ASPIRIN

Use: Labeled Indications Treatment of mild-to-moderate pain, inflammation, and fever; may be used as prophylaxis of myocardial infarction; prophylaxis of stroke and/or transient ischemic episodes; management of rheumatoid arthritis, rheumatic fever, osteoarthritis, and gout (high dose); adjunctive therapy in revascularization procedures (coronary artery bypass graft [CABG], percutaneous transluminal coronary angioplasty [PTCA], carotid endarterectomy), stent implantation (DIH) Aspirin (section 2.9) in a dose of 75 mg daily reduces the risk of cardiovascular events and myocardial infarction.Unduly high blood pressure must be controlled before aspirin is given. Unless contra-indicated, aspirin is recommended for all patients with established cardiovascular disease or those with a 10-year cardiovascular disease risk1 of 20% or more and aged over 50 years. Aspirin is also of benefit in those with diabetes (see also section 2.9). Prevention of cardiovascular events Patients with stable and unstable angina should be given advice and treatments to reduce their cardiovascular risk. The importance of life-style changes, especially stopping smoking, should be emphasised. Patients should take aspirin indefinitely in a dose of 75 mg daily. A combination of aspirin and clopidogrel is given for up to 12 months in patients with non-ST-segment elevation acute coronary syndromes (section 2.9).

Long-term use of aspirin, in a dose of 75 mg daily, is also of benefit for all patients
with established cardiovascular disease, for patients with a 10-year cardiovascular disease risk1 of 20% or more and aged over 50 years, for patients with diabetes aged over 50 years or who have had diabetes for more than 10 years, and for patients with diabetes who are receiving antihypertensive treatment. Unduly high blood pressure must be controlled before aspirin is given. If the patient is at a high risk of gastro-intestinal bleeding, a proton pump inhibitor (section 1.3.5) can be added. Long-term management Long-term management involves the use of several drugs which should ideally be started before the patient is discharged from hospital. Lowering the concentration of low-density lipoprotein (LDL) cholesterol and raising highdensity lipoprotein (HDL) cholesterol slows the progression of atherosclerosis and may even induce regression. All patients at high risk of cardiovascular disease should be advised to make lifestyle modifications that include beneficial changes to diet, exercise, weight management, alcohol consumption, and smoking cessation. Lipid-regulating drug treatment must be combined with advice on diet and lifestyle measures, lowering of raised blood pressure (section 2.5), the use of low-dose aspirin (section 2.9), and management of diabetes (section 6.1). (BNF 58, 2009) Use: Unlabeled/Investigational Low doses have been used in the prevention of pre-eclampsia, complications associated with autoimmune disorders such as lupus or antiphospholipid syndrome Use: Dental Treatment of postoperative pain Acute ischemic stroke:

Oral: 150-325 mg once daily, initiated within 48 hours (in patients who are not candidates for alteplase and not receiving systemic anticoagulation) Analgesic and antipyretic: Oral: 325-650 mg every 4-6 hours up to 4 g/day Rectal: 300-600 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 Atrial fibrillation (in patients not candidates for warfarin or at low risk of ischemic stroke): Oral: 75-325 mg once daily Bioprosthetic aortic valve: Oral: 50-100 mg once daily; usual dose: 81 mg once daily Bioprosthetic mitral valve (following 3 months of anticoagulation): Oral: 50-100 mg once daily; usual dose: 81 mg once daily CABG: Oral: 75-100 mg once daily (usual dose: 81 mg) initiated 6 hours following surgery; if bleeding prevents administration at 6 hours after CABG, initiate as soon as possible CABG (internal mammary bypass graft): Oral: 75-162 mg once daily Carotid artery stenting: Oral: 81-325 mg once daily beginning at least 24 hours (preferably 4 days) prior to procedure with concomitant clopidogrel Carotid endarterectomy: Oral: 50-100 mg once daily preoperatively and daily thereafter; usual dose: 81 mg once daily Infrainguinal arterial reconstruction/bypass: Oral: 75-100 mg once daily (begin preoperatively); usual dose: 81 mg once daily Mechanical heart valve (with additional risk factors for thromboembolism): Oral: 50-100 mg once daily (in addition to warfarin); usual dose: 81 mg once daily Mitral annular calcification (with documented stroke, TIA, or systemic embolism): Oral: 50-100 mg once daily; usual dose: 81 mg once daily Mitral valve prolapse (with documented stroke or TIA): Oral: 50-100 mg once daily; usual dose: 81 mg once daily Myocardial infarction (primary prevention): Oral: 75-162 mg once daily (Antman, 2004) or 75-100 mg (usual dose: 81 mg) once daily (Hirsh, 2008) Non-ST-segment elevation myocardial infarction (NSTEMI): Oral: Initial: 162-325 mg; Maintenance: 75-100 mg once daily indefinitely; usual maintenance dose: 81 mg once daily PCI: Oral: Initial: 75-325 mg (300-325 mg in aspirin native patients) starting at least 2 hours (preferably 24 hours) before procedure; post procedure: 162-325 mg once daily (dose and duration varies with type of stent implanted); Note: Dose may be reduced to 75-162 mg once daily after appropriate duration based on stent-type is complete Pericarditis associated with myocardial infarction: Oral: 162-325 mg once daily; doses as high as 650 mg every 4-6 hours may be required

