Version November 2024
Dosage guidance:
Safety: Avoid regular or frequent use of nonsteroidal anti-inflammatory drugs (NSAIDs) in patients taking aspirin for cardiovascular protection as these may reduce the cardioprotective effects of aspirin (Ref).
Dosing: Dosing information below is based on the IR formulations; do not use the ER formulation in situations when a rapid onset of action is necessary.
Clinical considerations: In patients who require concomitant therapeutic anticoagulation, antiplatelet selection and/or duration of therapy may differ in order to balance risks for thrombosis and bleeding (Ref).
Analgesic/Antipyretic: Immediate release: Oral: 325 mg to 1 g every 4 to 6 hours as needed; usual maximum daily dose: 4 g/day (Ref).
Note: If patient cannot take orally, rectal suppositories (300 or 600 mg) are available.
Anti-inflammatory for arthritis associated with rheumatic disease: Immediate release: Oral: 4 to 8 g/day in 4 to 5 divided doses as needed; titrate dose based on response and tolerability. Continue treatment until symptoms resolve (typically 1 to 2 weeks, but potentially up to 8 weeks). Use of aspirin at these high doses (4 to 8 g/day) may be limited by adverse effects (tinnitus, diminished auditory acuity, GI intolerance), making other available NSAIDs preferred (Ref).
Atherosclerotic cardiovascular disease:
Acute coronary syndrome:
Note: For rapid onset, non–enteric-coated IR tablet(s) should be chewed and swallowed upon identification of clinical and ECG findings suggesting an acute coronary syndrome. Enteric-coated aspirin is not preferred, since onset of action may be delayed. If it is the only product available, enteric-coated IR tablet(s) may be chewed and swallowed (Ref). For maintenance therapy, any oral formulation is acceptable for use.
Non–ST-elevation acute coronary syndromes or ST-elevation myocardial infarction:
Note: For initial therapy, administer aspirin in combination with an IV anticoagulant and a P2Y12 inhibitor (Ref).
Initial:
Immediate release (non–enteric-coated): Oral: 162 to 325 mg administered once (chew and swallow) at the time of diagnosis (Ref).
Rectal (alternative route): 600 mg administered once at the time of diagnosis if an IR oral formulation is unavailable or oral route is not feasible (Ref).
Maintenance (secondary prevention):
Immediate release: Oral: 75 to 100 mg once daily (Ref).
Duration of therapy:
Preferred approach: Aspirin plus a P2Y12 inhibitor (dual antiplatelet therapy [DAPT]) should be continued for ≥12 months, unless major bleeding is a concern. For patients at high risk of bleeding or who experience overt bleeding, DAPT for 6 months may be reasonable. If there have been no major bleeding complications after 12 months, continuation of DAPT may be considered. Reevaluate the need for DAPT at regular intervals based on bleeding and thrombotic risks. When DAPT is complete, discontinue the P2Y12 inhibitor and continue aspirin indefinitely for secondary prevention (Ref).
Alternative approach in select patients to minimize bleeding events: Aspirin in combination with a P2Y12 inhibitor (DAPT) should be continued for 1 to 3 months after PCI, then discontinue aspirin and continue P2Y12 inhibitor monotherapy. When the P2Y12 inhibitor is discontinued, restart aspirin for secondary prevention (Ref).
Percutaneous coronary intervention for stable ischemic heart disease (off-label use):
Initial:
Note: For initial therapy, non–enteric-coated IR tablet(s) should be administered. Enteric-coated aspirin is not preferred since onset of action is delayed. For patients who receive a coronary stent during percutaneous coronary intervention, administer aspirin in combination with a parenteral anticoagulant and a P2Y12 inhibitor (clopidogrel or ticagrelor; prasugrel is not recommended in this patient population) (Ref).
Immediate release (non–enteric-coated): Oral: 162 to 325 mg given ≥2 hours (preferably 24 hours) before the procedure (Ref).
Maintenance:
Immediate release: Oral: 75 to 100 mg once daily in combination with clopidogrel or ticagrelor (DAPT) (Ref). Refer to clopidogrel or ticagrelor monograph for information on duration of DAPT and subsequent management.
Atherosclerotic cardiovascular disease, primary prevention (off-label use):
Note: Use should be a shared decision between health care professionals and patients ≥40 years of age who are at increased risk for cardiovascular disease, after weighing risks versus benefits. Some experts recommend against this use for patients ≥60 years of age (Ref), while others recommend against this use for patients >70 years of age (Ref).
Immediate release: Oral: 75 to 100 mg once daily (Ref).
Atherosclerotic cardiovascular disease, secondary prevention:
Carotid artery atherosclerosis, asymptomatic or symptomatic (off-label use): Immediate release: Oral: 75 to 325 mg once daily (Ref).
Coronary artery bypass graft surgery: Immediate release: Oral: 75 to 81 mg once daily beginning preoperatively; continue indefinitely following surgery (Ref). Following surgery, some experts restart aspirin (with or without a one-time, 325 mg loading dose) approximately 6 hours after completion of the procedure or after extubation, whichever comes first (Ref).
Off-pump coronary artery bypass graft surgery:Following surgery, consider adding clopidogrel in combination with aspirin for 12 months then discontinue clopidogrel and continue aspirin indefinitely (Ref).
Patients with acute coronary syndrome followed by coronary artery bypass graft surgery: Administer aspirin in combination with a P2Y12 inhibitor for 12 months then continue aspirin indefinitely (Ref). Some experts do not use P2Y12 inhibitors postoperatively in these patients (Ref).
Ischemic stroke/transient ischemic attack:
Note: In patients who receive IV thrombolytic therapy, antiplatelet therapy is generally delayed for at least 24 hours, but administered as soon as possible thereafter (Ref).
Due to intracranial large artery atherosclerosis (50% to 99%), secondary prevention:
Note: Avoid dual antiplatelet therapy (DAPT) in patients with hemorrhagic transformation (Ref).
Immediate release: Oral:
Monotherapy: 325 mg once daily. May consider a short course of DAPT as outlined below. (Ref).
Short-term (90 days) DAPT with concomitant clopidogrel in patients with recent (≤30 days) stroke or TIA due to 70% to 99% stenosis of an intracranial large artery: 325 mg once daily followed by long-term aspirin monotherapy (Ref).
Short-term (21 days) DAPT with concomitant clopidogrel in patients with recent (≤30 days) minor stroke or high-risk TIA due to 50% to 69% stenosis of an intracranial large artery: 160 to 325 mg loading dose followed by 50 to 100 mg once daily (Ref).
Short-term (21 to 30 days) DAPT with concomitant ticagrelor in patients with recent (≤24 hours) minor stroke or high-risk TIA and >30% stenosis of ipsilateral major intracranial artery: 300 to 325 mg loading dose followed by 75 to 100 mg once daily (Ref).
Due to other noncardioembolic causes (eg, small vessel disease), secondary prevention:
Note: For patients with recent (eg, ≤24 hours) minor stroke or high-risk TIA, may consider short-term DAPT with concomitant clopidogrel (21 to 90 days) or ticagrelor (21 to 30 days) followed by long-term single-agent antiplatelet therapy with aspirin, clopidogrel, or aspirin/ER dipyridamole. Avoid DAPT in patients with hemorrhagic transformation (Ref).
Initial:
Immediate release: Oral: 160 to 325 mg administered once at the time of diagnosis (Ref).
Rectal (alternative route): 300 mg administered once at the time of diagnosis if oral route is not feasible (Ref).
Maintenance :
Immediate release: Oral: 50 to 325 mg once daily; some experts recommend 50 to 100 mg once daily when used with clopidogrel for DAPT and as long-term single-agent therapy (Ref). When used with ticagrelor for DAPT, 75 to 100 mg once daily is recommended (Ref).
