NSAIDs

ASPIRIN

Adult Dosing

• 2019 ACC/AHA guidelines for primary prevention of ASCVD
  • Recommended for 40-70 yo with increased ASCVD risk AND no increased risk of bleeding:
    • 75-100 mg PO qD
  • Recommends against daily ASA if no ASCVD risk and/or any increased bleeding risk
• Most CV uses: 81 mg PO qD
• ACS:
  • Initial: 162-325 mg PO, OR
    • 600 mg PR
  • Maintenance (secondary prevention): 81-325 mg PO qD
    • With concomitant ticagrelor: 81 mg/day
  • STEMI: recommend concomitant P2Y₁₂ inhibitor AND parenteral anticoagulant
  • NSTE-ACS (early-invasive strategy):
    • Recommend concomitant clopidogrel or ticagrelor AND parenteral anticoagulant
      • High-risk Pts (troponin positive): consider GP IIb/IIIa inhibitor IV
    • Tx duration if post-PCI with stenting: ≥12 months
  • NSTE-ACS (ischemia-guided/noninvasive strategy):
    • Recommend concomitant clopidogrel or ticagrelor for ≤12 months
• Analgesic/antipyretic:
  • 325-650 mg PO q4h PRN, OR
    • 975 mg PO q6h PRN, OR
    • 500-1,000 mg PO q4-6h PRN, OR
    • 300-600 mg PR q4h
    • NMT 4 g/day AND NMT 10 days duration
• CAD, chronic/established:
  • ER cap: 162.5 mg PO qD
  • IR (off-label): 75-100 mg PO qD
• Stroke/TIA, acute ischemic:
  • Initial:
    • (off-label): 160-325 mg PO within 24-48 hrs of onset
    • Do NOT administer within 24 hrs after alteplase
    • Minor stroke/TIA (within 24 hrs): consider concomitant clopidogrel ≤21 days
  • Maintenance (secondary prevention):
    • ER cap: 162.5 mg PO qD
    • IR (off-label): 75-100 mg PO qD
• Off-label uses:
  • Anti-inflammatory/OA/RA:
    • NOTE: non-ASA NSAIDs are preferred
    • 2.1-7.3 g/day PO div into individualized doses
  • Lynch Syndrome (HNPCC):
    • 600 mg PO qD ≥2 years
  • Pericarditis:
    • Initial: 2.4-3.6 g/day PO div
    • Maintenance: 3.6-5.4 g/day PO div, THEN taper gradually over 2-3 weeks as indicated
    • Secondary to MI: 650 mg PO QID; may titrate to 975 mg PO QID
  • Primary stroke prevention in high-risk females:
    • 81 mg PO qD, OR 100 mg qOD
  • 50-100 mg PO qD:
    • Aortic valve repair
    • Cryptogenic stroke/TIA with patent foramen ovale OR atrial septal aneurysm
  • 75-100 mg PO qD:
    • Carotid artery stenosis, asymptomatic; if symptomatic, DOC is clopidogrel or ASA/dipyridamole
    • Carotid endarterectomy; DOC is clopidogrel or ASA/dipyridamole
    • Peripheral arterial disease; if symptomatic, consider concomitant clopidogrel
    • Peripheral artery percutaneous transluminal angioplasty
    • Peripheral artery bypass graft surgery, postprocedure
      • Below-knee bypass graft surgery with prosthetic grafts: add concomitant clopidogrel
    • Polycythemia vera
    • Prosthetic heart valve replacement (thromboprophylaxis)
      • Bioprosthetic aortic/mitral valve (3-6 mos post-surgery): consider concomitant warfarin
      • Mechanical aortic/mitral valve (with warfarin): may titrate to 325 mg/day
      • Pregnant: during 2nd/3rd trimesters; if mechanical = concomitant warfarin
      • TAVR: with clopidogrel; may consider anticoagulant + ASA or clopidogrel
    • Secondary stroke/TIA prevention, cardioembolic
      • Noncardioembolic: may titrate to 75-325 mg/day; DOC is clopidogrel or ASA/dipyridamole
  • 75-162 mg PO qD:
    • CVD primary prevention in ≥50 yo with T1DM/T2DM AND a 3^rd RF
    • CVD secondary prevention with diabetes
  • 81-325 mg PO qD:
    • Colorectal cancer, reduce risk; assess risks/benefits prior to starting
    • Thromboembolism prevention with A-fib (low risk; CHADS = 1)
    • PCI, non-emergent: initiate 325 mg 2-24 hrs before procedure, THEN 81 mg/day ≤12 months
      • With concomitant P2Y12 inhibitor
    • Secondary prevention post-CABG: administer before AND immediately after; continue indefinitely
  • 162-325 mg PO qD:
    • Primary PCI; 325 mg/day is preferred
  • 81 mg PO qD:
    • Preeclampsia prevention (at-risk Pt); may titrate to 100-150 mg/day
      • Start ^~12 weeks gestation; D/C ^~36-37 weeks gestation
  • 100 mg PO qD:
    • VTE, secondary prevention
  • 325 mg PO qD:
    • Secondary prevention of IC atherosclerosis; consider concomitant clopidogrel x90 days
• Renal impairment, CrCl <10 mL/min:
  • Avoid
• Hepatic impairment, severe liver disease:
  • Avoid
• Administration:
  • With food and/or 8-12 ounces water

