Thromboembolism Associated with Prosthetic Heart Valves
Used as an adjunct to coumarin anticoagulants for the prevention of postoperative thromboembolic complications of heart valve replacement. Data are insufficient to recommend the use of dipyridamole over the combination of low-dose aspirin and warfarin in such patients.
Should not be used alone, without an oral anticoagulant, in patients with prosthetic heart valves.
Cerebral Thromboembolism
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.
American College of Chest Physicians (ACCP), American Stroke Association (ASA), and AHA consider the fixed combination of aspirin and extended-release dipyridamole an acceptable option for initial antiplatelet therapy for secondary prevention of noncardioembolic ischemic stroke and TIAs. In such patients, ACCP, ASA, and AHA suggest the combination of aspirin and extended-release dipyridamole or clopidogrel alone over therapy with aspirin alone.
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.
ACC and AHA recommend myocardial stress perfusion imaging with dipyridamole or adenosine or dobutamineechocardiography before or early after hospital discharge in patients with ST-segment elevation MI who are not undergoing cardiac catheterization and who are unable to exercise.
Embolism Associated with Valvular Heart Disease
ACCP recommends use as an adjunct to oral anticoagulation to prevent breakthrough thromboembolic complications in aspirin-intolerant patients with rheumatic mitral valve disease with atrial fibrillation or a history of recurrent systemic embolism†.
Dosage and Administration
Administration
Administer orally or IV.
Oral Administration
Conventional tablets: Administer 4 times daily.
Extended-release dipyridamole and aspirin fixed-combination capsules: Administer 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.
Cerebral Thromboembolism
Secondary Prevention
Oral
Fixed combination with aspirin: 200 mg of extended-release dipyridamole and 25 mg of aspirin (one capsule) twice daily in the morning and evening.
Dose of aspirin in fixed-combination product may not be adequate to prevent recurrent MI or angina pectoris in patients with stroke or TIA.
Embolism Associated with Valvular Heart Disease
Rheumatic Mitral Valve Disease and History of Systemic Embolism or Atrial Fibrillation with aspirin intolerance
Oral
400 mg daily.†
Oral
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 when near maximal vasodilatory effect is achieved.
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.
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). 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.
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 with tablets.
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 in children not established; should not be used in pediatric patients because of aspirin component.
Injection: Safety and efficacy in children not established.
Possible increased risk of bleeding, particularly during or after surgery
Some clinicians recommend maintenance of PT in the lower end of the therapeutic range
Pharmacokinetics
Absorption
Bioavailability
Conventional tablets: Oral bioavailability is 37–66%.
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
Extended-release capsules containing 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 in 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).
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 reuptake 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.
Weakly 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 little if any increase in blood flow in stenotic arteries (“coronary steal”). Myocardial oxygen consumption not markedly affected and cardiac work not decreased.
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. May decrease myocardial perfusion distal to stenotic coronary arteries.
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.
This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 09/2009. For the most current and up-to-date pricing information, please visit www.drugstore.com. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.
† Use is not currently included in the labeling approved by the US Food and Drug Administration.
Remember, keep this and all other medicines out of the reach of children,
never share your medicines with others, and use this medication only for the indication prescribed.
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