ATC Class:36:18
Dipyridamole is a non-nitrate coronary vasodilator that also inhibits platelet aggregation.100, 170, 171, 172
Dipyridamole is used orally as an adjunct to coumarin anticoagulants (e.g., warfarin) in the prevention of postoperative thromboembolic complications of heart valve replacement.100, 101, 103, 104, 105, 106, 107, 108 Because warfarin therapy alone may not completely prevent thrombosis in patients with mechanical prosthetic heart valves, dipyridamole has been used in conjunction with warfarin in an effort to reduce the risk of thrombosis in these patients.101, 103, 104, 105, 106, 107, 108 While some evidence suggests that dipyridamole used in conjunction with warfarin may be more effective in reducing postoperative thromboembolic events in patients with mechanical prosthetic heart valves than use of warfarin alone,100, 101, 103, 104, 105, 106, 107, 108 the American College of Chest Physicians (ACCP) and other experts generally recommend the addition of low-dose aspirin (rather than dipyridamole) to warfarin therapy in such patients.990, 996, 1008 (See Thrombosis: Prosthetic Heart Valves, under Uses, in Aspirin 28:08.04.24.) Dipyridamole should not be used alone, without warfarin, for the prevention of postoperative thromboembolic complications in patients undergoing placement of mechanical prosthetic heart valves since there is no evidence to date that dipyridamole (or other platelet-aggregation inhibitors) would be effective when used alone.101, 105, 108, 109, 140, 141, 142
Transient Ischemic Attacks and Completed Thrombotic Stroke
Extended-release dipyridamole in fixed combination with aspirin is used to reduce the risk of stroke in patients who have had transient ischemic attacks (TIAs) or completed thrombotic stroke (secondary prevention).145, 146, 148, 990, 1009
In a randomized, comparative, placebo-controlled study, patients who had experienced either an ischemic stroke or TIAs were assigned to receive treatment with aspirin (25 mg twice daily), extended-release dipyridamole (200 mg twice daily), aspirin plus extended-release dipyridamole (25 and 200 mg twice daily, respectively), or placebo.145, 148 All active treatments reduced the risk of the primary end points of stroke (nonfatal or fatal) or stroke and/or death compared with placebo.148 Aspirin plus dipyridamole reduced the risk of stroke by about 23% compared with aspirin alone and by about 25% compared with dipyridamole alone at 2 years of follow-up; the effects of combined therapy on risk reductions with aspirin and dipyridamole were additive but not synergistic.148 Aspirin, dipyridamole, and the combination also reduced the incidence of TIAs and other vascular events in a manner consistent with these treatments' effects on the risk of stroke.148 None of the treatments had a statistically significant effect on the end point of death (i.e., no effect on survival).145, 148 Headache and GI events were the most common adverse effects in this study, occurring more frequently in the dipyridamole-treated groups, while bleeding from the GI tract or from any site was more common in the aspirin-treated groups.148
ACCP, the American Stroke Association (ASA), and the American Heart Association (AHA) recommend antiplatelet therapy for secondary prevention of ischemic atherothrombotic (noncardioembolic) stroke or TIAs in patients with prior TIAs or stroke.150, 990, 1009 (See Transient Ischemic Attacks and Acute Ischemic Stroke under Uses: Thrombosis, in Aspirin 28:08.04.24.) These experts consider the combination of aspirin and dipyridamole (25 mg aspirin/200 mg extended-release dipyridamole twice daily) an acceptable antiplatelet option for the prevention of recurrent stroke or other cardiovascular events in such patients; other options include aspirin monotherapy, cilostazol, or clopidogrel.150, 990, 1009 When selecting an appropriate antiplatelet regimen for the secondary prevention of noncardioembolic stroke, factors such as the patient's individual risk for recurrent stroke, tolerance, and cost of the different agents should be considered.990
Adjunct to Thallium Myocardial Perfusion Imaging
Dipyridamole is used IV as an adjunct to thallous (thallium) chloride Tl 201 myocardial stress perfusion imaging in patients unable to exercise adequately.158, 159
