Aspirin - Drug Monograph

Introduction

Aspirin (acetylsalicylic acid) is one of the most widely used medications worldwide, belonging to the salicylate drug class. First synthesized in 1897 by Felix Hoffmann at Bayer, it has remained a cornerstone of therapy for pain, inflammation, fever, and cardiovascular protection. Aspirin is available in various formulations including immediate-release tablets, enteric-coated tablets, chewable tablets, and suppositories.

Mechanism of Action

Aspirin exerts its effects through irreversible inhibition of cyclooxygenase (COX) enzymes. It acetylates serine residues on both COX-1 and COX-2 isoforms, preventing the conversion of arachidonic acid to prostaglandin H2. This results in:

• Analgesic effect: Reduced prostaglandin-mediated pain sensitization
• Antipyretic effect: Inhibition of prostaglandin E2 in the hypothalamus
• Anti-inflammatory effect: Decreased prostaglandin and thromboxane production
• Antiplatelet effect: Irreversible inhibition of thromboxane A2 synthesis in platelets

The antiplatelet effect persists for the lifespan of platelets (7-10 days) due to irreversible enzyme inhibition.

Indications

• Mild to moderate pain
• Fever
• Inflammatory conditions (rheumatoid arthritis, osteoarthritis, juvenile arthritis)
• Acute ischemic stroke
• Myocardial infarction prevention and treatment
• Secondary prevention of cardiovascular events
• Revascularization procedures (CABG, PCI, carotid endarterectomy)
• Primary prevention of cardiovascular events in selected patients

• Pre-eclampsia prevention in high-risk women
• Colorectal cancer prevention in high-risk individuals

Dosage and Administration

• Adults: 325-650 mg every 4-6 hours as needed (max 4 g/day)
• Children: 10-15 mg/kg/dose every 4-6 hours (max 80 mg/kg/day)

• Adults: 2.4-3.6 g/day in divided doses
• Children: 60-130 mg/kg/day in divided doses

• Primary prevention: 75-100 mg daily
• Secondary prevention: 81-325 mg daily
• Acute MI: 160-325 mg chewed initially

• Renal impairment: Use with caution; avoid high doses in severe impairment
• Hepatic impairment: Use with caution; avoid in severe liver disease
• Elderly: Use lower doses due to increased sensitivity

Pharmacokinetics

Contraindications

• Hypersensitivity to salicylates or NSAIDs
• Patients with aspirin-exacerbated respiratory disease (asthma, rhinitis, nasal polyps)
• Active peptic ulcer disease
• Hemophilia or other bleeding disorders
• Severe hepatic impairment
• Severe renal failure
• Third trimester of pregnancy

Warnings and Precautions

• Risk of serious gastrointestinal bleeding, ulceration, and perforation
• Increased cardiovascular thrombotic events with NSAID use

• Reye's syndrome in children and teenagers with viral infections
• Hepatotoxicity at high doses
• Nephrotoxicity with chronic use
• Bronchospasm in aspirin-sensitive asthmatics
• Hearing loss and tinnitus at high doses
• Hypoglycemic effects
• Pregnancy: Avoid in third trimester; Category D

Drug Interactions

• Anticoagulants (warfarin, DOACs): Increased bleeding risk
• Other NSAIDs: Reduced cardioprotective effects, increased GI risk
• ACE inhibitors/ARBs: Reduced antihypertensive effect
• Methotrexate: Reduced renal clearance, increased toxicity
• Valproic acid: Increased valproate levels
• Corticosteroids: Increased ulcer risk
• Probenecid: Reduced uricosuric effect
• Alcohol: Increased GI bleeding risk

Adverse Effects

• Dyspepsia
• Nausea
• Heartburn
• Gastrointestinal discomfort
• Tinnitus (at high doses)

• Gastrointestinal bleeding/ulceration
• Hemorrhagic stroke
• Anaphylaxis
• Hepatotoxicity
• Renal impairment
• Reye's syndrome
• Severe skin reactions
• Bronchospasm

Monitoring Parameters

• Pain relief and functional status (analgesic use)
• Inflammatory markers (anti-inflammatory use)
• Fever resolution (antipyretic use)

• Complete blood count (for anemia)
• Renal function tests
• Liver function tests
• Stool for occult blood
• Hearing assessment (with high doses)
• Signs of bleeding
• Gastrointestinal symptoms

• Bleeding assessment
• Cardiovascular event reduction
• Adherence monitoring

Patient Education

• Take with food or milk to reduce stomach upset
• Do not crush or chew enteric-coated tablets
• Report any signs of bleeding (unusual bruising, black stools, blood in urine)
• Seek immediate medical attention for allergic reactions
• Avoid alcohol consumption during therapy
• Inform all healthcare providers about aspirin use
• Do not use in children/teens with viral infections
• Store at room temperature away from moisture
• Report ringing in ears or hearing changes
• Follow prescribed dosing exactly

• Pregnancy: Discuss risks/benefits with provider
• Elderly: Use lowest effective dose
• Surgical patients: Inform surgeon about aspirin use

References

1. Patrono C, et al. Platelet-active drugs: the relationships among dose, effectiveness, and side effects. Chest. 2004;126(3 Suppl):234S-264S. 2. Antithrombotic Trialists' Collaboration. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009;373(9678):1849-1860. 3. FDA. Aspirin prescribing information. 2020. 4. Whitlock EP, et al. Aspirin for the prevention of cancer incidence and mortality: systematic evidence reviews for the U.S. Preventive Services Task Force. Ann Intern Med. 2016;164(12):814-825. 5. Bibbins-Domingo K, et al. Aspirin use for the primary prevention of cardiovascular disease and colorectal cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2016;164(12):836-845. 6. American Geriatrics Society. Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc. 2019;67(4):674-694. 7. ASCEND Study Collaborative Group. Effects of aspirin for primary prevention in persons with diabetes mellitus. N Engl J Med. 2018;379(16):1529-1539. 8. Gaziano JM, et al. Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): a randomised, double-blind, placebo-controlled trial. Lancet. 2018;392(10152):1036-1046.