Brand name: Persantine
Drug class: Platelet-aggregation Inhibitors
ATC class: 36:18

Medically reviewed by Drugs.com on Mar 10, 2025. Written by ASHP.

Introduction

A non-nitrate coronary vasodilator and platelet aggregation inhibitor.^{100 170 171 172}

Uses for Dipyridamole

Thromboembolism Associated with Prosthetic Heart Valves

Used as an adjunct to coumarin anticoagulants for the prevention of postoperative thromboembolic complications of heart valve replacement.^{100 101 103 104 105 106 107 108}

Should not be used alone, without an oral anticoagulant, in patients with mechanical prosthetic heart valves.^{101 105 108 109 140 141 142}

TIAs and Completed Thrombotic Stroke

Used in extended-release form in fixed combination with aspirin for secondary prevention of stroke in patients who have had TIAs or completed thrombotic stroke.^{145 146 148 990 1009}

The American College of Chest Physicians (ACCP), American Stroke Association (ASA), and AHA consider the fixed combination of aspirin and extended-release dipyridamole an acceptable antiplatelet therapy for secondary prevention of noncardioembolic ischemic stroke and TIAs; other options include aspirin monotherapy, cilostazol, or clopidogrel.^{150 990 1009} When selecting an appropriate antiplatelet regimen, consider factors such as the patient's individual risk for recurrent stroke, tolerance, and cost of the different agents.⁹⁹⁰

Adjunct to Thallium Myocardial Perfusion Imaging

Used IV as an adjunct to thallous (thallium) chloride Tl 201 myocardial perfusion imaging in patients unable to exercise adequately.^{158 159 165}

Dipyridamole Dosage and Administration

Administration

Administer orally or IV.^{100 158}

Oral Administration

Administer conventional tablets 4 times daily.¹⁰⁰

Administer extended-release dipyridamole and aspirin fixed-combination capsules twice daily in the morning and evening without regard to food.¹⁴⁵ Swallow capsules whole without chewing.¹⁴⁵

Extended-release dipyridamole in fixed combination with aspirin is not interchangeable with the individual components of aspirin and conventional dipyridamole tablets (e.g., Persantine).¹⁴⁵

IV Administration

Dilution

Dilute injection in ≥1:2 ratio with 0.45% sodium chloride injection, 0.9% sodium chloride injection, or 5% dextrose injection to a final volume of approximately 20–50 mL.¹⁵⁸

Rate of Administration

Adjunct to thallium myocardial perfusion imaging: 0.142 mg/kg per minute for 4 minutes.¹⁵⁸

Administration Risks

Infusion of undiluted injection may cause local irritation.¹⁵⁸

Dosage

Adults

Thromboembolism Associated with Prosthetic Heart Valves

Prophylaxis

Oral

Conventional tablets: 75–100 mg 4 times daily; use in conjunction with coumarin anticoagulant therapy.^{100 101 104 105 106 107 108}

TIAs and Completed Thrombotic Stroke

Secondary Prevention

Oral

Fixed combination with aspirin: 200 mg of extended-release dipyridamole and 25 mg of aspirin (1 capsule) twice daily in the morning and evening.¹⁴⁵

If headaches become intolerable during initial treatment, reduce dosage to 200 mg of dipyridamole and 25 mg of aspirin (1 capsule) once daily at bedtime; administer low-dose aspirin in the morning.¹⁴⁵ Resume the usual regimen (200 mg of extended-release dipyridamole and 25 mg of aspirin twice daily) as soon as possible (usually within 1 week) because no outcome data available with the reduced-dose regimen and headaches diminish during continued treatment.¹⁴⁵

Dose of aspirin in fixed-combination product may not be adequate to prevent recurrent MI or angina pectoris in patients with stroke or TIA.¹⁴⁵

Adjunct to Thallium Myocardial Perfusion Imaging

IV

Single IV dose of 0.57 mg/kg, infused at a rate of 0.142 mg/kg per minute for 4 minutes.^{158 165} Maximum tolerated IV dose not determined; clinical experience suggests that a total dose >60 mg is not needed for any patient.¹⁵⁸

Inject thallium-201 IV ≤5 minutes following completion of the dipyridamole infusion.¹⁵⁸

Prescribing Limits

Adults

Adjunct to Thallium Myocardial Perfusion Imaging

IV

Clinical experience suggests that a total dipyridamole dose >60 mg is not needed for any patient.¹⁵⁸

Cautions for Dipyridamole

Contraindications

• Known hypersensitivity to dipyridamole or any ingredient in the formulation.^{100 145 158}