Peripheral atherosclerotic disease (upper or lower extremity; with or without a revascularization procedure) (off-label use): Immediate release: Oral: 75 to 100 mg once daily (Ref).
Stable ischemic heart disease: Immediate release: Oral: 75 to 100 mg once daily (Ref).
Carotid artery stenting (off-label use):
Percutaneous approach:
Initial:
Initiation ≥48 hours before procedure: Immediate release: Oral: 325 mg twice daily in combination with clopidogrel (Ref).
Initiation <48 hours before procedure: Immediate release: Oral: 650 mg once at least 4 hours before procedure in combination with clopidogrel (Ref).
Maintenance:
Immediate release: Oral: 75 to 325 mg once daily in combination with clopidogrel for at least 4 weeks, then discontinue clopidogrel and continue aspirin 75 to 325 mg once daily indefinitely thereafter. In patients with history of neck irradiation, some experts recommend continuing aspirin plus clopidogrel indefinitely (Ref).
Transcarotid approach:
Initial:
Initiation ≥72 hours before procedure: Immediate release: Oral: 75 to 325 mg once daily in combination with clopidogrel (Ref).
Initiation <72 hours before procedure : Immediate release: Oral: 650 mg once at least 4 hours before procedure in combination with clopidogrel (Ref).
Maintenance:
Immediate release: Oral: 75 to 325 mg once daily in combination with clopidogrel for at least 4 weeks, then discontinue clopidogrel and continue aspirin 75 to 325 mg once daily indefinitely thereafter. In patients with history of neck irradiation, some experts recommend continuing aspirin plus clopidogrel indefinitely (Ref).
Carotid endarterectomy: Immediate release: Oral: 75 to 325 mg once daily starting prior to surgery and continued indefinitely (Ref).
Colorectal cancer risk reduction, primary prevention (off-label use):
Note: The optimal dose and duration of therapy for colorectal cancer risk reduction are unknown. Utilization should be a shared decision between health care professionals and patients that weighs the risk versus benefits of treatment (Ref).
Immediate release: Oral: 75 to 325 mg once daily (Ref).
Pericarditis, acute or recurrent (off-label use):
Note: Aspirin is preferred over other nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with ischemic heart disease. If pericarditis occurs secondary to acute myocardial infarction (MI), avoid NSAIDs (other than once-daily, low-dose aspirin for treatment of MI) and use acetaminophen for analgesia. If this does not suffice or if additional pericarditis treatment is necessary after 7 to 10 days, aspirin is preferred and other NSAIDs should continue to be avoided (Ref).
Immediate release: Oral: Initial: 650 mg to 1 g every 8 hours until resolution of symptoms for at least 24 hours and normalization of inflammatory biomarkers (eg, C-reactive protein) if monitored; initial therapy typically lasts for ≥1 to 2 weeks. Gradually taper over several weeks by decreasing each dose by 250 to 500 mg every 1 to 2 weeks; during taper, ensure patient remains asymptomatic and inflammatory biomarkers remain normal (if monitored). Use in combination with colchicine. In patients at risk of NSAID-related GI toxicity, prophylaxis (generally with a proton pump inhibitor) is recommended (Ref).
Preeclampsia prevention (off-label use):
Note: Consider for use in pregnant women with ≥2 moderate risk factors or ≥1 high risk factor for preeclampsia (Ref).
Immediate release: Oral: 81 to 162 mg once daily, ideally beginning between 12 to 16 weeks' gestation but may be started up to 28 weeks' gestation; continue therapy until delivery (Ref).
Valvular heart disease:
Surgical prosthetic heart valve replacement, thromboprophylaxis:
Bioprosthetic aortic or mitral heart valve replacement (off-label use): Note: Timing of aspirin initiation is based on bleeding risk. For patients at low risk of bleeding, treat with warfarin monotherapy for 3 to 6 months, then transition to aspirin monotherapy. For patients at elevated risk of bleeding, initiate aspirin within 24 hours of surgery (ie, no initial treatment with warfarin) (Ref).
Immediate release: Oral: 75 to 100 mg once daily (Ref).
Mechanical aortic or mitral heart valve replacement (off-label use): Note: Aspirin is required, in combination with warfarin, for patients who receive an On-X mechanical aortic valve. For other mechanical valve types, consider risks of thromboembolism and bleeding before adding aspirin; warfarin monotherapy is typically sufficient. Addition of aspirin is not routinely required in the absence of another indication for antiplatelet therapy (Ref).
Immediate release: Oral: 75 to 100 mg once daily in combination with warfarin (Ref).
Transcatheter aortic valve replacement, thromboprophylaxis (off-label use):
Note: Refer to institutional policies and procedures on use of antiplatelet therapy for patients who require therapeutic anticoagulation for a different indication.
Immediate release: Oral: 75 to 100 mg once daily; may use in combination with clopidogrel for 3 to 6 months after transcatheter aortic valve replacement, depending on type of valve implanted (Ref). To minimize risk of bleeding complications, may give aspirin or clopidogrel alone and reserve dual antiplatelet therapy during the first 3 to 6 months for patients at high risk of a thrombotic event; for either strategy, continue aspirin indefinitely after the initial 3 to 6 months of therapy (Ref).
Transcatheter mitral valve repair with MitraClip device, thromboprophylaxis (off-label use):
Note: Patients are generally treated with antithrombotic therapy (antiplatelet or anticoagulant if there is a concurrent indication) for at least 6 months following the procedure.
Immediate release: Oral:
Loading dose: 325 mg once immediately following MitraClip insertion or within 24 hours prior to the procedure; use in combination with clopidogrel (Ref).
Maintenance: 81 mg once daily for at least 6 months; may use as monotherapy or in combination with clopidogrel (Ref).
Venous thromboembolism prevention, indefinite therapy (off-label use):
Note: For use in select patients to prevent recurrent venous thromboembolism (VTE) if unable to take an anticoagulant. In patients who have completed ≥6 months of anticoagulation and in whom indefinite therapeutic anticoagulation is indicated, aspirin is not recommended since it is less effective (Ref).
Immediate release: Oral: 100 mg once daily after completion of a conventional treatment course with therapeutic anticoagulation (Ref).
Venous thromboembolism prophylaxis for total hip or total knee arthroplasty (off-label use):
Note: Some experts limit this strategy to lower-risk patients who undergo elective unilateral total hip arthroplasty (THA) or total knee arthroplasty (TKA), ambulate within 24 hours after surgery, and do not have additional risk factors for VTE, indications for long-term anticoagulation, lower limb or hip fracture in the previous 3 months, or expected major surgery in the upcoming 3 months (Ref).
Immediate release: Oral: Begin postoperative prophylaxis with rivaroxaban or a low-molecular-weight heparin, then discontinue therapy after 5 days for TKA or after 5 to 10 days for THA, and initiate aspirin 81 mg once daily. For TKA, continue aspirin through postoperative day 10 to 14 (if not fully ambulatory by day 14, may continue through postoperative day 35). For THA, continue aspirin through postoperative day 35 (Ref).
Venous thromboembolism prophylaxis in lower-risk patients with multiple myeloma receiving immunomodulatory therapy (eg, lenalidomide, pomalidomide, thalidomide) (off-label use): Oral: 81 to 100 mg once daily during immunomodulatory therapy (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS
Antiplatelet uses:
Note: In general the benefit of low-dose aspirin outweighs any risk associated with nephropathy or other adverse effects even in the setting of severe kidney impairment; the recommended aspirin dose should not be reduced in any patient with suspected or documented cardiovascular disease, or other antithrombotic indication (Ref).
Altered kidney function: No dosage adjustment necessary for any degree of kidney impairment (Ref).
Hemodialysis, intermittent (thrice weekly): No dosage adjustment necessary (Ref).
Peritoneal dialysis: No dosage adjustment necessary (Ref).
CRRT: No dosage adjustment necessary (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary (Ref).
