Aspirin

Aspirin

Pronunciation

U.S. Brand Names

Anacin®[OTC]; Arthritis Foundation® Pain Reliever [OTC]; A.S.A. [OTC]; Ascriptin®[OTC]; Aspergum®[OTC]; Asprimox®[OTC]; Bayer® Aspirin [OTC]; Bayer® Buffered Aspirin [OTC]; Bayer® Low Adult Strength [OTC]; Bufferin®[OTC]; Buffex®[OTC]; Cama® Arthritis Pain Reliever [OTC]; Easprin®; Ecotrin®[OTC]; Ecotrin® Low Adult Strength [OTC]; Empirin®[OTC]; Extra Strength Adprin-B®[OTC]; Extra Strength Bayer® Enteric 500 Aspirin [OTC]; Extra Strength Bayer® Plus [OTC]; Halfprin® 81®[OTC]; Heartline®[OTC]; Regular Strength Bayer® Enteric 500 Aspirin [OTC]; St Joseph® Adult Chewable Aspirin [OTC]; ZORprin®

Generic Available

Yes

Canadian Brand Names

Apo®-ASA; ASA®; Asaphen; Entrophen®; MSD® Enteric Coated ASA; Novasen

Synonyms

Acetylsalicylic Acid; ASA

Pharmacological Index

Salicylate

Use

Treatment of mild to moderate pain, inflammation, and fever; prophylaxis for myocardial infarction and transient ischemic episodes; management of rheumatoid arthritis, rheumatic fever, osteoarthritis, and gout (high dose)

Pregnancy Risk Factor

C (D if full-dose aspirin in 3rd trimester)

Contraindications

Hypersensitivity to salicylates or other NSAIDs; asthma; rhinitis; nasal polyps; inherited or acquired bleeding disorders (including factor VII and factor IX deficiency); pregnancy (in 3rd trimester especially); do not use in children (<16 years of age) for viral infections (chickenpox or flu symptoms), with or without fever, due to a potential association with Reye's syndrome

Warnings/Precautions

Use with caution in patients with platelet and bleeding disorders, renal dysfunction, dehydration, erosive gastritis, or peptic ulcer disease. Heavy alcohol use (>3 drinks/day) can increase bleeding risks. Avoid use in severe renal failure or in severe hepatic failure. Discontinue use if tinnitus or impaired hearing occurs. Caution in mild-moderate renal failure (only at high dosages). Patients with sensitivity to tartrazine dyes, nasal polyps and asthma may have an increased risk of salicylate sensitivity. Surgical patients should avoid ASA if possible, for 1-2 weeks prior to surgery, to reduce the risk of excessive bleeding.

Adverse Reactions

As with all drugs which may affect hemostasis, bleeding is associated with aspirin. Hemorrhage may occur at virtually any site. Risk is dependent on multiple variables including dosage, concurrent use of multiple agents which alter hemostasis, and patient susceptibility. Many adverse effects of aspirin are dose-related, and are rare at low dosages. Other serious reactions are idiosyncratic, related to allergy or individual sensitivity. Accurate estimation of frequencies is not possible. The reactions listed below have been reported for aspirin.

Central nervous system: Fatigue, insomnia, nervousness, agitation, confusion, dizziness, headache, lethargy, cerebral edema, hyperthermia, coma

Cardiovascular: Hypotension, tachycardia, dysrhythmias, edema

Dermatologic: Rash, angioedema, urticaria

Endocrine and metabolic: Acidosis, hyperkalemia, dehydration, hypoglycemia (children), hyperglycemia, hypernatremia (buffered forms)

Gastrointestinal: Nausea, vomiting, dyspepsia, epigastric discomfort, heartburn, stomach pains, gastrointestinal ulceration (6% to 31%), gastric erosions, gastric erythema, duodenal ulcers

Hematologic: Anemia, disseminated intravascular coagulation, prolongation of prothrombin times, coagulopathy, thrombocytopenia, hemolytic anemia, bleeding, iron deficiency anemia