Warnings/Precautions

Warnings

Cardiovascular and Cerebrovascular Effects

Serious adverse effects, including acute myocardial ischemia or MI, cardiac death, VF, symptomatic VT, stroke, transient cerebral ischemia, and seizures, reported with IV infusion.¹⁵⁸ Asystole, sinus node arrest, sinus node depression, and conduction block reported also reported with IV infusion.¹⁵⁸ Patients with abnormalities of cardiac impulse formation or conduction or severe CAD (e.g., unstable angina) may be at increased risk for these events.¹⁵⁸

Weigh the important clinical information to be gained by myocardial perfusion thallium imaging with IV dipyridamole against the risk to the patient. ¹⁵⁸ Consider the rate of false positive and false negative results of dipyridamole-assisted thallium imaging compared with coronary arteriography when choosing to use such imaging.¹⁵⁸

Monitor vital signs during and for 10–15 minutes after IV infusion; obtain an ECG using ≥1 chest lead.¹⁵⁸

Appropriate resuscitative measures should be readily available for relieving adverse effects such as severe chest pain.¹⁵⁸ If severe chest pain occurs, administer IV aminophylline in doses of 50–250 mg by slow IV injection (e.g., 50–100 mg over 30–60 seconds).¹⁵⁸ (See Specific Drugs under Interactions.) Place patients with severe hypotension in a supine position with the head tilted down, if necessary, before administration of IV aminophylline.¹⁵⁸ If the highest recommended dosage of aminophylline (250 mg) does not relieve chest pain within a few minutes, may administer sublingual nitroglycerin.¹⁵⁸ If chest pain continues despite such combination therapy, consider the possibility of MI.¹⁵⁸

If the clinical condition of the patient with an adverse event permits a 1-minute delay, may perform thallium imaging before reversal of the pharmacologic effects occurs.^{158 165}

Sensitivity Reactions

Anaphylactoid reactions and bronchospasm reported with IV dipyridamole.¹⁵⁸ Patients with a history of asthma may be at greater risk for bronchospasm.¹⁵⁸

Appropriate resuscitative measures should be readily available for relieving adverse effects such as severe bronchospasm.^{158 165} If severe bronchospasm occurs, administer aminophylline in doses of 50–250 mg by slow IV injection (e.g., 50–100 mg over 30–60 seconds).¹⁵⁸ (See Cardiovascular and Cerebrovascular Effects under Cautions.)

General Precautions

Use of Fixed Combinations

When used in fixed combination with aspirin, consider the cautions, precautions, and contraindications associated with aspirin.¹⁴⁵

Cardiovascular Effects

Use with caution in patients with hypotension or severe CAD (e.g., unstable angina, recently sustained MI) since peripheral vasodilation may occur.^{100 145} Dipyridamole may precipitate chest pain in patients with CAD.^{100 145}

Amount of aspirin in the commercially available fixed-combination product may not be adequate to prevent recurrent MI or angina pectoris in patients with stroke or TIA.¹⁴⁵

Hepatic Effects

Liver dysfunction (e.g., elevations of hepatic enzymes, hepatic failure) reported.^{100 145}

Specific Populations

Pregnancy

Category B: Conventional tablets and injection.^{100 158}

Category D: Fixed combination with aspirin.¹⁴⁵

Lactation

Distributed into milk.^{100 145 158} Use caution.^{100 145}

Pediatric Use

Conventional tablets: Safety and efficacy not established in pediatric patients <12 years of age.¹⁰⁰

Fixed combination with aspirin: Safety and efficacy not established;¹⁴⁵ should not be used in pediatric patients because of aspirin component.¹⁴⁵

Injection: Safety and efficacy not established.¹⁵⁸

Common Adverse Effects

Conventional tablets: Headache,¹⁰⁰ dizziness,¹⁰⁰ GI intolerance (e.g., abdominal distress),¹⁰⁰ vomiting,¹⁰⁰ diarrhea,¹⁰⁰ flushing,¹⁰⁰ rash,¹⁰⁰ pruritus.¹⁰⁰

Injection: Chest pain/angina pectoris,¹⁵⁸ ECG changes (most commonly ST-T changes),¹⁵⁸ headache,¹⁵⁸ dizziness.¹⁵⁸

Drug Interactions

Specific Drugs

Dipyridamole Pharmacokinetics

Absorption

Bioavailability

Absorption from GI tract is variable and incomplete;^{101 134 135 137 138 171} 37–66% of an oral dose (extended-release capsules containing dipyridamole in fixed combination with aspirin) may be absorbed.¹⁷¹

Following oral administration of conventional tablets, peak plasma concentrations attained in about 45–150 minutes (mean: 75 minutes).^{100 134 135 136 138} Peak plasma dipyridamole concentrations attained in about 2 hours (range: 1–6 hours) with twice-daily dosing of extended-release capsules containing dipyridamole in fixed combination with aspirin.¹⁴⁵

