aspirin
A.S.A., Ascriptin, Aspergum, Bufferin, Ecotrin, Empirin, Halfprin, Novasen ◆, ZORprin

Pharmacologic classification: salicylate
Therapeutic classification: nonnarcotic analgesic, antipyretic, anti-inflammatory, antiplatelet
Pregnancy risk category D


Available forms
Available by prescription only
Tablets (enteric-coated): 975 mg
Tablets (extended-release): 800 mg
Chewing gum: 227.5 mg
Suppositories: 60 mg, 120 mg, 200 mg, 300 mg, 600 mg, 650 mg
Tablets: 325 mg (5 grains), 500 mg, 650 mg
Tablets (chewable): 81 mg
Tablets (enteric-coated): 81 mg, 162 mg, 165 mg, 325 mg, 500 mg, 650 mg
Tablets (extended-release): 650 mg

Indications and dosages
 Arthritis. Adults: Initially, 2.4 to 3.6 g P.O. daily in divided doses. Increase 325 mg to 1.2 g daily no more frequently than at weekly intervals. Maintenance dosage is 3.6 to 5.4 g P.O. daily in divided doses.
Children: 60 to 130 mg/kg P.O. daily in divided doses.
 Juvenile arthritis. Children who weigh more than 25 kg (55 lb): 2.4 to 3.6 g P.O. daily in divided doses.
Children who weigh 25 kg or less: 60 to 130 mg/kg P.O. daily in divided doses. Increase 10 mg/kg daily no more than at weekly intervals. Maintenance dosages usually range from 80 to 100 mg/kg daily; up to 130 mg/kg daily.
 Mild pain or fever. Adults: 650 mg to 1.3 g extended-release tablets P.O. q 8 hours, p.r.n.; not to exceed 3.9 g daily.
Adults and children older than age 11: 325 to 650 mg P.O. or P.R. q 4 hours, p.r.n.; not to exceed 4 g daily. Or, 454 mg chewing gum chewed for 15 minutes and discarded, p.r.n.; not to exceed 3.63 g daily.
Children ages 6 to 11: 227 mg to 454 mg chewed for 15 minutes and discarded, p.r.n.; not to exceed 1.82 g daily.
Children ages 3 to 5: 227 mg chewed for 15 minutes and discarded, p.r.n.; not to exceed 681 mg per day.
 Mild pain. Children ages 2 to 11: 65 mg/kg P.O. or P.R. daily divided q 4 to 6 hours, p.r.n.; not to exceed 2.5 g/m2.
 Transient ischemic attacks and thromboembolic disorders. Adults: 50 to 325 mg P.O. daily (prophylactic in men) and 160 mg to 325 mg (treatment) P.O. daily immediately or within 48 hours of CVA onset.
 Treatment or reduction of the risk of MI in patients with previous MI or unstable angina. Adults: For primary prevention, 75 to 325 mg P.O. daily. For secondary prevention, 75 to 325 mg P.O. daily. For treatment, 160 to 325 mg P.O. once daily.
 Kawasaki (mucocutaneous lymph node) syndrome. Adults: 80 to 100 mg/kg P.O. daily in four divided doses. Some patients may require up to 120 mg/kg daily to maintain acceptable serum salicylate levels of over 200 mcg/ml during the febrile phase. After the fever subsides, reduce dosage to 3 to 5 mg/kg once daily. Therapy is usually continued for 6 to 8 weeks.
 Rheumatic fever ◇. Adults: 4.9 to 7.8 g P.O. daily divided q 4 to 6 hours for 1 to 2 weeks. Then decrease to 60 to 70 mg/kg daily for 1 to 6 weeks. Then gradually withdraw over 1 to 2 weeks.
Children: 90 to 130 mg/kg P.O. daily divided q 4 to 6 hours.
 Pericarditis following acute MI ◇. Adults: 160 to 325 mg P.O. daily.
 Prevention of reocclusion in coronary revascularization procedures. Adults: 325 mg P.O. 6 hours after surgery and continued daily for at least 1 year.
 Stent implantation ◇. Adults: 160 to 325 mg P.O. 2 hours before stent placement and continued daily indefinitely.

