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 (Ref).
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 (Ref). Limited data available: Infants, Children, and Adolescents: Oral: 2 to 5 mg/kg/day in divided doses, most commonly in 3 divided doses (Ref).
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) (Ref). 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 (Ref).
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.
(For additional information see "Dipyridamole: Drug information")
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 (Ref).
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 (Ref).
There are no dosage adjustment provided in manufacturer’s labeling.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Oral: Adverse reactions may include combination therapy with warfarin.
>10%: Nervous system: Dizziness (14%)
1% to 10%:
Dermatologic: Skin rash (2%)
Gastrointestinal: Abdominal distress (6%)
Nervous system: Headache (2%)
Frequency not defined:
Cardiovascular: Flushing
Dermatologic: Pruritus
Gastrointestinal: Diarrhea, vomiting
IV:
>10%:
Cardiovascular: Angina pectoris (≤20%), chest pain (≤20%)
Nervous system: Dizziness (12%), headache (12%)
1% to 10%:
Cardiovascular: Extrasystoles (5%), flushing (3%), hypertension (2%), hypotension (5%), ST segment changes on ECG (8%), tachycardia (3%)
Gastrointestinal: Dyspepsia (1%), nausea (5%)
Nervous system: Fatigue (1%), pain (3%), paresthesia (1%)
Respiratory: Dyspnea (3%)
<1%:
Cardiovascular: Acute myocardial infarction, atrial fibrillation, atrioventricular block, bradycardia, cardiac arrhythmia, cardiomyopathy, ECG abnormality, edema, heart block, intermittent claudication, orthostatic hypotension, palpitations, supraventricular tachycardia, syncope, ventricular arrhythmia, ventricular tachycardia
Dermatologic: Diaphoresis
Endocrine & metabolic: Increased thirst
Gastrointestinal: Abdominal pain, dysgeusia, dysphagia, eructation, flatulence, increased appetite, tenesmus, vomiting, xerostomia
Genitourinary: Mastalgia, perineal pain
Local: Injection-site reaction (including pain at injection site)
Nervous system: Anxiety, asthenia, ataxia, depersonalization, drowsiness, hypertonia, hypoesthesia, malaise, migraine, nervousness, tremor, vertigo, voice disorder
Neuromuscular & skeletal: Arthralgia, back pain, lower limb cramp, muscle rigidity, myalgia
Ophthalmic: Eye pain, visual disturbance
Otic: Otalgia, tinnitus
Renal: Renal pain
Respiratory: Bronchospasm, cough, hyperventilation, pharyngitis, pleuritic chest pain, rhinitis
Frequency not defined:
Cardiovascular: Ventricular fibrillation
Nervous system: Seizure, transient ischemic attacks
Postmarketing (any formulation):
Cardiovascular: Asystole, shock (Dioverti 2011), sinus node dysfunction (arrest and depression) (Khalili 2022)
Dermatologic: Alopecia
Gastrointestinal: Cholelithiasis
Hematologic & oncologic: Thrombocytopenia
Hepatic: Hepatic failure, hepatic impairment, hepatitis, increased liver enzymes
Hypersensitivity: Hypersensitivity reaction (including anaphylaxis, angioedema, and nonimmune anaphylaxis) (Weinmann 1994)
Nervous system: Cerebrovascular accident (Whiting 1993)
Neuromuscular & skeletal: Arthritis
Respiratory: Laryngeal edema, pulmonary edema (Dioverti 2011)
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.
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
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
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
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]
10 mg/mL Oral Suspension
A 10 mg/mL oral suspension may be made with tablets and one of three different vehicles (cherry syrup, a 1:1 mixture of Ora-Sweet and Ora-Plus, or a 1:1 mixture of Ora-Sweet SF and Ora-Plus). Crush twenty-four 50 mg tablets in a mortar and reduce to a fine powder. Add 20 mL of the chosen vehicle and mix to a uniform paste; mix while adding the vehicle in incremental proportions to almost 120 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 120 mL. Label "shake well" and "protect from light". Stable for 60 days when stored in amber plastic prescription bottles in the dark at room temperature or refrigerated.
Oral: Administer without regard to meals.
IV: Infuse diluted solution over 4 minutes.
IV: Infuse diluted solution over 4 minutes.
IV: Store between 15°C to 25°C (59°F to 77°F); do not freeze. Protect from light.
Oral: Used with warfarin to decrease thrombosis in patients after artificial heart valve replacement (FDA approved in ages ≥12 years and adults); has also been used for management of proteinuria
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 (eg, warfarin) with other antiplatelet agents (eg, low-dose aspirin) are recommended (ACCP [Monagle 2012]; ACCP [Whitlock 2012]).
IV: Diagnostic agent for coronary artery disease that is used as an alternative to exercise in thallium cardiac perfusion scans (FDA approved in adults)
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 2023]).
Persantine [US, Canada, Belgium, Denmark, France] may be confused with Permitil brand name for sildenafil [Argentina]
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 drug interactions program by clicking on the “Launch drug interactions program” link above.
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 drug interactions program
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
Beta-Blockers: Dipyridamole may enhance the bradycardic effect of Beta-Blockers. 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
Desirudin: Dipyridamole may enhance the adverse/toxic effect of Desirudin. Specifically, the risk of bleeding may be increased. Risk C: Monitor therapy
Enoxaparin: Dipyridamole may enhance the adverse/toxic effect of Enoxaparin. Specifically, the risk of bleeding may be increased. Management: If possible, discontinue dipyridamole prior to initiating enoxaparin. If coadministration is unavoidable, monitor closely for clinical and laboratory evidence of bleeding. Risk D: Consider therapy modification
Heparin: Dipyridamole may enhance the adverse/toxic effect of Heparin. Specifically, the risk of bleeding may be increased. Management: Use caution and reduce the dose of heparin or dipyridamole if these agents are combined. Risk D: Consider therapy modification
Phenindione: Dipyridamole may enhance the adverse/toxic effect of Phenindione. Specifically, the risk of bleeding may be increased. Management: Avoid coadministration of dipyridamole and phenindione if possible. If coadministration is required, monitor closely for clinical and laboratory evidence of bleeding. Risk D: Consider therapy modification
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
Tinzaparin: Dipyridamole may enhance the adverse/toxic effect of Tinzaparin. Specifically, the risk of bleeding may be increased. Risk C: Monitor therapy
Adverse events have not been observed in animal reproduction studies.
Oral: Blood pressure, heart rate; chronic therapy: Liver function (baseline, periodically during therapy)
IV: During stress perfusion imaging and for 10 to 15 minutes after 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)
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