Onset

Injection: Peak increase in coronary blood flow occurs 6.5 minutes after initiation of infusion.¹⁵⁸

Duration

Following IV infusion, vital signs return to baseline in approximately 30 minutes.^{158 165}

Food

Capsules containing extended-release dipyridamole in fixed combination with aspirin: High-fat meal reduces peak plasma dipyridamole concentrations and total absorption at steady state by 20–30% compared with fasting state; not clinically relevant.¹⁴⁵

Distribution

Extent

In animals, widely distributed into body tissues; small amounts cross placenta.^a

Does not cross the blood-brain barrier in animals.^{145 171}

Distributed into milk.^{100 158 172}

Plasma Protein Binding

91–99%,^{101 134 138 139 158 158 171} principally to α₁-acid glycoprotein (α₁-AGP) but also to albumin.^{158 161 162}

Elimination

Metabolism

Metabolized in liver principally to monoglucuronide; small amount metabolized to diglucuronide.^{100 145 158}

Elimination Route

Metabolites eliminated principally in feces via biliary excretion^{100 145 158} and to a much lesser extent in urine.¹⁴⁵

Half-life

Conventional tablets: Biphasic; initial half-life approximately 40–80 minutes and terminal half approximately 10–12 hours.^{100 101 134 138}

Extended-release capsules containing dipyridamole in fixed combination with aspirin: 13.6 hours.¹⁴⁵

IV: Triphasic; mean half-lives of 3–12 minutes, 33–62 minutes, and 11.6–15.5 hours.¹⁵⁸

Stability

Storage

Oral

Capsules and Tablets

Conventional tablets: 25°C (may be exposed to 15–30°C).¹⁰⁰

Extended-release capsules containing dipyridamole in fixed combination with aspirin: 25°C (may be exposed to 15–30°C); protect from excessive moisture.¹⁴⁵

Parenteral

Solution for Injection

20–25°C; avoid freezing and protect from light.¹⁵⁸

Compatibility

Parenteral

Do not mix with other drugs in the same syringe or infusion container.¹⁵⁸

Actions

• Mechanism of antiplatelet effects not fully elucidated.^{100 101 134 170}

• Inhibits the uptake and metabolism of adenosine in platelets, endothelial cells and erythrocytes.^{100 145 171} Increased local concentrations of adenosine at the platelet surface stimulate platelet adenyl cyclase and increase platelet cyclic-3′,5′-adenosine monophosphate (cAMP) concentrations.^{100 145 171} Increased platelet cAMP concentrations affect platelet-activating factor, collagen, and adenosine diphosphate and inhibit mobilization of free calcium, which is involved in platelet activation.^{100 170 171} Also stimulates prostacyclin synthesis and potentiates antiplatelet effects of prostacyclin.¹⁷¹

• Inhibits platelet cyclic-3′,5′-guanosine monophosphate phosphodiesterase (cGMP-PDE).^{100 145 171 182} Augments increase in platelet cGMP concentrations produced by nitric oxide;^{100 145} increased cGMP platelet concentrations inhibit platelet activation and aggregation.^{171 182}

• Prolongs platelet survival time in patients with prosthetic heart valves or valvular heart disease in whom platelet survival is shortened.^{100 a}

• Mediates coronary vasodilation by inhibiting reuptake and thereby allowing accumulation of adenosine in vascular smooth muscle.^{158 165 182}

• Methylxanthine derivatives (e.g., theophylline, aminophylline) block adenosine receptors on vascular smooth muscle and abolish vasodilatory effects of dipyridamole.^{158 165} (See Specific Drugs under Interactions.)

• Increases blood flow in normal coronary arteries while producing reduced blood flow in stenotic arteries (“coronary steal”).^{158 165} Myocardial oxygen consumption and cardiac work not increased.¹⁶⁵

• Myocardial uptake of thallous (thallium) chloride Tl 201 is directly proportional to coronary blood flow.^{159 165} Less thallous chloride Tl 201 uptake¹⁵⁹ occurs in myocardium perfused by stenotic versus normal coronary arteries.^{158 159 160} Enhances the differences in blood flow between areas served by stenotic versus normal arteries during thallium testing.^{158 159 160 165}

• With IV administration, decreases BP and increases heart rate and cardiac output because of dilation of systemic resistance vessels.^{158 170 a} With usual oral dosages, generally no change in BP or blood flow in peripheral arteries.^{170 a}

Advice to Patients

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.^{100 145 158}

• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.^{100 145 158}

• Importance of informing patients of other important precautionary information.^{100 145 158} (See Cautions.)

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

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Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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