Analgesia or anti-inflammatory uses:
Altered kidney function:
CrCl >10 mL/minute: No dosage adjustment necessary; however, high doses have been associated with acute kidney injury (AKI) (Ref). Use lowest effective dosage and limit duration of therapy, particularly for patients at high risk for developing AKI (eg, patients with chronic kidney disease, volume depletion, older age) (Ref).
CrCl <10 mL/minute: Avoid use (manufacturer's labeling; expert opinion). May exacerbate uremic GI and hematologic symptoms (Ref).
Hemodialysis, intermittent (thrice weekly): Avoid use. May exacerbate uremic GI and hematologic symptoms (Ref).
Peritoneal dialysis: Avoid use. May exacerbate uremic GI and hematologic symptoms (Ref).
CRRT: Avoid use (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): Avoid use (Ref).
Avoid use in severe liver disease.
Refer to adult dosing. Avoid for the primary prevention of cardiovascular disease. In older adults already taking for primary prevention, consider deprescribing. Unless alternative agents are ineffective and a gastroprotective agent can be administered, avoid short-term scheduled use of doses >325 mg in combination with corticosteroids, anticoagulants, or antiplatelet agents or chronic use with or without medications that increase risk for bleeding (Ref).
(For additional information see "Aspirin: Pediatric drug information")
Dosage guidance:
Dosing: Two immediate-release formulations are available: tablets and liquid-filled capsules (Vazalore). Immediate-release capsules cannot be divided and may not be an appropriate dosage form for some pediatric patients. All pediatric dosing for immediate-release formulations unless otherwise specified. Doses are typically rounded to a convenient amount (eg, 1/4 of 81 mg tablet).
Analgesic: Oral, rectal: Note: Do not use aspirin in pediatric patients <18 years who have or who are recovering from chickenpox or flu symptoms (eg, viral illness) due to the association with Reye syndrome (Ref):
Infants, Children, and Adolescents weighing <50 kg: Limited data available: 10 to 15 mg/kg/dose every 4 to 6 hours; maximum daily dose: 90 mg/kg/day or 4,000 mg/day whichever is less (Ref).
Children ≥12 years and Adolescents weighing ≥50 kg: 325 to 650 mg every 4 to 6 hours; maximum daily dose: 4,000 mg/day (Ref).
Anti-inflammatory: Limited data available: Infants, Children, and Adolescents: 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 (Ref). Note: Although included in some product labeling, the use of salicylates including aspirin for the treatment of juvenile idiopathic arthritis has been replaced by other pharmacologic agents with improved efficacy and adverse effect profiles (eg, nonsalicylate nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, glucocorticoids, biologic modifiers) (Ref).
Antiplatelet effect: Limited data available: Infants, Children, and Adolescents: Oral: Adequate pediatric studies have not been performed; pediatric dosage is derived from adult studies. Usual adult maximum daily dose for antiplatelet effects is 325 mg/day.
Acute ischemic stroke (AIS):
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 (Ref).
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 (Ref).
Prosthetic heart valve:
Bioprosthetic aortic valve (with normal sinus rhythm): 1 to 5 mg/kg/dose once daily for 3 months (Ref).
Mechanical aortic and/or mitral valve: 1 to 5 mg/kg/dose once daily combined with vitamin K antagonist (eg, warfarin) is recommended as first-line antithrombotic therapy (Ref). Alternative regimens: 6 to 20 mg/kg/dose once daily in combination with dipyridamole (Ref).
Shunts: Blalock-Taussig; Glenn; postoperative; primary prophylaxis: 1 to 5 mg/kg/dose once daily (Ref).
Norwood, Fontan surgery, postoperative; primary prophylaxis: 1 to 5 mg/kg/dose once daily (Ref).
Transcatheter Atrial Septal Defect (ASD) or Ventricular Septal Defect (VSD) devices, postprocedure prophylaxis: 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 (Ref).
Ventricular assist device (VAD) placement: 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) and with or without dipyridamole (Ref).
Kawasaki disease, treatment: Limited data available: Note: Patients with Kawasaki disease and presenting with influenza or viral illness should not receive aspirin; acetaminophen is suggested as an alternate antipyretic in these patients and an alternate antiplatelet agent is suggested for a minimum of 2 weeks (Ref).
Initial therapy (acute phase): Note: Optimal dose not established. Use in combination with IV immune globulin.
Infants and Children:
Moderate dose: Oral: 30 to 50 mg/kg/day divided every 6 hours until fever resolves for at least 48 to 72 hours (Ref).
High dose: Oral: 80 to 100 mg/kg/day divided every 6 hours until fever resolves for at least 48 to 72 hours (Ref).
Subsequent therapy (low-dose; antiplatelet effects): Infants and Children: Oral: 3 to 5 mg/kg/day once daily; initiate at least 48 to 72 hours after resolution of fever and continue for 6 to 8 weeks in patients without coronary artery abnormalities. In patients with coronary artery abnormalities ranging from dilation to large/giant aneurysms, low-dose aspirin should be continued (with or without dual antiplatelet therapy, warfarin or low molecular weight heparin); duration of aspirin therapy is based upon severity of coronary artery involvement; recommend consulting published treatment and institutional guidelines, and expert medical consultation for additional guidance (Ref).
Multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2 (antiplatelet/antithrombotic effects): Limited data available:
Note: Recommended for all MIS-C patients without active bleeding, significant bleeding risk, or platelet count ≤80,000 cells/mm3 (Ref). Use is based on limited experience in patients with MIS-C, emerging data in adults with COVID-19, and extrapolation from Kawasaki disease and myocarditis (Ref).
Infants, Children, and Adolescents: Oral: 3 to 5 mg/kg/day once daily; maximum daily dose: 81 mg/day; continue until normalization of platelet count, confirmed normal coronary arteries at ≥4 weeks after diagnosis, and ejection fraction >35% (Ref).
Rheumatic fever: 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 (Ref).
Migratory polyarthritis, with carditis without cardiomegaly or congestive heart failure: Oral: Initial: 50 to 70 mg/kg/day in 4 divided doses for 3 to 5 days, followed by 50 mg/kg/day in 4 divided doses for 2 to 3 weeks, followed by 25 mg/kg/day in 4 divided doses for 2 to 4 weeks (Ref); escalation to doses up to 80 to 100 mg/kg/day in 4 or 5 divided doses has been described for arthritis management (Ref).
Carditis and more than minimal cardiomegaly or congestive heart failure: Note: Aspirin should be initiated at the beginning of prednisone taper regimen to prevent rebound inflammation: Oral: 50 mg/kg/day in 4 divided doses for 6 weeks (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Infants, Children, and Adolescents: There are no recommendations in the manufacturer's labeling; however, the following adjustments have been recommended (Ref):
GFR ≥10 mL/minute/1.73 m2: No dosage adjustment necessary.
GFR <10 mL/minute/1.73 m2: Avoid use.
Intermittent hemodialysis: Dialyzable: 50% to 100% (concentration dependent; higher salicylate concentrations are more readily dialyzable) (Ref); administer daily dose after dialysis session on dialysis days (Ref).
Peritoneal dialysis: Avoid use.
CRRT: No dosage adjustment necessary; monitor serum concentrations.
All ages: Avoid use in severe liver disease.
Aspirin use is associated with a 2- to 4-fold increase in upper gastrointestinal (UGI) events, such as symptomatic or complicated gastrointestinal ulcers and GI mucosal damage (Ref). Lower GI (LGI) events have also been reported with chronic aspirin use (Ref). Symptoms can range from mild (dyspepsia) to severe (peptic ulcer disease, gastrointestinal hemorrhage). The use of enteric-coated preparations of aspirin does not decrease the risk of UGI events (Ref).