The sensitivity and specificity of dipyridamole-assisted thallium imaging versus coronary arteriography in the detection of coronary artery disease were determined by comparing the results of thallium imaging with those of coronary arteriography under blinded conditions.158 The sensitivity of dipyridamole-assisted thallium imaging (true positive thallium imaging divided by the number of patients with positive angiograms) was 85% and the specificity (true negative thallium imaging divided by the number of patients with negative angiograms) was about 50%.158 In a subset of patients who had exercise thallium imaging or dipyridamole-assisted thallium imaging, the sensitivity and specificity of the 2 tests were almost identical.158
Dipyridamole also has been used orally to decrease platelet aggregation in a number of other thromboembolic disorders†. ACCP suggests postoperative anticoagulant therapy with unfractionated heparin and antiplatelet therapy with aspirin and/or dipyridamole to reduce thromboembolic events in children with heart failure who require implantation of ventricular assist devices†.1013 However, for most thromboembolic disorders, it has not been established whether the inclusion of dipyridamole in an antithrombotic regimen substantially enhances the potential benefit compared with that of the other antithrombotic agents (e.g., aspirin) alone,101, 103, 106, 107, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 131, 132, 133, 134 and some evidence suggests that in certain disorders, it may not (e.g., for prevention of thromboembolic complications in patients surviving a myocardial infarction (MI) or following PCI, coronary artery bypass graft [CABG] surgery, lower extremity vascular reconstruction).101, 103, 114, 117, 118, 119, 122, 131, 133, 134, 163
ACCP recommends the use of dipyridamole in combination with aspirin as an option for long-term antiplatelet therapy in patients with symptomatic carotid stenosis†, including those who have undergone recent carotid endarterectomy.1011
There currently is no evidence that antiplatelet agents such as dipyridamole or ticlopidine have any advantage over aspirin for mortality reduction following an acute MI†.
Dipyridamole has been used in the long-term therapy of chronic angina pectoris† based on the premise that prolonged therapy with the drug may reduce the frequency of or eliminate anginal episodes, improve exercise tolerance, and reduce requirements for nitroglycerin. However, well-controlled clinical studies showed that long-term oral administration of dipyridamole does not prevent ECG signs of myocardial ischemia in patients with angina pectoris following exercise or decrease the frequency or severity of anginal attacks, and experts state that there is evidence and/or general agreement that dipyridamole is not useful or effective for the management of chronic angina pectoris. The drug also is not effective for the treatment of acute episodes of angina† and is not a substitute for appropriate medical programs for the treatment of angina pectoris†.
Dipyridamole is administered orally or IV.100, 158 Capsules containing the fixed-combination of extended-release dipyridamole and aspirin should be swallowed whole and should not be chewed.145 The fixed-combination capsules containing extended-release dipyridamole and aspirin may be administered without regard to food.145
Prior to IV administration, dipyridamole injection should be diluted in at least twice the injection volume 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 Infusion of undiluted dipyridamole may cause local irritation.158
The usual adult oral dosage of dipyridamole for adjunctive use with coumarin anticoagulant (e.g., warfarin) therapy in the prevention of postoperative thromboembolic complications of cardiac valve replacement is 75-100 mg 4 times daily.100, 101, 104, 105, 106, 107, 108
For the prevention of thromboembolic complications in patients with various other thromboembolic disorders†, oral dosage of dipyridamole generally has ranged from 150-400 mg daily, in combination with another platelet-aggregation inhibitor (e.g., aspirin) or warfarin.
