Dipyridamole is a platelet adhesion inhibitor and vasodilator with a well-established role in cardiovascular medicine. As a phosphodiesterase inhibitor, it modulates platelet function through multiple pathways, primarily by increasing intracellular cyclic adenosine monophosphate (cAMP) levels. This comprehensive profile details its pharmacological characteristics, clinical applications, and practical prescribing considerations for healthcare professionals managing thromboembolic disorders. The drug represents a valuable therapeutic option, particularly in combination regimens for secondary stroke prevention.

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, adenosine reuptake blockade
• Bioavailability: Approximately 40% (oral administration)
• Protein binding: 91-99%
• Metabolism: Hepatic glucuronidation
• Half-life: 10-12 hours
• Excretion: Primarily biliary (feces), minimal renal clearance

Benefits

• Reduces platelet aggregation through multiple synergistic mechanisms
• Provides vasodilatory effects that may improve coronary blood flow
• Demonstrates favorable safety profile in long-term administration
• Offers flexible dosing options including extended-release formulations
• Shows efficacy in combination therapy for secondary stroke prevention
• May provide neuroprotective benefits beyond antiplatelet effects

Common use

Dipyridamole is primarily indicated for the prevention of thromboembolic complications, particularly in patients with a history of cerebrovascular events. Its most evidence-supported application is in combination with aspirin for secondary prevention of ischemic stroke and transient ischemic attacks (TIAs). The drug is also used in myocardial perfusion imaging as a pharmacologic stress agent, where it induces coronary vasodilation similar to exercise. Off-label applications include adjunctive therapy in prosthetic heart valve patients (though largely superseded by warfarin) and investigationally in certain vascular disorders. The combination formulation with aspirin has demonstrated particular efficacy in reducing stroke recurrence without significantly increasing hemorrhagic risk compared to monotherapy.

Dosage and direction

The standard maintenance dosage for stroke prevention is 200 mg twice daily of the extended-release formulation in combination with aspirin 25 mg twice daily. For immediate-release preparations, 75-100 mg four times daily is typical. When used as a pharmacologic stress agent for cardiac imaging, intravenous dipyridamole is administered at 0.57 mg/kg over 4 minutes. 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 hepatic impairment due to extensive liver metabolism. No renal dosage adjustment is typically required. Therapy is generally continued long-term unless contraindications develop.

Precautions

Hepatic function should be monitored periodically during long-term therapy due to extensive hepatic metabolism. Caution is advised in patients with hypotension or unstable angina, as the vasodilatory effects may exacerbate these conditions. Patients with myasthenia gravis may experience worsening symptoms. The antiplatelet effects persist for the duration of the drug’s presence in circulation, requiring careful consideration before surgical procedures. Elderly patients may require closer monitoring due to potential age-related changes in pharmacokinetics. Pregnancy category B: use only if clearly needed, with careful risk-benefit assessment. Breastfeeding should be avoided unless essential, as excretion in human milk occurs.

Contraindications

Hypersensitivity to dipyridamole or any component of the formulation. Acute myocardial infarction or unstable angina pectoris. Severe hypotension (systolic BP <90 mmHg). Concurrent use of adenosine in patients with asthma or COPD. Hemodynamic instability or decompensated heart failure. Known bleeding disorders or active pathological bleeding. Severe hepatic impairment (Child-Pugh class C). Concomitant use with strong CYP3A4 inhibitors in patients with cardiovascular instability.

Possible side effect

Common adverse effects (≥5% incidence) include headache (39%), dizziness (12%), gastrointestinal disturbances (15%), and flushing (7%). These often diminish with continued therapy. Less frequent effects (1-5%) include hypotension, tachycardia, rash, and fatigue. Rare but serious adverse events (<1%) include myocardial ischemia (particularly with IV administration), bleeding complications, hepatotoxicity, and severe hypersensitivity reactions. The incidence of bleeding events is generally lower than with aspirin monotherapy when used at recommended doses. Most adverse effects are dose-dependent and reversible upon discontinuation.

Drug interaction

Significant interactions occur with adenosine (potentiates cardiovascular effects), cholinesterase inhibitors (may counteract effects in myasthenia gravis), and antihypertensive agents (additive hypotensive effects). Moderate interactions with strong CYP3A4 inhibitors (ketoconazole, clarithromycin) may increase dipyridamole concentrations. Additive antiplatelet effects occur with aspirin, NSAIDs, clopidogrel, and warfarin, increasing bleeding risk. The vasodilatory effects may potentiate nitrate therapy. Adenosine deaminase inhibitors such as pentostatin may enhance dipyridamole 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. Doubling of doses is not recommended due to increased risk of adverse effects. Consistent adherence is important for maintaining antiplatelet effects, particularly in stroke prevention. Patients should be educated about the importance of regular dosing and advised to develop routine administration habits.

Overdose

Symptoms of overdose primarily include peripheral vasodilation with hypotension, tachycardia, and flushing. Severe cases may involve cardiac ischemia, arrhythmias, or bleeding complications. There is no specific antidote. Management is supportive with careful monitoring of cardiovascular status and bleeding parameters. Hypotension should be managed with fluid resuscitation and vasopressors if necessary. Activated charcoal may be effective if administered within one hour of ingestion. Hemodialysis is not effective due to high protein binding. Platelet transfusion may be considered in significant bleeding events.

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. Do not freeze. Keep out of reach of children and pets. Do not use beyond the expiration date printed on packaging. Proper disposal of unused medication through take-back programs is recommended to prevent environmental contamination and accidental ingestion.

Disclaimer

This information is provided for educational purposes and professional reference only. It does not constitute medical advice. Healthcare providers should exercise clinical judgment and consult primary literature when making treatment decisions. Dosage and administration may vary based on individual patient factors. The prescriber remains responsible for determining appropriate therapy and monitoring patient response. Always verify current prescribing information before administration.

Reviews

Clinical trials demonstrate dipyridamole’s efficacy in stroke prevention, with the ESPRIT trial showing number needed to treat of 42 for stroke prevention over 3.5 years when combined with aspirin. Meta-analyses confirm significant reduction in vascular events compared to placebo. Practical experience suggests good long-term tolerability, though initial headaches may affect adherence. The vasodilatory properties are particularly valued in patients with coronary artery disease. Most experts consider the combination with aspirin a valuable option in secondary stroke prevention, especially when other antiplatelets are contraindicated or poorly tolerated.