Oral Secondary prophylaxis of ischaemic stroke, Secondary prophylaxis of transient ischaemic attack
Adult: Available preparation:
Each extended- or modified-release cap contains aspirin 25 mg (in standard release form) and dipyridamole 200 mg (in extended- or modified-release form)
1 cap bid. For patients with intolerable headache during therapy initiation: Reduce to 1 cap at bedtime and low-dose aspirin in the morning; may return to the usual dose regimen as soon as tolerance to headache develops (usually within 1 week).
Renal Impairment
Severe (GFR <10 mL/min): Contraindicated.
Hepatic Impairment
Severe: Contraindicated.
Administration
May be taken with or without food. Swallow whole, do not chew/crush.
Contraindications
Hypersensitivity to aspirin, dipyridamole, or NSAIDs. Syndrome of asthma, rhinitis and nasal polyps; active gastric or duodenal ulcers, history of active peptic ulcer disease, experienced gastric pain with previous use of aspirin/dipyridamole; bleeding disorders, history of haemorrhagic CVA, haemorrhagic diathesis or coagulation disorders (e.g. hypoprothrombinaemia, haemophilia). Children and adolescents with viral infections. Severe renal (GFR <10 mL/min) and hepatic impairment. Pregnancy (3rd trimester). Concomitant use with methotrexate (>15 mg/week doses).
Special Precautions
Patient with erosive gastritis, CV disease (e.g. hypotension, coronary artery disease, unstable angina, recent MI, left ventricular outflow obstruction, haemodynamic instability), myasthenia gravis, G6PD deficiency. Patient undergoing surgery; discontinue treatment 1-2 weeks prior to procedure. Interrupt treatment for 24-48 hours before pharmacological stress testing with IV dipyridamole or other adenosinergic agents. Not interchangeable with the individual preparations of aspirin and dipyridamole. Mild to moderate renal and hepatic impairment. Pregnancy (1st-2nd trimester) and lactation.
This drug may cause dizziness and confusion, if affected, do not drive or operate machinery.
Monitoring Parameters
Monitor blood pressure, CBC, Fe studies, ferritin, stools for occult blood, LFTs and renal function tests with prolonged therapy. Assess for signs and symptoms of gastrointestinal ulcers and bleeding, including occult bleeding; stroke or TIA particularly in patients taking concurrent aspirin for cardiac indications.
Overdosage
Symptoms: Feeling warm, flushes, sweating, restlessness, weakness, dizziness, angina, fall in blood pressure and tachycardia; hyperventilation, tinnitus, nausea, vomiting, dehydration, acid-base disturbance, and confusion. In severe cases, hyperthermia and hypovolaemia. Management: Supportive treatment. Consider performing gastric lavage as soon as possible. Administer activated charcoal if the ingestion occurred within 1-2 hours; ensure the airway is protected. Closely follow acid-base status with serial blood gas and serum pH measurements. Maintain fluid and electrolyte balance. Slow IV administration of xanthine derivatives (e.g. aminophylline) may reverse the haemodynamic effects of dipyridamole. May increase aspirin elimination through urinary alkalinisation by giving 1.26% Na bicarbonate. Monitor plasma electrolytes and urinary pH.
Drug Interactions
Increased risk of bleeding with anticoagulants (e.g. coumarins, heparin), antiplatelets (e.g. clopidogrel, ticlopidine), anagrelide, fibrinolytics, NSAIDs (chronic use), SSRIs.
Aspirin: Increased risk of gastrointestinal bleeding with corticosteroids. May diminish the hypotensive effects of ACE inhibitors and β-blockers. May result in high serum levels and toxicity of acetazolamide. Enhanced effects of phenytoin, valproic acid. May decrease the effects of diuretics. May antagonise the action of uricosuric agents (e.g. probenecid, sulfinpyrazone). May increase the effectiveness of oral hypoglycaemics.
