Inhibitor): Aspirin may enhance the adverse/toxic effect of NSAID (COX-2
Inhibitor). Management: Concurrent use of aspirin at doses beyond cardioprotective
levels is not recommended. While concurrent use of low-dose aspirin with a COX-2
inhibitor is permissable, patients should be monitored closely for signs/symptoms of GI
ulceration/bleeding. Risk D: Consider therapy modification

NSAID (Nonselective): May enhance the adverse/toxic effect of Salicylates. An increased

risk of bleeding may be associated with use of this combination. NSAID (Nonselective)
may diminish the cardioprotective effect of Salicylates. Salicylates may decrease the
serum concentration of NSAID (Nonselective). Risk D: Consider therapy modification

Obinutuzumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of
Obinutuzumab. Specifically, the risk of serious bleeding-related events may be
increased. Risk C: Monitor therapy
Omacetaxine: Aspirin may enhance the adverse/toxic effect of Omacetaxine. Specifically, the
risk for bleeding-related events may be increased. Management: Avoid concurrent use of
aspirin with omacetaxine in patients with a platelet count of less than 50,000/uL. Risk X:
Avoid combination

Omega-3 Fatty Acids: May enhance the antiplatelet effect of Agents with Antiplatelet
Properties. Risk C: Monitor therapy

Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Agents with
Antiplatelet Properties. Specifically, the risk of bleeding may be increased by concurrent
use of these agents. Risk C: Monitor therapy

Pentoxifylline: May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Risk C: Monitor therapy

Potassium Acid Phosphate: May increase the serum concentration of Salicylates. Risk C:
Monitor therapy

PRALAtrexate: Salicylates may increase the serum concentration of PRALAtrexate.

Salicylate doses used for prophylaxis of cardiovascular events are unlikely to be of
concern. Risk D: Consider therapy modification

Probenecid: Salicylates may diminish the therapeutic effect of Probenecid. Risk C: Monitor
therapy

Prostacyclin Analogues: May enhance the antiplatelet effect of Agents with Antiplatelet
Properties. Risk C: Monitor therapy

Rivaroxaban: Aspirin may enhance the adverse/toxic effect of Rivaroxaban. Specifically, the
risk of bleeding may be increased. Management: Carefully consider risks and benefits of
this combination and monitor closely. Risk D: Consider therapy modification

Salicylates: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of
Salicylates. Increased risk of bleeding may result. Risk C: Monitor therapy

Salicylates: May enhance the anticoagulant effect of other Salicylates. Risk C: Monitor
therapy

Selective Serotonin Reuptake Inhibitors: May enhance the antiplatelet effect of Aspirin. Risk
C: Monitor therapy

Serotonin/Norepinephrine Reuptake Inhibitors: May enhance the antiplatelet effect of

Aspirin. Risk C: Monitor therapy

Sulfinpyrazone: Salicylates may decrease the serum concentration of Sulfinpyrazone. Risk X:

Avoid combination

Talniflumate: Aspirin may enhance the adverse/toxic effect of Talniflumate. Management:

When possible, consider alternatives to this combination. Concurrent use is generally
not recommended. Risk D: Consider therapy modification
Thrombolytic Agents: Agents with Antiplatelet Properties may enhance the anticoagulant
effect of Thrombolytic Agents. Risk C: Monitor therapy

Thrombolytic Agents: Salicylates may enhance the adverse/toxic effect of Thrombolytic

Agents. An increased risk of bleeding may occur. Risk C: Monitor therapy

Ticagrelor: Aspirin may enhance the antiplatelet effect of Ticagrelor. Aspirin may diminish
the therapeutic effect of Ticagrelor. More specifically, the benefits of ticagrelor relative
to clopidogrel may be diminished in adult patients receiving daily aspirin doses greater
than 100-150 mg daily. Management: Avoid daily aspirin doses greater than 100 mg in
adults receiving ticagrelor. Canadian recommendations are to avoid adult daily aspirin
doses greater than 150 mg. Daily low-dose aspirin (U.S.: 75-100 mg; Canada: 75-150
mg) is recommended. Risk D: Consider therapy modification

Tiludronate: Aspirin may decrease the serum concentration of Tiludronate. Risk C: Monitor
therapy

