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Dipyridamole

Class: Vasodilating Agents, Miscellaneous
VA Class: BL117
CAS Number: 58-32-2
Brands: Persantine

Medically reviewed by Drugs.com. Last updated on Sep 8, 2020.

Introduction

A non-nitrate coronary vasodilator and platelet aggregation inhibitor.

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.

Should not be used alone, without an oral anticoagulant, in patients with mechanical prosthetic heart valves.

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.

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. 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.

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.

Dipyridamole Dosage and Administration

Administration

Administer orally or IV.

Oral Administration

Administer conventional tablets 4 times daily.

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

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

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.

Rate of Administration

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

Administration Risks

Infusion of undiluted injection may cause local irritation.

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.

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.

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. 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.

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

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. Maximum tolerated IV dose not determined; clinical experience suggests that a total dose >60 mg is not needed for any patient.

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

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.

Cautions for Dipyridamole

Contraindications

  • Known hypersensitivity to dipyridamole or any ingredient in the formulation.

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. Asystole, sinus node arrest, sinus node depression, and conduction block reported also reported with IV infusion. Patients with abnormalities of cardiac impulse formation or conduction or severe CAD (e.g., unstable angina) may be at increased risk for these events.

Weigh the important clinical information to be gained by myocardial perfusion thallium imaging with IV dipyridamole against the risk to the patient. 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.

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

Appropriate resuscitative measures should be readily available for relieving adverse effects such as severe chest pain. 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). (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. If the highest recommended dosage of aminophylline (250 mg) does not relieve chest pain within a few minutes, may administer sublingual nitroglycerin. If chest pain continues despite such combination therapy, consider the possibility of MI.

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.

Sensitivity Reactions

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

Appropriate resuscitative measures should be readily available for relieving adverse effects such as severe bronchospasm. 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). (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.

Cardiovascular Effects

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

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.

Hepatic Effects

Liver dysfunction (e.g., elevations of hepatic enzymes, hepatic failure) reported.

Specific Populations

Pregnancy

Category B: Conventional tablets and injection.

Category D: Fixed combination with aspirin.

Lactation

Distributed into milk. Use caution.

Pediatric Use

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

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

Injection: Safety and efficacy not established.

Common Adverse Effects

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

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

Interactions for Dipyridamole

Specific Drugs

Drug

Interaction

Comments

Adenosine

Potentiation of adenosine vasoactive effects

Increased plasma adenosine concentrations

Dosage adjustment of adenosine may be necessary

Anticholinesterase agents

Antagonizes anticholinesterase effects

Potential to aggravate myasthenia gravis

Heparin

Possible increased risk of bleeding complications

Use with caution and monitor closely

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

Inhibits dipyridamole vasodilatory and bronchospastic effects

Aminophylline used to terminate persistent adverse effects of dipyridamole

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

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 alone

Some clinicians recommend maintenance of PT in the lower end of the therapeutic range

Dipyridamole Pharmacokinetics

Absorption

Bioavailability

Absorption from GI tract is variable and incomplete; 37–66% of an oral dose (extended-release capsules containing dipyridamole in fixed combination with aspirin) may be absorbed.

Following oral administration of conventional tablets, peak plasma concentrations attained in about 45–150 minutes (mean: 75 minutes). 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.

Onset

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

Duration

Following IV infusion, vital signs return to baseline in approximately 30 minutes.

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.

Distribution

Extent

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

Does not cross the blood-brain barrier in animals.

Distributed into milk.

Plasma Protein Binding

91–99%, principally to α1-acid glycoprotein (α1-AGP) but also to albumin.

Elimination

Metabolism

Metabolized in liver principally to monoglucuronide; small amount metabolized to diglucuronide.

Elimination Route

Metabolites eliminated principally in feces via biliary excretion and to a much lesser extent in urine.

Half-life

Conventional tablets: Biphasic; initial half-life approximately 40–80 minutes and terminal half approximately 10–12 hours.

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

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

Stability

Storage

Oral

Capsules and Tablets

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

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

Parenteral

Solution for Injection

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

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

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

Actions

  • Mechanism of antiplatelet effects not fully elucidated.

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

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

  • Prolongs platelet survival time in patients with prosthetic heart valves or valvular heart disease in whom platelet survival is shortened.

  • Mediates coronary vasodilation by inhibiting reuptake and thereby allowing accumulation of adenosine in vascular smooth muscle.

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

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

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

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

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.

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.

  • Importance of informing patients of other important precautionary information. (See Cautions.)

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 2021, Selected Revisions September 18, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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