Dipyridamole: Increased plasma levels and CV effects of adenosine. Increased CV effects of regadenoson. May antagonise the anticholinesterase effects of cholinesterase inhibitors causing potential aggravation of myasthenia gravis. May increase the hypotensive effects of blood pressure-lowering agents. Potentially Fatal: Aspirin: Increased risk of bone marrow toxicity of methotrexate.
Food Interaction
Increased risk of gastrointestinal irritation and bleeding with heavy or chronic alcohol use.
Lab Interference
May impair the test sensitivity of pharmacologic stress testing with IV dipyridamole or other adenosinergic agents (e.g. regadenoson, adenosine).
Aspirin: May cause false-positive result in the aldosterone/renin ratio (ARR). False-negative result for glucose oxidase urinary glucose tests and false-positives using the cupric sulfate method. Interferes with Gerhardt test, vanillylmandelic acid (VMA) determination, 5-hydroxyindoleacetic acid (5-HIAA), T3 and T4, and xylose tolerance test.
Dipyridamole: May cause false-negative result with dipyridamole-thallium myocardial imaging when used with caffeine or theophylline.
Action
Description: Mechanism of Action: Aspirin and dipyridamole combination exert additive antiplatelet effects to produce its antithrombotic activity.
Aspirin inhibits platelet aggregation by irreversible inhibition of cyclooxygenase-1 and 2 via acetylation which results in decreased formation of prostaglandin precursors, thus inhibits the formation of thromboxane A2.
Dipyridamole causes an accumulation of adenosine, adenine nucleotides and cyclic adenosine monophosphate (cAMP) by inhibiting the activity of adenosine deaminase and phosphodiesterase, thereby inhibiting platelet aggregation.
Synonym: Aspirin: acetylsalicylic acid. Onset: Aspirin: Platelet inhibition: <1 hour (nonenteric-coated); 3-4 hours (enteric-coated). Duration: Aspirin: 4-6 hours (immediate-release). Pharmacokinetics: Absorption: Aspirin: Rapidly absorbed from the gastrointestinal tract. Bioavailability: 50-75% (immediate-release). Time to peak plasma concentration: Approx 1-2 hours (immediate release, nonenteric-coated); 3-4 hours (immediate-release, enteric coated); approx. 2 hours (extended-release).
Dipyridamole: Readily but variable absorption. Absolute bioavailability: Approx 70%. Time to peak plasma concentration: 2-3 hours. Distribution: Aspirin: Distributed widely and readily into most body fluids and tissues. Crosses the placenta and enters breastmilk. Volume of distribution: 10 L. Plasma protein binding: 80-90% (salicylic acid).
Dipyridamole: Widely distributed into organs. Crosses the placenta (small amounts); enters breast milk. Volume of distribution: 2-3 L/kg. Plasma protein binding: 91-99%, mainly to α1-acid glycoprotein and albumin. Metabolism: Aspirin: Metabolised in the liver by esterases to salicylic acid (active); further conjugated into salicyluric acid, salicylic acyl glucuronide, salicyl phenolic glucuronide, gentisic acid, and gentisuric acid.
Dipyridamole: Metabolised in the liver via conjugation with glucuronic acid primarily to monoglucuronide conjugate. Excretion: Aspirin: Via urine (75% as salicyluric acid, 10% as salicylic acid). Elimination half-life: 15-20 minutes (in plasma); dose-dependent (salicylic acid).
Dipyridamole: Via faeces (as glucuronide conjugates and unchanged drug). Terminal elimination half-life: 10-12 hours.
Chemical Structure
Aspirin Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 2244, Aspirin. https://pubchem.ncbi.nlm.nih.gov/compound/Aspirin. Accessed Nov. 23, 2022.
Source: National Center for Biotechnology Information. PubChem Database. Dipyridamole, CID=3108, https://pubchem.ncbi.nlm.nih.gov/compound/Dipyridamole (accessed on Jan. 21, 2020)
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