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Pronunciation
(AS pir in)
Generic Available (U.S.)
Yes: Excludes gum
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of mild-to-moderate pain, inflammation, and fever; prevention and treatment of myocardial infarction (MI), acute ischemic stroke, and transient ischemic episodes; management of rheumatoid arthritis, rheumatic fever, osteoarthritis; adjunctive therapy in revascularization procedures (coronary artery bypass graft [CABG], percutaneous transluminal coronary angioplasty [PTCA], carotid endarterectomy), stent implantation
Use: Dental
Treatment of postoperative pain
Use: Unlabeled
Low doses have been used in the prevention of pre-eclampsia, complications associated with autoimmune disorders such as lupus or antiphospholipid syndrome; colorectal cancer; Kawasaki disease; alternative therapy for prevention of thromboembolism associated with atrial fibrillation in patients not candidates for warfarin; pericarditis associated with MI; prosthetic valve thromboprophylaxis; peripheral arterial occlusive disease
Pregnancy Considerations
Salicylates have been noted to cross the placenta and enter fetal circulation. Adverse effects reported in the fetus include mortality, intrauterine growth retardation, salicylate intoxication, bleeding abnormalities, and neonatal acidosis. Use of aspirin close to delivery may cause premature closure of the ductus arteriosus. Adverse effects reported in the mother include anemia, hemorrhage, prolonged gestation, and prolonged labor. Aspirin has been used for the prevention of pre-eclampsia; however, the ACOG currently recommends that it not be used in low-risk women. Low-dose aspirin is used to treat complications resulting from antiphospholipid syndrome in pregnancy (either primary or secondary to SLE). In general, low doses during pregnancy needed for the treatment of certain medical conditions have not been shown to cause fetal harm, however, discontinuing therapy prior to delivery is recommended. Use of safer agents for routine management of pain or headache should be considered.
Lactation
Enters breast milk (AAP recommends use “with caution”; AAP 2001 update pending)
Breast-Feeding Considerations
Low amounts of aspirin can be found in breast milk. Milk/plasma ratios ranging from 0.03-0.3 have been reported. Peak levels in breast milk are reported to be at ~9 hours after a dose. Metabolic acidosis was reported in one infant following an aspirin dose of 3.9 g/day in the mother. The WHO considers occasional doses of aspirin to be compatible with breast-feeding, but to avoid long-term therapy and consider monitoring the infant for adverse effects. Other sources suggest avoiding aspirin while breast-feeding due to the theoretical risk of Reye's syndrome.
Contraindications
Hypersensitivity to salicylates, other NSAIDs, or any component of the formulation; asthma; rhinitis; nasal polyps; inherited or acquired bleeding disorders (including factor VII and factor IX deficiency); do not use in children (<16 years of age) for viral infections (chickenpox or flu symptoms), with or without fever, due to a potential association with Reye's syndrome; pregnancy (3rd trimester especially)
Warnings/Precautions
Concerns related to adverse effects:
• Salicylate sensitivity: Patients with sensitivity to tartrazine dyes, nasal polyps, and asthma may have an increased risk of salicylate sensitivity.
• Tinnitus: Discontinue use if tinnitus or impaired hearing occurs.
• Upper gastrointestinal (UGI) events (eg, symptomatic or complicated ulcers): Low-dose aspirin for cardioprotective effects is associated with a two- to fourfold increase in UGI events. The risks of these events increase with increasing aspirin dose; during the chronic phase of aspirin dosing, doses >81 mg are not recommended unless indicated (Bhatt, 2008).
Disease-related concerns:
• Bleeding disorders: Use with caution in patients with platelet and bleeding disorders.
• Dehydration: Use with caution in patients with dehydration.
• Ethanol use: Heavy ethanol use (>3 drinks/day) can increase bleeding risks.
• Gastrointestinal disease: Use with caution in patients with erosive gastritis or peptic ulcer disease.
• Hepatic impairment: Avoid use in severe hepatic failure.
• Renal impairment: Use with caution in patients with mild-to-moderate renal impairment (only at high dosages); avoid in severe impairment.
Concurrent drug therapy issues:
• Alteplase: In the treatment of acute ischemic stroke, avoid aspirin for 24 hours following administration of alteplase; administration within 24 hours increases the risk of hemorrhagic transformation.
• Aspirin: Concurrent use of aspirin and clopidogrel is not recommended for secondary prevention of ischemic stroke or TIA in patients unable to take oral anticoagulants due to hemorrhagic risk (Furie, 2011).
• COX-2 inhibitors/NSAIDs: When used concomitantly with ≤325 mg of aspirin, NSAIDs (including selective COX-2 inhibitors) substantially increase the risk of gastrointestinal complications (eg, ulcer); concomitant gastroprotective therapy (eg, proton pump inhibitors) is recommended (Bhatt, 2008).
Special populations:
• Elderly: Avoid chronic use of doses >325 mg/day (unless alternative agents ineffective and patient can receive concomitant gastroprotective agent); nonselective oral NSAID use is associated with an increased risk of GI bleeding and peptic ulcer disease in older adults in high risk category (eg, >75 years or age or receiving concomitant oral/parenteral corticosteroids, anticoagulants, or antiplatelet agents) (Beers Criteria).