Tipranavir: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk
C: Monitor therapy

Tositumomab and Iodine I 131 Tositumomab: Agents with Antiplatelet Properties may
enhance the adverse/toxic effect of Tositumomab and Iodine I 131 Tositumomab.
Specifically, the risk of bleeding-related adverse events may be increased. Risk C:
Monitor therapy

Treprostinil: May enhance the adverse/toxic effect of Salicylates. Bleeding may occur. Risk
C: Monitor therapy

Urokinase: Agents with Antiplatelet Properties may enhance the anticoagulant effect of
Urokinase. Risk X: Avoid combination

Valproate Products: Salicylates may increase the serum concentration of Valproate Products.
Risk C: Monitor therapy

Varicella Virus-Containing Vaccines: Salicylates may enhance the adverse/toxic effect of

Varicella Virus-Containing Vaccines. Reye's Syndrome may develop. Risk D: Consider
therapy modification

Vitamin E: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C:
Monitor therapy

Vitamin E (Oral): May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Risk C: Monitor therapy

Vitamin K Antagonists (eg, warfarin): Salicylates may enhance the anticoagulant effect of
Vitamin K Antagonists. Risk D: Consider therapy modification

Food Interactions
Food may decrease the rate but not the extent of oral absorption. Benedictine liqueur, prunes,
raisins, tea, and gherkins have a potential to cause salicylate accumulation. Fresh fruits
containing vitamin C may displace drug from binding sites, resulting in increased urinary
excretion of aspirin. Curry powder, paprika, licorice; may cause salicylate accumulation.
These foods contain 6 mg salicylate/100 g. An ordinary American diet contains 10-200
mg/day of salicylate. Management: Administer with food or large volume of water or milk to
minimize GI upset. Limit curry powder, paprika, licorice.

Test Interactions

False-negative results for glucose oxidase urinary glucose tests (Clinistix); false-positives
using the cupric sulfate method (Clinitest); also, interferes with Gerhardt test, VMA
determination; 5-HIAA, xylose tolerance test and T3 and T4

Genes of Interest

Integrin, Beta 3 (Platelet Glycoprotein IIIa, Antigen CD61)

Leukotriene C4 Synthase

Reference Range

Timing of serum samples: Peak levels usually occur 2 hours after ingestion. Salicylate serum
concentrations correlate with the pharmacological actions and adverse effects observed. The
serum salicylate concentration (mcg/mL) and the corresponding clinical correlations are as
follows: See table.

Serum Salicylate: Clinical Correlations

Serum Salicylate
Concentration
Desired Effects Adverse Effects / Intoxication
(mcg/mL)

Antiplatelet
GI intolerance and bleeding, hypersensitivity,
~100 Antipyresis
hemostatic defects
Analgesia

Anti-
150-300 Mild salicylism
inflammatory

250-400 Treatment of Nausea/vomiting, hyperventilation, salicylism,

flushing, sweating, thirst, headache, diarrhea, and
 Serum Salicylate: Clinical Correlations

Serum Salicylate
Concentration
Desired Effects Adverse Effects / Intoxication
(mcg/mL)

rheumatic fever tachycardia

Respiratory alkalosis, hemorrhage, excitement,

confusion, asterixis, pulmonary edema, convulsions,
>400-500
tetany, metabolic acidosis, fever, coma, cardiovascular
collapse, renal and respiratory failure

Table has been converted to the following text.

Serum Salicylate: Clinical Correlations

Serum salicylate level ~100 mcg/mL:

Desired effects: Analgesia, antiplatelet, antipyresis

Adverse effects/intoxication: GI intolerance and bleeding, hemostatic defects,

hypersensitivity

Serum salicylate level 150-300 mcg/mL:

Desired effects: Anti-inflammatory

Adverse effects/intoxication: Mild salicylism

Serum salicylate level 250-400 mcg/mL:

Desired effects: Treatment of rheumatic fever

Adverse effects/intoxication: Diarrhea, flushing, headache, hyperventilation,

nausea/vomiting, salicylism, sweating, tachycardia, thirst

Serum salicylate level >400-500 mcg/mL:

Adverse effects/intoxication: Asterixis, cardiovascular collapse, coma, confusion,

convulsions, excitement, fever, hemorrhage, metabolic acidosis, pulmonary edema,
renal and respiratory failure, respiratory alkalosis, tetany
Nursing: Physical Assessment/Monitoring

Discuss patient-specific situations with the cardiologist. Obtain CBC, iron studies, ferritin,
and stools for occult blood with prolonged therapy. Assess other medicines patient may be
taking; alternate therapy or dosage adjustments may be needed.

