Dipyridamole is a platelet adhesion inhibitor and vasodilator with a well-established role in cardiovascular medicine. As a phosphodiesterase inhibitor, it increases intracellular cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) levels, resulting in multiple pharmacodynamic effects. This medication represents a sophisticated therapeutic option for preventing thromboembolic events, particularly in patients with prosthetic heart valves or history of cerebrovascular accidents. Its unique mechanism provides complementary antiplatelet activity when combined with other anticoagulant therapies, offering clinicians a valuable tool in comprehensive thromboprophylaxis strategies.

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
• Mechanism: Phosphodiesterase inhibition with increased cAMP/cGMP
• Bioavailability: Approximately 37-66% (dose-dependent)
• Protein binding: 91-99%
• Metabolism: Hepatic glucuronidation
• Elimination half-life: 10-12 hours
• Excretion: Primarily biliary (as glucuronide metabolite)

Benefits

• Reduces risk of thromboembolic complications in patients with prosthetic heart valves
• Prevents recurrent transient ischemic attacks and strokes when combined with aspirin
• Provides complementary antiplatelet mechanism to aspirin therapy
• Exhibits coronary vasodilatory properties useful in diagnostic testing
• Maintains therapeutic effect with twice-daily dosing convenience
• Offers well-tolerated antiplatelet option for patients with aspirin intolerance

Common use

Dipyridamole is primarily indicated for the prevention of postoperative thromboembolic complications associated with prosthetic heart valves, typically in combination with warfarin. It is also FDA-approved for use with aspirin to reduce the risk of stroke in patients who have had transient ischemia of the brain or completed ischemic stroke due to thrombosis. Off-label uses include adjunctive therapy in peripheral arterial disease, maintenance of patency in coronary artery bypass grafts, and as a pharmacological stress agent in myocardial perfusion imaging. The medication has demonstrated particular efficacy in cerebrovascular protection, with the ESPS-2 trial showing significant reduction in stroke risk when combined with low-dose aspirin.

Dosage and direction

For thromboembolism prophylaxis with prosthetic heart valves: 75-100 mg four times daily in combination with warfarin. For stroke prevention: 200 mg extended-release capsule twice daily in combination with aspirin 25 mg twice daily (Aggrenox formulation). Standard tablet formulation: 75-100 mg three to four times daily, taken at least one hour before or two hours after meals for optimal absorption. Dosage adjustment is required in hepatic impairment. Therapy should be initiated under careful medical supervision, particularly in patients with coronary artery disease due to the “coronary steal” phenomenon. The extended-release formulation should be swallowed whole, not crushed or chewed.

Precautions

Monitor patients for signs of bleeding, including unusual bruising, petechiae, hematuria, or melena. Use with caution in patients with hypotension due to vasodilatory effects. Hepatic function should be assessed periodically as metabolism occurs primarily in the liver. Patients with severe coronary artery disease may experience angina exacerbation due to coronary steal phenomenon. Caution is advised when administering to patients with bleeding diatheses or thrombocytopenia. Ophthalmologic examinations are recommended during prolonged therapy due to possible retinal edema. Abrupt discontinuation should be avoided due to potential rebound hypercoagulability.

Contraindications

Hypersensitivity to dipyridamole or any component of the formulation. Patients with unstable angina or recent myocardial infarction due to risk of coronary steal. Severe hepatic impairment (Child-Pugh Class C). Concurrent use with adenosine in patients with asthma or COPD. Combination with other potent antiplatelet or anticoagulant agents requires careful risk-benefit assessment. Not recommended in patients with hemorrhagic cerebrovascular accidents or active pathological bleeding.

Possible side effect

Common adverse effects (>10%): headache (39%), dizziness (15%), gastrointestinal distress (12%). Less frequent effects (1-10%): flushing, hypotension, nausea, diarrhea, myalgia, rash. Rare but serious effects (<1%): bleeding complications (cerebral hemorrhage, gastrointestinal bleeding), angina pectoris, liver function abnormalities, thrombocytopenia, hypersensitivity reactions including bronchospasm. The vasodilatory headache typically diminishes with continued therapy over 1-2 weeks. Gastrointestinal effects are often mitigated by taking with food despite reduced absorption.

Drug interaction

Potentiates effects of anticoagulants (warfarin, heparin), antiplatelet agents (aspirin, clopidogrel), and thrombolytics, increasing bleeding risk. Adenosine effects are potentiated and prolonged—reduce adenosine dose for stress testing. Cholinesterase inhibitors may have reduced efficacy. Hepatic enzyme inducers (rifampin, phenobarbital) may decrease dipyridamole concentrations. May increase blood levels of adenosine and endogenous vasoactive substances. Concomitant use with antihypertensives may cause additive hypotensive effects.

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 one. Maintain regular dosing schedule to ensure consistent antiplatelet effect. For patients on quarter-daily dosing, missing a single dose may not significantly affect therapeutic efficacy due to the drug’s 10-12 hour half-life, but consistent adherence is important for optimal thromboprophylaxis.

Overdose

Symptoms include peripheral vasodilation with marked hypotension, tachycardia, warmth and flushing. Bleeding complications may occur with massive overdose. Management is supportive: maintain blood pressure with intravenous fluids and vasopressors if needed. Gastric lavage may be considered if presented early. There is no specific antidote; hemodialysis is not effective due to high protein binding. Platelet transfusion may be considered for significant bleeding. Monitor coagulation parameters and provide symptomatic treatment for at least 24 hours due to the drug’s prolonged half-life.

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 other humid areas. Keep out of reach of children and pets. Do not use after expiration date printed on packaging. Extended-release capsules should be protected from high humidity environments to maintain integrity of the release mechanism.

Disclaimer

This information is for educational purposes only and does not constitute medical advice. Treatment decisions should be made by qualified healthcare professionals based on individual patient circumstances. The prescribing physician should be consulted for specific dosage recommendations and therapeutic monitoring. Safety and efficacy in pediatric patients have not been established. Use during pregnancy only if clearly needed, as adequate human studies are lacking. Caution is advised in nursing women as dipyridamole is excreted in breast milk.

Reviews

Clinical studies demonstrate dipyridamole’s efficacy in stroke prevention, with the ESPS-2 trial showing 37% relative risk reduction compared to placebo when combined with aspirin. Cardiologists note its value in prosthetic valve patients requiring additional antiplatelet protection beyond warfarin. Some neurologists prefer dipyridamole-aspirin combination over clopidogrel for certain stroke patients based on trial evidence. The main limitation reported is the headache side effect, which leads to discontinuation in approximately 8% of patients. Overall, it is considered a well-established option with a distinct mechanism of action in the antiplatelet arsenal.