For reducing the risk of stroke in patients who have had transient ischemic attacks (TIAs) or completed stroke caused by thrombosis, the usual dosage of oral extended-release dipyridamole is 200 mg in fixed combination with aspirin 25 mg (1 capsule) twice daily in the morning and evening.145, 1009 If headaches become intolerable during initial treatment, the dosage of the dipyridamole/aspirin fixed combination should be reduced to 200 mg of dipyridamole and 25 mg of aspirin (1 capsule) once daily at bedtime and low-dose aspirin should be administered in the morning.145 Because no outcome data are available with this regimen and headaches diminish during continued treatment, patients should 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).145 The amount of aspirin in the fixed-combination preparation may not be adequate to prevent recurrent myocardial infarction (MI) or angina pectoris in patients with stroke or TIA.145
When used as an adjunct to thallium myocardial imaging, dipyridamole usually is administered as a single IV dose of 0.57 mg/kg, infused at a rate of 0.142 mg/kg per minute for 4 minutes.100 Although the maximum tolerated IV dose of dipyridamole has not been determined, clinical experience suggests that a total dose exceeding 60 mg is not needed for any patient.158 Thallium-201 should be injected within 5 minutes following completion of the dipyridamole infusion.158
Adverse effects associated with oral dipyridamole therapy are generally dose related and reversible and may include headache,100 dizziness,100 GI intolerance (e.g., abdominal distress),100 nausea,100 vomiting, diarrhea,100 peripheral vasodilation, flushing,100 weakness, syncope, rash,100 and pruritus.100 Headache is the most common adverse effect of dipyridamole and is most notable during the first month of treatment.145 (See Dosage and Administration: Dosage, for details on dosage adjustment for headache.) Rarely, angina pectoris or aggravation of angina pectoris100 has been reported, usually at the beginning of therapy. During postmarketing experience, hypersensitivity reactions (e.g., rash, urticaria, severe bronchospasm, angioedema), laryngeal edema, fatigue, myalgia, arthritis, nausea, dyspepsia, paresthesia, hepatitis, thrombocytopenia, alopecia, cholelithiasis, hypotension, palpitation, and tachycardia have been reported rarely.100 Most adverse effects of oral dipyridamole are transient and resolve during long-term therapy with the drug; rarely, adverse effects are persistent or intolerable but are reversible when the drug is discontinued.100 In a large randomized, comparative, placebo-controlled trial, there was no clear safety benefit of treatment with extended-release dipyridamole in fixed combination with aspirin compared with aspirin alone.145
Liver dysfunction (e.g., elevations of hepatic enzymes, hepatic failure) have been reported rarely in association with oral dipyridamole.100
IV dipyridamole has been associated with serious adverse effects, including acute myocardial ischemia or infarction, cardiac death, ventricular fibrillation, symptomatic ventricular tachycardia, stroke, transient cerebral ischemia, and seizures.158 Asystole, sinus node arrest, sinus node depression, and conduction block also have been reported with IV dipyridamole therapy.158 Patients with abnormalities of cardiac impulse formation and conduction or severe coronary artery disease (e.g., unstable angina) may be at increased risk for these events.158 Anaphylactoid reactions and bronchospasm also have been reported in patients with coronary artery disease undergoing IV dipyridamole-assisted thallium imaging.158 Patients with a history of asthma may be at greater risk for bronchospasm during IV dipyridamole use.158
The most common adverse effects reported in a large clinical trial in which IV dipyridamole was used as an adjunct to thallium myocardial perfusion imaging were chest pain/angina pectoris, electrocardiographic changes (most commonly ST-T changes), headache, and dizziness.158 Other adverse effects occurring in greater than 1% of patients receiving IV dipyridamole were hypotension, nausea, flushing, dyspnea, unspecified pain, blood pressure lability, hypertension, paresthesia, and fatigue.158 Cardiovascular adverse effects occurring in 1% or less of patients receiving IV dipyridamole included unspecified ECG abnormalities, unspecified arrhythmia, palpitation, ventricular tachycardia, bradycardia, myocardial infarction (MI), atrioventricular block, syncope, orthostatic hypotension, atrial fibrillation, supraventricular