Pharmacodynamics
Analgesic action: Aspirin produces analgesia by an ill-defined effect on the hypothalamus (central action) and by blocking generation of pain impulses (peripheral action). The peripheral action may involve blocking of prostaglandin synthesis via inhibition of cyclo-oxygenase enzyme.
Anti-inflammatory action: Although the exact mechanism is unknown, aspirin is believed to inhibit prostaglandin synthesis; it may also inhibit the synthesis or action of other mediators of inflammation.
Antipyretic action: Aspirin relieves fever by acting on the hypothalamic heat-regulating center to produce peripheral vasodilation. This increases peripheral blood supply and promotes sweating, which leads to loss of heat and to cooling by evaporation.
Anticoagulant action: At low doses, aspirin appears to impede clotting by blocking prostaglandin synthetase action, which prevents formation of the platelet-aggregating substance thromboxane A2. This interference with platelet activity is irreversible and can prolong bleeding time. However, at high doses, aspirin interferes with prostacyclin production, a potent vasoconstrictor and inhibitor of platelet aggregation, possibly negating its anticlotting properties.

Pharmacokinetics
Absorption: Absorbed rapidly and completely from the GI tract. Therapeutic blood salicylate concentrations for analgesia and anti-inflammatory effect are 150 to 300 mcg/ml; responses vary with the patient.
Distribution: Distributed widely into most body tissues and fluids. Protein-binding to albumin is concentration dependent, ranges from 75% to 90%, and decreases as serum level increases. Severe toxic effects may occur at serum levels greater than 400 mcg/ml.
Metabolism: Hydrolyzed partially in the GI tract to salicylic acid with almost complete metabolism in the liver.
Excretion: Excreted in urine as salicylate and its metabolites. Elimination half-life ranges from 15 to 20 minutes.

Route Onset Peak Duration
P.O.
 Tablets  5-30 min  25-40 min  1-4 hr
 Buffered  5-30 min  1-2 hr  1-4 hr
 Extended  5-30 min  1-4 hr  1-4 hr
 Enteric-coated  5-30 min  4-8 hr  Unknown
 Solution  5-30 min  15-40 min  1-4 hr
P.R. Unknown 3-4 hr Unknown


Contraindications and precautions
Contraindicated in patients hypersensitive to drug and in those with G6PD deficiency or bleeding disorders such as hemophilia, von Willebrand’s disease, or telangiectasia. Also contraindicated in patients with NSAID-induced sensitivity reactions and in children with chickenpox or flulike symptoms.
  Use cautiously in patients with GI lesions, impaired renal function, hypoprothrombinemia, vitamin K deficiency, thrombotic thrombocytopenic purpura, or hepatic impairment.

Interactions
Drug-drug. Aminoglycosides, bumetanide, capreomycin, cisplatin, erythromycin, ethacrynic acid, furosemide, vancomycin: May potentiate ototoxic effects. Monitor patient for this effect.
Ammonium chloride, other urine acidifiers: Increase blood aspirin level. Monitor patient for aspirin toxicity.
Antacids in high doses, other urine alkalizers: Decrease blood aspirin level. Monitor patient for decreased salicylate effect.
Antibiotics, corticosteroids, NSAIDs: May potentiate adverse GI effects of aspirin. Use together cautiously.
Anticoagulants, thrombolytics: May potentiate platelet-inhibiting effects of aspirin. Monitor PT and INR.
Corticosteroids: Enhance aspirin elimination. Monitor patient for decreased salicylate effect.
Lithium: Decreases renal clearance of lithium carbonate, thus increasing serum lithium levels and risk of adverse effects. Monitor lithium levels.
Phenylbutazone, probenecid, sulfinpyrazone: Aspirin is antagonistic to uricosuric effect of these drugs. Avoid use together.
Phenytoin, sulfonylureas, warfarin: May cause displacement of either drug and adverse effects. Monitor therapy closely.
Drug-herb. Feverfew, ginkgo, horse chestnut, kelpware, prickly ash, red clover: May increase risk of Drug-herb. Feverfew, ginkgo, horse chestnut, kelpware, prickly ash, red clover: May increase risk of bleeding. Discourage use together.
Red clover: May enhance anticoagulation effect. Avoid use together. If these agents must be used together, monitor PT and INR closely.
Drug-food. Any food: Delays and decreases absorption of aspirin. Watch for decreased salicylate effect.
Drug-lifestyle. Alcohol use: May potentiate adverse GI effects of aspirin. Discourage alcohol use.

Adverse reactions
EENT: tinnitus, hearing loss.
GI: nausea, GI distress, occult bleeding, dyspepsia, GI bleeding.
GU: acute renal insufficiency.
Hematologic: leukopenia, thrombocytopenia, prolonged bleeding time.
Hepatic: liver dysfunction, hepatitis.
Skin: rash, bruising, urticaria.
Other: hypersensitivity reactions (anaphylaxis, asthma), Reye’s syndrome, angioedema.