• Pediatrics: When used for self-medication (OTC labeling): Children and teenagers who have or are recovering from chickenpox or flu-like symptoms should not use this product. Changes in behavior (along with nausea and vomiting) may be an early sign of Reye's syndrome; patients should be instructed to contact their healthcare provider if these occur.
• Surgical patients: ASA should be avoided (if possible) in surgical patients for 1-2 weeks prior to surgery, to reduce the risk of excessive bleeding (except in patients with cardiac stents that have not completed their full course of dual antiplatelet therapy [aspirin, clopidogrel]; patient specific situations need to be discussed with cardiologist; AHA/ACC/SCAI/ACS/ADA Science Advisory provides recommendations).
Adverse Reactions
As with all drugs which may affect hemostasis, bleeding is associated with aspirin. Hemorrhage may occur at virtually any site. Risk is dependent on multiple variables including dosage, concurrent use of multiple agents which alter hemostasis, and patient susceptibility. Many adverse effects of aspirin are dose related, and are rare at low dosages. Other serious reactions are idiosyncratic, related to allergy or individual sensitivity. Accurate estimation of frequencies is not possible. The reactions listed below have been reported for aspirin.
Cardiovascular: Dysrhythmias, edema, hypotension, tachycardia
Central nervous system: Agitation, cerebral edema, coma, confusion, dizziness, fatigue, headache, hyperthermia, insomnia, lethargy, nervousness
Dermatologic: Angioedema, rash, urticaria
Endocrine & metabolic: Acidosis, dehydration, hyperglycemia, hypoglycemia (children), hyperkalemia, hypernatremia (buffered forms)
Gastrointestinal: Duodenal ulcers, dyspepsia, epigastric discomfort, gastric erosions, gastric erythema, gastrointestinal ulceration (6% to 31%), heartburn, nausea, stomach pain, vomiting
Hematologic: Anemia, bleeding, coagulopathy, disseminated intravascular coagulation (DIC), hemolytic anemia, iron-deficiency anemia, prothrombin times prolonged, thrombocytopenia
Hepatic: Hepatitis (reversible), hepatotoxicity, transaminases increased
Neuromuscular & skeletal: Acetabular bone destruction (OA), rhabdomyolysis, weakness
Otic: Hearing loss, tinnitus
Renal: BUN increased, interstitial nephritis, papillary necrosis, proteinuria, renal failure (including cases caused by rhabdomyolysis), renal impairment, serum creatinine increased
Respiratory: Asthma, bronchospasm, dyspnea, hyperpnea, laryngeal edema, noncardiogenic pulmonary edema, respiratory alkalosis, tachypnea
Miscellaneous: Anaphylaxis, low birth weight, peripartum bleeding, prolonged pregnancy and labor, Reye's syndrome, stillbirths
Postmarketing and/or case reports: Cholestatic jaundice, colitis, colonic ulceration, conduction defect and atrial fibrillation (toxicity), coronary artery spasm, delirium, esophageal stricture, esophageal hematoma, esophagitis with esophageal ulcer, ischemic brain infarction, oral mucosal ulcers (aspirin-containing chewing gum), periorbital edema, rectal stenosis (suppository), rhinosinusitis
Metabolism/Transport Effects
Substrate of CYP2C9 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Drug Interactions
ACE Inhibitors: Salicylates may diminish the antihypertensive effect of ACE Inhibitors. They may also diminish other beneficial pharmacodynamic effects desired for the treatment of CHF. The effects are likely dose-related. 100 mg doses aspirin appear to cause no problems, whereas 300 mg doses appear to significantly affect ACE Inhibitor efficacy. Risk C: Monitor therapy
Alendronate: Aspirin may enhance the adverse/toxic effect of Alendronate. Specifically gastrointestinal adverse events. Risk C: Monitor therapy
Ammonium Chloride: May increase the serum concentration of Salicylates. Risk C: Monitor therapy
Anticoagulants: Salicylates may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Antidepressants (Tricyclic, Tertiary Amine): May enhance the antiplatelet effect of Aspirin. Risk C: Monitor therapy
Antiplatelet Agents: May enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result. Risk C: Monitor therapy
Calcium Channel Blockers (Nondihydropyridine): May enhance the anticoagulant effect of Salicylates. Exceptions: Bepridil [Off Market]. Risk C: Monitor therapy
Carbonic Anhydrase Inhibitors: Salicylates may enhance the adverse/toxic effect of Carbonic Anhydrase Inhibitors. Salicylate toxicity might be enhanced by this same combination. Exceptions: Brinzolamide; Dorzolamide. Risk D: Consider therapy modification
Collagenase (Systemic): Antiplatelet Agents 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
Dasatinib: May enhance the anticoagulant effect of Antiplatelet Agents. Risk C: Monitor therapy
Divalproex: Salicylates may increase the serum concentration of Divalproex. Risk C: Monitor therapy
Drotrecogin Alfa (Activated): Salicylates may enhance the adverse/toxic effect of Drotrecogin Alfa (Activated). Bleeding may occur. Management: Weigh potential benefits of drotrecogin against increased bleeding risk in patients who have received platelet inhibitors including aspirin (over 650 mg daily within 1 week). Monitor for bleeding and stop infusion if clinically important bleeding occurs. Risk D: Consider therapy modification
Floctafenine: May enhance the adverse/toxic effect of Aspirin. Risk X: Avoid combination