Pediatric Dosing

• <12 yo: safety and efficacy not established; risk of Reye's Syndrome
• <18 yo with (or recovering from) chickenpox/flu Sx:
  • Safety and efficacy not established; risk of Reye's Syndrome
• Analgesic/Antipyretic:
  • <50 kg: 10-15 mg/kg/dose PO/PR q4-6h;
    • NMT 90 mg/kg/day OR 4 g/day, whichever is less
  • ≥50 kg: 325-650 mg PO/PR q4-6h; NMT 3.9 g/24 hrs
• Anti-inflammatory:
  • Initial: 60-90 mg/kg/day PO div doses
  • Maintenance: 80-100 mg/kg/day PO div q6-8h
• Antiplatelet (dosing derived from ADULT studies - use extreme caution):
  • 1-5 mg/kg/dose qD; ADULT daily max is NMT 325 mg/day
    • Noncardioembolic AIS: continue ≥2 years; if recurrent AIS/TIAs = switch to clopidogrel, LMWH, warfarin
    • AIS secondary to non-Moyamoya vasculopathy: continue to 3 months
    • Bioprosthetic aortic valve (with normal sinus rhythm): continue to 3 months
    • Mechanical aortic/mitral valve: with concomitant vit. K antagonist
    • Transcatheter ASD or VSD devices, postprocedure prophylaxis: start ≥1 day before and continue to ≥6 months
    • VAD placement: start ≤72 hrs of placement with concomitant heparin
• Juvenile Rheumatoid Arthritis:
  • 60-110 mg/kg/day div q4-6h PO
    • Maintain serum salicylate 150-300 mcg/mL
• Kawasaki Disease
  • Febrile phase: 80-100 mg/kg/day divided q6h PO
  • After defervesces: 3-6 mg/kg PO qD
• Toxic dose: 200 mg/kg

Contraindications and Cautions

• Contraindications
  • Hypersensitivity to aspirin or NSAIDs
  • Allergy to tartrazine dye
  • Asthma
  • Rhinitis
  • Nasal polyp
  • Active bleeding
• Cautions
  • Anemia, GI malabsorption, history of peptic ulcers, gout, hepatic disease, hypochlorhydria, hypoprothrombinemia, renal impairment, thyrotoxicosis, vitamin K deficiency, renal calculi
  • Peds with varicella or influenza-like illness: associated with increased incidence of Reye's Syndrome
  • Can cause serious skin adverse reactions, including:
    • SJS, TENs, exfoliative dermatitis
    • Fixed drug eruption, OR
    • A more severe variant known as generalized bullous fixed drug eruption
  • Risk of premature closure of fetal ductus arteriosus and renal dysfunction
    • Avoid at wk 20 of gestation; unless low-dose (see Pregnancy/Lactation)

Indications & Uses

• Pain, fever, inflammatory conditions, myocardial reinfarction prophylaxis, platelet aggregation prophylaxis, thromboembolism, transient ischemic attack
• Primary prevention of ASCVD (Go to Evidence-Based Inquiry)
  • ACC/AHA recommends only for 40-70 yo with increased ASCVD risk AND no increased risk of bleeding
• Limitations of use
  • Use immediate release if needed for rapid onset of action

Mechanism of Action

• Inhibits prostaglandin synthesis by cyclooxygenase; inhibits platelet aggregation

Adverse Drug Reactions

• Frequency not defined
  • angioedema
  • bronchospasm
  • CNS alteration
  • dermatologic problems
  • GI pain/ulceration/bleeding
  • hepatotoxicity
  • hearing loss
  • premature hemolysis
  • pulmonary edema (salicylate-induced/noncardiogenic)
  • renal damage
  • tinnitus
  • urticaria

Pregnancy and Lactation

• Pregnancy
  • Risk Summary: Increased risk of closure of fetal ductus arteriosus and renal dysfunction
    • Recommend <48 hrs Tx at 20-30 wks gestation if deemed necessary
    • Avoid use at >30 wks gestation; unless low-dose
  • Human Data: renal dysfunction/oligohydramnios reported; usually reversible with NSAID D/C
  • Animal Data: increased pre/post-implantation loss, diaphragmatic hernia, skeletal malformations
• Lactation
  • Risk Summary: low levels present in human milk; potential for serious adverse reaction in nursing infants
  • Effect on production: unknown
• Minimizing exposure: consider risk/benefit of Tx vs breastfeeding
• Reproductive Risk
  • Contraception: no data available
  • Fertility: may reversibly delay or prevent rupture of ovarian follicles
    • Consider D/C in women who have difficulties conceiving or who are undergoing investigation of infertility

