AspirinRx

Trade Names
Plain aspirin: Bayer Aspirin
Buffered aspirin: Ascriptin, Alka-Seltzer, Buffferin
Enteric coated aspirin:  Ecotrin,
Extended-release aspirin:  Zorprin

Synonyms: Acetylsalicylic acid, ASA

Drug Class: NSAID

Preparations
Chewable aspirin tablet: 81 mg
Tablets: 325 and 500 mg
Enteric coated tablets 81,  325 mg
Timed-/controlled-release tablets: 800 mg

Dose
Analgesic/antipyretic effect: 325–650 mg q 4–6 h (as high as 4 g/day) Antiinflammatory effect: Divided doses of 3.6–5.4 g/day. In acute rheumatic fever higher doses have been used but dose-related toxicity is common.
Antithrombotic effect: 81–325 mg/day (usually 81 mg)

Indications: Used for antithrombotic effect in myocardial infarction, anticardiolipin antibody syndrome, and transient ischemic attacks. Treatment of minor pain, inflammation, pyrexia, antithrombotic prophylaxis and Kawasaki disease. Seldom used in RA, osteoarthritis, rheumatic fever, Still’s disease and inflammatory conditions such as bursitis.

Mechanism of Action: Nonselective COX inhibitor; decreases formation of prostaglandins and thromboxane from arachidonic acid. Antiplatelet effect is due to inhibition of thromboxane synthesis.

Contraindications: Hypersensitivity to aspirin (especially in those with asthma and nasal polyps), GI ulceration, hemorrhagic state, last trimester of pregnancy (may induce premature closure of ductus arteriosus), breast-feeding, children (risk of Reye syndrome), and G6PD deficiency (hemolysis)

Precautions: Fluid retention with high doses may aggravate heart failure and hypertension. Use with caution or avoid in patients at high risk of GI bleeding (i.e., previous GI bleeding, peptic ulcer, elderly, concurrent corticosteroid or warfarin treatment), but if prescribed, consider misoprostol or proton pump inhibitor prophylaxis. Administer with food. Use with caution in asthma, bleeding disorders, and hepatic or renal disease.

Monitoring: In  anti-inflammatory doses monitor hematocrit, creatinine, and liver enzymes periodically (1 month after starting and then every 3–6 months). In patients at high risk of renal impairment (i.e., diuretics, receiving ACE inhibitors, edematous states, heart failure, renal failure, diabetes), monitor renal function more closely. Consider measuring salicylate levels if using high doses. Serum concentrations of 150–300 mcg/mL are antiinflammatory. Salicylism (e.g., tinnitus) is common at levels >200 mcg/mL.

Pregnancy Risk: C (D in third trimester of pregnancy)

Adverse Effects
Common: GI irritation (dyspepsia, esophageal reflux, epigastric pain); dose-related side effects at concentrations >200 mcg/mL (tinnitus/deafness)
Less common: GI ulceration or hemorrhage, minor elevations of liver enzymes, hypersensitivity (asthma; urticaria; angioedema, particularly in patients with nasal polyps), impaired renal function, acidosis with overdose, and high serum concentrations (>400 mcg/mL), especially in the elderly

Drug Interactions
Antacids: Decreased salicylate levels through increased elimination in alkaline urine
Anticoagulants: Activity of warfarin increased; increased hemorrhagic risk with other anticoagulants and thrombolytics
NSAIDs: Increased risk of GI side effects if aspirin is used with other NSAIDs. Coadministration of traditional NSAIDs such as ibuprofen or naproxen (but not COX-2–selective NSAIDs) may antagonize the long-term antiplatelet effect of aspirin.
Methotrexate: Aspirin may increase levels of MTX (however, with the doses of MTX used in RA, this is usually clinically insignificant); may potentiate MTX toxicity with high doses
Lithium: Increased lithium levels
Valproic acid: Aspirin may increase  free valproate concentrations and toxicity
Probenecid: Aspirin may antagonize effects

Patient Instructions: Take with food. Discontinue and seek medical advice if unusual bleeding develops.

Comments: With high doses, metabolic pathways become saturated, and a small dose increase can result in large increases in plasma concentrations. Enteric coated or delayed-release formulations aspirin may be better tolerated than regular aspirin but are not recommended for prophylaxis of thrombosis.

Clinical Pharmacology: Rapidly and well absorbed after oral administration. Hydrolyzed to salicylate with hepatic metabolism and renal excretion of conjugated metabolites. Urinary pH alters elimination (alkaline urine increases elimination). Wide variation in plasma concentrations exists in individuals receiving the same dose. Half-life varies with dose (2–3 hours with low doses, >10 hours with anti-inflammatory doses). At high doses, the elimination pathway is saturated, and a small increase in dose can lead to a large increase in serum concentration.

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