Ginkgo Biloba: May enhance the anticoagulant effect of Salicylates. Management: Consider alternatives to this combination of agents. Monitor for signs and symptoms of bleeding (especially intracranial bleeding) if salicylates are used in combination with ginkgo biloba. Risk D: Consider therapy modification
Glucosamine: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
Heparin: Aspirin may enhance the anticoagulant effect of Heparin. Risk C: Monitor therapy
Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Salicylates. Bleeding may occur. Risk D: Consider therapy modification
Hyaluronidase: Salicylates may diminish the therapeutic effect of Hyaluronidase. Management: Patients receiving salicylates (particularly at larger doses) may not experience the desired clinical response to standard doses of hyaluronidase. Larger doses of hyaluronidase may be required. Risk D: Consider therapy modification
Ibritumomab: Antiplatelet Agents may enhance the adverse/toxic effect of Ibritumomab. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Risk C: Monitor therapy
Influenza Virus Vaccine (Live/Attenuated): May enhance the adverse/toxic effect of Salicylates. Specifically, Reye's syndrome may develop. Risk X: Avoid combination
Ketorolac: May enhance the adverse/toxic effect of Aspirin. Risk X: Avoid combination
Ketorolac (Nasal): May enhance the adverse/toxic effect of Aspirin. Risk X: Avoid combination
Ketorolac (Systemic): May enhance the adverse/toxic effect of Aspirin. Risk X: Avoid combination
Loop Diuretics: Salicylates may diminish the diuretic effect of Loop Diuretics. Loop Diuretics may increase the serum concentration of Salicylates. Risk C: Monitor therapy
Methotrexate: Salicylates may increase the serum concentration of Methotrexate. Salicylate doses used for prophylaxis of cardiovascular events are not likely to be of concern. Risk D: Consider therapy modification
Nonsteroidal Anti-Inflammatory Agents: May enhance the adverse/toxic effect of Antiplatelet Agents. An increased risk of bleeding may occur. Nonsteroidal Anti-Inflammatory Agents may diminish the cardioprotective effect of Antiplatelet Agents. This interaction is likely specific to aspirin, and not to other antiplatelet agents. Risk C: Monitor therapy
NSAID (Nonselective): May enhance the adverse/toxic effect of Salicylates. An increased risk of bleeding may be associated with use of this combination. NSAID (Nonselective) may diminish the cardioprotective effect of Salicylates. Salicylates may decrease the serum concentration of NSAID (Nonselective). Exceptions: Diclofenac. Risk D: Consider therapy modification
Omega-3-Acid Ethyl Esters: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Antiplatelet Agents. 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 Antiplatelet Agents. Risk C: Monitor therapy
Potassium Acid Phosphate: May increase the serum concentration of Salicylates. Risk C: Monitor therapy
PRALAtrexate: Salicylates may increase the serum concentration of PRALAtrexate. Salicylate doses used for prophylaxis of cardiovascular events are unlikely to be of concern. Risk D: Consider therapy modification
Probenecid: Salicylates may diminish the therapeutic effect of Probenecid. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
Rivaroxaban: Antiplatelet Agents may enhance the anticoagulant effect of Rivaroxaban. Management: Avoid concurrent use of clopidogrel with rivaroxaban unless the anticipated benefits outweigh the risks of bleeding. Avoid concurrent use of rivaroxaban with other antiplatelet agents whenever possible. 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
Serotonin/Norepinephrine Reuptake Inhibitors: May enhance the antiplatelet effect of Aspirin. Risk C: Monitor therapy
Sulfonylureas: Salicylates may enhance the hypoglycemic effect of Sulfonylureas. Of concern with regular, higher doses of salicylates, not sporadic, low doses. 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 patients receiving daily aspirin doses greater than 100-150 mg daily. Management: Avoid daily aspirin doses greater than 100 mg in patients receiving ticagrelor. Canadian recommendations are to avoid daily aspirin doses greater than 150 mg. Daily low-dose aspirin (U.S.: 75-100 mg; Canada: 75-150 mg) is recommended. Risk D: Consider therapy modification
Tiludronate: Aspirin may decrease the serum concentration of Tiludronate. Risk C: Monitor therapy
Tositumomab and Iodine I 131 Tositumomab: Antiplatelet Agents may enhance the adverse/toxic effect of Tositumomab and Iodine I 131 Tositumomab. Specifically, the risk of bleeding-related adverse events may be increased. Risk C: Monitor therapy
Treprostinil: May enhance the adverse/toxic effect of Salicylates. Bleeding may occur. Risk C: Monitor therapy
Valproic Acid: Salicylates may increase the serum concentration of Valproic Acid. Risk C: Monitor therapy
Varicella Virus-Containing Vaccines: Salicylates may enhance the adverse/toxic effect of Varicella Virus-Containing Vaccines. Reye's Syndrome may develop. Risk D: Consider therapy modification
Vitamin E: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Salicylates may enhance the anticoagulant effect of Vitamin K Antagonists. Risk D: Consider therapy modification
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid ethanol (may enhance gastric mucosal damage).