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult
specific product labeling. [DSC] = Discontinued product

Caplet, oral: 500 mg

Bayer Aspirin Extra Strength: 500 mg

Bayer Genuine Aspirin: 325 mg

Bayer Women's Low Dose Aspirin: 81 mg [contains elemental calcium 300 mg]

Caplet, oral [buffered]:

Ascriptin Maximum Strength: 500 mg [contains aluminum hydroxide, calcium

carbonate, magnesium hydroxide]

Bayer Plus Extra Strength: 500 mg [contains calcium carbonate]

Caplet, enteric coated, oral:

Bayer Aspirin Regimen Regular Strength: 325 mg

Capsule Extended Release, oral:

Durlaza: 162.5 mg

Suppository, rectal: 300 mg (12s); 600 mg (12s)

Tablet, oral: 325 mg

Aspercin: 325 mg

Aspirtab: 325 mg

Bayer Genuine Aspirin: 325 mg

Tablet, oral [buffered]: 325 mg

Ascriptin Regular Strength: 325 mg [contains aluminum hydroxide, calcium carbonate,

magnesium hydroxide]

Buffasal: 325 mg [contains magnesium oxide]

 Bufferin: 325 mg [contains calcium carbonate, magnesium carbonate, magnesium oxide]

Bufferin Extra Strength: 500 mg [contains calcium carbonate, magnesium carbonate,

magnesium oxide]

Buffinol: 324 mg [sugar free; contains magnesium oxide]

Tri-Buffered Aspirin: 325 mg [contains calcium carbonate, magnesium carbonate,

magnesium oxide]

Tablet, chewable, oral: 81 mg

Bayer Aspirin Regimen Children's: 81 mg [cherry flavor]

Bayer Aspirin Regimen Children's: 81 mg [orange flavor]

St Joseph Adult Aspirin: 81 mg

Tablet, enteric coated, oral: 81 mg, 325 mg, 650 mg

Aspir-low: 81 mg

Bayer Aspirin Regimen Adult Low Strength: 81 mg

Ecotrin: 325 mg

Ecotrin Arthritis Strength: 500 mg

Ecotrin Low Strength: 81 mg

Halfprin: 81 mg [DSC]

St Joseph Adult Aspirin: 81 mg

Anatomic Therapeutic Chemical (ATC) Classification

A01AD05

B01AC06

N02BA01

Generic Available (US)

May be product dependent

Pricing: US

Capsule ER 24 Hour Therapy Pack (Durlaza Oral)

 162.5 mg (30): $216.00

Chewable (Aspirin Oral)

81 mg (36): $1.45

Chewable (St Joseph Aspirin Oral)

81 mg (36): $2.10

Chewable (St Joseph Low Dose Oral)

81 mg (36): $1.62

Pack (Stanback Headache Powders Oral)

650-200-32 mg (6): $1.02

845-65 mg (24): $2.83

Suppository (Aspirin Rectal)

120 mg (100): $11.88

200 mg (100): $12.31

300 mg (12): $1.68

600 mg (12): $1.77

Tablet, EC (Aspir-Low Oral)

81 mg (250): $6.40

Tablet, EC (Aspirin Oral)

81 mg (120): $2.55

325 mg (30): $14.55

Tablet, EC (Bayer Aspirin EC Low Dose Oral)

81 mg (32): $2.36

Tablet, EC (Ecotrin Low Strength Oral)

81 mg (150): $6.50

Tablet, EC (Ecotrin Maximum Strength Oral)

 500 mg (75): $6.13

Tablet, EC (Ecotrin Oral)

325 mg (125): $6.13

Tablet, EC (EcPirin Oral)

325 mg (100): $2.90

Tablet, EC (Miniprin Low Dose Oral)

81 mg (120): $3.85

Tablet, EC (St Joseph Aspirin Oral)

