Evaluation of coronary artery disease, diagnostic agent : IV: 0.56 mg/kg over 4 minutes; maximum dose: 70 mg/day. Following completion of dipyridamole infusion, inject radiotracer (eg, thallium-201) in 3 to 5 minutes. Note: To reverse complications and side effects of dipyridamole, aminophylline should be available for urgent/emergent use (ASNC [Henzlova 2016]).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustment provided in manufacturer’s labeling.
Hemodialysis: Not dialyzable (NCS/SCCM [Frontera 2016])
There are no dosage adjustment provided in manufacturer’s labeling.
(For additional information see "Dipyridamole: Pediatric drug information")
Antiplatelet, general dosing: Limited data available: Infants, Children, and Adolescents: Oral: 2 to 6 mg/kg/day in 3 divided doses; usual adult maximum dose: 100 mg/dose (Park 2014).
Antiplatelet, mechanical prosthetic heart valves: Note: Although FDA approved for this indication, expert recommendations do not include dipyridamole as a first-line option for thrombotic prophylaxis for mechanical prosthetic heart valves in pediatric patients; vitamin K antagonists with other antiplatelet agents (eg, low-dose aspirin) are recommended (ACCP [Monagle 2012]; ACCP [Whitlock 2012]). Limited data available: Infants, Children, and Adolescents: Oral: 2 to 5 mg/kg/day in divided doses, most commonly in 3 divided doses (ACCP [Monagle 2012]; Park 2014).
Cardiac perfusion scans: Limited data available: Children ≥6 years and Adolescents: IV: 0.56 mg/kg administered over 4 minutes; maximum adult dose: 70 mg/dose (ASNC [Henzlova 2016]; Vijarnsorn 2017). Note: To reverse complications and side effects of dipyridamole, aminophylline should be available for urgent/emergent use (ASNC [Henzlova 2016]).
Proteinuria (IgA nephropathy, Henoch-Schönlein purpura), adjunct therapy: Limited data available: Children ≥7 years and Adolescents: Oral: Initial: 3 to 5 mg/kg/day in 3 divided doses; may titrate to reported range: 5 to 6 mg/kg/day in 3 divided doses; maximum daily dose: 400 mg/day; in trials dipyridamole was given as part of a 3 or 4 drug combination therapy (eg, immunosuppressant agents, antihypertensive agents, and an anticoagulant) (Kamei 2011; Kano 2003; Ninchoji 2011; Yoshikawa 2008). Note: Antiplatelet therapy is not recommended by national guidelines because efficacy results in trials cannot be directly associated with dipyridamole as opposed to the other agents in the drug regimen (KDIGO 2012).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; however, dipyridamole is likely not dialyzable secondary to high protein binding (99% protein bound).
There are no dosage adjustments provided in the manufacturer's labeling.
Refer to adult dosing.
IV: Dosing is not well established; it is customary to use weight-based doses up to a weight of 125 kg (maximum dose: 70 mg/day) (ASNC [Henzlova 2016]).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Generic: 5 mg/mL (10 mL)
Tablet, Oral:
Generic: 25 mg, 50 mg, 75 mg
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Intravenous:
Persantine: 5 mg/mL (10 mL)
Generic: 5 mg/mL (2 mL, 10 mL)
Tablet, Oral:
Generic: 25 mg [DSC], 50 mg [DSC], 75 mg [DSC]
IV: Infuse diluted solution over 4 minutes.
Oral: Administer without regard to meals.
IV: Infuse diluted solution over 4 minutes.
Evaluation of coronary artery disease, diagnostic agent (IV): Diagnostic agent for evaluation of coronary artery disease.
Dipyridamole may be confused with disopyramide
Persantine may be confused with Periactin
Beers Criteria: Dipyridamole (oral, short-acting formulation; does not apply to the extended-release combination with aspirin) is identified in the Beers Criteria as a potentially inappropriate medication to be avoided in patients 65 years and older (independent of diagnosis or condition) due to its potential for causing orthostatic hypotension and availability of more effective alternatives. Of note, dipyridamole intravenous is acceptable for use in cardiac stress testing (Beers Criteria [AGS 2019]).
Pharmacy Quality Alliance (PQA): Dipyridamole (oral, short-acting formulation; does not apply to the extended-release combination with aspirin) is identified as a high-risk medication in patients 65 years and older on the PQAs Use of High-Risk Medications in the Elderly (HRM) performance measure, a safety measure used by the Centers for Medicare and Medicaid Services (CMS) for Medicare plans (PQA 2017).
Persantine [US, Canada, Belgium, Denmark, France] may be confused with Permitil brand name for sildenafil [Argentina]
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Oral: Frequency not always defined.