Food: Food may decrease the rate but not the extent of oral absorption.
Folic acid: Hyperexcretion of folate; folic acid deficiency may result, leading to macrocytic anemia.
Iron: With chronic aspirin use and at doses of 3-4 g/day, iron-deficiency anemia may result.
Sodium: Hypernatremia resulting from buffered aspirin solutions or sodium salicylate containing high sodium content. Avoid or use with caution in CHF or any condition where hypernatremia would be detrimental.
Benedictine liqueur, prunes, raisins, tea, and gherkins: Potential salicylate accumulation.
Fresh fruits containing vitamin C: Displace drug from binding sites, resulting in increased urinary excretion of aspirin.
Herb/Nutraceutical: Avoid cat's claw, dong quai, evening primrose, feverfew, garlic, ginger, ginkgo, red clover, horse chestnut, green tea, ginseng (all have additional antiplatelet activity). Limit 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.
Storage
Keep suppositories in refrigerator; do not freeze. Hydrolysis of aspirin occurs upon exposure to water or moist air, resulting in salicylate and acetate, which possess a vinegar-like odor. Do not use if a strong odor is present.
Mechanism of Action
Irreversibly inhibits cyclooxygenase-1 and 2 (COX-1 and 2) enzymes, via acetylation, which results in decreased formation of prostaglandin precursors; irreversibly inhibits formation of prostaglandin derivative, thromboxane A2, via acetylation of platelet cyclooxygenase, thus inhibiting platelet aggregation; has antipyretic, analgesic, and anti-inflammatory properties
Pharmacodynamics/Kinetics
Duration: 4-6 hours
Absorption: Rapid
Distribution: Vd: 10 L; readily into most body fluids and tissues
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: 50% to 75% reaches systemic circulation
Half-life elimination: Parent drug: 15-20 minutes; Salicylates (dose dependent): 3 hours at lower doses (300-600 mg), 5-6 hours (after 1 g), 10 hours with higher doses
Time to peak, serum: ~1-2 hours
Excretion: Urine (75% as salicyluric acid, 10% as salicylic acid)
Dosage
Children:
Analgesic and antipyretic: Oral, rectal: 10-15 mg/kg/dose every 4-6 hours, up to a total of 4 g/day
Anti-inflammatory: Oral: Initial: 60-90 mg/kg/day in divided doses; usual maintenance: 80-100 mg/kg/day divided every 6-8 hours; monitor serum concentrations
Antiplatelet effects: Adequate pediatric studies have not been performed; pediatric dosage is derived from adult studies and clinical experience and is not well established; suggested doses have ranged from 3-5 mg/kg/day to 5-10 mg/kg/day given as a single daily dose. Doses are rounded to a convenient amount (eg, 1/2 of 81 mg tablet).
Mechanical prosthetic heart valves: 6-20 mg/kg/day given as a single daily dose (used in combination with an oral anticoagulant in children who have systemic embolism despite adequate oral anticoagulation therapy (INR 2.5-3.5) and used in combination with low-dose anticoagulation (INR 2-3) and dipyridamole when full-dose oral anticoagulation is contraindicated)
Blalock-Taussig shunts (unlabeled use): 1-5 mg/kg/day given as a single daily dose (Monagle, 2008)
Cerebrovascular accident (non-sickle cell-related ischemic stroke) (unlabeled use): 1-5 mg/kg/day for at least 2 years (Monagle, 2008)
Kawasaki disease (unlabeled use): Oral: 80-100 mg/kg/day divided every 6 hours; monitor serum concentrations; after fever resolves: 1-5 mg/kg/day once daily; in patients without coronary artery abnormalities, give lower dose for at least 6-8 weeks or until ESR and platelet count are normal; in patients with coronary artery abnormalities, low-dose aspirin should be continued indefinitely (Monagle, 2008)
Adults:
Analgesic and antipyretic:
Oral: 325-650 mg every 4-6 hours up to 4 g/day
Rectal: 300-600 mg every 4-6 hours up to 4 g/day
Anti-inflammatory: Oral: Initial: 2.4-3.6 g/day in divided doses; usual maintenance: 3.6-5.4 g/day; monitor serum concentrations
Atrial fibrillation (in patients not candidates for warfarin or at low risk of ischemic stroke): Oral: 75-325 mg once daily (Fuster, 2006; Singer, 2008) or 75-100 mg once daily (Furie, 2011)
CABG: Oral: 100-325 mg once daily initiated either preoperatively or within 6 hours postoperatively; continue indefinitely (Hillis, 2011)
Carotid artery stenting: Oral: 81-325 mg once daily beginning at least 24 hours (preferably 4 days) prior to procedure with concomitant clopidogrel (Bates, 2007)
Carotid endarterectomy: Oral: 50-100 mg once daily preoperatively and daily thereafter; usual dose: 81 mg once daily (Albers, 2008)
Heart valve (bioprosthetic, mechanical): Oral: 50-100 mg once daily (in addition to warfarin) (Furie, 2011); usual dose: 81 mg once daily (Salem, 2008)
Mechanical heart valve (history of thromboembolism while receiving oral anticoagulants): Oral: 75-100 mg once daily (in addition to warfarin) (Furie, 2011); usual dose: 81 mg once daily
Mitral valve (prolapse, annular calcification) (with documented stroke or TIA): Oral: 50-100 mg once daily; usual dose: 81 mg once daily (Salem, 2008)
Myocardial infarction (primary prevention): Oral: 75-162 mg once daily (Antman, 2004) or 75-100 mg (usual dose: 81 mg) once daily (Hirsh, 2008)
Myocardial infarction (ST-segment elevation myocardial infarction [STEMI], non-ST-segment elevation myocardial infarction [NSTEMI]): Oral: Initial: 162-325 mg given on presentation (patient should chew nonenteric-coated aspirin especially if not taking before presentation); for patients unable to take oral, may use rectal suppository (300 mg). Maintenance (secondary prevention): 75-162 mg once daily indefinitely (Anderson, 2007; Antman, 2004).