81 mg (100): $5.32

Tablets (Ascriptin MS Oral)

500-33-33-237 mg (85): $10.45

Tablets (Ascriptin Oral)

325 mg (100): $7.62

Tablets (Aspirin Oral)

325 mg (100): $2.20

Tablets (Bayer Aspirin Oral)

325 mg (24): $2.95

Tablets (Bayer Womens Oral)

81-300 mg (60): $7.20

Tablets (Bufferin Extra Strength Oral)

500 mg (65): $6.65

Tablets (Bufferin Low Dose Oral)

81 mg (130): $5.03

Tablets (Bufferin Oral)

325 mg (65): $4.85

Disclaimer: The pricing data provide a representative AWP and/or AAWP price from a single
manufacturer of the brand and/or generic product, respectively. The pricing data should be
used for benchmarking purposes only, and as such should not be used to set or adjudicate any
prices for reimbursement or purchasing functions. Pricing data is updated monthly.

Mechanism of Action

Irreversibly inhibits cyclooxygenase-1 and 2 (COX-1 and 2) enzymes, via acetylation, which
results in decreased formation of prostaglandin precursors; irreversibly inhibits formation of
prostaglandin derivative, thromboxane A2, via acetylation of platelet cyclooxygenase, thus
inhibiting platelet aggregation; has antipyretic, analgesic, and anti-inflammatory properties

Pharmacodynamics/Kinetics

Onset: Immediate release: Platelet inhibition: Within 1 hour (nonenteric-coated). Onset of

enteric-coated aspirin expected to be delayed (Eikelboom, 2012). Note: Chewing
nonenteric-coated or enteric-coated tablets results in inhibition of platelet aggregation
within 20 minutes; therefore, nonenteric-coated tablets should be chewed in settings
where a more rapid onset is required (eg, acute MI) and enteric-coated tablets may be
chewed when a rapid effect is required and immediate release nonenteric-coated tablets
are not available (Eikelboom, 2012; Feldman, 1999; Sai, 2011).

Duration: Immediate release: 4 to 6 hours; however, platelet inhibitory effects last the lifetime
of the platelet (~10 days) due to its irreversible inhibition of platelet COX-1 (Eikelboom,
2012).

Absorption: Immediate release: Rapidly absorbed in stomach and upper intestine (Eikelboom,
2012); Extended-release capsule: Rate of absorption is dependent upon food, alcohol,
and gastric pH.

Distribution: Vd: 10 L; readily into most body fluids and tissues; hydrolyzed to salicylate
(active) by esterases in the GI mucosa, red blood cells, synovial fluid and blood

Protein binding: Concentration dependent; as salicylate concentration increases, protein

binding decreases: ~90% to 94% (to albumin) at concentrations 80 mcg/mL
(Rosenberg 1981; Juurlink 2015); ~30% with concentrations seen in overdose (Juurlink,
2015).

Metabolism: Hydrolyzed to salicylate (active) by esterases in GI mucosa, red blood cells,

synovial fluid, and blood; metabolism of salicylate occurs primarily by hepatic
conjugation; metabolic pathways are saturable

Bioavailability: Immediate release: 50% to 75% reaches systemic circulation

Half-life elimination: Parent drug: Plasma concentration: 15 to 20 minutes; Salicylates (dose

dependent): 3 hours at lower doses (300 to 600 mg), 5 to 6 hours (after 1 g), 10 hours
with higher doses

Time to peak, serum: Immediate release: ~1 to 2 hours (nonenteric-coated), 3 to 4 hours

(enteric-coated) (Eikelboom, 2012); Extended-release capsule: ~2 hours. Note: Chewing
 nonenteric-coated tablets results in a time to peak concentration of 20 minutes (Feldman,
1999). Chewing enteric-coated tablets results in a time to peak concentration of 2 hours
(Sai, 2011).

