Action

Reduces pain and inflammation by inhibiting prostaglandin production. Fever reduction mechanism unknown; may be linked to decrease in endogenous pyrogens in hypothalamus resulting from prostaglandin inhibition. Exerts antiplatelet effect by inhibiting synthesis of prostacyclin and thromboxane A₂.

Availability

Gum (chewable): 227 mg

Suppositories: 60 mg, 120 mg, 200 mg, 300 mg, 325 mg, 600 mg, 650 mg

Tablets: 81 mg, 325 mg, 500 mg

Tablets (chewable): 81 mg

Tablets (enteric-coated, delayed-release): 81 mg, 162 mg, 325 mg, 500 mg, 650 mg, 975 mg

Tablets (extended-release): 650 mg, 800 mg

Tablets (film-coated): 325 mg, 500 mg

Indications and dosages

➣ Mild pain or fever

Adults: 325 to 500 mg P.O. q 3 hours, or 325 to 650 mg P.O. q 4 hours, or 650 to 1,000 mg P.O. q 6 hours, to a maximum dosage of 4,000 mg/day.

Extended-release tablets-650 mg to 1,300 mg q 8 hours, not to exceed 3,900 mg/day; or 800 mg q 12 hours.

Children: 10 to 15 mg/kg P.O. or P.R. q 4 hours, not to exceed total daily dosage of 3.6 g, or up to 60 to 80 mg/kg/day. See chart below.

➣ Mild to moderate pain caused by inflammation (as in rheumatoid arthritis or osteoarthritis)

Adults: Initially, 2,400 to 3,600 mg P.O. daily in divided doses. Dosage may be increased by 325 to 1,200 mg daily at intervals of at least 1 week. Usual maintenance dosage is 3.6 to 5.4 g/day P.O. in divided doses, to a maximum dosage of 6 g/day.

➣ Juvenile rheumatoid arthritis

Children: 60 to 130 mg/kg/day P.O. in children weighing 25 kg (55 lb) or less, or 2,400 to 3,600 mg P.O. daily in children weighing more than 25 kg P.O.; give in divided doses q 6 to 8 hours.

➣ Acute rheumatic fever

Adults: 5 to 8 g/day P.O. in divided doses

Children: Initially, 100 mg/kg/day P.O. in individual doses for first 2 weeks; then maintenance dosage of 75 mg/kg/day P.O. in divided doses for next 4 to 6 weeks

➣ To reduce the risk of transient ischemic attacks (TIAs) or cerebrovascular accident in men with a history of TIAs caused by emboli

Adults: 650 mg P.O. b.i.d. or 325 mg P.O. q.i.d.

➣ To reduce the risk of myocardial infarction (MI) in patients with a history of MI or unstable angina

Adults: 75 to 325 mg/day P.O.

➣ Kawasaki disease

Children: Initially during acute febrile period, 80 to 180 mg/kg/day P.O. in four divided doses. Maintenance dosage is 3 to 10 mg/kg/day given as a single dose for up to 8 weeks or until platelet count and erythrocyte sedimentation rate return to normal.

➣ Thromboembolic disorders

Adults: 325 to 650 mg P.O. once or twice daily

Contraindications

• Hypersensitivity to salicylates, other NSAIDs, or tartrazine

• Renal impairment

• Severe hepatic impairment

• Hemorrhagic states or blood coagulation defects

• Vitamin K deficiency caused by dehydration

• Concurrent anticoagulant use

• Pregnancy (third trimester) or breastfeeding

Precautions

Use with extreme caution, if at all, in:

• hepatic disorders, anemia, asthma, gastritis, Hodgkin's disease

• heart failure or other conditions in which high sodium content is harmful (buffered aspirin)

• patients receiving other salicylates or NSAIDs concurrently

• elderly patients

• children and adolescents.

Administration

☞ Never administer to child or adolescent who has signs or symptoms of chickenpox or flulike illness.

☞ Don't give within 6 weeks after administration of live varicella virus vaccine, because of risk of Reye's syndrome.

• Give with food or large amounts of water or milk to minimize GI irritation.

• Know that extended-release and enteric-coated forms are best for long-term therapy.