Hepatic: Hepatotoxicity, increased transaminases, hepatitis (reversible)

Neuromuscular and skeletal: Rhabdomyolysis, weakness, acetabular bone destruction (OA)

Otic: Hearing loss, tinnitus

Renal: Interstitial nephritis, papillary necrosis, proteinuria, renal impairment, renal failure (including cases caused by rhabdomyolysis), increased BUN, increased serum creatinine

Respiratory: Asthma, bronchospasm, dyspnea, laryngeal edema, hyperpnea, tachypnea, respiratory alkalosis, noncardiogenic pulmonary edema

Miscellaneous: Anaphylaxis, prolonged pregnancy and labor, stillbirths, low birth weight, peripartum bleeding, Reye's syndrome

Case reports: Colonic ulceration, esophageal stricture, esophagitis with esophageal ulcer, esophageal hematoma, oral mucosal ulcers (aspirin-containing chewing gum), coronary artery spasm, conduction defect and atrial fibrillation (toxicity), delirium, ischemic brain infarction, colitis, rectal stenosis (suppository), cholestatic jaundice, periorbital edema, rhinosinusitis

Overdosage/Toxicology

Refer to the nomogram in Toxicology Information in the Appendix

Symptoms of overdose include tinnitus, headache, dizziness, confusion, metabolic acidosis, hyperpyrexia, hypoglycemia, coma

Treatment should also be based upon symptomatology. Toxic symptoms and corresponding treatments are as follows:

Overdose: Induce emesis with ipecac, and/or lavage with saline, followed with activated charcoal
Dehydration: I.V. fluids with KCl (no D₅W only)
Metabolic acidosis (must be treated): Sodium bicarbonate
Hyperthermia: Cooling blankets or sponge baths
Coagulopathy/hemorrhage: Vitamin K I.V.
Hypoglycemia (with coma, seizures, or change in mental status): Dextrose 25 g I.V.
Seizures: Diazepam 5-10 mg I.V.

Drug Interactions

ACE inhibitors: The effects of ace inhibitors may be blunted by aspirin administration, particularly at higher dosages.

Buspirone increases aspirin's free % in vitro.

Carbonic anhydrase inhibitors and corticosteroids have been associated with alteration in salicylate serum concentrations.

Heparin and low molecular weight heparins: Concurrent use may increase the risk of bleeding.

Methotrexate serum levels may be increased; consider discontinuing aspirin 2-3 days before high-dose methotrexate treatment or avoid concurrent use.

NSAIDs may increase the risk of gastrointestinal adverse effects and bleeding. Serum concentrations of some NSAIDs may be decreased by aspirin.

Platelet inhibitors (IIb/IIa antagonists): Risk of bleeding may be increased.

Probenecid effects may be antagonized by aspirin.

Sulfonylureas: The effects of older sulfonylurea agents (tolazamide, tolbutamide) may be potentiated due to displacement from plasma proteins. This effect does not appear to be clinically significant for newer sulfonylurea agents (glyburide, glipizide, glimepiride).

Valproic acid may be displaced from its binding sites which can result in toxicity.

Verapamil may potentiate the prolongation of bleeding time associated with aspirin.

Warfarin and oral anticoagulants may increase the risk of bleeding.

Stability

Keep suppositories in refrigerator, do not freeze; hydrolysis of aspirin occurs upon exposure to water or moist air, resulting in salicylate and acetate, which possess a vinegar-like odor; do not use if a strong odor is present

Mechanism of Action

Inhibits prostaglandin synthesis, acts on the hypothalamus heat-regulating center to reduce fever, blocks prostaglandin synthetase action which prevents formation of the platelet-aggregating substance thromboxane A₂

Pharmacodynamics/Kinetics

Duration: 4-6 hours

Absorption: From stomach and small intestine

Distribution: Readily distributes into most body fluids and tissues

Metabolism: Hydrolyzed to salicylate (active) by esterases in the GI mucosa, red blood cells, synovial fluid and blood; metabolism of salicylate occurs primarily by hepatic microsomal enzymes; metabolic pathways are saturable