PCI: Oral: Preprocedure: 81-325 mg (325 mg [nonenteric coated] in aspirin-naive patients) starting at least 2 hours (preferably 24 hours) before procedure; postprocedure: 81 mg once daily continued indefinitely (Levine, 2011).
Pericarditis associated with myocardial infarction: Oral: 162-325 mg once daily; doses as high as 650 mg every 4-6 hours may be required; enteric-coated recommended (Antman, 2004)
Peripheral arterial disease: Oral: 75-100 mg once daily; usual dose: 81 mg once daily (Sobel, 2008) or 75-325 mg once daily; may use in conjunction with clopidogrel in those who are not at an increased risk of bleeding but are of high cardiovascular risk (Class IIb recommendation). Note: These recommendations also pertain to those with intermittent claudication or critical limb ischemia, prior lower extremity revascularization, or prior amputation for lower extremity ischemia (Rooke, 2011).
Pre-eclampsia prevention: Oral: 60-81 mg once daily (usual dose: 81 mg) during gestational weeks 13-26 (patient selection criteria not established) (Bates, 2008; CLASP, 1994)
Stroke (acute ischemic): Oral: Initial: 150-325 mg within 48 hours of stroke onset (in patients who are not candidates for thrombolytic therapy), followed by 50-100 mg once daily (Albers, 2008)
Stroke (cardioembolic, anticoagulation contraindicated): Oral: 75-325 mg once daily (Albers, 2008)
Stroke/TIA (noncardioembolic, secondary prevention): Oral: 50-325 mg once daily (Adams, 2007; Smith, 2011) or 50-100 mg once daily; usual dose: 81 mg once daily (Hirsh, 2008). Note: Combination aspirin 25 mg and extended release dipyridamole 200 mg twice daily is preferred over aspirin alone (Albers, 2008)
Stroke (women at high risk for CVA, primary prevention): Oral: 81 mg once daily or 100 mg every other day (Goldstein, 2010)
Dosing adjustment in renal impairment: Clcr <10 mL/minute: Avoid use.
Hemodialysis: Dialyzable (50% to 100%)
Dosing adjustment in hepatic disease: Avoid use in severe liver disease.
Dental Usual Dosing
Postoperative pain:
Analgesic and antipyretic: Oral, rectal:
Children: 10-15 mg/kg/dose every 4-6 hours, up to a total of 4 g/day
Adults: 325-650 mg every 4-6 hours up to 4 g/day
Anti-inflammatory: Oral: Initial:
Children: 60-90 mg/kg/day in divided doses; usual maintenance: 80-100 mg/kg/day divided every 6-8 hours; monitor serum concentrations
Adults: 2.4-3.6 g/day in divided doses; usual maintenance: 3.6-5.4 g/day; monitor serum concentrations
Administration: Oral
Do not crush enteric coated tablet. Administer with food or a full glass of water to minimize GI distress. For acute myocardial infarction, have patient chew tablet.
Reference Range
Timing of serum samples: Peak levels usually occur 2 hours after ingestion. Salicylate serum concentrations correlate with the pharmacological actions and adverse effects observed. The serum salicylate concentration (mcg/mL) and the corresponding clinical correlations are as follows: See table.
Serum Salicylate: Clinical Correlations
Serum Salicylate Concentration
(mcg/mL)
Desired Effects
Adverse Effects / Intoxication
~100
Antiplatelet
Antipyresis
Analgesia
GI intolerance and bleeding, hypersensitivity, hemostatic defects
150-300
Anti-inflammatory
Mild salicylism
250-400
Treatment of rheumatic fever
Nausea/vomiting, hyperventilation, salicylism, flushing, sweating, thirst, headache, diarrhea, and tachycardia
>400-500
Respiratory alkalosis, hemorrhage, excitement, confusion, asterixis, pulmonary edema, convulsions, tetany, metabolic acidosis, fever, coma, cardiovascular collapse, renal and respiratory failure
Table has been converted to the following text.