tachycardia, ventricular arrhythmia unspecified, heart block unspecified, cardiomyopathy, intermittent claudication, and edema.158 Nervous system adverse effects occurring in 1% or less of patients receiving IV dipyridamole included hypoesthesia, hypertonia, nervousness/anxiety, tremor, abnormal coordination, somnolence, dysphonia, migraine, malaise, asthenia, depersonalization, and vertigo.158 GI system adverse effects occurring in 1% or less of patients receiving IV dipyridamole included dyspepsia, dry mouth, abdominal pain, flatulence, vomiting, eructation, dysphagia, tenesmus, dysgeusia, thirst, and increased appetite.158 Respiratory system adverse effects occurring in 1% or less of patients receiving IV dipyridamole included pharyngitis, bronchospasm, hyperventilation, rhinitis, coughing, and pleural pain.158 Musculoskeletal system adverse effects occurring in 1% or less of patients receiving IV dipyridamole included myalgia, back pain, arthralgia, rigor, and leg cramping.158 Other adverse effects occurring in 1% or less of patients receiving IV dipyridamole include unspecified injection site reaction, diaphoresis, injection site pain, earache, tinnitus, unspecified vision abnormalities, eye pain, renal pain, perineal pain, and breast pain.158 Allergic reactions including urticaria, pruritus, dermatitis, and rash have been reported rarely during postmarketing experience.158
Precautions and Contraindications
When dipyridamole is used orally in fixed combination with aspirin, the cautions, precautions, and contraindications associated with aspirin therapy must be considered in addition to those associated with dipyridamole.
Dipyridamole is contraindicated in patients with hypersensitivity to dipyridamole or any ingredient in the formulation.100, 145, 158
Dipyridamole should be used cautiously in patients with hypotension or severe coronary artery disease (e.g., unstable angina or recently sustained MI) since it can cause peripheral vasodilation.100, 145
In considering the use of IV dipyridamole-assisted thallium imaging in patients with coronary artery disease, the important clinical information to be gained by the procedure should be weighed against the risk to the patient. 158 The rate of false positive and false negative results of IV dipyridamole-assisted thallium imaging as compared with coronary arteriography should also be considered when choosing to use dipyridamole-assisted thallium imaging.158
When thallium myocardial perfusion imaging is performed with IV dipyridamole, parenteral aminophylline (an adenosine receptor antagonist) should be readily available for relieving adverse effects such as bronchospasm or chest pain.158 Vital signs should be monitored during and for 10-15 minutes after IV infusion of dipyridamole, and an ECG should be obtained using at least 1 chest lead.158 Should severe chest pain or bronchospasm occur, parenteral aminophylline should be administered by slow IV injection (e.g., 50-100 mg over 30-60 seconds) in doses of 50-250 mg.158 Patients with severe hypotension should be placed in a supine position with the head tilted down, if necessary, before administration of parenteral aminophylline.158 If the highest recommended dosage of aminophylline (250 mg) does not relieve chest pain within a few minutes, sublingual nitroglycerin may be administered.158 If chest pain continues despite such combination therapy, the possibility of MI should be considered.158 If the clinical condition of the patient with an adverse event permits a 1-minute delay, thallium imaging may be performed during such a time period before reversal of the pharmacologic effects of dipyridamole.158
Commercially available 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
For patients with stroke or TIA for whom aspirin is indicated to prevent recurrent MI or angina pectoris, the amount of aspirin in the commercially available fixed-combination product may not provide adequate treatment for these cardiac indications.145
Safety and efficacy of oral dipyridamole in pediatric patients younger than 12 years of age have not been established.100 Safety and efficacy of IV dipyridamole in children have not been established.158 The safety and efficacy of extended-release dipyridamole in fixed combination with aspirin in children have not been established.145 The manufacturer of Aggrenox® states that because of the aspirin component, this preparation should not be used in pediatric patients.145 (See Cautions: Pediatric Precautions, in the Salicylates General Statement 28:08.04.24.).
