Aspirin

Aspirin (acetylsalicylic acid) irreversibly blocks platelet cyclooxygenase 1, preventing thromboxane A2 formation for the life of the platelet (7 to 10 days). At low doses it prevents arterial clots in coronary, cerebral and peripheral disease; it is also used in Kawasaki disease and to prevent pre-eclampsia in high risk pregnancy. At high doses it is an analgesic, antipyretic and anti-inflammatory. Gastrointestinal bleeding is its main risk. It is cheap and universally available in East Africa.

Classification. Antiplatelet; non steroidal anti-inflammatory drug (salicylate).

Mechanism. Acetylates serine 529 of platelet cyclooxygenase 1, blocking thromboxane A2. High doses also block cyclooxygenase 2 and prostaglandin synthesis, which lowers fever and inflammation. In the gut, loss of prostaglandin protects mucosa less.

Pharmacodynamics. Platelet inhibition within 1 hour of an uncoated dose (3 to 4 hours for enteric coated tablets); lasts for the life of the platelet. Recovery is about 10% a day as new platelets form.

Pharmacokinetics. Absorbed in the stomach and small intestine; bioavailability about 50 to 70% (lower for enteric coated). Aspirin half life 15 to 20 minutes; salicylate half life 2 to 4 hours at low doses (up to 15 to 30 hours at high doses by saturation). Metabolised in the liver; excreted in urine (alkaline urine raises excretion).

Acute coronary syndrome and acute myocardial infarction, adult. 300 mg (150 to 325 mg) chewed or dissolved as a single loading dose, then 75 to 100 mg once daily indefinitely (with a second antiplatelet drug for 6 to 12 months).

Secondary prevention of cardiovascular disease (stable coronary disease, previous stroke, peripheral artery disease), adult. 75 to 100 mg once daily.

Acute ischaemic stroke (after excluding haemorrhage), adult. 300 mg once daily for 14 days (or 160 to 325 mg within 24 to 48 hours), then long term 75 to 100 mg or clopidogrel; if thrombolysis is given, delay aspirin for 24 hours.

Minor stroke or high risk transient ischaemic attack, adult. 300 mg loading, then 75 to 100 mg daily with clopidogrel 75 mg for 21 days, then a single antiplatelet drug.

Prevention of pre-eclampsia, adult women at high risk. 75 to 150 mg once daily at night from 12 weeks (before 16 weeks) until delivery.

Kawasaki disease, children (specialist). 30 to 50 mg/kg daily (or 80 to 100 mg/kg daily) in 4 divided doses until afebrile for 48 to 72 hours, then 3 to 5 mg/kg once daily for 6 to 8 weeks (longer if coronary changes).

Pain and fever, adult (short term). 300 to 900 mg every 4 to 6 hours as needed; maximum 4 g daily. Avoid in children under 16 years.

Contraindications.

• Active peptic ulcer or gastrointestinal bleeding.
• Haemorrhagic stroke.
• Bleeding disorders (haemophilia, thrombocytopenia).
• Aspirin or non steroidal anti-inflammatory drug induced asthma or urticaria.
• Children under 16 years (except Kawasaki disease, because of Reye syndrome).
• Severe hepatic or kidney impairment.
• Third trimester at analgesic doses.
• Suspected dengue or other viral haemorrhagic fever.
• Hypersensitivity.

Warnings.

• Gastrointestinal bleeding (risk rises with age, alcohol, steroids, anticoagulants and Helicobacter pylori)
• raised bleeding with surgery (stop 7 days before elective surgery unless a recent stent)
• bronchospasm in aspirin exacerbated respiratory disease
• salicylate toxicity (tinnitus, hyperventilation, metabolic acidosis)
• haemolysis in glucose 6 phosphate dehydrogenase deficiency at high doses
• gout (low doses raise urate)
• kidney injury with dehydration

Primary prevention in low risk patients and in most older adults adds more bleeding than benefit.

Adverse effects. Dyspepsia, gastric erosions, ulcer, gastrointestinal bleeding, bruising, bleeding, bronchospasm, tinnitus (high doses), rash, rarely kidney injury.

Interactions.

• Warfarin, direct oral anticoagulants, heparin, other antiplatelet drugs: bleeding.
• Other non steroidal anti-inflammatory drugs (ibuprofen blocks the antiplatelet effect): bleeding and kidney injury.
• Corticosteroids, selective serotonin reuptake inhibitors: gastrointestinal bleeding.
• Methotrexate: raised levels and toxicity.
• Angiotensin converting enzyme inhibitors, loop diuretics: reduced effect and kidney injury.
• Alcohol: gastric damage.
• Ticagrelor: keep the aspirin dose to 100 mg or less.
• Spironolactone: reduced effect.
• Valproate: raised levels.

Special groups.

• Pregnancy: low dose is acceptable for pre-eclampsia prevention; avoid analgesic doses, especially after 20 weeks (foetal kidney effects and ductus constriction) and in the third trimester.

• Breastfeeding: low dose acceptable; avoid analgesic doses (Reye syndrome and platelet effects in the infant).

• Patients of African ancestry: check for glucose 6 phosphate dehydrogenase deficiency before high dose use.

• Older adults: use 75 mg; consider a proton pump inhibitor for gastric protection.

• Kidney impairment: low dose is acceptable; avoid analgesic doses when creatinine clearance is under 10 mL/min.

• Liver impairment: avoid in severe disease (bleeding risk).

Formulations. Tablets 75, 81, 100, 150, 300, 325, 500 mg (plain, dispersible and enteric coated); suppositories 150 and 300 mg.

Administration. Oral after food. For acute coronary syndrome or stroke, give an uncoated tablet chewed or dispersed (not enteric coated) for faster action. Swallow enteric coated tablets whole.

Baseline. History of ulcer or bleeding, asthma, allergy, haemoglobin, platelet count, creatinine, blood pressure, current drugs.

Monitoring. Haemoglobin and signs of bleeding (black stools, haematemesis) at each visit; creatinine in kidney disease; blood pressure. Add a proton pump inhibitor (pantoprazole preferred with clopidogrel) when at risk of gastrointestinal bleeding.

Stopping. Do not stop after a recent stent or acute coronary event without cardiology advice. Stop 7 days before elective surgery when safe.

Common prescribing errors. Using aspirin in children with fever; giving enteric coated tablets for urgent loading; adding ibuprofen; prescribing for primary prevention in older adults; omitting gastric protection in high risk patients; giving to patients with suspected dengue.