Effects on lab test results
• May increase serum creatinine and BUN levels.
• May increase liver function test values. May decrease WBC and platelet counts.

Overdose and treatment
Signs and symptoms of overdose include GI discomfort, oliguria, acute renal failure, hyperthermia, EEG abnormalities, and restlessness as well as metabolic acidosis with respiratory alkalosis, hyperpnea, and tachypnea because of increased carbon dioxide production and direct stimulation of the respiratory center.
 To treat aspirin overdose, empty the patient’s stomach immediately by inducing emesis with ipecac syrup if patient is conscious, or by gastric lavage. Administer activated charcoal via nasogastric tube. Provide symptomatic and supportive measures (respiratory support and correction of fluid and electrolyte imbalances). Closely monitor laboratory parameters and vital signs. Enhance renal excretion by administering sodium bicarbonate to alkalinize urine. Use cooling blanket or sponging if patient’s rectal temperature is more than 104° F (40° C). Hemodialysis is effective in removing aspirin but is only used in severely poisoned individuals or those at risk for pulmonary edema.

Special considerations
• Aspirin interferes with urinary glucose analysis performed with Diastix, Chemstrip uG, glucose enzymatic test strip, Clinitest, and Benedict’s solution, and with urinary 5-hydroxyindoleacetic acid and vanillylmandelic acid tests. Serum uric acid levels may be falsely increased. Aspirin may interfere with the Gerhardt test for urine acetoacetic acid.
• Salicylates must be used cautiously in patients with history of GI disease (especially peptic ulcer disease), increased risk of GI bleeding, or decreased renal function.
• Tablets may be chewed, broken, or crumbled and administered with food or fluids to aid swallowing. Uncoated plain aspirin tablets allowed to remain in contact with mucous membranes of the mouth and aspirin-containing chewing gum have produced mucosal erosions and mouth ulcerations.
• Patient should take 8 oz (240 ml) of water or milk with salicylates to ensure passage into stomach. Advise patient to sit up for 15 to 30 minutes after taking salicylates to prevent lodging of salicylate in esophagus.
• Enteric-coated products are absorbed slowly and aren’t suitable for acute therapy. They’re ideal for long-term therapy, such as that for arthritis.
• There’s no evidence that aspirin reduces the risk of transient ischemic attacks in women.
• Monitor vital signs frequently, especially temperature.
• Salicylates may mask the signs and symptoms of acute infection (fever, myalgia, erythema); carefully evaluate patients at risk for infections, such as those with diabetes.
• Monitor CBC, platelets, PT, BUN, serum creatinine, and liver function studies periodically during salicylate therapy to detect abnormalities.
• Assess patient for signs and symptoms of hemorrhage, such as petechiae, bruising, coffee ground vomitus, and black tarry stools.
• Stop aspirin therapy 1 week before elective surgery, if possible.
• Adults shouldn’t use drug for self-medication for longer than 10 days.
• Consider dose reduction if fever or illness causes fluid depletion.
• Moisture may cause aspirin to lose potency. Store in a cool, dry place, and avoid using if tablets smell like vinegar.
Pregnant patients
• Aspirin has been used for the prevention of complications in pregnancy including preeclampsia, pregnancy loss with history of antiphospholipid syndrome, and recurrent loss. Generally, avoid use in pregnancy.
Breast-feeding patients
• Salicylates appear in breast milk; avoid use during breast-feeding.
Pediatric patients
• Because of epidemiologic association with Reye’s syndrome, the Centers for Disease Control and Prevention recommend that children with chickenpox or flulike symptoms not be given aspirin or other salicylates. Don’t use long-term salicylate therapy in children younger than age 14; safety hasn’t been established. Don’t use more than 5 times per day or for longer than 5 days.
Geriatric patients
• Patients older than age 60 may be more susceptible to the toxic effects of aspirin. Use cautiously. Effects of aspirin on renal prostaglandins may cause fluid retention and edema, a significant drawback for geriatric patients and those with heart failure.

Patient education
• Tell parents to keep aspirin out of children’s reach; encourage use of child-resistant closures because aspirin is a leading cause of poisoning.
• Advise patients receiving high-dose, long-term aspirin therapy to watch for petechiae, bleeding gums, and signs of GI bleeding.
• Instruct patient to avoid use of aspirin if allergic to tartrazine dye.
• Tell patient to take drug with food or after meals to avoid GI upset.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use