Half-life: Parent drug: 15-20 minutes; Salicylates (dose-dependent): From 3 hours at lower doses (300-600 mg), to 5-6 hours (after 1 g) to 10 hours with higher doses

Time to peak serum concentration: ~1-2 hours

Usual Dosage

Children:

Analgesic and antipyretic: Oral, rectal: 10-15 mg/kg/dose every 4-6 hours, up to a total of 60-80 mg/kg/24 hours

Anti-inflammatory: Oral: Initial: 60-90 mg/kg/day in divided doses; usual maintenance: 80-100 mg/kg/day divided every 6-8 hours, maximum dose: 3.6 g/day; monitor serum concentrations

Kawasaki disease: Oral: 80-100 mg/kg/day divided every 6 hours; after fever resolves: 8-10 mg/kg/day once daily; monitor serum concentrations

Antirheumatic: Oral: 60-100 mg/kg/day in divided doses every 4 hours

Adults:

Analgesic and antipyretic: Oral, rectal: 325-650 mg every 4-6 hours up to 4 g/day

Anti-inflammatory: Oral: Initial: 2.4-3.6 g/day in divided doses; usual maintenance: 3.6-5.4 g/day; monitor serum concentrations

TIA: Oral: 1.3 g/day in 2-4 divided doses

Myocardial infarction prophylaxis: 160-325 mg/day; a lower aspirin dosage has been recommended in patients receiving ACE inhibitors

Dosing adjustment in renal impairment: Cl_cr <10 mL/minute: Avoid use.

Hemodialysis: Dialyzable (50% to 100%)

Dosing adjustment in hepatic disease: Avoid use in severe liver disease.

Dietary Considerations

Alcohol: Combination causes GI irritation, possible bleeding; avoid or limit alcohol. Patients at increased risk include those prone to hypoprothrombinemia, vitamin K deficiency, thrombocytopenia, thrombotic thrombocytopenia purpura, severe hepatic impairment, and those receiving anticoagulants.

Food: May decrease the rate but not the extent of oral absorption. Drug may cause GI upset, bleeding, ulceration, perforation. Take with food or large volume of water or milk to minimize GI upset.

Folic acid: Hyperexcretion of folate; folic acid deficiency may result, leading to macrocytic anemia. Supplement with folic acid if necessary.

Iron: With chronic aspirin use and at doses of 3-4 g/day, iron deficiency anemia may result; supplement with iron if necessary

Sodium: Hypernatremia resulting from buffered aspirin solutions or sodium salicylate containing high sodium content. Avoid or use with caution in CHF or any condition where hypernatremia would be detrimental.

Curry powder, paprika, licorice, Benedictine liqueur, prunes, raisins, tea and gherkins: Potential salicylate accumulation. These foods contain 6 mg salicylate/100 g. An ordinarily American diet contains 10-200 mg/day of salicylate. Foods containing salicylates may contribute to aspirin hypersensitivity. Patients at greatest risk for aspirin hypersensitivity include those with asthma, nasal polyposis or chronic urticaria.

Fresh fruits containing vitamin C: Displaces drug from binding sites, resulting in increased urinary excretion of aspirin. Educate patients regarding the potential for a decreased analgesic effect of aspirin with consumption of foods high in vitamin C.