Mechanism: Dose-related; related to the pharmacologic action; damage to the GI mucosa is typically caused by aspirin's effects on the epithelial and microvascular tissue of the GI tract via inhibition of cyclooxygenase-1 and subsequent prostaglandin depletion, which is gastro-protective (Ref). Additionally, aspirin accumulates in gastric mucosal cells, altering the permeability, resulting in an increased risk of ulceration (Ref).
Onset: Varied; topical gastric mucosa toxicity can be seen on endoscopy within minutes of aspirin administration (Ref). Other studies reported GI ulcers after at least 3 months of use (Ref). Risk of GI events is generally seen when beginning aspirin therapy; however, long-term administration of aspirin is associated with a greater risk of GI events (Ref).
Risk factors:
• Dose >100 mg (Ref)
• Bleeding ulcers (Ref)
• Peptic ulcer disease (Ref)
• Concurrent use of nonsteroidal anti-inflammatory drugs (Ref)
• Concurrent corticosteroids (Ref)
• Concurrent dual antiplatelet and anticoagulant therapy (Ref)
• Helicobacter pylori infection (Ref)
• Smoking (Ref)
• Excessive alcohol consumption (Ref)
• Older age (>70 years) (Ref)
Hypersensitivity reactions (immediate and delayed) involving the skin (eg, angioedema, urticaria), airways (eg, dyspnea, rhinorrhea), and/or other organs (Ref) have been reported. Clinical phenotypes of aspirin/nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity reactions include aspirin/NSAID-exacerbated respiratory disease (AERD and NERD), aspirin/NSAID-induced urticaria/angioedema (NIUA), aspirin/NSAID-exacerbated cutaneous disease (NICD) and single NSAID-induced urticaria/angioedema or anaphylaxis (Ref). Delayed hypersensitivity reactions, including drug rash with eosinophilia and systemic symptoms (DRESS), have also been rarely associated with aspirin (Ref).
Mechanism: Immediate reactions: Non–dose-related; most reactions (ie, AERD, NERD, NECD, NIUA) are nonimmunologic related to inhibition of cyclooxygenase-1 (COX-1) with subsequent activation of mast cells and eosinophils causing release of inflammatory mediators including cysteinyl-leukotrienes (cysLTs) (Ref). Some immediate reactions are IgE-mediated (Ref); although, these are rare with aspirin and more common with NSAIDs, where they can be associated with an immediate reaction specific to the specific NSAID or class of NSAID. Delayed hypersensitivity reactions, including DRESS, are T-cell-mediated (Ref).
Onset: Immediate hypersensitivity reactions: Rapid; occur within 1 hour of administration but may occur up to 6 hours after exposure (Ref). Delayed hypersensitivity reactions, including DRESS: Varied, by definition occur after 6 hours of exposure but most commonly occur 2 to 8 weeks after initiation (Ref).
Risk factors:
• Presence of chronic rhinosinusitis with nasal polyps, family history of AERD/NERD, and/or severe asthma may increase the risk of AERD/NERD (Ref). The prevalence of NERD in adult patients with asthma is ~10% to 20% (Ref).
• Chronic urticaria increases the risk of NECD (Ref). Aspirin-induced reactions are less frequent and less intense when chronic urticaria is in remission or under control (Ref). Approximately 12% to 30% of patients with chronic idiopathic urticaria develop exacerbations of their disease with use of aspirin and other COX-1 inhibitors (Ref).
• Cross-reactivity between aspirin and NSAIDs (with predominant COX-1 inhibition) have been described in patients with a history of NERD, NECD, and NIUA (Ref). Patients who develop a reaction (immediate or delayed) to only aspirin or a single NSAID are often able to tolerate chemically unrelated NSAIDs (Ref).
• Pharmacological cross-reactivity between aspirin and acetaminophen, a weak COX-1 inhibitor, and between aspirin and nonselective COX-2 inhibitors (eg, meloxicam, nimesulide) may occur (Ref). Due to the weak COX-1 inhibitory activity, AERD reactions associated with acetaminophen typically only occur with higher doses such as >4 g/day. Although selective COX-2 inhibitors (eg, celecoxib, etoricoxib) are generally tolerated in patients with AERD or NERD (Ref), pharmacological cross-reactions may occur, especially in patients with histories of urticaria/angioedema (Ref).
• Although earlier reports suggested that tartrazine and aspirin/NSAIDs may cross react, more recent clinical evidence has indicated that tartrazine is well-tolerated in patients with AERD/NERD (Ref)
• Despite structural similarity between aspirin and 5-aminosalicylic acid (ASA) (mesalamine), there is lack of evidence demonstrating occurrence of AERD in association with 5-ASA (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. 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 reactions with 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.
Frequency not defined:
Cardiovascular: Cardiac arrhythmia, hypotension, tachycardia
Endocrine & metabolic: Dehydration, hyperglycemia, hyperkalemia, hypoglycemia (children), increased thirst, metabolic acidosis
Gastrointestinal: Abdominal pain, dyspepsia, gastrointestinal perforation, gastrointestinal ulcer, heartburn, nausea, vomiting
Genitourinary: Postpartum hemorrhage, post-term pregnancy, prolonged labor, proteinuria, stillborn infant
Hematologic & oncologic: Disorder of hemostatic components of blood, disseminated intravascular coagulation, hemorrhage, prolonged bleeding time, prolonged prothrombin time, thrombocytopenia
Hepatic: Hepatitis, increased liver enzymes
Nervous system: Agitation, brain edema, coma, confusion, dizziness, headache, hypothermia, lethargy, seizure
Renal: Increased blood urea nitrogen, increased serum creatinine, interstitial nephritis, renal failure syndrome, renal insufficiency, renal papillary necrosis
Respiratory: Hyperventilation, laryngeal edema, pulmonary edema, respiratory alkalosis, tachypnea
Miscellaneous: Fever, low birth weight
Postmarketing:
Dermatologic: Urticaria (Kowalski 2013)
Endocrine & metabolic: Hyperuricemia (doses ≤325 mg/day) (Caspi 2000; Segal 2006)
Gastrointestinal: Gastrointestinal hemorrhage (Garcia Rodriguez 2019), pancreatitis (Hoyte 2012)
Hypersensitivity: Anaphylaxis (Kowalski 2013), angioedema (Kowalski 2013)
Immunologic: Drug reaction with eosinophilia and systemic symptoms (Kawakami 2009)
Nervous system: Intracranial hemorrhage (Huang 2019), Reye's syndrome (McGovern 2001)
Neuromuscular & skeletal: Rhabdomyolysis (Leventhal 1989)
Ophthalmic: Macular degeneration (age-related) (Li 2015)
Otic: Hearing loss (Koren 2009), tinnitus (Koren 2009)
Respiratory: Asthma (Kowalski 2013), bronchospasm (Kowalski 2013)
Hypersensitivity to NSAIDs; patients with asthma, rhinitis, and nasal polyps; use in children or teenagers for viral infections, with or without fever.
Disease-related concerns:
• Bariatric surgery:
– Altered absorption and efficacy: Altered absorption and efficacy may occur. The Tmax of salicylic acid after gastric bypass was observed to be significantly shorter after surgery. Cmax and AUC0-24 were also significantly higher (Mitrov-Winkelmolen 2016). In a mixed surgery population (80% gastric bypass, 20% sleeve), aspirin-induced platelet reactivity was significantly reduced and correlated to the extent of weight loss after surgery (Norgard 2017).
– Gastric ulceration: Evaluate the risk vs benefit of aspirin after surgery; if aspirin therapy is continued (eg, cardiovascular indications), use the lowest possible dose with concurrent administration of proton pump inhibitor (PPI); risk of gastric ulceration after gastric bypass and sleeve gastrectomy may be increased. A population-based study of over 20,000 patients identifying risk factors for marginal ulceration after gastric bypass suggests limited doses of aspirin may not increase risk whereas higher doses may (Sverden 2016). Another study identified that following gastric bypass, there is no significant difference in marginal ulceration rate between those given low-dose aspirin and those not on aspirin; however, long-term PPI therapy (>90 days) was found to significantly reduce marginal ulceration rate in both groups (Kang 2017).