Serum Salicylate: Clinical Correlations
Serum salicylate level ~100 mcg/mL:
• Desired effects: Analgesia, antiplatelet, antipyresis
• Adverse effects/intoxication: GI intolerance and bleeding, hemostatic defects, hypersensitivity
Serum salicylate level 150-300 mcg/mL:
• Desired effects: Anti-inflammatory
• Adverse effects/intoxication: Mild salicylism
Serum salicylate level 250-400 mcg/mL:
• Desired effects: Treatment of rheumatic fever
• Adverse effects/intoxication: Diarrhea, flushing, headache, hyperventilation, nausea/vomiting, salicylism, sweating, tachycardia, thirst
Serum salicylate level >400-500 mcg/mL:
• Adverse effects/intoxication: Asterixis, cardiovascular collapse, coma, confusion, convulsions, excitement, fever, hemorrhage, metabolic acidosis, pulmonary edema, renal and respiratory failure, respiratory alkalosis, tetany
Test Interactions
False-negative results for glucose oxidase urinary glucose tests (Clinistix®); false-positives using the cupric sulfate method (Clinitest®); also, interferes with Gerhardt test, VMA determination; 5-HIAA, xylose tolerance test and T3 and T4
Dietary Considerations
Take with food or large volume of water or milk to minimize GI upset.
Patient Education
Take with food or milk. Do not use aspirin with strong vinegar-like odor. While using this medication, avoid alcohol, salicylate-containing foods, other medications containing aspirin or salicylate, or other NSAIDs without consulting prescriber. Maintain adequate hydration, unless instructed to restrict fluid intake. Inform prescribers and dentists that you are taking this medication prior to scheduling any surgery or dental procedure. You may experience nausea, vomiting, gastric discomfort, GI bleeding, ulceration, perforation (can occur with or without pain), or blood in stool. Stop taking aspirin and report ringing in ears, persistent stomach pain, unresolved nausea or vomiting, respiratory difficulty or shortness of breath, unusual bruising or bleeding (mouth, urine, stool), or skin rash.
Geriatric Considerations
Elderly are a high-risk population for adverse effects from nonsteroidal anti-inflammatory agents. As much as 60% of elderly with GI complications to NSAIDs can develop peptic ulceration and/or hemorrhage asymptomatically. The concomitant use of H2 blockers and sucralfate is not effective as prophylaxis with the exception of NSAID-induced duodenal ulcers which may be prevented by the use of ranitidine. Misoprostol and proton pump inhibitors are the only prophylactic agents proven to help prevent the development of NSAID-induced ulcers. Also, concomitant disease and drug use contribute to the risk for GI adverse effects. Use lowest effective dose for shortest period possible. Consider renal function decline with age. Use of NSAIDs can compromise existing renal function especially when Clcr is ≤30 mL/minute. Tinnitus may be a difficult and unreliable indication of toxicity due to age-related hearing loss or eighth cranial nerve damage. CNS adverse effects such as confusion, agitation, and hallucination are generally seen in overdose or high dose situations, but elderly may demonstrate these adverse effects at lower doses than younger adults.
This medication is considered to be potentially inappropriate in this patient population (Beers Criteria: Quality of evidence - moderate; Strength of recommendation - strong).
Cardiovascular Considerations
Primary Prevention: The U.S. Preventive Services Task Force (USPSTF) recommends the use of aspirin in the following patients:
• Men age 45-79 when the potential benefit due to a reduction in MI risk outweighs the potential harm due to an increase risk of GI hemorrhage
• Women age 55-79 when the potential benefit due to a reduction in ischemic stroke risk outweighs the potential harm due to an increase risk of GI hemorrhage
The use of aspirin for primary prevention is not recommended for women <55 years of age or men <45 years. In patients >80 years, there is insufficient evidence to recommend routine use of aspirin for primary prevention of cardiovascular disease. Risk assessment for coronary heart disease (CHD) events may be calculated at www.med-decisions.com. Risk assessment for ischemic stroke may be calculated at www.westernstroke.org/PersonalStrokeRisk1.xls. The net benefit is substantial for men at increased risk of MI and women at increased risk of stroke when the risk of GI bleeding is low. Risk factors for GI bleeding with the use of aspirin include increasing age, gender (men>women), upper GI pain, GI ulcers, and concomitant use of NSAIDs. Other risk factors for serious bleeding include uncontrolled hypertension and the concomitant use of anticoagulants. To determine whether the potential benefit of MI prevention (men) and stroke prevention (women) outweighs the potential harm of increased GI hemorrhage, both 10-year cardiovascular (CVD) event risk and age must be considered (see table below). Shared decision making should be encouraged with patients in whom the potential benefits and risks for GI bleeding are closely balanced.
Risk Level at Which CVD Events Prevented (Benefit) Exceeds GI Bleeding Risk (Harm)
Men
Women
Age (in years)
10-year CHD Risk
Age (in years)
10-year Stroke Risk
45-59
≥4%
55-59
≥3%
60-69
≥9%
60-69
≥8%
70-79
≥12%
70-79
≥11%
Note: Table applies to those patients not taking NSAIDs and who do not have upper GI pain or history of GI ulcers. In patients taking NSAIDS or history of GI ulcers, the risk for serious GI bleeding is increased and should be considered when determining the balance of benefit versus harm.