Mutagenicity and Carcinogenicity
Studies using dipyridamole have not revealed evidence of mutagenicity.100 No evidence of significant carcinogenic effects was seen in mice or rats receiving 111 or 128-142 weeks, respectively, of oral dipyridamole in dosages not exceeding 75 mg/kg (1 or 2 times the maximum recommended daily human oral dosage in mice or rats, respectively, on a mg/m2 basis).100 In vitro mutagenicity tests using dipyridamole in bacterial and mammalian cell systems also did not reveal evidence of mutagenicity.100, 158
Pregnancy, Fertility, and Lactation
Safe use of dipyridamole during pregnancy has not been established.100 Reproduction studies in mice receiving dipyridamole dosages up to 125 mg/kg daily (1.5 times the maximum recommended daily human oral dosage on a mg/m2 basis), rats receiving dosages not exceeding 1000 mg/kg daily (25 times the maximum recommended daily human oral dosage on a mg/m2 basis), and rabbits receiving dosages not exceeding 40 mg/kg daily (2 times the maximum recommended daily human oral dosage on a mg/m2 basis) have not revealed evidence of harm to the fetus.100 There are no adequate and controlled studies to date using dipyridamole in pregnant women, and the drug should be used during pregnancy only when clearly needed.100 Extended-release dipyridamole in fixed combination with aspirin should be avoided in the third trimester of pregnancy and during labor and delivery because of the aspirin component of this preparation; aspirin has been shown to be teratogenic in animals and to cause fetal harm when administered to a pregnant woman.145 If dipyridamole in fixed combination with aspirin is used during pregnancy or the patient becomes pregnant while taking the fixed combination, the patient should be apprised of the potential hazard to the fetus.145 (See Cautions: Pregnancy, Fertility, and Lactation, in the Salicylates General Statement 28:08.04.24.)
Reproduction studies in rats receiving dipyridamole dosages up to 12 times the maximum recommended daily human oral dosage on a mg/m2 basis have not revealed evidence of impaired fertility.100 However, a substantial reduction in the number of corpora lutea with a subsequent reduction in the number of implantations and live fetuses was observed in rats receiving 30 times the maximum recommended daily human oral dosage of the drug on a mg/m2 basis.100
Because dipyridamole is distributed into milk, the drug should be used with caution in nursing women.100
Since dipyridamole may inhibit platelet aggregation, heparin and dipyridamole should be used concomitantly with caution and patients should be monitored closely to prevent bleeding; however, the actual incidence of this reaction has not been established.166, 167
In a dosage of 400 mg daily, dipyridamole does not affect prothrombin time and can be administered with warfarin. Concomitant use of dipyridamole and warfarin does not appear to increase the frequency or severity of bleeding compared with use of warfarin alone.100 However, in rare instances, increased bleeding during or after surgery has been observed during such concurrent therapy.100 Some clinicians recommend maintenance of prothrombin time in the lower end of the therapeutic range during concomitant administration of these drugs to avoid possible bleeding.
Dipyridamole may increase the plasma concentrations and the cardiovascular effects of adenosine; adjustment of adenosine dosage may be necessary.100, 169 Methylxanthines are competitive adenosine receptor antagonists,158, 159, 165 and aminophylline has been used effectively to terminate persistent adverse effects of dipyridamole.158 Use of other xanthine derivatives (e.g., caffeine) or maintenance dosages of oral theophylline may abolish the coronary vasodilation of dipyridamole and lead to false negative thallium imaging results.158, 165 (See Pharmacology.)