• 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.
• 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: Use high dosages (eg, analgesic or anti-inflammatory uses) with caution (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:
• Thrombolytics: In the treatment of acute ischemic stroke, avoid aspirin for 24 hours following administration of a thrombolytic; administration within 24 hours increases the risk of hemorrhagic transformation (AHA/ASA [Powers 2019]; Jauch 2013).
Special populations:
• GI bleed patients: An individualized and multidisciplinary approach should be used to manage patients with an acute GI bleed who are on antiplatelet medications. Aspirin for primary prevention of cardiovascular events should be avoided in most patients with GI bleed who do not have high risk factors for cardiovascular events. However, aspirin for secondary cardiovascular prevention should not be discontinued in patients with established cardiovascular disease, even in the setting of a GI bleed. If held in the setting of a GI bleed, aspirin for secondary cardiovascular prevention should be resumed on the day hemostasis is confirmed by endoscopy (ACG/CAG [Abraham 2022]).
• 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 syndrome; patients should be instructed to contact their healthcare provider if these occur.
• Surgical patients: Patients who have recently undergone percutaneous coronary intervention with stenting or balloon angioplasty should continue antiplatelet therapy until it is safe to temporarily hold treatment. In patients undergoing CABG, aspirin may be continued until the time of surgery. Elective surgery for these patients should be delayed. Aspirin can typically be continued perioperatively in patients who undergo elective non-cardiac surgery. If aspirin interruption is necessary, discontinue therapy ≤7 days before surgery, and resume as soon as possible (eg, ≤24 hours) after surgery based on bleeding and thrombotic risks. Patient-specific situations should be discussed with cardiologist (ACC/AHA [Fleisher 2014]; ACC/AHA [Lawton 2022]; ACCP [Douketis 2022]; AHA/ACC/SCAI/ACS/ADA [Grines 2007]).
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 manufacturer's 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.
Do not use aspirin in pediatric patients <18 years of age (APS 2016) who have or who are recovering from chickenpox or flu symptoms (due to the association with Reye syndrome); when using aspirin, changes in behavior (along with nausea and vomiting) may be an early sign of Reye syndrome; instruct patients and caregivers to contact their health care provider if these symptoms occur; patients should be kept current on their influenza and varicella immunizations. Although Reye syndrome has been observed in patients receiving prolonged, high-dose aspirin therapy after Kawasaki disease presentation; it has not been observed in pediatric patients receiving low (antiplatelet) dosing regimens. Patients with Kawasaki disease and presenting with influenza or viral illness should not receive aspirin; acetaminophen is suggested as an antipyretic in these patients, and an alternate antiplatelet agent is suggested for a minimum of 2 weeks (AHA [McCrindle 2017]).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral:
Vazalore: 81 mg, 325 mg [contains carrageenan, fd&c blue #1 (brilliant blue), soybean oil]
Capsule Extended Release 24 Hour, Oral:
Durlaza: 162.5 mg [DSC]
Packet, Oral:
Stanback Headache Powders: 650-200-32 MG (2 ea [DSC], 6 ea [DSC], 24 ea [DSC], 50 ea [DSC])
Suppository, Rectal:
Generic: 60 mg (12 ea, 100 ea, 1000 ea); 300 mg (12 ea); 600 mg (12 ea [DSC])
Tablet, Oral:
Aspirin Adult: 325 mg [DSC] [contains corn starch]
Aspirtab Maximum Strength: 500 mg [DSC]
Bayer Aspirin: 325 mg [contains corn starch]
FT Aspirin: 325 mg [contains corn starch]
GoodSense Aspirin: 325 mg [contains corn starch]
GoodSense Aspirin: 325 mg [gluten free; contains corn starch]
Medi-First Aspirin: 325 mg [contains corn starch]
Medique Aspirin: 325 mg [contains corn starch]
Generic: 325 mg
Tablet, Oral, (buffered):
Ascriptin: 325 mg [contains methylparaben, saccharin sodium]
Bufferin: 325 mg [DSC]
Bufferin: 325 mg [contains benzoic acid, fd&c blue #1 (brilliant blue)]
Bufferin Extra Strength: 500 mg [contains benzoic acid, fd&c blue #1 (brilliant blue)]
Tri-Buffered Aspirin: 325 mg
Tablet Chewable, Oral:
Aspirin Adult Low Strength: 81 mg [DSC] [contains fd&c yellow #6(sunset yellow)alumin lake]
Aspirin Childrens: 81 mg [orange flavor]
Aspirin Childrens: 81 mg [contains fd&c yellow #6 (sunset yellow)]
Aspirin Low Dose: 81 mg [orange flavor]
Aspirin Low Dose: 81 mg [contains corn starch, fd&c yellow #6 (sunset yellow), saccharin sodium]
Aspirin Low Dose: 81 mg [contains corn starch, fd&c yellow #6 (sunset yellow), saccharin sodium; orange flavor]
Aspirin Low Dose: 81 mg [contains corn starch, fd&c yellow #6(sunset yellow)alumin lake; orange flavor]
Bayer Low Dose: 81 mg [caffeine free, sodium free; contains corn starch, fd&c yellow #6(sunset yellow)alumin lake, saccharin sodium]
Childrens Aspirin Low Strength: 81 mg [DSC] [caffeine free]
GoodSense Aspirin: 81 mg [gluten free; contains fd&c red #40(allura red ac)aluminum lake, saccharin sodium; cherry flavor]
GoodSense Aspirin: 81 mg [gluten free; contains fd&c yellow #6(sunset yellow)alumin lake, saccharin sodium]
GoodSense Aspirin: 81 mg [gluten free; contains fd&c yellow #6(sunset yellow)alumin lake, saccharin sodium; orange flavor]
GoodSense Aspirin Adult Low St: 81 mg [DSC] [gluten free; contains fd&c yellow #6(sunset yellow)alumin lake, saccharin sodium; orange flavor]
St Joseph Low Dose: 81 mg [contains corn starch, fd&c yellow #6(sunset yellow)alumin lake; orange flavor]
Generic: 81 mg
Tablet Delayed Release, Oral:
Aspirin 81: 81 mg [DSC] [contains fd&c yellow #6 (sunset yellow), quinoline yellow (d&c yellow #10)]
Aspirin 81: 81 mg [DSC] [contains fd&c yellow #6(sunset yellow)alumin lake, quinoline yellow (d&c yellow #10)]
Aspirin Adult Low Dose: 81 mg [contains fd&c yellow #6 (sunset yellow), quinoline yellow (d&c yellow #10)]
Aspirin Adult Low Dose: 81 mg [DSC] [contains quinoline (d&c yellow #10) aluminum lake]
Aspirin Adult Low Dose: 81 mg [contains quinoline (d&c yellow #10) aluminum lake, soybeans (glycine soja)]
Aspirin Adult Low Strength: 81 mg [contains corn starch, quinoline yellow (d&c yellow #10)]
Aspirin Adult Low Strength: 81 mg [contains fd&c yellow #6 (sunset yellow), quinoline yellow (d&c yellow #10)]
Aspirin Adult Low Strength: 81 mg [DSC] [contains quinoline (d&c yellow #10) aluminum lake]
Aspirin EC Low Strength: 81 mg [contains corn starch, quinoline (d&c yellow #10) aluminum lake]
Aspirin Low Dose: 81 mg [contains corn starch, fd&c yellow #6 (sunset yellow), quinoline yellow (d&c yellow #10)]
Aspirin Low Dose: 81 mg [contains fd&c yellow #6 (sunset yellow), quinoline yellow (d&c yellow #10)]
Aspirin Low Dose: 81 mg [contains fd&c yellow #6(sunset yellow)alumin lake, quinoline (d&c yellow #10) aluminum lake]
Aspirin Low Dose: 81 mg [contains quinoline (d&c yellow #10) aluminum lake]
Bayer Aspirin: 325 mg [contains corn starch, fd&c yellow #6(sunset yellow)alumin lake, quinoline (d&c yellow #10) aluminum lake]
Bayer Aspirin EC Low Dose: 81 mg [contains corn starch, fd&c yellow #6(sunset yellow)alumin lake, quinoline (d&c yellow #10) aluminum lake]
