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Dipyridamole (Monograph)

Brand name: Persantine
Drug class: Cardiac Function

Medically reviewed by Drugs.com on Mar 10, 2024. 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

Detailed Dipyridamole dosage information

Cautions for Dipyridamole

Contraindications

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

Drug

Interaction

Comments

Adenosine

Potentiation of adenosine vasoactive effects100 169

Increased plasma adenosine concentrations100 169

Dosage adjustment of adenosine may be necessary100 169

Anticholinesterase agents

Antagonizes anticholinesterase effects100 158

Potential to aggravate myasthenia gravis100 158

Heparin

Possible increased risk of bleeding complications166 167

Use with caution and monitor closely166 167

Methylxanthines (e.g., aminophylline, caffeine [e.g., coffee], theophylline

Inhibits dipyridamole vasodilatory and bronchospastic effects158 165

Aminophylline used to terminate persistent adverse effects of dipyridamole158

Caffeine or theophylline may lead to false-negative thallium imaging results;158 some clinicians recommend withholding caffeine (e.g., coffee) for 24 hours prior to testing165

Warfarin

Possible increased risk of bleeding, particularly during or after surgery; however, concomitant use does not appear to increase frequency or severity of bleeding compared with use of warfarin alone100

Some clinicians recommend maintenance of PT in the lower end of the therapeutic rangea
Dipyridamole drug interactions (more detail)

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 excretion100 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

Advice to Patients

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

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

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Dipyridamole

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

25 mg*

Dipyridamole Tablets

Persantine

Boehringer Ingelheim

50 mg*

Dipyridamole Tablets

Persantine

Boehringer Ingelheim

75 mg*

Dipyridamole Tablets

Persantine

Boehringer Ingelheim

Parenteral

Injection, for IV use

5 mg/mL*

Dipyridamole Injection
Dipyridamole Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules, extended-release (containing dipyridamole pellets and 25 mg immediate-release aspirin tablet)

200 mg with Aspirin 25 mg

Aggrenox

Boehringer Ingelheim

AHFS DI Essentials™. © Copyright 2024, Selected Revisions March 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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