In patients receiving an anticholinesterase agent for the treatment of myasthenia gravis, concomitant use of dipyridamole may counteract the anticholinesterase effects of such inhibitors and potentially aggravate myasthenia gravis.100, 158
Limited information is available on the acute toxicity of dipyridamole in humans. The oral LD50 of the drug exceeds 6 g/kg in rats and approximately 400 mg/kg in dogs.100 Overdosage of dipyridamole is likely to produce symptoms that are mainly extensions of the usual pharmacologic effects of the drug. Based on the known hemodynamic effects of dipyridamole, symptoms such as warm feeling, flushes, sweating, restlessness, feelings of weakness, or dizziness may occur.100 Hypotension and tachycardia might also be observed.100 Overdosage with IV dipyridamole has not been reported.158
In cases of overdosage, seek medical attention immediately; careful medical management is essential.100 Symptomatic treatment of overdosage is recommended and may include use of a vasopressor.100 Gastric lavage should be considered.100 Administration of a xanthine derivative (e.g., aminophylline) may reverse the hemodynamic effects of dipyridamole.100 Dialysis is not likely to be of benefit in the management of dipyridamole overdosage since the drug is highly protein bound.100
The coronary vasodilator effect of dipyridamole probably results from its ability to inhibit cellular reuptake of adenosine, thereby increasing extracellular concentrations of endogenous adenosine available for receptor binding and vascular vasodilation.158, 165, 182 The vasodilatory effects of dipyridamole are abolished by the adenosine receptor antagonists theophylline and aminophylline.158, 165 (See Drug Interactions.) Dipyridamole also may cause vasodilation by delaying the hydrolysis of cyclic 3',5'-adenosine monophosphate (cAMP) by inhibiting the enzyme phosphodiesterase.
The mechanism(s) by which dipyridamole inhibits platelet aggregation has not been fully elucidated.100, 101, 134, 170, 171 The mechanism(s) may be related to inhibition of platelet uptake and metabolism of adenosine (an inhibitor of platelet reactivity); inhibition of platelet phosphodiesterase, which leads to accumulation of cAMP within platelets; direct stimulation of the release of eicosanoids such as prostacyclin or prostaglandin D2 from endothelial cells; and/or inhibition of thromboxane A2 formation.100, 101, 108, 133, 134, 145, 170, 171 Increased local concentrations of adenosine at the platelet surface act on the platelet A2 receptor and stimulate platelet adenyl cyclase, thereby increasing platelet 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, 145, 170, 171 Therapeutic concentrations of dipyridamole inhibit platelet cyclic-3',5'-guanosine monophosphate phosphodiesterase (cGMP-PDE), thereby augmenting the increase in platelet cGMP concentrations produced by nitric oxide.100, 145, 171, 182 Increased cGMP platelet concentrations inhibit platelet activation and aggregation.171, 182 Dipyridamole also stimulates prostacyclin synthesis and potentiates the antiplatelet effects of prostacyclin.171 Dipyridamole prolongs platelet survival time in patients with valvular heart disease in whom platelet survival is shortened.100
The mechanism by which IV dipyridamole-induced vasodilation aids in thallium myocardial perfusion imaging has not been fully elucidated, but may be a result of a “coronary steal” phenomenon in which normal coronary arteries dilate and sustain increased blood flow while shunting blood away from stenotic arteries.158, 165 Because myocardial uptake of thallous (thallium) chloride Tl 201 is directly proportional to coronary blood flow,159, 165 relatively less thallous chloride Tl 201 uptake159 as well as slower washout160 occurs in myocardium perfused by stenotic versus normal coronary arteries and the differences in blood flow between areas served by stenotic versus normal arteries are enhanced during thallium testing with dipyridamole infusion.158, 159, 160, 165 Myocardial oxygen consumption and cardiac work are not increased.165
IV dipyridamole may decrease blood pressure and increase heart rate and cardiac output, because of dilation of systemic resistance vessels.158, 170 However, usual oral doses of the drug generally produce no change in blood pressure or in blood flow in peripheral arteries.170
