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Dipyridamole


Pronunciation

 (dye peer ID a mole)


U.S. Brand Names

 Persantine®


Generic Available

 Yes


Canadian Brand Names

 Apo-Dipyridamole FC®; Novo-Dipiradol; Persantine®


Use

Oral: Used with warfarin to decrease thrombosis in patients after artificial heart valve replacement

I.V.: Diagnostic agent in CAD


Use - Unlabeled/Investigational

 Treatment of proteinuria in pediatric renal disease


Pregnancy Risk Factor

 B


Pregnancy Implications

 Teratogenic effects were not observed in animal studies.


Lactation

 Enters breast milk/use caution


Contraindications

 Hypersensitivity to dipyridamole or any component of the formulation


Warnings/Precautions

 Use caution in patients with hypotension and severe cardiac disease. Use caution in patients on other antiplatelet agents or anticoagulation. Severe adverse reactions have occurred rarely with I.V. administration. Use the I.V. form with caution in patients with bronchospastic disease or unstable angina. Have aminophylline ready in case of urgency or emergency with I.V. use.


Adverse Reactions

Oral:

>10%: Dizziness (14%)

1% to 10%:

Central nervous system: Headache (2%)

Dermatologic: Rash (2%)

Gastrointestinal: Abdominal distress (6%)

Frequency not defined: Diarrhea, vomiting, flushing, pruritus, angina pectoris, liver dysfunction

Postmarketing and/or case reports: Alopecia, arthritis, cholelithiasis, dyspepsia, fatigue, hepatitis, hypersensitivity reaction, hypotension, larynx edema, malaise, myalgia, nausea, palpitation, paresthesia, tachycardia, thrombocytopenia

I.V.:

>10%:

Cardiovascular: Exacerbation of angina pectoris (20%)

Central nervous system: Dizziness (12%), headache (12%)

1% to 10%:

Cardiovascular: Hypotension (5%), hypertension (2%), blood pressure lability (2%), ECG abnormalities (ST-T changes, extrasystoles; 5% to 8%), pain (3%), tachycardia (3%)

Central nervous system: Flushing (3%), fatigue (1%)

Gastrointestinal: Nausea (5%)

Neuromuscular & skeletal: Paresthesia (1%)

Respiratory: Dyspnea (3%)

<1% (Limited to important or life-threatening): Abdominal pain, abnormal coordination, appetite increased; arrhythmia (ventricular tachycardia, bradycardia, AV block, SVT, atrial fibrillation, asystole); arthralgia, asthenia, back pain, breast pain, bronchospasm, cardiomyopathy, cough, depersonalization, diaphoresis, dry mouth, dysgeusia, dyspepsia, dysphagia, earache, ECG abnormalities (unspecified), edema, eructation, flatulence, hypertonia, hyperventilation, injection site reaction, intermittent claudication leg cramping, malaise, MI, myalgia, orthostatic hypotension, palpitation, perineal pain, pharyngitis, pleural pain, renal pain, rhinitis, rigor, syncope, tenesmus, thirst, tinnitus, tremor, vertigo, vision abnormalities, vomiting

Postmarketing and/or case reports: Allergic reaction


Overdosage/Toxicology

 Symptoms of overdose include hypotension and peripheral vasodilation. Dialysis is not effective. Treatment is symptomatic and supportive.


Drug Interactions

Adenosine: Blood levels and pharmacologic effects of adenosine are increased; consider reduced doses of adenosine.

Cholinesterase inhibitors: May counteract effect of cholinesterase inhibitor and may aggravate myasthenia gravis.

Xanthine derivatives (eg, theophylline): May reduce the pharmacologic effects of dipyridamole; hold theophylline preparations for 36-48 hours before dipyridamole facilitated stress test.


Ethanol/Nutrition/Herb Interactions

 Herb/Nutraceutical: Avoid cat's claw, dong quai, evening primrose, feverfew, garlic, ginger, ginkgo, red clover, horse chestnut, green tea, ginseng (all have additional antiplatelet activity).


Stability

 I.V.: Store between 15°C to 25°C (59°F to 77°F). Do not freeze, protect from light. Prior to administration, dilute to a 1:2 ratio in NS, 1/2NS, or D5W. Total volume should be ~20-50 mL.


Mechanism of Action

 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


Pharmacodynamics/Kinetics

Absorption: Readily, but variable

Distribution: Adults: Vd: 2-3 L/kg

Protein binding: 91% to 99%

Metabolism: Hepatic

Half-life elimination: Terminal: 10-12 hours

Time to peak, serum: 2-2.5 hours

Excretion: Feces (as glucuronide conjugates and unchanged drug)


Dosage

Children: Oral:

Proteinuria (unlabeled use): 4-10 mg/kg/day have been used investigationally to treat proteinuria in pediatric renal disease

Mechanical prosthetic heart valves (unlabeled use): 2-5 mg/kg/day (used in combination with an oral anticoagulant in children who have systemic embolism despite adequate oral anticoagulant therapy, and used in combination with low-dose oral anticoagulation (INR 2-3) plus aspirin in children in whom full-dose oral anticoagulation is contraindicated)

Adults:

Oral: Adjunctive therapy for prophylaxis of thromboembolism with cardiac valve replacement: 75-100 mg 4 times/day

I.V.: Evaluation of coronary artery disease: 0.14 mg/kg/minute for 4 minutes; maximum dose: 60 mg


Monitoring Parameters

 Blood pressure, heart rate, ECG (stress test)


Dietary Considerations

 Should be taken with water 1 hour before meals.