Table has been converted to the following text:
Risk Level at Which CVD Events Prevented (Benefit) Exceeds GI Bleeding Risk (Harm)
Men:
45-59 years of age and 10-year CHD risk ≥4%
60-69 years of age and 10-year CHD risk ≥9%
70-79 years of age and 10-year CHD risk ≥12%
Women:
55-59 years of age and 10-year stroke risk ≥3%
60-69 years of age and 10-year stroke risk ≥8%
70-79 years of age and 10-year stroke risk ≥11%
Note: Applies to those patients not taking NSAIDs and who do not have upper GI pain or history of GI ulcers. In patients taking NSAIDS or history of GI ulcers, the risk for serious GI bleeding is increased and should be considered when determining the balance of benefit versus harm.
Secondary Prevention: In unstable angina, aspirin reduces the rate of refractory angina, nonfatal MI, and death. Aspirin reduces the rate of recurrent ischemia and infarction, stroke, and death following MI. In patients who have acute coronary syndrome (ACS) but are not already receiving aspirin, the first dose may be chewed to rapidly establish a high blood level.
Resistance: The definition of biochemical aspirin resistance is measurable, persistent platelet activation that occurs in patients prescribed a therapeutic dose of aspirin. Clinical aspirin resistance is considered aspirin treatment failure; the recurrence of some vascular event despite a regular therapeutic dose of aspirin. 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. Aspirin resistance has been evaluated clinically. A stable group of 326 cardiovascular patients taking 325 mg of aspirin a day for >7 days was prospectively evaluated (Gum, 2003). Platelet aggregation was evaluated by optical platelet aggregation using ADP and AA. The primary outcome was defined as a composite of death, MI, or CVA. Seventeen (~5%) patients had biochemical aspirin resistance. Patients who were aspirin-resistant were more likely to have a CV event than those who were aspirin-sensitive (24% vs 10%, CI 1.1-8.9, p = 0.03). There have been other studies evaluating biochemical and clinical aspirin resistance; different methods have been used to determine aspirin resistance. Patient adherence has not been evaluated. Aspirin resistance is likely dose related, may be influenced by dynamic factors yet to be identified and further research is required.
Coronary Artery Stents: The AHA/ACC/SCAI/ACS/ADA Science Advisory (2007) published recommendations (Circulation, February 13, 2007) to prevent premature discontinuation of dual antiplatelet therapy (clopidogrel, aspirin) in patients with coronary artery stents. This advisory panel agreed with the 2004 ACC/AHA guidelines stressing the importance of 12 months of dual antiplatelet therapy after placement of a drug-eluting stent (DES) in patients who are not at high risk of bleeding. The advisory panel included these recommendations. Minor surgery, teeth cleaning, and tooth extraction can usually be performed without increased bleeding on the dual antiplatelet regimen. If increased bleeding is anticipated, then the procedure should be delayed until the antiplatelet regimen is completed. Elective procedures with a significant risk of bleeding should be postponed until the antiplatelet regimen is completed. The Advisory panel recommends healthcare providers who perform invasive or surgical procedures contact the patient's cardiologist before discontinuing antiplatelet therapy. For patients with drug-eluting stents who must undergo a procedure that requires discontinuation of thienopyridine therapy, aspirin should be continued if possible and the thienopyridine restarted as soon as possible after the procedure. “Bridging” stent patients with warfarin, other antithrombins, or glycoprotein IIb/IIIa agents is not supported by the Advisory Committee.
For the complete review and additional recommendations, refer to http://circ.ahajournals.org/content/115/6/813.full.pdf+html
Drug Interactions: The question frequently arises as to whether or not concurrent NSAID use interferes with the antiplatelet effects of aspirin. It is known that if taken within 2 hours following an aspirin dose or if taken regularly in a patient on cardioprotective doses of aspirin, ibuprofen will interfere with the antiplatelet effects of aspirin. Less is known about the other NSAIDs, but some data are available. In a pharmacodynamic trial, diclofenac did not interfere with aspirin's antiplatelet effects after six straight days of combined use. In a retrospective analysis, diclofenac did not impact cardiovascular and all-cause morality when taken regularly in patients receiving daily aspirin. A subgroup analysis of the Physician's Health Study (a primary prevention trial) identified that the use of NSAIDs (specific agents were not identified) at <60 days/year did not diminish aspirin's ability to prevent an initial MI in contrast to taking NSAIDs more frequently. It is surmised that ibuprofen may exhibit greater affinity than aspirin for the COX-1 site or if dosed regularly (or prior to aspirin), it would gain first access to the active site. In either case, aspirin inhibition of COX (irreversible) would be limited in favor of ibuprofen inhibition (reversible).
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: As with all drugs which may affect hemostasis, bleeding is associated with aspirin. Hemorrhage may occur at virtually any site; risk is dependent on multiple variables including dosage, concurrent use of multiple agents which alter hemostasis, and patient susceptibility. Many adverse effects of aspirin are dose related, and are rare at low dosages. Other serious reactions are idiosyncratic, related to allergy or individual sensitivity (see Dental Health Professional Considerations).
Aspirin and clopidogrel (Plavix®) in combination is the primary prevention strategy against stent thrombosis after placement of drug-eluting metal stents in coronary patients. Premature discontinuation of this combination antiplatelet therapy strongly increases the risk of a catastrophic event of stent thrombosis leading to myocardial infarction and/or death, so says a science advisory issued in January 2007 from the American Heart Association in collaboration with the American Dental Association and other professional healthcare organizations. The advisory stresses a 12-month therapy of aspirin and Plavix® combination after placement of a drug-eluting stent in order to prevent thrombosis at the stent site. Any elective surgery should be postponed for 1 year after stent implantation, and if surgery must be performed, consideration should be given to continuing the antiplatelet therapy during the perioperative period in high-risk patients with drug-eluting stents.