Ecotrin Maximum Strength: 500 mg [DSC]
EcPirin: 325 mg [DSC] [contains fd&c yellow #6(sunset yellow)alumin lake, quinoline (d&c yellow #10) aluminum lake]
FT Aspirin Low Dose: 81 mg [contains fd&c red #40(allura red ac)aluminum lake, fd&c yellow #6(sunset yellow)alumin lake]
FT Aspirin Low Dose: 81 mg [contains quinoline (d&c yellow #10) aluminum lake]
FT Aspirin Low Dose: 81 mg [contains quinoline yellow (d&c yellow #10)]
FT Enteric Coated Aspirin: 325 mg [contains corn starch, fd&c yellow #6(sunset yellow)alumin lake, quinoline (d&c yellow #10) aluminum lake]
GoodSense Aspirin: 325 mg [DSC] [contains corn starch, fd&c yellow #6(sunset yellow)alumin lake, quinoline (d&c yellow #10) aluminum lake]
GoodSense Aspirin Low Dose: 81 mg [contains fd&c yellow #6 (sunset yellow), quinoline yellow (d&c yellow #10)]
GoodSense Aspirin Low Dose: 81 mg [contains quinoline (d&c yellow #10) aluminum lake]
Miniprin Low Dose: 81 mg [DSC] [contains quinoline (d&c yellow #10) aluminum lake]
St Joseph Aspirin: 81 mg [contains fd&c red #40 (allura red ac dye), fd&c yellow #6 (sunset yellow); orange flavor]
St Joseph Low Dose: 81 mg [gluten free; contains fd&c red #40 (allura red ac dye), fd&c yellow #6 (sunset yellow); orange flavor]
Generic: 81 mg, 325 mg
May be product dependent
Capsules (Vazalore Oral)
81 mg (per each): $0.93
325 mg (per each): $0.90
Chewable (Aspirin Oral)
81 mg (per each): $0.02 - $0.06
Chewable (St Joseph Low Dose Oral)
81 mg (per each): $0.05
Suppository (Aspirin Rectal)
300 mg (per each): $1.46
Tablet, EC (Aspirin Oral)
81 mg (per each): $0.01 - $0.03
325 mg (per each): $0.02 - $0.05
Tablet, EC (Bayer Aspirin EC Low Dose Oral)
81 mg (per each): $0.04
Tablet, EC (Bayer Aspirin Oral)
325 mg (per each): $0.08
Tablets (Ascriptin Oral)
325 mg (per each): $0.08
Tablets (Aspirin Oral)
325 mg (per each): $0.01 - $0.03
Tablets (Bayer Aspirin Oral)
325 mg (per each): $0.14
Tablets (Bufferin Extra Strength Oral)
500 mg (per each): $0.10
Tablets (Bufferin Oral)
325 mg (per each): $0.07
Tablets (Medi-First Aspirin Oral)
325 mg (per each): $0.04
Tablets (Medique Aspirin Oral)
325 mg (per each): $0.04
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Oral:
IR tablets: 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 myocardial infarction), have patient chew IR tablet.
Preeclampsia (prevention): Administration as an evening dose may be more beneficial than administration in the morning (Ref).
ER 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.
Bariatric surgery: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. Switch to IR formulation.
Rectal: Remove suppository from plastic packet and insert into rectum as far as possible.
Oral: Administer with water, food, or milk to decrease GI upset.
Immediate release:
Capsule: Swallow whole; do not cut, crush, or chew. Administer with a full glass of water.
Tablets: Do not crush or chew enteric-coated tablets; these preparations should be swallowed whole. In situations for which rapid onset of action is required, patient should chew immediate-release tablet.
Extended release: Do not cut, crush, or chew. Administer with a full glass of water at the same time each day.
Rectal: Remove suppository from plastic packet and insert into rectum as far as possible.
Immediate release:
Analgesic, antipyretic, and anti-inflammatory: 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: For use in patients who have undergone revascularization procedures (ie, coronary artery bypass graft, percutaneous transluminal coronary angioplasty, or carotid endarterectomy).
Vascular indications, including ischemic stroke, transient ischemic attack, acute coronary syndromes (ST-elevation myocardial infarction or non-ST-elevation acute coronary syndromes [non-ST-elevation myocardial infarction or unstable angina]), secondary prevention after acute coronary syndromes, and management of stable ischemic heart disease: 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 stable ischemic heart disease.
ER capsules:
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.
Stable ischemic heart disease: To reduce the risk of death and MI in patients with stable ischemic heart disease.
Limitations of use: Do not use ER capsules in situations for which a rapid onset of action is required (such as acute treatment of MI or before percutaneous coronary intervention); use IR formulations instead.
Atherosclerotic cardiovascular disease, primary prevention; Carotid artery atherosclerosis, asymptomatic or symptomatic; Carotid artery stenting; Colorectal cancer risk reduction, primary prevention; Migraine, acute treatment; Percutaneous coronary intervention for stable ischemic heart disease; Pericarditis, acute or recurrent; Peripheral atherosclerotic disease (upper or lower extremity; with or without a revascularization procedure); Polycythemia vera, prevention of thrombosis; Preeclampsia prevention; Surgical prosthetic heart valve replacement, thromboprophylaxis; Transcatheter aortic valve replacement, thromboprophylaxis; Transcatheter mitral valve repair with MitraClip device, thromboprophylaxis; Venous thromboembolism prevention, indefinite therapy; Venous thromboembolism prophylaxis for total hip or knee arthroplasty; Venous thromboembolism prophylaxis in lower-risk patients with multiple myeloma receiving immunomodulatory therapy
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
Anacin 81 [Puerto Rico] may be confused with Anacin brand name for lidocaine/prilocaine [Korea]; Anacin-3 brand name for acetaminophen [Taiwan]; Anacin New brand name for acetaminophen/caffeine [India]
Cartia [multiple international markets] may be confused with Cartia XT brand name for dilTIAZem [US]
Beers Criteria: Aspirin is identified in the Beers Criteria as a potentially inappropriate medication to be avoided in patients ≥65 years of age for the primary prevention of cardiovascular disease due to increased risk for major bleeding. A potential for harm and lack of benefit when initiated as primary prevention in older adults is suggested by studies. In older adults already taking for primary prevention, deprescribing should be considered. In addition, aspirin, when used chronically at doses more than 325 mg/day, is identified in the Beers Criteria as a potentially inappropriate medication to be avoided in patients ≥65 years of age (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, >75 years of age or receiving concomitant oral/parenteral corticosteroids, anticoagulants, or antiplatelet agents) (Beers Criteria [AGS 2023]).
Aspirin is identified in the Screening Tool of Older Person's Prescriptions (STOPP) criteria as a potentially inappropriate medication in older adults (≥65 years of age) at risk of major bleeding (eg, uncontrolled hypertension, recent significant bleeding, bleeding diathesis) or for long-term use at doses >100 mg/day. Use is also potentially inappropriate for primary prevention of cardiovascular disease, stroke prevention in patients with chronic atrial fibrillation, and long-term use for relief of symptoms in osteoarthritis or gout. Some disease states of concern include gastric antral vascular ectasia (GAVE), peptic ulcer disease, renal impairment, gastrointestinal bleeding, and severe hypertension (O’Mahony 2023).
