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Dipyridamole

Pronunciation

Pronunciation: DIE-pih-RID-uh-mole
Class: Antiplatelet agent, In vivo diagnostic agent

Trade Names

Persantine
- Tablets 25 mg
- Tablets 50 mg
- Tablets 75 mg

Dipyridamole
- Injection 5 mg/mL

Apo-Dipyridamole-FC (Canada)

Pharmacology

Lengthens abnormally shortened platelet survival time in a dose-dependent manner by inhibiting platelet aggregation in response to various stimuli, such as platelet activating factor, collagen, and adenosine diphosphate. Vasodilation may result from inhibition of adenosine uptake, which is an important mediator of coronary vasodilation.

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Pharmacokinetics

Absorption

Two minutes after a 4 min IV infusion, the mean serum level is 4.6 mcg/mL.

Distribution

Highly bound to plasma protein (99%). Vd is 1 to 2.5 L/kg.

Metabolism

Metabolized in the liver (conjugated as a glucuronide).

Elimination

Excreted in the bile. Average total body Cl is 2.3 to 3.5 mL/min/kg. The alpha t ½ (initial decline following C max ) is about 40 min, while the beta t ½ (terminal decline in plasma level) is approximately 10 h (oral). Triexponential: the t ½ range is 3 to 13 min, 33 to 62 min, and 11.6 h (IV).

Peak

The average time to C max is about 75 min.

Indications and Usage

Adjunct to coumarin anticoagulants in prevention of postoperative thromboembolic complication of cardiac valve replacement (oral). Alternative to exercise in thallium myocardial perfusion imaging for evaluating coronary artery disease in patients who cannot exercise adequately (IV).

Contraindications

Standard considerations.

Dosage and Administration

Adjunctive Use in Prophylaxis of Thromboembolism after Cardiac Valve Replacement
Adults and children 12 yr of age and older

PO 75 to 100 mg 4 times daily is recommended as an adjunct to the usual warfarin therapy.

Adjunct to Thallium Myocardial Perfusion Imaging
Adults

IV 0.142 mg/kg/min (0.57 mg/kg total) infused over 4 min is recommended. Total doses exceeding 60 mg are not needed for any patient.

General Advice

  • For IV infusion only.
  • Dilute prescribed dose, following manufacturer's instructions, before administration.
  • Do not mix with other drugs in same syringe or infusion container.
  • Do not administer if solution is cloudy, discolored, or contains particulate matter.
  • Infuse prescribed dose over 4 min.
  • Thallium-201 should be injected within 5 min of completion of the 4-min infusion of dipyridamole.
  • If other drugs are being administered through same IV line, administer each medication separately.
  • Discard any unused solution. Do not save for future use.

Storage/Stability

Store tablets at controlled room temperature (59° to 86°F). Store injection at controlled room temperature (59° to 77°F). Protect from light and freezing.

Drug Interactions

Adenosine

Plasma levels of adenosine may be elevated, increasing the CV effects.

Cholinesterase inhibitors

Anticholinesterase effects may be counteracted by dipyridamole, potentially aggravating myasthenia gravis.

Theophyllines, xanthine derivatives (eg, caffeine)

May abolish coronary vasodilation induced by IV dipyridamole.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Oral Angina pectoris; hypotension, palpitation, tachycardia (postmarketing).

IV Chest pain, angina pectoris (20%).

CNS

Oral Dizziness (14%); headache (2%); fatigue, malaise, (postmarketing).

IV Headache, dizziness (12%); paresthesia, fatigue (1%).

Dermatologic

Oral Rash (2%); pruritus; alopecia (postmarketing).

EENT

Oral Larynx edema (postmarketing).

GI

Oral Abdominal distress (6%); diarrhea; vomiting; nausea, dyspepsia (postmarketing).

IV Nausea (5%); dyspepsia (1%).

Hematologic-Lymphatic

Thrombocytopenia (postmarketing).

Hepatic

Oral Hepatic failure; elevated liver enzymes; hepatitis, cholelithiasis (postmarketing).

Lab Tests

IV ECG abnormalities/ST-T changes (8%); ECG abnormalities/extrasystoles, hypotension (5%); ECG abnormalities/tachycardia (3%); BP lability, hypertension (2%).

Musculoskeletal

Oral Myalgia (postmarketing).

Respiratory

IV Dyspnea (3%).

Miscellaneous

Oral Flushing; hypersensitivity (including rash, urticaria, severe bronchospasm, angioedema), arthritis, paresthesia (postmarketing).

IV Flushing, unspecific pain (3%).

Precautions

Monitor

Ensure that parenteral aminophylline and sublingual nitroglycerin are available before administering infusion. Monitor vital signs and ECG during and for 10 to 15 min after infusion has been completed. Be prepared to treat hypotension, bronchospasm, or ischemic chest pain.


Pregnancy

Category B .

Lactation

Excreted in breast milk.

Children

Safety and efficacy not established in children under 12 yr of age (oral).

Safety and efficacy not established (IV).

Coronary artery disease

Because dipyridamole has a vasodilatory effect, use with caution in patients with severe coronary artery disease.

Hypotension

Because dipyridamole can produce peripheral vasodilation, use with caution in patients with hypotension.

Serious adverse reactions

Administration of IV dipyridamole has been associated with cardiac death, fatal and nonfatal MI, ventricular fibrillation, symptomatic ventricular tachycardia, stroke, transient cerebral ischemia, seizures, anaphylactoid reaction, and bronchospasm.

Overdosage

Symptoms

Warm feeling, flushes, sweating, restlessness, feeling of weakness, dizziness.

Patient Information

  • Tablets
  • Advise patient to take as prescribed without regard to meals but to take with food if stomach upset occurs.
  • Advise patient that if a dose is missed to take as soon as remembered unless it is nearing time for the next dose. Caution patient not to double the dose to catch up.
  • Advise patient not to stop taking or change the dose unless advised by health care provider.
  • Caution patient that drug may cause dizziness and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.
  • Advise patient to notify health care provider immediately if any of the following occur: rash or hives, difficulty breathing, persistent dizziness when arising from a sitting or lying position, fainting, yellowing of the skin or eyes.
  • Advise patient to notify health care provider if bothersome side effects occur.
  • Injection
  • Advise patient that medication will be prepared and administered by a health care provider in a health care setting.

Copyright © 2009 Wolters Kluwer Health.

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