This advisory was issued from a science panel made up of representatives from the American Heart Association (AHA), the American College of Cardiology, the Society for Cardiovascular Angiography and Interventions, the American College of Surgeons, the American Dental Association (ADA), and the American College of Physicians (Grines, 2007).
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Dental Comment
The Food and Drug Administration (FDA), has issued a letter updating information and considerations regarding the use of ibuprofen (400 mg doses) in patients who are taking low dose aspirin (81 mg, immediate release; not enteric coated) for cardioprotection and stroke prevention. Ibuprofen, at these doses, may interfere with aspirin's antiplatelet effect depending upon when it is administered. Patients initiated on aspirin first (for ~1 week) then ibuprofen (400 mg 3 times/day for 10 days) seem to maintain aspirin's platelet effect (Cryer, 2005). Ibuprofen has the greatest impact on aspirin if administered less than 8 hours before aspirin (Catella-Lawson, 2001).
Patients may require counseling about the appropriate timing of ibuprofen dosing in relationship to aspirin therapy. With occasional use of ibuprofen, a clinically-significant interaction with aspirin in unlikely. To avoid interference during chronic dosing, a single dose of ibuprofen should be taken 30-120 minutes after aspirin ingestion or at least 8 hours should elapse after ibuprofen dosing before giving aspirin (FDA, 2006; Catella-Lawson, 2001).
The clinical implications of the interaction are unclear. There have not been any clinical endpoint studies conducted at this time. Avoidance of this interaction is potentially important because aspirin's vascular protection could be decreased or negated.
Other nonselective NSAIDs may have potential for a similar interaction with aspirin. Such has been described with naproxen (Capone, 2005). Acetaminophen does not appear to interfere with the antiplatelet effect of aspirin. Other clinical scenarios (use of smaller ibuprofen doses, other aspirin products, other doses of aspirin) have not been evaluated.
Additional information is available at: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm125222.htm
Mental Health: Effects on Mental Status
May cause drowsiness
Mental Health: Effects on Psychiatric Treatment
May cause leukopenia; use caution with clozapine and carbamazepine; may displace valproic acid from binding sites resulting in an increase of unbound drug; monitor for toxicity
Nursing: Physical Assessment/Monitoring
Do not use for persons with allergic reaction to salicylate or other NSAIDs.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Caplet, oral: 500 mg
Bayer® Aspirin Extra Strength: 500 mg
Bayer® Genuine Aspirin: 325 mg
Bayer® Women's Low Dose Aspirin: 81 mg [contains elemental calcium 300 mg]
Caplet, oral [buffered]:
Ascriptin® Maximum Strength: 500 mg [contains aluminum hydroxide, calcium carbonate, magnesium hydroxide]
Bayer® Plus Extra Strength: 500 mg [contains calcium carbonate]
Caplet, enteric coated, oral:
Bayer® Aspirin Regimen Regular Strength: 325 mg
Gum, chewing, oral:
Aspergum®: 227 mg (12s) [cherry flavor]
Aspergum®: 227 mg (12s) [orange flavor]
Suppository, rectal: 300 mg (12s); 600 mg (12s)
Tablet, oral: 325 mg
Aspercin: 325 mg
Aspirtab: 325 mg
Bayer® Genuine Aspirin: 325 mg
Tablet, oral [buffered]: 325 mg
Ascriptin® Regular Strength: 325 mg [contains aluminum hydroxide, calcium carbonate, magnesium hydroxide]
Buffasal: 325 mg [contains magnesium oxide]
Bufferin®: 325 mg [contains calcium carbonate, magnesium carbonate, magnesium oxide]
Bufferin® Extra Strength: 500 mg [contains calcium carbonate, magnesium carbonate, magnesium oxide]
Buffinol: 324 mg [sugar free; contains magnesium oxide]
Tri-Buffered Aspirin: 325 mg [contains calcium carbonate, magnesium carbonate, magnesium hydroxide]
Tri-Buffered Aspirin: 325 mg [contains calcium carbonate, magnesium oxide]
Tablet, chewable, oral: 81 mg
Bayer® Aspirin Regimen Children's: 81 mg [cherry flavor]
Bayer® Aspirin Regimen Children's: 81 mg [orange flavor]
St Joseph® Adult Aspirin: 81 mg
Tablet, enteric coated, oral: 81 mg, 325 mg, 650 mg
Aspir-low: 81 mg
Bayer® Aspirin Regimen Adult Low Strength: 81 mg
Ecotrin®: 325 mg
Ecotrin® Arthritis Strength: 500 mg
Ecotrin® Low Strength: 81 mg
Halfprin®: 81 mg, 162 mg
St Joseph® Adult Aspirin: 81 mg
Pricing: U.S. (www.drugstore.com)
Chewable (Aspirin)
81 mg (36): $11.99
Tablets (Aspirin)
325 mg (100): $11.99
325 mg (500): $14.99
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Last full review/revision March 2012
Content last modified March 2012
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