Dipyridamole is a platelet adhesion inhibitor and coronary vasodilator used primarily in the prevention of thromboembolic complications. As a phosphodiesterase inhibitor, it modulates platelet function through multiple pathways, offering a unique mechanism of action distinct from other antiplatelet agents. Its clinical applications span various cardiovascular indications, particularly in patients with prosthetic heart valves or history of stroke. This comprehensive profile details the pharmacological characteristics, therapeutic benefits, and clinical considerations essential for healthcare professionals managing antithrombotic therapy.

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 and adenosine reuptake blockade
• Bioavailability: Approximately 40% with significant first-pass metabolism
• Protein binding: 91-99% primarily to alpha-1-acid glycoprotein
• Half-life: 10-12 hours with active metabolites
• Administration: Oral formulation (tablets) with extended-release options available
• Pregnancy category: B (animal studies show no risk, human data limited)

Benefits

• Reduces platelet aggregation through multiple synergistic mechanisms including increased intracellular cAMP and cGMP levels
• Provides coronary vasodilation improving myocardial perfusion in specific patient populations
• Demonstrates endothelial protective effects through enhanced prostacyclin release
• Offers alternative antithrombotic option for patients with aspirin intolerance
• Shows particular efficacy in secondary stroke prevention when combined with aspirin
• Maintains therapeutic effect with twice-daily dosing in extended-release formulations

Common use

Dipyridamole is primarily indicated for thromboembolism prophylaxis in patients with prosthetic heart valves, typically in combination with warfarin. It is also FDA-approved for secondary prevention of ischemic stroke and transient ischemic attacks when used in combination with aspirin. Off-label uses include adjunctive therapy in coronary artery disease, particularly for patients undergoing coronary artery bypass grafting. Some clinicians employ dipyridamole in myocardial perfusion imaging studies due to its vasodilatory properties. The medication has also been investigated for its potential anti-inflammatory and anticancer properties, though these applications remain experimental.

Dosage and direction

The standard dosage for stroke prevention is 200 mg extended-release capsule combined with 25 mg aspirin twice daily. For prosthetic heart valve patients, the typical dose is 75-100 mg four times daily when used with warfarin. Administration should occur on an empty stomach至少 one hour before or two hours after meals to optimize absorption. Tablets should be swallowed whole without crushing or chewing. Dose adjustment is necessary in hepatic impairment, with recommended reduction of 25-50% in patients with Child-Pugh class B or C cirrhosis. Renal impairment typically does not require dosage adjustment, though careful monitoring is advised. Therapy initiation should include gradual titration when appropriate to minimize adverse effects.

Precautions

Regular monitoring of bleeding parameters including complete blood count and coagulation studies is recommended, particularly during initial therapy. Patients should be advised about increased bleeding risk and instructed to report unusual bruising, bleeding, or signs of hemorrhage promptly. Caution is warranted in patients with hypotension due to the drug’s vasodilatory effects. Hepatic function should be assessed periodically as metabolism occurs primarily in the liver. The drug should be used cautiously in patients with severe coronary artery disease due to potential coronary steal phenomenon. Discontinuation should be gradual when possible to avoid rebound hypercoagulability.

Contraindications

Absolute contraindications include known hypersensitivity to dipyridamole or any component of the formulation. The medication is contraindicated in patients with active pathological bleeding such as peptic ulcer disease or intracranial hemorrhage. Should not be used in patients with unstable angina or recent myocardial infarction due to risk of coronary steal. Contraindicated in combination with adenosine in patients with asthma or COPD. Avoid use in patients with severe hypotension or decompensated heart failure. Not recommended in patients with severe hepatic impairment without close monitoring.

Possible side effect

Common adverse effects (≥5% incidence) include headache (39%), dizziness (12%), gastrointestinal distress (15%), and flushing (7%). Less frequent effects (1-5%) include hypotension, tachycardia, rash, and fatigue. Rare but serious side effects (<1%) include severe bleeding episodes, myocardial ischemia, hepatotoxicity, and thrombocytopenia. Headache typically diminishes with continued therapy over 1-2 weeks. Gastrointestinal effects can often be managed with administration adjustments. Cardiovascular effects require careful assessment, particularly in patients with underlying heart disease. Any signs of bleeding warrant immediate medical evaluation.

Drug interaction

Significant interactions occur with adenosine, potentiating its cardiovascular effects—require dose reduction of adenosine by 50-75%. Enhances effects of other antiplatelet agents and anticoagulants, increasing bleeding risk. Cholinesterase inhibitors may have reduced efficacy. CYP2C19 inhibitors may increase dipyridamole concentrations. Antacids and H2-receptor antagonists may decrease absorption. May potentiate hypotensive effects of antihypertensive medications. Interaction with adenosine deaminase inhibitors may enhance effects. Caution with strong CYP3A4 inducers which may decrease efficacy.

Missed dose

If a dose is missed, it should be taken as soon as remembered unless it is接近 time for the next scheduled dose. In that case, the missed dose should be skipped and the regular dosing schedule resumed. Patients should not double the dose to make up for a missed administration. Consistent dosing is important for maintaining therapeutic antiplatelet effects. If multiple doses are missed, healthcare provider should be consulted regarding potential need for additional monitoring or dose adjustment.

Overdose

Symptoms of overdose include severe hypotension, tachycardia, flushing, and dizziness. Significant overdose may lead to hemorrhagic complications or myocardial ischemia. Management involves immediate discontinuation and supportive care including blood pressure support with fluids and vasopressors if needed. Activated charcoal may be effective if administered within one hour of ingestion. There is no specific antidote; hemodialysis is not effective due to high protein binding. Coagulation parameters and complete blood count should be monitored closely. Symptomatic treatment should be provided based on clinical manifestations.

Storage

Store at controlled room temperature (20-25°C or 68-77°F) in original container. Protect from moisture and light. Keep tightly closed and out of reach of children. Do not store in bathroom or other humid areas. Do not freeze. Dispense in original container with child-resistant closure. Check expiration date before administration. Do not use if capsules are damaged or show signs of moisture exposure.

Disclaimer

This information is provided for educational purposes only and does not constitute medical advice. Healthcare professionals should consult official prescribing information and clinical guidelines. Treatment decisions must be based on individual patient assessment and professional judgment. The prescribing physician remains responsible for determining appropriate therapy and monitoring parameters. Always verify dosage and administration recommendations with current references.

Reviews

Clinical studies demonstrate dipyridamole’s efficacy in stroke prevention, with the ESPS-2 trial showing 37% relative risk reduction in stroke recurrence with combination therapy. Meta-analyses support its use in prosthetic heart valve patients, though warfarin remains primary therapy. Patient tolerance varies, with headache being the most frequently reported adverse effect leading to discontinuation in approximately 10% of patients. Many clinicians report successful long-term use with appropriate patient selection and management of side effects. The unique mechanism of action provides valuable options for patients requiring alternative antiplatelet strategies.