Excretion: Urine (75% as salicyluric acid, 10% as salicylic acid)

Dental Use

Treatment of postoperative pain

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Dental Health Professional Considerations

The Food and Drug Administration (FDA), has issued a letter updating information and
considerations regarding the use of ibuprofen (400 mg doses) in patients who are taking low
dose aspirin (81 mg, immediate release; not enteric coated) for cardioprotection and stroke
prevention. Ibuprofen, at these doses, may interfere with aspirins antiplatelet effect
depending upon when it is administered. Patients initiated on aspirin first (for ~1 week) then
ibuprofen (400 mg 3 times/day for 10 days) seem to maintain aspirins platelet effect (Cryer,
2005). Ibuprofen has the greatest impact on aspirin if administered less than 8 hours before
aspirin (Catella-Lawson, 2001).

Patients may require counseling about the appropriate timing of ibuprofen dosing in
relationship to aspirin therapy. With occasional use of ibuprofen, a clinically-significant
interaction with aspirin in unlikely. To avoid interference during chronic dosing, a single dose
of ibuprofen should be taken 30 to 120 minutes after aspirin ingestion or at least 8 hours
should elapse after ibuprofen dosing before giving aspirin (Catella-Lawson, 2001; FDA,
2006).

The clinical implications of the interaction are unclear. There have not been any clinical
endpoint studies conducted at this time. Avoidance of this interaction is potentially important
because aspirins vascular protection could be decreased or negated.

Other nonselective NSAIDs may have potential for a similar interaction with aspirin. Such
has been described with naproxen (Capone, 2005). Acetaminophen does not appear to
interfere with the antiplatelet effect of aspirin. Other clinical scenarios (use of smaller
ibuprofen doses, other aspirin products, other doses of aspirin) have not been evaluated.

Additional information is available at:

http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProvi
ders/ucm125222.htm

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: As with all drugs which may affect
hemostasis, bleeding is associated with aspirin. Hemorrhage may occur at virtually any site;
risk is dependent on multiple variables including dosage, concurrent use of multiple agents
which alter hemostasis, and patient susceptibility. Many adverse effects of aspirin are dose
related, and are rare at low dosages. Other serious reactions are idiosyncratic, related to
allergy or individual sensitivity (see Dental Health Professional Considerations).

Aspirin as sole antiplatelet agent: Patients taking aspirin for ischemic stroke prevention are
safe to continue it during dental procedures (Armstrong, 2013).

Concurrent aspirin use with other antiplatelet agents: Aspirin in combination with
clopidogrel (Plavix), prasugrel (Effient), or ticagrelor (Brilinta) is the primary prevention
strategy against stent thrombosis after placement of drug-eluting metal stents in coronary
patients. Premature discontinuation of combination antiplatelet therapy (ie, dual antiplatelet
therapy) strongly increases the risk of a catastrophic event of stent thrombosis leading to
myocardial infarction and/or death, so says a science advisory issued in January 2007 from
the American Heart Association in collaboration with the American Dental Association and
other professional healthcare organizations. The advisory stresses a 12-month therapy of dual
antiplatelet therapy after placement of a drug-eluting stent in order to prevent thrombosis at
the stent site. Any elective surgery should be postponed for 1 year after stent implantation,
and if surgery must be performed, consideration should be given to continuing the antiplatelet
therapy during the perioperative period in high-risk patients with drug-eluting stents.

This advisory was issued from a science panel made up of representatives from the American
Heart Association (AHA), the American College of Cardiology, the Society for
Cardiovascular Angiography and Interventions, the American College of Surgeons, the
American Dental Association (ADA), and the American College of Physicians (Grines,
2007).

Effects on Bleeding

Aspirin irreversibly inhibits platelet aggregation which can prolong bleeding. Upon
discontinuation, normal platelet function returns only when new platelets are released (~7 to
10 days). However, in the case of dental surgery, there is no scientific evidence to support
discontinuation of aspirin. This was recently supported by the American Academy of
Neurology in patients with ischemic cerebrovascular disease (Armstrong, 2013). A recent
study compared blood loss after a single tooth extraction in coronary artery disease patients
who were either on aspirin (100 mg daily) or off aspirin for the extraction. The mean volume
of bleeding was not statistically different between the groups. Local hemostatic measures
were sufficient to control bleeding and there were no reported episodes of hemorrhaging
intra- or postoperatively (Medeiros, 2011).

