Dipyridamole: Optimized Platelet Inhibition for Vascular Protection
Dipyridamole
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Synonyms
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Dipyridamole is an established antiplatelet agent with vasodilatory properties, primarily indicated for thromboembolism prophylaxis in patients with cardiac valve replacements. This adenosine reuptake and phosphodiesterase inhibitor demonstrates a unique dual mechanism of action, effectively reducing platelet aggregation while improving coronary blood flow. Its well-characterized pharmacokinetic profile and favorable safety record make it a valuable therapeutic option in specific cardiovascular contexts, particularly when combined with other antithrombotic agents. Clinical evidence supports its role in secondary stroke prevention and adjunctive therapy in certain vascular disorders.
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: Adenosine reuptake inhibition and phosphodiesterase (PDE) inhibition
- Bioavailability: Approximately 70% with considerable interindividual variation
- Protein binding: 91-99% primarily to alpha-1-acid glycoprotein and albumin
- Metabolism: Hepatic glucuronidation via UGT1A9
- Elimination half-life: 10-12 hours
- Excretion: Primarily biliary (as glucuronide metabolite), minimal renal excretion
Benefits
- Provides effective platelet aggregation inhibition through multiple complementary mechanisms
- Reduces risk of thromboembolic complications in prosthetic heart valve patients
- Demonstrates coronary vasodilation properties improving myocardial perfusion
- Offers favorable safety profile with lower bleeding risk compared to some antiplatelet agents
- Maintains stable antiplatelet effect with twice-daily dosing regimen
- Shows synergistic effects when combined with aspirin for stroke prevention
Common use
Dipyridamole is primarily indicated for the prevention of thromboembolic complications in patients with cardiac valve replacements, typically in combination with warfarin. It is also approved for use in combination with aspirin for secondary prevention of ischemic stroke and transient ischemic attacks (TIAs). Off-label applications include adjunctive therapy in peripheral arterial disease, maintenance of patency in coronary artery bypass grafts, and prevention of thrombosis in arteriovenous shunts. The medication finds particular utility in patients requiring antiplatelet therapy who may have contraindications to aspirin or other platelet inhibitors.
Dosage and direction
The standard adult dosage for thromboembolism prophylaxis is 75-100 mg four times daily when used alone, or 200 mg twice daily in extended-release form. When combined with aspirin for stroke prevention, the typical regimen is extended-release dipyridamole 200 mg plus aspirin 25 mg twice daily. Administration should occur on an empty stomach, at least one hour before or two hours after meals, as food significantly reduces bioavailability. Dosage adjustments may be necessary in elderly patients or those with hepatic impairment. Therapy should be initiated under medical supervision with careful monitoring of coagulation parameters.
Precautions
Patients should be monitored for signs of bleeding, particularly during the initial treatment period. Caution is advised in patients with hypotension, as dipyridamole’s vasodilatory effects may exacerbate low blood pressure. Hepatic function should be assessed periodically due to extensive hepatic metabolism. The medication may cause dizziness; patients should be advised against operating machinery until their response is known. Special consideration is required in patients with coronary artery disease, as dipyridamole-induced coronary steal phenomenon may occur during diagnostic testing. Pregnancy category B—use only if clearly needed.
Contraindications
Hypersensitivity to dipyridamole or any component of the formulation. Absolute contraindications include active bleeding disorders, hemorrhagic diathesis, and recent cerebral hemorrhage. Not recommended in patients with severe hepatic impairment or decompensated cardiac failure. Contraindicated in patients with known hypersensitivity to aspirin when used in combination products. Should not be administered to patients with unstable angina or recent myocardial infarction without careful risk-benefit assessment.
Possible side effect
Common adverse effects (≥1%) include headache (39%), dizziness (12%), gastrointestinal disturbances (18%), and flushing (7%). Less frequent reactions include hypotension (3%), tachycardia (2%), and rash (2%). Rare but serious side effects include hemorrhagic complications, severe hypotension, angina pectoris exacerbation, and hepatotoxicity. The extended-release formulation may cause fewer peak concentration-related side effects. Most adverse reactions are dose-dependent and often diminish with continued therapy. Headache typically resolves within one week of continued treatment in most patients.
Drug interaction
Dipyridamole potentiates the effects of other antithrombotic agents including warfarin, heparin, and direct oral anticoagulants, increasing bleeding risk. Cholinesterase inhibitors may have reduced effectiveness. Adenosine administration during stress testing may cause profound bradycardia or heart block when combined with dipyridamole. Proton pump inhibitors may reduce dipyridamole absorption. Strong inducers of UGT1A9 (e.g., rifampin) may decrease dipyridamole concentrations. May increase concentrations of drugs metabolized by CYP2C9. Concurrent use with antihypertensive agents may potentiate hypotensive effects.
Missed dose
If a dose is missed, it should be taken as soon as remembered unless it is nearly 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 adherence is important for maintaining therapeutic antiplatelet effects. If multiple doses are missed, medical advice should be sought regarding potential need for additional monitoring or dose adjustment.
Overdose
Symptoms of overdose may include severe hypotension, tachycardia, warmth and flushing sensations, dizziness, and syncope. Bleeding complications may occur with massive overdoses. Management is primarily supportive with careful monitoring of vital signs and coagulation parameters. Activated charcoal may be effective if administered within one hour of ingestion. Hypotension should be managed with fluid replacement and vasopressors if necessary. There is no specific antidote; hemodialysis is not effective due to high protein binding. Medical attention should be sought immediately for suspected overdose.
Storage
Store at controlled room temperature (20-25°C/68-77°F) in the original container protected from light and moisture. Keep tightly closed and away from excessive heat or humidity. Do not store in bathroom cabinets where moisture levels may fluctuate. Keep out of reach of children and pets. Do not use if capsules are cracked or tablets show signs of deterioration. Proper disposal of unused medication should follow local regulations for pharmaceutical waste.
Disclaimer
This information is provided 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 guidance. While every effort has been made to ensure accuracy, medical knowledge evolves rapidly and this information may not reflect the most current research or clinical guidelines.
Reviews
Clinical studies demonstrate dipyridamole’s efficacy in reducing stroke recurrence by approximately 20% when combined with aspirin compared to aspirin alone. The European Stroke Prevention Study 2 showed a 37% relative risk reduction in stroke with combination therapy. In cardiac valve patients, dipyridamole plus warfarin reduces thromboembolic events by 60-75% compared to warfarin monotherapy. Most meta-analyses confirm its favorable benefit-risk profile, though headache remains a common reason for discontinuation in approximately 10-15% of patients. Long-term data support maintained efficacy with consistent dosing over years of therapy.