Reference Range

Timing of serum samples: Peak levels usually occur 2 hours after ingestion. Salicylate serum concentrations correlate with the pharmacological actions and adverse effects observed. The serum salicylate concentration (mcg/mL) and the corresponding clinical correlations are as follows:

Serum salicylate level ~100

Desired effects: Antiplatelet, antipyresis, analgesia

Adverse effects/Intoxication: GI intolerance and bleeding, hypersensitivity, hemostatic defects

Serum salicylate level 150-300

Desired effects: Anti-inflammatory

Adverse effects/Intoxication: Mild salicylism

Serum salicylate level 250-400

Desired effects: Treatment of rheumatic fever

Adverse effects/Intoxication: Nausea/vomiting, hyperventilation, salicylism, flushing, sweating, thirst, headache, diarrhea, and tachycardia

Serum salicylate level >400-500

Adverse effects/Intoxication: Respiratory alkalosis, hemorrhage, excitement, confusion, asterixis, pulmonary edema, convulsions, tetany, metabolic acidosis, fever, coma, cardiovascular collapse, renal and respiratory failure

Test Interactions

False-negative results for glucose oxidase urinary glucose tests (Clinistix®); false-positives using the cupric sulfate method (Clinitest®); also, interferes with Gerhardt test, VMA determination; 5-HIAA, xylose tolerance test and T₃ and T₄

Cardiovascular Considerations

The most dramatic benefits of aspirin are evident when used in the treatment of myocardial infarction. Time is of the essence. Therapy should be acutely initiated as 325 mg of nonenteric-coated aspirin, preferably chewed if possible. While the optimum dose of aspirin in ischemic heart disease is not known, 325 mg is generally the dose of choice; 80 mg doses are used in patients who are less tolerant of aspirin therapy. The morbidity and mortality benefit from aspirin therapy after infarction is similar to the benefit achieved by thrombolytic therapy. The benefits of these therapeutic interventions are additive. Aspirin therapy is also indicated in patients with atrial fibrillation to prevent thromboembolic events. In this setting, aspirin is indicated in those patients with atrial fibrillation who are <65 years of and age and who have no other risk factors for stroke.

Mental Health: Effects on Mental Status

May cause drowsiness

Mental Health: Effects on Psychiatric Treatment

May cause leukopenia; use caution with clozapine and carbamazepine; may displace valproic acid from binding sites resulting in an increase of unbound drug; monitor for toxicity

Dental Health: Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Dental Health: Effects on Dental Treatment

Avoid aspirin, if possible, for 1 week prior to surgery because of the possibility of postoperative bleeding

Patient Information

If self-administered, use exactly as directed (do not increase dose or frequency); adverse reactions can occur with overuse. Take with food or milk. Do not use aspirin with strong vinegar-like odor. Do not crush or chew extended release products. While using this medication, avoid alcohol, excessive amounts of vitamin C, or salicylate-containing foods (curry powder, prunes, raisins, tea, or licorice), other prescription or OTC medications containing aspirin or salicylate, or other NSAIDs without consulting prescriber. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). You may experience nausea, vomiting, gastric discomfort (frequent mouth care, small frequent meals, sucking lozenges, or chewing gum may help). GI bleeding, ulceration, or perforation can occur with or without pain. May discolor stool (pink/red). Stop taking aspirin and report ringing in ears; persistent pain in stomach; unresolved nausea or vomiting; difficulty breathing or shortness of breath; unusual bruising or bleeding (mouth, urine, stool); or skin rash. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Consult prescriber if breast-feeding.

Nursing Implications

Do not crush sustained release or enteric coated tablet

Dosage Forms

Capsule: 356.4 mg and caffeine 30 mg

Suppository, rectal: 60 mg, 120 mg, 125 mg, 130 mg, 195 mg, 200 mg, 300 mg, 325 mg, 600 mg, 650 mg, 1.2 g

Tablet: 65 mg, 75 mg, 81 mg, 325 mg, 500 mg

Tablet: 400 mg and caffeine 32 mg

Tablet:

Buffered: 325 mg and magnesium-aluminum hydroxide 150 mg; 325 mg, magnesium hydroxide 75 mg, aluminum hydroxide 75 mg, buffered with calcium carbonate; 325 mg and magnesium-aluminum hydroxide 75 mg

Chewable: 81 mg

Controlled release: 800 mg

Delayed release: 81 mg

Enteric coated: 81 mg, 325 mg, 500 mg, 650 mg, 975 mg

Gum: 227.5 mg

Timed release: 650 mg

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