Dental Usual Dosing

Postoperative pain:

Analgesic and antipyretic: Oral, rectal:

 Children: 10 to 15 mg/kg/dose every 4 to 6 hours, up to a total of 4 g/day

Adults: 325 to 650 mg every 4 to 6 hours up to 4 g/day

Anti-inflammatory: Oral: Initial:

Children: 60 to 90 mg/kg/day in divided doses; usual maintenance: 80 to 100 mg/kg/day

divided every 6 to 8 hours; monitor serum concentrations

Adults: 2.4 to 3.6 g/day in divided doses; usual maintenance: 3.6 to 5.4 g/day; monitor
serum concentrations

Related Information

Acute Postoperative Pain

Antithrombotic Therapy in Adult Patients With Prosthetic Heart Valves

Antithrombotic Therapy in Patients With Atrial Fibrillation

Beers Criteria Potentially Inappropriate Medications for Geriatrics

Chronic Pain Management (Cancer)

Desensitization Protocols

Management of Chemotherapy-Induced Nausea and Vomiting in Adults

Oral Antiplatelet Comparison Chart

Oral Medications That Should Not Be Crushed or Altered

Perioperative/Periprocedural Management of Anticoagulant and Antiplatelet Therapy

Regional Anesthesia in Patients Receiving Antithrombotic or Thrombolytic Therapy

Spine and Pain Procedures in Patients Receiving Antithrombotic Therapy

Index Terms

Acetylsalicylic Acid

ASA

Baby Aspirin

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23451245

International Brand Names

AAS (AR, BR, ES)

Acard (PL)

Aceprin (HK, MY)

Acetard (FI)

Aceticil (BR)

Acetysal (BG)

Acitab (LI)

Adiprin (KW, QA)

Adiprin EC (JO)

Adiro (ES, MX, VE)

Albyl-E (NO)

Algina (PY)

Andol (HR)

Ansin (TW)

Antacsal-E (MX)

Anthrom (PH)

Aptor (ID)
 Artebin (KR)

Asactal (HU)

Asapor (FI)

Asawin (CO)

Ascardia (ID)

ASP (HK)

Aspa (TW)

Aspec (LK, NZ)

Aspen (PH)

Aspenorm (UA)

Aspent (TH)

Aspex (IL)

Aspicard (ET, KW, SA)

Aspicot (KW, LB)

Aspilets (ID, PH, VN)

Aspilets EC (PH)

Aspimed (AE)

Aspin (BD)

Aspinal (EG, QA)

Aspirax (RO)

Aspire (TW)

Aspirem (BB, BM, BS, BZ, CY, GY, JM, PR, SR, TT)

Aspirin (AE, BF, BH, BJ, CI, CY, EG, ET, GH, GM, GN, HK, IL, IQ, IR, JO, KE,
KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, QA, SA, SC, SD, SL, SN,
SY, TN, TZ, UG, YE, ZM, ZW)

Aspirin Bayer (HK)

 Aspirin Cardio (IL, SG)

Aspirina (CL, CO, CU, EC)

Aspirina efervescente (MX)

Aspirina Junior (MX)

Aspitor (PH)

Aspro (AT, CH, CZ, FR, GB, IT, KW, NL, NZ, SA)

Aspro Junior (QA)

Asprovit (EE)

Asrina (TH)

ASS (DE)

Asthromed (PH)

Astrix (HU, KR, LK, PH)

B-Aspirin (TH)

Bamyl (SE)

Bayaspirin Protect 100 (CN)

Bayaspirina (AR)

Bayer Aspirin Cardio (ZA)

Bayprin EC (PH)

Besprin (PH)

Bokey (SG, TW)

Bufferin (JO, UY)

Cafemol Childrens Size (ZW)

Caprin (GB)

Cardioaspirina (CO, PE)

Cardiomagnyl (UA)
 Cardioprin (HR, TW)

Cardioprin 100 (IL)

Cardioton (PE)

Cardiprin (HK, LK)

Cartia (PT)

Caspirin (MY)

Circlevein (KR)

Colfarit (CZ, HN)

Comoprin (TH)

Cortal (PH)

Dispril (AE, BE, BH, CY, EG, IQ, IR, JO, LB, LY, NO, OM, QA, SA, SY, TR, YE)