• Be aware that aspirin should be discontinued at least 1 week before surgery because it may inhibit platelet aggregation.

Adverse reactions

EENT: hearing loss, tinnitus, ototoxicity

GI: nausea, vomiting, abdominal pain, dyspepsia, epigastric distress, heartburn, anorexia, GI bleeding

Hematologic: thrombocytopenia, hemolytic anemia, leukopenia, agranulocytosis, shortened red blood cell life span

Hepatic: hepatotoxicity

Metabolic: hyponatremia, hypokalemia, hypoglycemia

Respiratory: wheezing, hyperpnea, pulmonary edema with toxicity

Skin: rash, urticaria, bruising, angioedema

Other: hypersensitivity reactions, salicylism or acute toxicity

Interactions

Drug-drug. Acidifying drugs (such as ammonium chloride): increased salicylate blood level

Activated charcoal: decreased salicylate absorption

Alkalinizing drugs (such as antacids): decreased salicylate blood level Angiotensin-converting enzyme (ACE) inhibitors: decreased antihypertensive effect

Anticoagulants, NSAIDs, thrombolytics: increased bleeding risk

Carbonic anhydrase inhibitors (such as acetazolamide): salicylism

Corticosteroids: increased salicylate excretion and decreased blood level Furosemide: increased diuretic effect Live varicella virus vaccine: increased risk of Reye's syndrome

Methotrexate: decreased methotrexate excretion and increased blood level, causing greater risk of toxicity Nizatidine: increased salicylate blood level

Spironolactone: decreased spironolactone effect

Sulfonylureas (such as chlorpropamide, tolbutamide): enhanced sulfonylurea effects

Tetracycline (oral): decreased absorption of tetracycline (with buffered aspirin)

Drug-diagnostic tests. Alanine aminotransferase, alkaline phosphatase, amylase, aspartate aminotransferase, coagulation studies, PaCO₂, uric acid: increased values

Cholesterol, glucose, potassium, protein-bound iodine, sodium, thyroxine, tri-iodothyronine: decreased levels

Pregnancy test, protirelin-induced thyroid stimulating hormone, radionuclide thyroid imaging, serum theophylline (Schack and Waxler method), urine catecholamines, urine glucose, urine hydroxyindoleacetic acid, urine ketones (ferric chloride method), urine vanillylmandelic acid: test interference

Tests using phenosulfonphthalein as diagnostic agent: decreased urinary excretion of phenosulfonphthalein Urine protein: increased level

Drug-food. Urine-acidifying foods: increased salicylate blood level

Drug-herbs. Anise, arnica, cayenne, chamomile, clove, fenugreek, feverfew, garlic, ginger, ginkgo biloba, ginseng, horse chestnut, kelpware, licorice: increased bleeding risk

Drug-behaviors. Alcohol use: increased bleeding risk

Patient monitoring

☞ Watch for signs and symptoms of hypersensitivity and other adverse reactions, especially bleeding tendency.

• Stay alert for signs and symptoms of acute toxicity, such as diplopia, ECG abnormalities, generalized seizures, hallucinations, hyperthermia, oliguria, acute renal failure, incoherent speech, irritability, restlessness, tremor, vertigo, confusion, disorientation, mania, lethargy, laryngeal edema, anaphylaxis, and coma.

• Monitor elderly patients carefully because they're at greater risk for salicylate toxicity.

• With prolonged therapy, frequently assess hemoglobin, hematocrit, International Normalized Ratio, and kidney function test results.

• Check salicylate blood levels frequently.

• Evaluate patient for signs and symptoms of ototoxicity (hearing loss, tinnitus, ataxia, and vertigo).

Patient teaching

• Tell patient to report ototoxicity symptoms, unusual bleeding, and bruising.

• Caution patient to avoid activities that may cause injury. Advise him to use soft toothbrush and electric razor to avoid gum and skin injury.

• Instruct patient to tell all prescribers he's taking the drug, because it may cause serious interactions with many common medications.

• Tell patient not to take other over-the-counter preparations containing aspirin.

• Inform patient that he may need to undergo regular blood testing during therapy.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, herbs, and behaviors mentioned above.