Aspirin Data - Uses, Dosage, Drug class, Brand name, Warnings, etc

Pharmacology	Aspirin is an analgesic, antipyretic, and anti-inflammatory agent. Anti-inflammatory properties are related to the inhibition of prostaglandin biosynthesis. Aspirin nonselectively inhibits cyclo-oxygenase-1 (COX-1), associated with GI and renal effects and inhibition of platelet aggregation, and cyclo-oxygenase-2 (COX-2), associated with the inflammatory response. Unlike other NSAIDs, its antiplatelet effect is irreversible and permanent (due to transacetylation of platelet COX) for the life of the platelet (8–11 days). Salicylates without acetyl groups (e.g., sodium salicylate) have essentially no antiplatelet effect but retain analgesic, antipyretic, and anti-inflammatory activities. Low dosages (1–2 g/day) decrease urate excretion; high dosages (>5 g/day) induce uricosuria.
Administration and Adult Dosage	- PO or PR for fever or minor pain: 325–1000 mg every 4–6 hr, to a maximum of 4 g/day - PO for arthritis and rheumatic conditions: 3.6–5.4 g/day in 3–4 divided doses - PO for acute rheumatic fever: 5–8 g/day in divided doses - PO for prevention of TIAs or stroke: 81–325 mg/day - PO for myocardial infarction risk reduction: • Primary prevention (healthy men >50 yr with at least one major cardiovascular risk factor): 81–325 mg/day • Secondary prevention: 162–325 mg/day - PO for unstable angina: 162–325 mg/day - PO for prevention of coronary artery bypass graft occlusion: 325 mg/day started 6 hr postoperatively, continued for 1 yr - PO for nonrheumatic atrial fibrillation: • Poor candidates for/decline oral anticoagulants: 325 mg/day • Patients <75 yr with no stroke risk factors: 325 mg/day
Special Populations - Pediatric Dosage	- PO for juvenile rheumatoid arthritis: 60–110 mg/kg/day in divided doses - PO for acute rheumatic fever: 100 mg/kg/day in divided doses initially for 2 weeks, then 75 mg/kg/day for 4–6 weeks - PO for Kawasaki disease: 80–120 mg/kg/day; decrease to 10 mg/kg/day after fever resolves - PO as analgesic/antipyretic: 10–15 mg/kg/dose every 4 hr, to a maximum of 60–80 mg/kg/day; or by age: • 2–3 yr: 162 mg every 4 hr • 4–5 yr: 243 mg every 4 hr • 6–8 yr: 325 mg every 4 hr • 9–10 yr: 405 mg every 4 hr • 11 yr: 486 mg every 4 hr • ≥12 yr: 650 mg every 4 hr
Special Populations - Geriatric Dosage	- Use minimal effective dosages; elderly are more susceptible to GI bleeding and acute renal insufficiency - PO for MI risk reduction (primary prevention in healthy men >50 yr with cardiovascular risk factors): 81–325 mg/day
Other Conditions	- Uremia or reduced albumin levels may produce higher unbound drug levels, increasing pharmacologic or toxic effects; dosage reduction might be required (e.g., in kidney disease, malnutrition)
Dosage Forms	- Chewable Tablet: 81 mg - Enteric-Coated Tablet: 81, 165, 325, 500, 650, 975 mg - Sustained-Release Tablet: 650, 800 mg - Tablet: 81, 325, 500 mg - Suppository: 120, 200, 300, 600 mg
Patient Instructions	- Children and teenagers (<16 yr) should not use aspirin-containing medications for chickenpox or flu symptoms due to the risk of Reye’s syndrome - Take with food, milk, or a full glass of water to minimize stomach upset - Report symptoms of gastrointestinal ulceration, bleeding, ringing in the ears, or gastrointestinal pain to your physician - Do not crush or chew enteric-coated or sustained-release preparations - Avoid other products containing aspirin or nonsteroidal anti-inflammatory drugs
Missed Doses	- If taken on a regular schedule, take a missed dose as soon as remembered - If near the time for the next dose, take that dose only; do not double the dose or take extra
Pharmacokinetics - Onset and Duration	- PO onset of analgesia: 30 min