Peripheral arterial disease: 75-100 mg once daily; usual dose: 81 mg once daily Pre-eclampsia prevention (unlabeled use): 60-81 mg once daily (usual dose: 81 mg) during gestational weeks 13-26 (patient selection criteria not established) Prosthetic valve thromboprophylaxis in pregnancy: 75-100 mg once daily; usual dose: 81 mg once daily ST-segment elevation myocardial infarction (STEMI): Initial: 162-325 mg given on presentation (patient should chew nonenteric-coated aspirin especially if not taking before presentation); for patients unable to take oral, may use rectal suppository (300 mg). Maintenance (secondary prevention): 75-162 mg once daily indefinitely Stroke (cardioembolic; anticoagulation contraindicated): Oral: 75-325 mg once daily Stroke/TIA (noncardioembolic; secondary prevention): Oral: 50-325 mg once daily (Adams, 2008) or 50-100 mg once daily; usual dose: 81 mg once daily (Hirsh, 2008) Dosing: Renal Impairment Clcr <10 mL/minute: Avoid use. Administration: Oral Do not crush sustained release or enteric coated tablet. Administer with food or a full glass of water to minimize GI distress. For acute myocardial infarction, have patient chew tablet. Dietary Considerations Take with food or large volume of water or milk to minimize GI upset. Storage 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. Contraindications Hypersensitivity to salicylates, other NSAIDs, or any component of the formulation; asthma; rhinitis; nasal polyps; inherited or acquired bleeding disorders (including factor VII and factor IX deficiency); 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; pregnancy (3rd trimester especially) Allergy Considerations

Surgical patients:

ASA should be avoided (if possible) in surgical patients for 1-2 weeks prior to surgery, to reduce the risk of excessive bleeding (except in patients with cardiac stents that have not completed their full course of dual antiplatelet therapy [aspirin,

clopidogrel]; patient specific situations need to be discussed with AHA/ACC/SCAI/ACS/ADA Science Advisory provides recommendations).

cardiologist;

As much as 60% of elderly with GI complications to NSAIDs can develop peptic ulceration and/or hemorrhage asymptomatically. The concomitant use of H2 blockers and sucralfate is not effective as prophylaxis with the exception of NSAID-induced duodenal ulcers which may be prevented by the use of ranitidine. Misoprostol and proton pump inhibitors are the only prophylactic agents proven to help prevent the development of NSAID-induced ulcers. Also, concomitant disease and drug use contribute to the risk for GI adverse effects. Use lowest effective dose for shortest period possible. Consider renal function decline with age. Use of NSAIDs can compromise existing renal function especially when Clcr is 30 mL/minute.

ESO: gastrointestinal ulceration (6% to 31%)

What side effects can this medication cause?
Aspirin may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away: nausea vomiting stomach pain heartburn

(ASHP, ?) 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: See table. Serum Salicylate: Clinical Correlations Serum Salicylate Concentration Desired Effects Adverse Effects / Intoxication (mcg/mL) Antiplatelet ~100 Antipyresis Analgesia 150-300 250-400 Antiinflammatory Mild salicylism GI intolerance and bleeding, hypersensitivity, hemostatic defects

Treatment of Nausea/vomiting, hyperventilation, salicylism, flushing, rheumatic fever sweating, thirst, headache, diarrhea, and tachycardia Respiratory alkalosis, hemorrhage, excitement, confusion, asterixis, pulmonary edema, convulsions, tetany, metabolic acidosis, fever, coma, cardiovascular collapse, renal and respiratory failure

>400-500

IO :

Sulfonylureas: Salicylates may enhance the hypoglycemic effect of Sulfonylureas. Of concern with regular, higher doses of salicylates, not sporadic, low doses. Risk C: Monitor therapy

(Tatro, 2004)