Disprin (BB, BF, BJ, BM, BS, BZ, CI, ET, GB, GH, GM, GN, GY, HK, IE, IN, JM,
KE, KW, LR, MA, ML, MR, MU, MW, NE, NG, NZ, PK, PR, SC, SD, SG, SL, SN,
SR, TN, TT, TZ, UG, ZM, ZW)

Ecasil (BR)

Ecorin (LK)

Ecosprin (BD)

Ecotrin (AR, CL, MX, NZ, TW)

Encine EM (TW)

Eskotrin (VE)

Frosit (ID)

Globentyl (DK)

Glocar (ID)

Godamed (IL)

Kardegic (HU)

Kidiprin (JO)
 Lodosprin (BD)

Lopirin (TW)

Magnecyl (SE)

Melabon (DE)

Micropirin (MT)

Miniaspi 80 (ID)

Naspro (ID)

Neospin (BD)

Norspirinal (ID)

Novasen (KW)

Nu-Seals (AE, BF, BH, BJ, CI, CY, EG, ET, GH, GM, GN, IQ, IR, JO, KE, KW, LB,
LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, QA, SA, SC, SD, SL, SN, SY, TN,
TR, TZ, UG, YE, ZM, ZW)

Plaquetasa (CR, GT, SV)

Proprin (GB)

Remin (AE)

Rhonal (KR, QA, VE)

Rodin (UA)

Salisalido (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE)

Salospir (GR)

Sedergine (BE)

Tevapirin (IL)

Thomapyrin (AT)

Thrombo-Aspilets (ID)

Thrombo-ASS (EE)

Tromcor (PH)
 V-AS (TH)

2016 Wolters Kluwer Clinical Drug Information, Inc. and its affiliates and/or licensors. All rights reserved.

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Clinical Pharmacology

Pharmacokinetics

Drug Distribution to Tissues

Volume of distribution

Binding

Blood-brain barrier

Drugs Mentioned In This Article

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Drug Distribution to Tissues

By Jennifer Le, PharmD, MAS, BCPS-ID, University of California San Diego, Skaggs
School of Pharmacy and Pharmaceutical Sciences

Click here for

Patient Education

NOTE: This is the Professional Version. CONSUMERS: Click here for the Consumer
Version

Pharmacokinetics

Overview of Pharmacokinetics

Drug Absorption

Drug Bioavailability

Drug Distribution to Tissues

Drug Metabolism

Drug Excretion

(See also Overview of Pharmacokinetics.)

After a drug enters the systemic circulation, it is distributed to the bodys tissues. Distribution
is generally uneven because of differences in blood perfusion, tissue binding (eg, because of
lipid content), regional pH, and permeability of cell membranes.

The entry rate of a drug into a tissue depends on the rate of blood flow to the tissue, tissue
mass, and partition characteristics between blood and tissue. Distribution equilibrium (when
entry and exit rates are the same) between blood and tissue is reached more rapidly in richly
vascularized areas, unless diffusion across cell membranes is the rate-limiting step. After
equilibrium, drug concentrations in tissues and in extracellular fluids are reflected by the
plasma concentration. Metabolism and excretion occur simultaneously with distribution,
making the process dynamic and complex.
After a drug has entered tissues, drug distribution to the interstitial fluid is determined
primarily by perfusion. For poorly perfused tissues (eg, muscle, fat), distribution is very slow,
especially if the tissue has a high affinity for the drug.

Volume of distribution
The apparent volume of distribution is the theoretical volume of fluid into which the total
drug administered would have to be diluted to produce the concentration in plasma. For
example, if 1000 mg of a drug is given and the subsequent plasma concentration is 10 mg/L,
that 1000 mg seems to be distributed in 100 L (dose/volume = concentration; 1000 mg/x L =
10 mg/L; therefore, x= 1000 mg/10 mg/L = 100 L).

Volume of distribution has nothing to do with the actual volume of the body or its fluid
compartments but rather involves the distribution of the drug within the body. For a drug that
is highly tissue-bound, very little drug remains in the circulation; thus, plasma concentration
is low and volume of distribution is high. Drugs that remain in the circulation tend to have a
low volume of distribution.

Volume of distribution provides a reference for the plasma concentration expected for a given
dose but provides little information about the specific pattern of distribution. Each drug is
uniquely distributed in the body. Some drugs distribute mostly into fat, others remain in
extracellular fluid, and others are bound extensively to specific tissues.