Cardiovascular: Angina pectoris, flushing
Central nervous system: Dizziness (14%), headache (2%)
Dermatologic: Skin rash (2%), pruritus
Gastrointestinal: Abdominal distress (6%), diarrhea, vomiting
Hepatic: Hepatic insufficiency
Postmarketing and/or case reports: Alopecia, arthritis, cholelithiasis, dyspepsia, fatigue, hepatitis, hypersensitivity reaction, hypotension, laryngeal edema, malaise, myalgia, nausea, palpitations, paresthesia, tachycardia, thrombocytopenia
IV:
>10%:
Cardiovascular: Exacerbation of angina pectoris (20%)
Central nervous system: Dizziness (12%), headache (12%)
1% to 10%:
Cardiovascular: ECG abnormality (5% to 8%; ST-T changes, extrasystoles), hypotension (5%), flushing (3%), tachycardia (3%), altered blood pressure (2%), hypertension (2%)
Central nervous system: Pain (3%), fatigue (1%), paresthesia (1%)
Gastrointestinal: Nausea (5%)
Respiratory: Dyspnea (3%)
<1%, postmarketing, and/or case reports (Limited to important or life-threatening): Abdominal pain, arthralgia, ataxia, back pain, bronchospasm, cardiac arrhythmia (ventricular tachycardia, bradycardia, AV block, SVT, atrial fibrillation, asystole), cardiomyopathy, cough, depersonalization, diaphoresis, dysgeusia, dyspepsia, dysphagia, ECG abnormality (unspecified), edema, eructation, flatulence, hypersensitivity reaction, hypertonia, hyperventilation, increased appetite, increased thirst, injection site reaction, leg cramps (intermittent claudication), malaise, mastalgia, muscle rigidity, myalgia, myocardial infarction, orthostatic hypotension, otalgia, palpitations, perineal pain, pharyngitis, pleuritic chest pain, pruritus, renal pain, rhinitis, skin rash, syncope, tenesmus, tinnitus, tremor, urticaria, vertigo, visual disturbance, vomiting, weakness, xerostomia
Hypersensitivity to dipyridamole or any component of the formulation.
Canadian labeling: Additional contraindications (not in the US labeling): Injection: shock; circulatory collapse.
According to the American Society of Nuclear Cardiology (ASNC) the following are additional contraindications for dipyridamole stress testing (ASNC [Henzlova 2016]): Bronchospastic lung disease with ongoing wheezing or history of significant reactive airway disease; systolic BP <90 mm Hg; uncontrolled hypertension (systolic BP >200 mm Hg or diastolic BP >110 mm Hg); ingestion of caffeinated foods or beverages within the last 12 hours; unstable angina, acute coronary syndrome, or myocardial infarction within 2 to 4 days. Relative contraindications include: Heart rate <40 beats/minute; second- or third-degree heart block without a pacemaker; severe aortic stenosis; seizure disorder (cannot receive aminophylline).
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with hypotension, unstable angina, and/or recent myocardial infarction; may enhance exercise induced myocardial ischemia in patients with chronic stable angina.
• Hepatic impairment: Use with caution in patients with hepatic impairment.
Concurrent drug therapy issues:
• Antiplatelet agents/anticoagulants: Use with caution in patients on other antiplatelet agents or anticoagulation.
• Pharmacologic stress testing: Interrupt oral dipyridamole therapy for 48 hours prior to stress testing with adenosine, IV dipyridamole, or regadenoson; may increase risk for cardiovascular adverse effects and impair the test sensitivity.
