Dipyridamole: Advanced Antiplatelet Therapy for Thrombosis Prevention
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Synonyms
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Dipyridamole is a platelet adhesion inhibitor and vasodilator used primarily in the prevention of thromboembolic events, particularly in patients with cardiac valve replacements or a history of stroke. It functions by increasing cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) levels in platelets, inhibiting their aggregation and adhesion. This mechanism, combined with its vasodilatory effects, makes it a valuable therapeutic option in cardiovascular medicine, often used in combination with other anticoagulants for synergistic protective benefits.
Features
- Chemical name: 2,2’,2’’,2’’’-(4,8-Di(piperidin-1-yl)pyrimido[5,4-d]pyrimidine-2,6-diyl)bis(azanetriyl))tetraethanol
- Molecular formula: C₂₄H₄₀N₈O₄
- Available in oral tablet formulations (25 mg, 75 mg, 100 mg, 200 mg)
- Extended-release and immediate-release formulations
- Often combined with aspirin in fixed-dose products for enhanced efficacy
- White to yellowish crystalline powder, sparingly soluble in water
Benefits
- Reduces the risk of stroke and transient ischemic attack (TIA) in high-risk patients
- Prevents thrombosis in patients with prosthetic heart valves
- Exhibits coronary vasodilation, improving myocardial perfusion
- Minimal effect on bleeding time compared to other antiplatelet agents when used alone
- Suitable for long-term maintenance therapy with established safety profile
- May provide endothelial protective effects through increased nitric oxide bioavailability
Common use
Dipyridamole is indicated for the prevention of postoperative thromboembolic complications associated with prosthetic heart valves, typically in combination with warfarin. It is also used in secondary prevention of ischemic stroke and transient ischemic attacks, often in combination with aspirin. Off-label uses include adjunctive therapy in peripheral arterial disease, maintaining patency of coronary artery bypass grafts, and as an alternative antiplatelet agent in patients with aspirin intolerance.
Dosage and direction
For thromboembolism prevention with prosthetic heart valves: 75-100 mg four times daily in combination with warfarin. For stroke prevention: 200 mg extended-release formulation twice daily in combination with aspirin 25 mg. Immediate-release tablets should be taken on an empty stomach at least one hour before or two hours after meals to maximize bioavailability. Dosage adjustments are required in hepatic impairment. Do not crush or chew extended-release formulations.
Precautions
Use with caution in patients with hypotension due to vasodilatory effects. Monitor for signs of bleeding, especially when used with other anticoagulants. Hepatic impairment requires dosage reduction and close monitoring. Use cautiously in patients with coronary artery disease as rapid vasodilation may cause coronary steal phenomenon. Regular complete blood counts and liver function tests are recommended during prolonged therapy. Discontinue 48 hours prior to surgical procedures when possible.
Contraindications
Hypersensitivity to dipyridamole or any component of the formulation. Acute myocardial infarction or unstable angina pectoris. Severe hypotension or hemodynamic instability. Concurrent use with adenosine in patients with asthma (may potentiate bronchoconstriction). Not recommended in patients with bleeding diatheses or active pathological bleeding.
Possible side effect
Common adverse effects (>10%): headache, dizziness, gastrointestinal disturbances (nausea, vomiting, diarrhea, abdominal pain). Less frequent (1-10%): flushing, hypotension, tachycardia, rash, pruritus. Rare (<1%): thrombocytopenia, liver enzyme elevations, angina pectoris, syncope, hypersensitivity reactions. Most side effects are dose-dependent and often diminish with continued therapy.
Drug interaction
Potentiates effects of other anticoagulants and antiplatelet agents (warfarin, heparin, aspirin, clopidogrel) increasing bleeding risk. Adenosine effects are potentiated and prolonged—reduce adenosine dose when used diagnostically. Cholinesterase inhibitors may have reduced efficacy. Hepatic enzyme inducers (rifampin, phenobarbital) may decrease dipyridamole concentrations. Proton pump inhibitors may reduce absorption of immediate-release formulations.
Missed dose
If a dose is missed, take it as soon as remembered unless it is nearly time for the next dose. Do not double the dose to make up for a missed dose. Maintain regular dosing schedule to ensure consistent antiplatelet effect. If multiple doses are missed, consult healthcare provider for guidance on resumption therapy.
Overdose
Symptoms may include severe hypotension, tachycardia, warmth and flushing, nausea, vomiting, diarrhea, and dizziness. Management is supportive: maintain blood pressure with intravenous fluids and vasopressors if needed. Gastric lavage may be considered if ingestion was recent. Hemodialysis is not effective due to high protein binding. There is no specific antidote; monitor for bleeding complications and provide symptomatic treatment.
Storage
Store at controlled room temperature (20-25°C or 68-77°F). Protect from light and moisture. Keep in original container with tight closure. Do not store in bathroom or damp areas. Keep out of reach of children and pets. Do not use after expiration date printed on packaging.
Disclaimer
This information is for educational purposes only and does not constitute medical advice. Always consult with a qualified healthcare professional before starting or changing any medication regimen. The prescribing physician should be aware of the patient’s complete medical history and concurrent medications. Dosage and administration may vary based on individual patient factors and clinical context.
Reviews
Clinical studies demonstrate dipyridamole’s efficacy in stroke prevention, with the ESPS-2 trial showing 37% relative risk reduction in stroke with combination therapy. Cardiologists report good tolerability in most patients, though headache is a frequent initial side effect. Patients with prosthetic valves show reduced thromboembolic events when used with warfarin. Some clinicians prefer newer agents but acknowledge dipyridamole’s established role in specific patient populations. Monitoring requirements are generally less intensive than with some other anticoagulants.