KI The following are absolute contraindications to the use of aspirin: _ children under 16; _ people with hypersensitivity to salicylates, NSAIDs, or tartrazine; _ people with peptic ulceration; _ people with known coagulopathies, including those induced as part of medical therapy. The following are relative contraindications to the use of long-term analgesic doses of aspirin: -gout, since normal analgesic doses impede the excretion of uric acid (high doses have a uricosuric effect); an additional problem in gout is that salicylates reduce the uricosuric effects of sulfinpyrazone and probenecid; _ variant angina; a daily dose of 4 g has been found to provoke attacks both at night-time and during the day (5,6), perhaps owing to direct triggering of coronary arterial spasm; blockade of the synthesis of PGIz, which normally protects against vasoconstriction, could be involved; _ diabetes mellitus, in which aspirin can in theory interfere with the actions of insulin and glucagon sufficiently to derange control; _ some days before elective surgery (even in coronary artery bypass grafting) or delivery, especially if extradural anesthesia is used (7), although recent data seem reassuring (8); aspirin increases bleeding at dental extraction or perioperatively; _ in elderly people, who may develop gastrointestinal bleeding; _ anorectal inflammation (suppositories); _ pre-existing gastrointestinal disease, liver disease, hypoalbuminemia, hypovolemia, in the third trimester of pregnancy, perioperatively, or in patients with threatening abortion. (Meyler) Nursing: Physical Assessment/Monitoring Do not use for persons with allergic reaction to salicylate or other NSAIDs. Assess other medications patient may be taking for additive or adverse interactions. Monitor therapeutic effectiveness and for signs of adverse reactions or overdose at beginning of therapy and periodically with long-term therapy. Assess knowledge/teach patient appropriate use. Teach patient to monitor for adverse reactions, adverse reactions to report, and appropriate interventions to reduce side effects. Patient Education 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 (eg, 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); or

discoloration of stool (pink/red). Stop taking aspirin and report ringing in ears; persistent stomach pain; unresolved nausea or vomiting; respiratory difficulty or shortness of breath; unusual bruising or bleeding (mouth, urine, stool); or skin rash.

Mechanism of Action
Irreversibly inhibits cyclooxygenase-1 and 2 (COX-1 and 2) enzymes, which result in decreased formation of prostaglandin precursors; has antiplatelet, antipyretic, analgesic, and antiinflammatory properties The antipyretic analgesics, with the non-steroidal anti-inflammatory drugs (NSAIDs), share a common mechanism of action, namely the inhibition of prostaglandin synthesis from arachidonic acid and their release. More precisely their mode of action is thought to result from inhibition of both the constitutive and theinducible isoenzymes (COX-1 and COX-2) of the cyclooxygenase pathway (4). However, aspirin and paracetamol are distinguishable from most of the NSAIDs by their ability to inhibit prostaglandin synthesis in the nervous system, and thus the hypothalamic center for body temperature regulation, rather than acting mainly in the periphery. Endogenous pyrogens (and exogenous pyrogens that have their effects through the endogenous group) induce the hypothalamic vascular endothelium to produce prostaglandins, which activate the thermoregulatory neurons by increasing AMP concentrations. The capacity of the antipyretic analgesics to inhibit hypothalamic prostaglandin synthesis appears to be the basis of their antipyretic action. Neither aspirin nor paracetamol affects the synthesis or release of endogenous pyrogens and neither will lower body temperature if it is normal. While aspirin significantly inhibits peripheral prostaglandin and thromboxane synthesis, paracetamol is less potent as a synthetase inhibitor than the NSAIDs, except in the brain, and paracetamol has only a weak anti-inflammatory action. It is simple to ascribe the analgesic activity of aspirin to its capacity to inhibit prostaglandin synthesis, with a consequent reduction in inflammatory edema and vasodilatation, since aspirin is most effective in the pain associated with inflammation or injury. However, such a peripheral effect cannot account for the analgesic activity of paracetamol, which is less well understood. As a prostaglandin synthesis inhibitor, aspirin, like other NSAIDs, is associated with irritation of and damage to the gastrointestinal mucosa. In low doses it can also increase bleeding by inhibiting platelet aggregation; in high doses, prolongation of the prothrombin time will contribute to the bleeding tendency. Intensive treatment can also produce unwanted nervous system effects (salicylism). Duration Absorption Distribution Metabolism : 4-6 hours : Rapid : Vd: 10 L; readily into most body fluids and tissues : Hydrolyzed to salicylate (active) by esterases in GI mucosa, red blood cells, synovial fluid, and blood; metabolism of salicylate occurs primarily by hepatic conjugation; metabolic pathways are saturable : 50% to 75% reaches systemic circulation

Bioavailability

Half-life elimination : Parent drug: 15-20 minutes; Salicylates (dose dependent): 3 hours at lower doses (300-600 mg), 5-6 hours (after 1 g), 10 hours with higher doses Time to peak, serum : ~1-2 hours Excretion : Urine (75% as salicyluric acid, 10% as salicylic acid) (Lacy et al, 2009)
What should I do if I forget a dose?
If your doctor has told you to take aspirin on a regular basis and you miss a dose, take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

(ASHP, ?)
What storage conditions are needed for this medicine?
Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom). Store aspirin suppositories in a cool place or in a refrigerator. Throw away any medication that is outdated or no longer needed and any tablets that have a strong vinegar smell. Talk to your pharmacist about the proper disposal of your medication.

(ASHP, ?)