KIDs List: Salicylates, when used in pediatric patients <18 years of age with suspicion of viral illness (influenza, chickenpox), are identified on the Key Potentially Inappropriate Drugs in Pediatrics (KIDs) list and should be used with caution due to risk of Reye syndrome (weak recommendation; very low quality of evidence) (PPA [Meyers 2020]).
Substrate of CYP2C9 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Abrocitinib: Aspirin may enhance the antiplatelet effect of Abrocitinib. Management: Do not use aspirin at doses greater than 81 mg/day with abrocitinib during the first 3 months of abrocitinib therapy. The abrocitinib prescribing information lists this combination as contraindicated. Risk D: Consider therapy modification
Acalabrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. 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
Agents with Blood Glucose Lowering Effects: Salicylates may enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. 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. Risk C: Monitor therapy
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
Anagrelide: May enhance the antiplatelet effect of Aspirin. Risk C: Monitor therapy
Angiotensin-Converting Enzyme Inhibitors: Salicylates may enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Salicylates may diminish the therapeutic effect of Angiotensin-Converting Enzyme Inhibitors. 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
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
Bemiparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Bemiparin. Management: Avoid concomitant use of bemiparin with antiplatelet agents. If concomitant use is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification
Benzbromarone: Salicylates may diminish the therapeutic effect of Benzbromarone. Risk C: Monitor therapy
Calcium Channel Blockers (Nondihydropyridine): May enhance the antiplatelet effect of Aspirin. Risk C: Monitor therapy
Caplacizumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Caplacizumab. Specifically, the risk of bleeding may be increased. Management: Avoid coadministration of caplacizumab with antiplatelets if possible. If coadministration is required, monitor closely for signs and symptoms of bleeding. Interrupt use of caplacizumab if clinically significant bleeding occurs. Risk D: Consider therapy modification
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. Risk D: Consider therapy modification
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
ClomiPRAMINE: May enhance the antiplatelet effect of Aspirin. Risk C: Monitor therapy
Collagenase (Systemic): Aspirin 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
Dexibuprofen: Aspirin may enhance the adverse/toxic effect of Dexibuprofen. Dexibuprofen may diminish the cardioprotective effect of Aspirin. Risk X: Avoid combination
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
Dipyrone: May diminish the antiplatelet effect of Aspirin. Management: Use caution and consider avoiding use of dipyrone in patients treated with aspirin for the treatment or prevention of cardiovascular events or stroke. Risk D: Consider therapy modification
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
Enoxaparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Enoxaparin. Management: Discontinue antiplatelet agents prior to initiating enoxaparin whenever possible. If concomitant administration is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification
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
Heparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Heparin. Management: Decrease the dose of heparin or agents with antiplatelet properties if coadministration is required. Risk D: Consider therapy modification
Herbal Products with Anticoagulant/Antiplatelet Effects (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Risk C: Monitor therapy
Herbal Products with Anticoagulant/Antiplatelet Effects (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Salicylates. Bleeding may occur. Risk C: Monitor therapy
Hyaluronidase: Salicylates may diminish the therapeutic effect of Hyaluronidase. Risk C: Monitor therapy
Ibritumomab Tiuxetan: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. 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
Icosapent Ethyl: May enhance the antiplatelet 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
Inotersen: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
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. Management: Concurrent use of nasal ketorolac with analgesic doses of aspirin is generally not recommended. If using low-dose, cardioprotective aspirin with nasal ketorolac, monitor the patient closely for evidence of adverse GI effects. Risk D: Consider therapy modification
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
Lecanemab: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of hemorrhage may be increased. Risk C: Monitor therapy
Limaprost: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Lipid Emulsion (Fish Oil Based): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Loop Diuretics: Salicylates may diminish the therapeutic effect of Loop Diuretics. Loop Diuretics may increase the serum concentration of Salicylates. Risk C: Monitor therapy
Macimorelin: Aspirin may diminish the diagnostic effect of Macimorelin. Risk X: Avoid combination
Methotrexate: Salicylates may increase the serum concentration of Methotrexate. Salicylate doses used for prophylaxis of cardiovascular events are not likely to be of concern. Management: Consider avoiding coadministration of methotrexate and salicylates. If coadministration cannot be avoided, monitor for increased toxic effects 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 Agents with Antiplatelet Properties. Risk C: Monitor therapy
Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Multivitamins/Minerals (with AE, No Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. 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
Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): Aspirin may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective). Specifically, the risk of gastrointestinal adverse effects may be increased. 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 permissible, patients should be monitored closely for signs/symptoms of GI ulceration/bleeding. Risk D: Consider therapy modification
Nonsteroidal Anti-Inflammatory Agents (Nonselective): May enhance the adverse/toxic effect of Salicylates. An increased risk of bleeding may be associated with use of this combination. Nonsteroidal Anti-Inflammatory Agents (Nonselective) may diminish the cardioprotective effect of Salicylates. Salicylates may decrease the serum concentration of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Management: Nonselective NSAIDs may reduce aspirin's cardioprotective effects. Administer ibuprofen 30-120 minutes after immediate-release aspirin, 2 to 4 hours after extended-release aspirin, or 8 hours before aspirin. Risk D: Consider therapy modification
Nonsteroidal Anti-Inflammatory Agents (Topical): May enhance the adverse/toxic effect of Salicylates. Specifically, the risk of gastrointestinal (GI) toxicity is increased. Management: Coadministration of salicylates and topical NSAIDs is not recommended. If salicylates and topical NSAIDs are coadministered, ensure the benefits outweigh the risks and monitor for increased NSAID toxicities. 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
Pirtobrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Potassium 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. Management: Consider avoiding concomitant use of salicylates and pralatrexate. If coadministered, monitor for increased pralatrexate adverse effects. Salicylate doses used for prophylaxis of cardiovascular events are not likely to be of concern. Risk D: Consider therapy modification
Probenecid: Salicylates may diminish the therapeutic effect of Probenecid. Risk X: Avoid combination
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: 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
Selumetinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Serotonin/Norepinephrine Reuptake Inhibitors: May enhance the antiplatelet effect of Aspirin. Risk C: Monitor therapy
Sincalide: Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Risk D: Consider therapy modification
Spironolactone: Aspirin may diminish the therapeutic effect of Spironolactone. Risk C: Monitor therapy
Sucroferric Oxyhydroxide: May decrease the serum concentration of Aspirin. Management: Administer aspirin at least 1 hour before administration of sucroferric oxyhydroxide. Risk D: Consider therapy modification
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
Thiopental: Aspirin may decrease the protein binding of Thiopental. Risk C: Monitor therapy
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 maintenance aspirin doses greater than 150 mg/day in patients receiving ticagrelor. After any initial dose, only low-dose aspirin (75 to 100 mg/day) 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
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. Specifically, the risk for Reye's syndrome may increase. Risk X: Avoid combination
Vitamin E (Systemic): 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. Management: Avoid as needed use of salicylates in patients taking vitamin K antagonists. Aspirin (80 to 325 mg/day) may be used with warfarin for prevention of cardiovascular events. If coadministering salicylates and vitamin K antagonists, monitor for bledding. Risk D: Consider therapy modification
Volanesorsen: May enhance the antiplatelet effect of Therapeutic Antiplatelets. Risk C: Monitor therapy
Zanubrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
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.
Low-dose aspirin has been evaluated to improve live birth rates in patients with antiphospholipid syndrome (APS) diagnosed with recurrent pregnancy loss (Hamulyák 2020; Hamulyák 2021). Recommendations for when to initiate treatment differ between guidelines. Some guidelines initiate aspirin prior to conception, while others prefer use of other agents (heparin or low-molecular-weight heparin) in patients planning to become pregnant (ACR [Sammaritano 2020]); ESHRE [Bender Atik 2018]; EULAR [Andreoli 2017]). Use of low-dose aspirin prior to conception in patients with a history of recurrent pregnancy loss but who are not diagnosed with APS has also been evaluated (Naimi 2021).