Many acidic drugs (eg, warfarin, aspirin) are highly protein-bound and thus have a small
apparent volume of distribution. Many basic drugs (eg, amphetamine, meperidine) are
extensively taken up by tissues and thus have an apparent volume of distribution larger than
the volume of the entire body.

Binding
The extent of drug distribution into tissues depends on the degree of plasma protein and
tissue binding. In the bloodstream, drugs are transported partly in solution as free (unbound)
drug and partly reversibly bound to blood components (eg, plasma proteins, blood cells). Of
the many plasma proteins that can interact with drugs, the most important are albumin, alpha-
1 acid glycoprotein, and lipoproteins. Acidic drugs are usually bound more extensively to
albumin; basic drugs are usually bound more extensively to alpha-1 acid glycoprotein,
lipoproteins, or both.

Only unbound drug is available for passive diffusion to extravascular or tissue sites where the
pharmacologic effects of the drug occur. Therefore, the unbound drug concentration in
systemic circulation typically determines drug concentration at the active site and thus
efficacy.

At high drug concentrations, the amount of bound drug approaches an upper limit determined
by the number of available binding sites. Saturation of binding sites is the basis of
displacement interactions among drugs (see DrugReceptor Interactions).

Drugs bind to many substances other than proteins. Binding usually occurs when a drug
associates with a macromolecule in an aqueous environment but may occur when a drug is
partitioned into body fat. Because fat is poorly perfused, equilibration time is long, especially
if the drug is highly lipophilic.

Accumulation of drugs in tissues or body compartments can prolong drug action because the
tissues release the accumulated drug as plasma drug concentration decreases. For example,
thiopental is highly lipid soluble, rapidly enters the brain after a single IV injection, and has a
marked and rapid anesthetic effect; the effect ends within a few minutes as the drug is
redistributed to more slowly perfused fatty tissues. Thiopental is then slowly released from
fat storage, maintaining subanesthetic plasma levels. These levels may become significant if
doses of thiopental are repeated, causing large amounts to be stored in fat. Thus, storage in fat
initially shortens the drugs effect but then prolongs it.

Some drugs accumulate within cells because they bind with proteins, phospholipids, or
nucleic acids. For example, chloroquine concentrations in WBCs and liver cells can be
thousands of times higher than those in plasma. Drug in cells is in equilibrium with drug in
plasma and moves into plasma as the drug is eliminated from the body.

Blood-brain barrier
Drugs reach the CNS via brain capillaries and CSF. Although the brain receives about one
sixth of cardiac output, drug penetration is restricted because of the brains permeability
characteristics. Although some lipid-soluble drugs (eg, thiopental) enter the brain readily,
polar compounds do not. The reason is the blood-brain barrier, which consists of the
endothelium of brain capillaries and the astrocytic sheath. The endothelial cells of brain
capillaries, which appear to be more tightly joined to one another than those of most
capillaries, slow the diffusion of water-soluble drugs. The astrocytic sheath consists of a layer
of glial connective tissue cells (astrocytes) close to the basement membrane of the capillary
endothelium. With aging, the blood-brain barrier may become less effective, allowing
increased passage of compounds into the brain.

Drugs may enter ventricular CSF directly via the choroid plexus, then passively diffuse into
brain tissue from CSF. Also in the choroid plexus, organic acids (eg, penicillin) are actively
transported from CSF to blood.

The drug penetration rate into CSF, similar to other tissue cells, is determined mainly by the
extent of protein binding, degree of ionization, and lipid-water partition coefficient of the
drug. The penetration rate into the brain is slow for highly protein-bound drugs and nearly
nonexistent for the ionized form of weak acids and bases. Because the CNS is so well
perfused, the drug distribution rate is determined primarily by permeability.

Last full review/revision April 2016 by Jennifer Le, PharmD, MAS, BCPS-ID

Drugs Mentioned In This Article

Drug Name

Select Trade

aspirin
 No US brand name

warfarin

COUMADIN

chloroquine

ARALEN

meperidine

DEMEROL

NOTE: This is the Professional Version. CONSUMERS: Click here for the Consumer
Version

Drug Bioavailability

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Drug Metabolism

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