Pharmacokinetics - Serum Levels	- Salicylate for rheumatic diseases: 150–300 mg/L (1.1–2.2 mmol/L), often with mild toxic symptoms - Toxicity: • Tinnitus: 200–400 mg/L (1.5–2.9 mmol/L) • Hyperventilation: >350 mg/L (2.6 mmol/L) • Acidosis: >450 mg/L (3.3 mmol/L) • Severe or fatal toxicity: >900 mg/L (6.6 mmol/L) 6 hr after acute ingestion
Pharmacokinetics - Fate	- Absorption: Rapidly absorbed from the GI tract; oral bioavailability 80–100%; enteric coating does not affect absorption - Peak Levels: Single analgesic/antipyretic dose produces salicylate levels of 30–60 mg/L (0.22–0.44 mmol/L) - Aspirin: • Protein Binding: 49%, decreased in uremia • Distribution: Vd = 0.15 ± 0.03 L/kg • Clearance: Cl = 0.56 ± 0.07 L/hr/kg • Metabolism: Rapidly hydrolyzed to salicylate • Excretion: 1% unchanged in urine - Salicylate: • Protein Binding: Dose-dependent, 95% at 15 mg/L, 80% at 300 mg/L; decreased in uremia, hypoalbuminemia, neonates, pregnancy • Distribution: Vd = 0.17 ± 0.03 L/kg • Clearance: Dose-dependent, 0.012 L/hr/kg at 134–157 mg/L; decreased in hepatitis and neonates • Metabolism: Primarily in the liver to 4 metabolites (salicyluric acid, phenolic and acyl glucuronides, gentisic acid)
Pharmacokinetics - t¹⁄₂	- Aspirin: 0.25 ± 0.03 hr - Salicylate: Dose-dependent; 2.4 hr with 0.25 g, 5 hr with 1 g, 6.1 hr with 1.3 g, 19 hr with 10–20 g
Adverse Reactions & Side Effects	Frequent: - Hearing impairment, GI upset, occult bleeding, acute hemorrhage from gastric erosion Other: - Renal dysfunction, particularly in pre-existing renal disease or CHF - Rare hepatotoxicity, primarily in children with rheumatic fever or rheumatoid arthritis and adults with SLE or pre-existing liver disease - Syndrome of asthma, angioedema, and nasal polyps in susceptible patients - Platelet aggregation suppression and prolonged bleeding time (up to 1 week); large doses can prolong PT
Contraindications	- Bleeding disorders - Asthma - Hypersensitivity to other NSAIDs or tartrazine dye
Precautions & Warnings	- Use with caution in patients with renal disease, gastric ulcer, bleeding tendencies, hypoprothrombinemia, history of asthma, or during anticoagulant therapy - Avoid in children and teenagers with flu-like symptoms or chickenpox due to Reye’s syndrome risk - Patients with aspirin-induced bronchospasm may react to other NSAIDs; nonacetylated salicylates (except diflunisal) are usually tolerated
Drug Interactions	- Alkalinizing agents (e.g., acetazolamide, antacids) reduce salicylate levels; acetazolamide enhances CNS penetration of salicylate - Corticosteroids reduce serum salicylate levels - Large doses of salicylates increase oral anticoagulant effect; small doses increase bleeding risk with anticoagulants or heparin due to antiplatelet effect - Alcohol and salicylates increase GI blood loss risk - Salicylates enhance sulfonylurea response, especially chlorpropamide - Salicylates decrease uricosuric effect of probenecid and sulfinpyrazone - Large doses decrease renal elimination of methotrexate and displace it from plasma protein binding sites
Parameters to Monitor	- Monitor for abnormal bleeding, bruising, and occult GI blood loss (periodic hematocrit) in regular users - Measure serum salicylate levels with higher dosage regimens due to variable serum levels - Monitor renal function and hearing changes (tinnitus); avoid using tinnitus as an index of maximum tolerance
Class and Drug Brand Name	- Class: Analgesic and Anti-Inflammatory Drugs - Brand Name: Various
Notes	- Optimal dosage for platelet inhibition not determined; doses as low as 50 mg/day inhibit platelet aggregation and protect against thrombosis - Enteric-coated formulations reduce GI irritation but do not affect absorption

References

Hand of Clinical Drug Data