Salicylate is present in umbilical cord and newborn serum following maternal use of aspirin prior to delivery (Garrettson 1975; Levy 1975; Palmisano 1969); salicylic acid and other metabolites can also be detected in the newborn urine following in utero exposure (Garrettson 1975).
Fetal outcomes are influenced by maternal dose; low dose aspirin (≤150 mg/day) is not associated with the same risks as higher doses and has a positive effect on some pregnancy outcomes (ACOG 2018; Choi 2021; Turner 2020). Adverse effects reported in the fetus following maternal use of high dose aspirin include mortality, intrauterine growth restriction, 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 (Corby 1978; Østensen 1998).
Except when used in lower doses for pregnancy-related conditions, maternal use of aspirin should be avoided beginning 20 weeks gestation (FDA Safety Communication 2020).
Due to pregnancy-induced physiologic changes, some pharmacokinetic properties of aspirin may be altered (Rymark 1994; Shanmugalingam 2019).
Low-dose aspirin is recommended to prevent preeclampsia in patients at risk. The definition of risk factors varies by guideline and dosing varies by country due to dosage form availability (ACOG 2018; FIGO [Poon 2019]; SOGC [Magee 2022]; USPSTF [Davidson 2021]). The American College of Obstetricians and Gynecologists and United States Preventive Services Task Force recommend the use of low-dose aspirin for patients with ≥1 of the following high-risk factors: history of preeclampsia, multifetal gestation, chronic hypertension, type 1 or type 2 diabetes mellitus, renal disease, autoimmune disease (eg, systemic lupus erythematosus, antiphospholipid syndrome), or combinations of multiple moderate risk factors. Low-dose aspirin is also recommended for patients with ≥2 of the following moderate risk factors: nulliparity, BMI >30, family history of preeclampsia, Black race (due to social, rather than biological, factors), lower income, age ≥35 years, personal history factors (eg, low birth weight or small for GA, previous adverse pregnancy outcome, >10-year pregnancy interval), or in vitro conception. Low-dose aspirin may also be considered in patients with ≥1 of the following moderate risk factors: Black race (due to social, rather than biological, factors), lower income (ACOG 2018; ACOG 2021; USPSTF [Davidson 2021]).
In addition to preventing preeclampsia, low-dose aspirin is also recommended to improve other pregnancy outcomes and decrease the risk of thrombosis in patients with a positive antiphospholipid antibody (aPL) test. The addition of heparin or low-molecular-weight heparin may also be needed in patients with obstetric or thrombotic antiphospholipid syndrome (APS). Low-dose aspirin is also recommended for pregnant patients with systemic lupus erythematosus (SLE) (ACR [Sammaritano 2020]; EULAR [Andreoli 2017]; SMFM [Silver 2022]).
Low-dose aspirin, in addition to anticoagulation, may be used to prevent thrombosis in pregnant patients with a mechanical heart valve (ACC/AHA [Otto 2021]).
Aspirin is not recommended for the treatment of migraine headaches during pregnancy (ACOG 2022).
Salicylic acid is present in breast milk following maternal use of aspirin (Bailey 1982; Findlay 1981; Jamali 1981).
Actual breast milk concentrations of salicylic acid vary by maternal dose. In a study of six breastfeeding women, 1 to 8 months' postpartum, the highest breast milk concentration of salicylic acid was 0.0001654 mcg/mL in six women, following a maternal dose of aspirin 81 mg/day (duration of treatment not presented). Authors of this study calculated the relative infant dose (RID) of aspirin to be <1% of the weight-adjusted maternal dose (Datta 2017). In general, breastfeeding is considered acceptable when the RID is <10% (Anderson 2016; Ito 2000). Significantly higher breast milk concentrations (48.1 mcg/mL) were reported following maternal administration of aspirin 1,500 mg as a single dose (Jamali 1981).
The reported time to peak milk concentration of salicylic acid is variable (2 to 9 hours), milk concentrations decline slowly, and do not correlate strongly to maternal serum concentration (Bailey 1982; Bar-Oz 2003; Datta 2017; Findlay 1981; Jamali 1981). Salicylate is measurable in the serum (Unsworth 1987) and urine (Clark 1981) of breastfed infants following maternal use of oral aspirin. Higher salicylate concentrations may be present in breast milk following multiple maternal doses. In addition, salicylate concentrations may be higher than reported as metabolite concentrations of salicylic acid were not evaluated in most studies; the longer elimination half-life in infants compared to adults should also be considered (Bar-Oz 2003; Spigset 2000).
Metabolic acidosis was reported in a 16-day old breastfed full-term infant following maternal doses of aspirin 3.9 g/day (Clark 1981). Thrombocytopenic purpura was also reported in one infant following salicylate exposure via breast milk (maternal dose not specified) (Spigset 2000; Terragna 1967). There were no cases of diarrhea, drowsiness, or irritability noted in breastfed infants in the study which included 15 mother-infant pairs following aspirin exposure (dose, duration, and relationship to breastfeeding not provided) (Ito 1993).
Low-dose aspirin may be used in breastfeeding patients (ACOG 2022; ESC [Regitz-Zagrosek 2018]); however, standard doses of aspirin should be avoided due to the possible risk of neonatal metabolic acidosis, hemolysis, and the theoretical risk of Reye syndrome (ACOG 2022). Nonopioid analgesics are preferred for breastfeeding patients who require pain control peripartum or for surgery outside of the postpartum period. Low doses of aspirin (75 to 162 mg/day) may be used; however, other agents are preferred if higher doses are needed (ABM [Martin 2018]; ABM [Reece-Stremtan 2017]; Sachs 2013). When used for vascular indications, breastfeeding may be continued during low-dose aspirin therapy (ESC [Regitz-Zagrosek 2018]; WHO 2002). The WHO considers occasional doses of aspirin to be compatible with breastfeeding patients for the treatment of rheumatic and musculoskeletal diseases or migraine but recommends avoiding long-term therapy and consider monitoring the infant for adverse effects (hemolysis, prolonged bleeding, metabolic acidosis) (WHO 2002). High doses of aspirin in breastfeeding patients for the treatment of rheumatic and musculoskeletal diseases or migraine are not recommended (ACOG 2022; ACR [Sammaritano 2020]).
Monitor for signs and symptoms of drug reaction with eosinophilia and systemic symptoms (eg, fever, rash, lymphadenopathy, eosinophilia in association with other organ system involvement such as hepatitis, nephritis, hematological abnormalities, myocarditis, myositis; early symptoms of hypersensitivity reaction may occur without rash).
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 and the corresponding clinical correlations are as follows: See table.
|
Serum Salicylate Concentration |
Desired Effects |
Adverse Effects / Intoxication |
|---|---|---|
|
~100 mcg/mL (SI: ~724 micromole/L) |
Antiplatelet Antipyresis Analgesia |
GI intolerance and bleeding, hypersensitivity, hemostatic defects |
|
150 to 300 mcg/mL (SI: 1,086 to 2,172 micromole/L) |
Anti-inflammatory |
Mild salicylism |
|
250 to 400 mcg/mL (SI: 1,810 to 2,896 micromole/L) |
Treatment of rheumatic fever |
Nausea/vomiting, hyperventilation, salicylism, flushing, sweating, thirst, headache, diarrhea, and tachycardia |
|
>400 to 500 mcg/mL (SI: >2,896 to 3,620 micromole/L) |
Respiratory alkalosis, hemorrhage, excitement, confusion, asterixis, pulmonary edema, convulsions, tetany, metabolic acidosis, fever, coma, cardiovascular collapse, renal and respiratory failure |
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
Onset: Immediate release: Platelet inhibition: Nonenteric-coated: <1 hour; enteric-coated: 3 to 4 hours (Eikelboom 2012). Note: Chewing nonenteric-coated or enteric-coated tablets results in inhibition of platelet aggregation within 20 minutes (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)
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