Kinetics/Dynamics

• Half-life
  • 2-3 hr (low-dose)
  • 15-30 hr (higher dose)
• Onset: PO 5-30 min; PR 1-2 hr
• Duration: PO 3-6 hr; PR >7 hr
• Peak Plasma
  • Time: PO 0.25-3 hr; PR 4-5 hr
  • Concentration:
    • Analgesia and antipyresis: 30-100 mcg/mL
    • Anti-inflammatory effect: 150-300 mcg/mL
    • Rheumatic fever: 250-350 mcg/ml
• Bioavailability: 80-100%
• Protein-Bound
  • 90-95% with concentrations up to 100 mcg/mL
  • 70-85% with concentrations up to 100-400 mcg/mL
  • 25-60% with higher concentrations
• Vd: 0.15-0.2 L/kg
• Metabolism: liver, microsomal enzyme system
• Metabolites: salicylate, salicyl phenolic glucuronide, salicyl acyl glucuronide, 2,5-dihydroxybenzoic acid (gentisic acid), 2,3-dihydroxybenzoic acid, 2,3,5-trihydroxybenzoic acid, gentisuric acid (active)
• Renal Clearance: 80-100% 24-72 hr
• Excretion: principally in urine (80-100%), sweat, saliva, feces
• Dialyzable: yes
• Enzymes inhibited: cyclooxygenase (insignificant)

Overdose Management

• See Salicylates OD

Interactions

• Go to Drug Interactions [DI]

Trade Names

• Dosing Strengths: (tablet) 81 mg, 300 mg, 325 mg, 500 mg, 650 mg, 800 mg; (chewable tablet) 81 mg; (enteric-coated tablet) 975 mg; (extended rel capsule) 162.5 mg; (suppository) 60 mg, 80 mg, 120 mg, 125 mg, 200 mg, 300 mg, 325 mg, 600 mg, 650 mg, 1.2 g

• United States: Bufferin; Durlaza; Ecotrin; Empirin; Fasprin; Zorprin
• Canada: Asaphen; CASA; Entrophen; PHL-ASA; PHL-ASA E.C.; Novasen

Other Information

• Class: NSAIDs
• OTC; some formulations require prescription
• ATC Code : A01AD05; B01AC06; N02BA01
• US Cost Info: Generic ($) | Brand ($$$$)
• Medicare Part D: Coverage

Evidence-Based Inquiry

1. Which healthy adults should take aspirin?
2. Is clopidogrel plus aspirin superior to aspirin alone for primary prevention of cardiovascular outcomes among patients with multiple risk factors?
3. Should all people with type 2 diabetes be on daily aspirin for primary prevention of cardiovascular events?

PURLs

1. Stroke Prevention: Age Alone Does Not Rule Out Warfarin

References

1. ASHP Drug Compendium (Aspirin; Salicylates)
2. FDA Monograph aspirin ER (Aggrenox) https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/020884s039lbledt.pdf (Accessed October 2020)
3. FDA Monograph aspirin ER (Durlaza) https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=4c2a1403-3862-1efd-0a91-444989222b37&type=display (Accessed March 2019)
4. FDA Monograph aspirin (chewable tablet) https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=56279fd2-bec3-4d77-86dd-2a3bd46c6109&type=display (Accessed March 2019)
5. FDA Monograph aspirin (tablet) https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=28c48336-c238-0141-e054-00144ff8d46c&type=display (Accessed March 2019)
6. Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease. J Am Coll Cardiol. 2019;3(10). (Accessed March 2019)
7. Birmann BM, Giovannucci EL, Rosner BA, Colditz GA. Regular aspirin use and risk of multiple myeloma: a prospective analysis in the Health Professionals Follow-up Study and Nurses' Health Study. Cancer Prev Res (Phila). 2013.
8. Calderaro D, Pastana AF, Flores da Rocha TR, et al. Aspirin responsiveness safely lowers perioperative cardiovascular risk. J Vasc Surg. 2013;58(6):1593-1599.
9. Dovizio M, Tacconelli S, Sostres C, Ricciotti E, Patrignani P. Mechanistic and Pharmacological Issues of Aspirin as an Anticancer Agent. Pharmaceuticals (Basel). 2012;5(12):1346-1371.
10. Forer B, Landsberg R, Kivity S. Aspirin challenge in patients with chronic rhinosinusitis with polyps correlates with local and systemic inflammatory markers. Am J Rhinol Allergy. 2013;27(6):170-173.
11. Habib MJ, Rogers JA. Simultaneous spectrofluorometric determination of aspirin and salicylic Acid in aqueous solution. Pharm Res. 1985;2(3):148-149.
12. Lala A, Hiatt WR, Berger JS. Aspirin in primary prevention: can we individualize care? Cardiovasc Diagn Ther. 2012;2(2):169-172.
13. Yao C, Yang D, Wan Z, et al. Aspirin-triggered lipoxin A4 attenuates lipopolysaccharide induced inflammatory response in primary astrocytes. Int Immunopharmacol. 2013.

Contributor(s)

1. Vaioleti, Alani, PharmD

Updated/Reviewed: March 2019