Oral dipyridamole is incompletely absorbed from the GI tract; the extent of absorption exhibits interindividual variation.101, 134, 135, 137, 138, 171 According to the manufacturer, the pharmacokinetics of dipyridamole and aspirin are not altered by concomitant administration in fixed combination.145, 145 Following oral administration of a dose of dipyridamole as conventional tablets, peak plasma concentrations of the drug are attained in about 45-150 minutes (mean: 75 minutes).100, 134, 135, 136, 138 The mean serum concentration of dipyridamole 2 minutes following administration of an IV dose of dipyridamole (0.568 mg/kg infused over 4 minutes) was 4.6 mcg/mL.158 Following oral administration of 200 mg of extended-release dipyridamole in fixed combination with aspirin, oral bioavailability of dipyridamole averages 37-66%171 and peak plasma dipyridamole concentrations are achieved in about 2 hours (range: 1-6 hours) with twice-daily dosing.145 Steady-state peak and trough plasma concentrations of dipyridamole average 1.98 and 0.53 mcg/mL, respectively, following administration as the fixed-combination extended-release capsules.145 When dipyridamole in fixed combination with aspirin was administered with a high-fat meal, dipyridamole peak plasma concentrations and total absorption (area under the concentration-time curve [AUC]) decreased at steady state by 20-30% compared with administration in the fasted state; this effect does not appear to be clinically important.145
Animal studies indicate that dipyridamole is widely distributed into body tissues and that small amounts of the drug cross the placenta. Dipyridamole does not cross the blood-brain barrier in animals.171, 173 Dipyridamole is distributed into human milk.100, 172, 173 The apparent volume of distribution of IV dipyridamole at steady state is 1-2.5 L/kg, with an apparent central volume of 3-5 liters.158 The drug is highly bound to plasma proteins, principally to α1-acid glycoprotein (α1-AGP) but also to albumin;158, 161, 162 91-99% of the drug reportedly is bound to protein.101, 134, 138, 139, 158, 171
Following oral administration, plasma concentrations of dipyridamole decline in a biphasic manner.100, 134, 136, 137, 138 Half-life of the drug in the initial phase (t½α) is approximately 40-80 minutes and half-life in the terminal elimination phase (t½β) is approximately 10-12 hours.100, 101, 134, 138
Following IV administration, plasma concentrations of dipyridamole decline in a triphasic manner, with mean half-lives of 3-12 minutes, 33-62 minutes, and 11.6-15 hours.158
Dipyridamole is metabolized in the liver and excreted in the bile, chiefly as the monoglucuronide and a small amount as the diglucuronide. Dipyridamole and its glucuronides may undergo enterohepatic circulation and are excreted mainly in feces. Small amounts are excreted in urine. The mean total body clearance is 2.3-3.5 mL/minute per kg.158
Dipyridamole is a non-nitrate coronary vasodilator. Dipyridamole occurs as an intensely yellow, crystalline powder or needles with a bitter taste. The drug is slightly soluble in water and very soluble in alcohol. Dipyridamole is commercially available as conventional tablets and in fixed combination with aspirin as a hard-gelatin capsule containing dipyridamole as extended-release pellets and aspirin as an immediate-release tablet. 100, 145 Dipyridamole injection is an odorless pale yellow liquid.158
Dipyridamole tablets should be stored in tight, light-resistant containers at a 25°C; excursions to 15-30°C are permitted.100 The fixed-combination preparation of extended-release dipyridamole with aspirin should be stored at a controlled room temperature of 25°C and protected from excessive moisture, but may be exposed to temperatures ranging from 15-30°C.145
Dipyridamole injection should be stored at 20-25°C; freezing should be avoided, and the injection should be protected from light.158 Dipyridamole should not be mixed with other drugs in the same syringe or infusion container.158 Parenteral drugs should be inspected visually for particulate matter and discoloration prior to administration, whenever container and solution permit.158
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.
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.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets | 25 mg* | ||
50 mg* | Dipyridamole Tablets | |||
Persantine® | Boehringer Ingelheim | |||
75 mg* | Dipyridamole Tablets | |||
Persantine® | Boehringer Ingelheim | |||
Parenteral | Injection, for IV Use | 5 mg/mL | Dipyridamole Injection |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
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 | Boehringer Ingelheim |
Only references cited for selected revisions after 1984 are available electronically.
100. Boehringer Ingelheim Pharmaceuticals, Inc. Persantine® (dipyridamole) prescribing information. Ridgefield, CT: 2006 June 20.
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