Yes

Antiplatelet Agent; Vasodilator

Maintains potency after surgical grafting procedures including coronary artery bypass; used with warfarin to decrease thrombosis in patients after artificial heart valve replacement; used with aspirin to prevent coronary artery thrombosis; in combination with aspirin or warfarin to prevent other thromboembolic disorders. Dipyridamole may also be given 2 days prior to open heart surgery to prevent platelet activation by extracorporeal bypass pump and as a diagnostic agent in CAD.

B

Hypersensitivity to dipyridamole or any component

Use caution in patients with hypotension. 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.

>10%:

Cardiovascular: Exacerbation of angina pectoris (19.7% - I.V.)

Central nervous system: Dizziness (13.6% - P.O.), headache (12.2% - I.V.)

1% to 10%:

Cardiovascular: Hypotension (4.6%), hypertension (1.5%), blood pressure lability (1.6%), EKG abnormalities(ST-T changes, extrasystoles), chest pain, tachycardia (3.2% - I.V.)

Central nervous system: Headache (2.3% - I.V.), flushing (3.4% - I.V.), fatigue (1.2% - I.V.)

Dermatologic: Rash (2.3% - P.O.)

Gastrointestinal: Abdominal distress (6.1% - P.O.), nausea (4.6% - I.V.)

Respiratory: Dyspnea (2.6% - I.V.)

Neuromuscular & Skeletal: Paresthesia (1.3% - I.V.)

<1% (Limited to important or life-threatening symptoms):

I.V.: EKG abnormalities, arrhythmias (ventricular tachycardia, bradycardia, AV block, SVT, atrial fibrillation, asystole), palpitations, MI, syncope, orthostatic hypotension, cardiomyopathy, edema, hypertonia, tremor, abnormal coordination, vertigo, dyspepsia, dry mouth, abdominal pain, flatulence, vomiting, eructation, dysphagia, tenesmus, increased appetite, pharyngitis, bronchospasm, hyperventilation, rhinitis, coughing, pleural pain, myalgia, back pain, injection site reaction, diaphoresis, asthenia, malaise, arthralgia, rigor, dysgeusia, leg cramping, earache, tinnitus, vision abnormalities, thirst, depersonalization, renal pain, perineal pain, breast pain, intermittent claudication.

P.O.: Diarrhea, vomiting, flushing, pruritus, angina pectoris, liver dysfunction.

Case reports: Rapidly progressive glomerulonephritis, thrombotic thrombocytopenic purpura, esophageal hematoma, gallstones, epistaxis, pharyngeal bleeding, respiratory arrest (I.V.)

Symptoms of overdose include hypotension, peripheral vasodilation; dialysis is not effective

Treatment includes fluids and vasopressors although hypotension is often transient

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

Theophylline may reduce the pharmacologic effects of dipyridamole; hold theophylline preparations for 36-48 hours before dipyridamole facilitated stress test.

Do not freeze, protect I.V. preparation from light

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 absorbed from GI tract but variable

Distribution: V_d: 2-3 L/kg in adults

Protein binding: 91% to 99%

Metabolism: Concentrated and metabolized in the liver

Half-life, terminal: 10-12 hours

Time to peak serum concentration: 2-2.5 hours

Elimination: In feces via bile as glucuronide conjugates and unchanged drug

Children: Oral: 3-6 mg/kg/day in 3 divided doses

Doses of 4-10 mg/kg/day have been used investigationally to treat proteinuria in pediatric renal disease

Mechanical prosthetic heart valves: Oral: 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: 75-400 mg/day in 3-4 divided doses

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

Hemodialysis: Significant drug removal is unlikely based on physiochemical characteristics

Should be administered with water 1 hour before meals

I.V.: Dilute in at least a 1:2 ratio with normal saline, 1/2 NS, or D₅W; infusion of undiluted dipyridamole may cause local irritation

In the treatment of myocardial infarction, dipyridamole can be used in patients intolerant of aspirin. However, the benefit of its use in terms of CV outcome is less clear. 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.

Dizziness is common

None reported

No information available to require special precautions

No effects or complications reported

Oral: Take exactly as directed, with or without food. You may experience mild headache, transient diarrhea, or temporary dizziness (sit or lie down when taking medication). You may have a tendency to bleed easy; 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, difficulty breathing, or swelling of extremities. Breast-feeding precautions: Consult prescriber if breast-feeding.

Monitor blood pressure, heart rate

Injection: 10 mg/2 mL

Tablet: 25 mg, 50 mg, 75 mg

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

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

Blumenthal MS and McCauley CS, "Cardiac Arrest During Dipyridamole Imaging," Chest, 1988, 93(5):1103-4.

Fitzgerald GA, "Dipyridamole," N Engl J Med, 1987, 316(20):1247-57.

Michelson AD, Bovill E, and Andrew M, "Antithrombotic Therapy in Children," Chest, 1995, 108(4 Suppl):506S-522S.

Michelson AD, Bovill E, Monagle P, et al, "Antithrombotic Therapy in Children," Chest, 1998, 114(5 Suppl):748S-69S.

Nielsen-Kudsk F and Pedersen SK, "Pharmacokinetics of Dipyridamole," Acta Pharmacol Toxicol (Copenh), 1979, 44(5):391-9.

Rao PS, Solymar L, Mardini MK, et al, "Anticoagulant Therapy in Children With Prosthetic Valves," Ann Thorac Surg, 1989, 47(4):589-92.

Shannon M and Maher T, "Anticonvulsant Effects of Intracerebroventricular Adenocard® in Theophylline-Induced Seizures," Ann Emerg Med, 1995, 26(1):65-8.

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