Patient Education

 Oral: Take exactly as directed, with water 1 hour before meals. You may experience mild headache, transient diarrhea, or temporary dizziness (sit or lie down when taking medication). You may have a tendency to bleed easily; use caution with sharps, needles, or razors. Report chest pain, redness around mouth, acute abdominal cramping or severe diarrhea, acute and persistent headache or dizziness, rash, respiratory difficulty, or swelling of extremities. Breast-feeding precaution: Consult prescriber if breast-feeding.


Anesthesia and Critical Care Concerns/Other Considerations

 For patients undergoing CABG, the Seventh American College of Chest Physicians Consensus Conference recommended against the addition of dipyridamole to aspirin therapy.


Cardiovascular Considerations

 Dipyridamole is frequently used in CV stress testing because it increases endogenous adenosine levels and thereby induces myocardial vasodilation in vessels that do not have fixed stenotic lesions. Thus, areas of ischemia are identified. May enhance exercise induced myocardial ischemia in patients with chronic stable angina.


Dental Health: Effects on Dental Treatment

 No significant effects or complications reported


Dental Health: Vasoconstrictor/Local Anesthetic Precautions

 No information available to require special precautions


Mental Health: Effects on Mental Status

 Dizziness is common


Mental Health: Effects on Psychiatric Treatment

 None reported


Dosage Forms

Injection, solution: 5 mg/mL (2 mL, 10 mL)

Tablet (Persantine®): 25 mg, 50 mg, 75 mg


Extemporaneously Prepared

 A 10 mg/mL oral suspension has been made using four 25 mg tablets and purified water USP qs ad to 10 mL; expected stability is 3 days. Dipyridamole 10 mg/mL was stable for up to 60 days at 5°C and 25°C in 1:1 mixtures of Ora-Sweet® and Ora-Plus®, Ora-Sweet® SF and Ora-Plus® and in cherry syrup

Allen LV and Erickson III MA, "Stability of Baclofen, Captopril, Diltiazem, Hydrochloride, Dipyridamole, and Flecainide Acetate in Extemporaneously Compounded Oral Liquids," Am J Health Syst Pharm , 1996, 53:2179-84.

Nahata MC and Hipple TF, Pediatric Drug Formulations , 2nd ed, Cincinnati, OH: Harvey Whitney Books Co, 1992.


References

Antman EM, Anbe SC, Alpert JS, et al, "ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction-Executive Summary. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction)," Circulation , 2004, 110:588-636. Available at: http://www.circulationaha.org/cgi/content/full/110/5/588. Last accessed August 26, 2004.

Monagle P, Michelson AD, Bovill E, et al, "Antithrombotic Therapy in Children," Chest , 2001, 119(1 Suppl):344-70.

Stein PD, Schunemann HJ, Dalen JE, et al, "Antithrombotic Therapy in Patients With Saphenous Vein and Internal Mammary Artery Bypass Grafts: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy," Chest , 2004, 126(3 Suppl):600-08.

Ueda N, Kawaguchi S, Niinomi Y, et al, "Effect of Dipyridamole Treatment on Proteinuria in Pediatric Renal Disease," Nephron , 1986, 44(3):174-9.


International Brand Names

 Agilease® (JP); Agremol® (TH); Anginal® (JP); Apo-Dipyridamole FC® (CA); Apo-Dipyridamole® (SG); Atrombin® (FI); Cardial® (ID); Cardoxin® (IL); Cerebrovase® (GB); Cléridium® (FR); Cordantin® (BR); Coronair® (BE); Coronamole® (JP); Corosan® (IT); Coroxin® (BD, CY, EG, JO, KW, LB, MA, MT, SY); Cortab® (ID); Curantyl® (CZ, DE, PL, RO, RU); Dipiridamol L.CH.® (CL); Dipiridamol® (RO, RU); Dipyphar® (BE); Dipyridamole® (BE, GB, LU); Dipyridan® (BE, LU); Dipyrin® (FI); Docdipyri® (BE); Drisentin® (TR); Gulliostin® (JP); Kardisentin® (TR); Miosen® (ES); Novo-Dipiradol (CA); Penselin® (JP); Perazodin® (CY, JO); Permiltin® (JP); Persantin® (AR, AT, AU, BR, CL, CO, CY, CZ, DK, EG, ES, FI, GB, HK, HR, ID, IE, IN, IT, JO, JP, KW, LB, MT, NL, NO, NZ, PL, PT, RO, RU, SE, SG, SI, TH, TR, YU, ZA); Persantin Depot® (SE); Persantine® (BE, CA, FR, LU); Piroan® (JP); Plato® (ZA); Posanin® (TH); Procardin® (SG); Pyrintin® (BD); Pytazen SR® (NZ); Ticinil® (CL); Tromboliz® (TR); Vasokor® (ID); Vasotin® (ID)


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