Dosage form specific issues:
• Injection: Severe adverse reactions have occurred rarely with IV administration. Use the IV form with caution in patients with bronchospastic disease or unstable angina. Have aminophylline ready in case of urgency or emergency with IV use.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Abrocitinib: Agents with Antiplatelet Properties may enhance the antiplatelet effect of Abrocitinib. Management: Do not use antiplatelet drugs with abrocitinib during the first 3 months of abrocitinib therapy. The abrocitinib prescribing information lists this combination as contraindicated. This does not apply to low dose aspirin (81 mg/day or less). Risk X: Avoid combination
Acalabrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Acetylcholinesterase Inhibitors: Dipyridamole may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Risk C: Monitor therapy
Adenosine: Dipyridamole may enhance the adverse/toxic effect of Adenosine. Specifically, cardiovascular effects of adenosine may be enhanced. Adenosine dose reduction may be needed. Management: For patients requiring pharmacologic stress testing with adenosine, hold dipyridamole tablets for 48 hours. Hold aspirin/dipyridamole capsules for 24 to 48 hours. For treatment of SVT, monitor for prolonged adenosine effects, consider lower initial doses. Risk D: Consider therapy modification
Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the antiplatelet effect of other Agents with Antiplatelet Properties. Risk C: Monitor therapy
Anticoagulants: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Apixaban: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Apixaban. Specifically, the risk for bleeding may be increased. Management: Carefully consider risks and benefits of this combination and monitor closely. Risk C: Monitor therapy
Bemiparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Bemiparin. Management: Avoid concomitant use of bemiparin with antiplatelet agents. If concomitant use is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification
Beta-Blockers: Dipyridamole may enhance the bradycardic effect of Beta-Blockers. Risk C: Monitor therapy
Caplacizumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Caplacizumab. Specifically, the risk of bleeding may be increased. Management: Avoid coadministration of caplacizumab with antiplatelets if possible. If coadministration is required, monitor closely for signs and symptoms of bleeding. Interrupt use of caplacizumab if clinically significant bleeding occurs. Risk D: Consider therapy modification
Cephalothin: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk for bleeding may be increased. Risk C: Monitor therapy
Cladribine: Inhibitors of Equilibrative Nucleoside (ENT1) and Concentrative Nucleoside (CNT3) Transport Proteins may increase the serum concentration of Cladribine. Management: Avoid concomitant use of ENT1 or CNT3 inhibitors during the 4 to 5 day oral cladribine treatment cycles whenever possible. If combined, consider an ENT1 or CNT3 inhibitor dose reduction and separation in the timing of administration. Risk D: Consider therapy modification
Collagenase (Systemic): Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and or bleeding may be increased. Risk C: Monitor therapy
Dabigatran Etexilate: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Dabigatran Etexilate. Agents with Antiplatelet Properties may increase the serum concentration of Dabigatran Etexilate. This mechanism applies specifically to clopidogrel. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor. Risk C: Monitor therapy
Dasatinib: May enhance the anticoagulant effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Deoxycholic Acid: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Risk C: Monitor therapy
Edoxaban: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased. Risk C: Monitor therapy
Enoxaparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Enoxaparin. Management: Discontinue antiplatelet agents prior to initiating enoxaparin whenever possible. If concomitant administration is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification
Heparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Heparin. Management: Decrease the dose of heparin or agents with antiplatelet properties if coadministration is required. Risk D: Consider therapy modification
Herbal Products with Anticoagulant/Antiplatelet Effects (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Risk C: Monitor therapy
Ibritumomab Tiuxetan: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Risk C: Monitor therapy
Ibrutinib: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Icosapent Ethyl: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Inotersen: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Limaprost: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Lipid Emulsion (Fish Oil Based): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Multivitamins/Fluoride (with ADE): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Multivitamins/Minerals (with AE, No Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Obinutuzumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Risk C: Monitor therapy
Omega-3 Fatty Acids: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of bleeding may be increased by concurrent use of these agents. Risk C: Monitor therapy
Pentoxifylline: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Regadenoson: Dipyridamole may enhance the adverse/toxic effect of Regadenoson. Specifically, adenosine mediated effects may be enhanced. Management: Avoid dipyridamole for 48 hours prior to the administration of regadenoson when possible. Risk D: Consider therapy modification
Riociguat: Dipyridamole may enhance the hypotensive effect of Riociguat. Risk X: Avoid combination
Rivaroxaban: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Rivaroxaban. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor. Risk C: Monitor therapy
Salicylates: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result. Risk C: Monitor therapy
Selumetinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Thrombolytic Agents: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents. Risk C: Monitor therapy
Tipranavir: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Urokinase: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Urokinase. Risk X: Avoid combination
Vitamin E (Systemic): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Zanubrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Adverse events have not been observed in animal reproduction studies.
Dipyridamole is excreted in breast milk. The manufacturer recommends that caution be exercised when administering dipyridamole to breastfeeding patients.
IV: During stress perfusion imaging, monitor blood pressure, heart rate, ECG, respiration. Monitor for signs of poor perfusion (pallor, cyanosis, cold skin) (ASNC [Henzlova 2016])
Inhibits the activity of adenosine deaminase and phosphodiesterase, which causes an accumulation of adenosine, adenine nucleotides, and cyclic AMP; these mediators then inhibit platelet aggregation and may cause vasodilation; may also stimulate release of prostacyclin or PGD2; causes coronary vasodilation
Absorption: Readily, but variable
Distribution: Adults: Vd: 2-3 L/kg
Protein binding: 91% to 99%
Metabolism: Hepatic to glucuronide conjugate
Half-life elimination: Terminal: 10-12 hours
Time to peak, serum: 2-2.5 hours
Excretion: Feces (as glucuronide conjugates and unchanged drug)
Solution (Dipyridamole Intravenous)
5 mg/mL (per mL): $2.38
Tablets (Dipyridamole Oral)
25 mg (per each): $0.26 - $1.42
50 mg (per each): $0.47 - $2.29
75 mg (per each): $0.62 - $3.06
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