Dipyridamole (Persantine) is a phosphodiesterase (PDE3) and adenosine deaminase inhibitor. It has antiplatelet and vasodilator properties.

Indications of Dipyridamole:

• Oral: It is recommended concurrently with warfarin to decrease thrombosis in patients after artificial heart valve replacement.
• IV: Diagnostic agent in coronary artery disease.

• Off Label Use of Dipyridamole in Adults:

  • For the prevention of Stroke (in combination with aspirin)

Dipyridamole dose in adults:

Dipyridamole dose as Adjunctive therapy for prophylaxis of thromboembolism with cardiac valve replacement:

• 75 to 100 mg per oral 4 times/day.

Dipyridamole dose in the evaluation of coronary artery disease:

• 0.56 mg/kg I/V over 4 minutes.
• maximum dose: 70 mg.
• Following the completion of dipyridamole infusion, inject radiotracer (eg, thallium-201) in 3 to 5 minutes.

Note:

• Aminophylline (50 to 250 mg IV push over 30 to 60 seconds given at least 1 minute after the radiotracer injection) should be available for urgent/emergent use in order to reverse any complications due to dipyridamol.

Dipyridamole Dose in Obese individuals:

• Dosing for patients who are obese or morbidly obese is not established; in these patients, it is customary to use doses up to the weight of 125 kg.

Dipyridamole dose in children:

General Dosing as antiplatelet:

• Infants, Children, and Adolescents:

  • 2 to 6 mg/kg/day per oral  in 3 divided doses.
  • The usual adult maximum dose: 100 mg/dose.

Dipyridamole Treatment dose as an Antiplatelet in mechanical prosthetic heart valves:

Note:

• Although FDA approved for this indication, it is not recommended as a first-line option for thrombotic prophylaxis for mechanical prosthetic heart valves in pediatric patients by experts.
• Vitamin K antagonists with other antiplatelet agents (eg, low-dose aspirin) are recommended.

• Infants, Children, and Adolescents:

  • 2 to 5 mg/kg/day per oral in divided doses, most commonly in 3 divided doses.

Dipyridamole Treatment dose in Cardiac perfusion scans:

• Children ≥6 years and Adolescents:

  • 0.56 mg/kg I/V administered over 4 minutes.
  • The maximum adult dose: 70 mg/dose.

Note: Aminophylline should be available for urgent/emergent use to reverse complications and side effects of dipyridamol.

Dipyridamole treatment dose of Proteinuria (IgA nephropathy, Henoch-Schönlein purpura), as an adjunct therapy:

• Children ≥7 Years And Adolescents:

  • Initial: 3 to 5 mg/kg/day per oral in 3 divided doses;
  • The dose may be titrated to the reported range: 5 to 6 mg/kg/day in 3 divided doses.
  • Maximum daily dose: 400 mg/day;
  • in trials, it was given as part of a 3 or 4 drug combination therapy (eg, immunosuppressant agents, antihypertensive agents, and an anticoagulant).

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.

Pregnancy Risk Factor B

• Studies on animal reproduction did not show any adverse results.

Use during breastfeeding:

• It is excreted from breast milk.
• As per the manufacturer, it is important to exercise caution when prescribing drug to nursing mothers.

Dose adjustment in renal Disease:

There are no dosage adjustments provided in the manufacturer’s labeling.

• Hemodialysis: Not dialyzable.

Dose adjustment in Liver disease:

There is no dosage adjustment provided in the manufacturer’s labeling.

Side effects of Oral Dipyridamole:

• Cardiovascular:

  • Angina pectoris
  • Flushing

• Central nervous system:

  • Dizziness
  • Headache

• Dermatologic:

  • Skin rash
  • Pruritus

• Gastrointestinal:

  • Abdominal distress
  • Diarrhea
  • Vomiting

• Hepatic:

  • Hepatic insufficiency

Common Side Effects of Intravenous Dipyridamole:

• Cardiovascular:

  • Exacerbation of angina pectoris

• Central nervous system:

  • Dizziness
  • Headache

Uncommon Side Effects of Persantine:

• Cardiovascular:

  • ECG abnormality
  • Hypotension
  • Flushing
  • Tachycardia
  • Altered blood pressure
  • Hypertension

• Central nervous system:

  • Pain
  • Fatigue
  • Paresthesia

• Gastrointestinal:

  • Nausea

• Respiratory:

  • Dyspnea

Contraindications to Dipyridamole:

• Hypersensitivity to dipyridamole and any component of the formulation
• The American Society of Nuclear Cardiology (ASNC), states that there are additional contraindications to stress testing.
  • Consumption of caffeine-containing foods and beverages within the past 12 hours
  • Hypertension uncontrolled (systolic blood pressure >200 mm Hg, or diastolic blood pressure >110 mmHg).
  • SystolicBP 90mm Hg
  • Unstable angina
  • Acute coronary syndrome
  • Myocardial Infarction in 2 to 4 Days
  • Bronchospastic pulmonary disease with wheezing and history of severe reactive airway disease
  • The following are some examples of relative contraindications:
  • Heart rate of 40 beats/minute
  • Severe aortic stasis
  • Without a pacemaker, second- or third-degree block of the heart can be achieved.
  • Seizure disorder (cannot receive aminophylline)

Warnings and precautions

• Cardiovascular disease

  • It can cause exercise-induced MI in patients who have chronic stable angina. Patients with hypotension, unstable and recent MI should not use it.

• Hepatic impairment

  • Patients with hepatic impairment should be cautious.

Dipyridamole: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

IV: During stress perfusion imaging, monitor:

• Pulse
• Respiration
• BP
• ECG
• Signs of poor perfusion (pallor, cyanosis, cold skin).

How to administer Dipyridamole?

It is given as an intravenous diluted solution over 4 minutes.

Mechanism of action of Dipyridamole:

• It leads to the accumulation of adenosine, adenine nucleotides, and cyclic AMP by inhibiting adenosine deaminase and phosphodiesterase.
• These mediators inhibit platelet aggregation and coronary vasodilation. They also stimulate prostacyclin or PGD release.

Absorption:

• Readily, but variable.

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).

International Brands of Dipyridamole:

• Persantine
• APO-Dipyridamole
• APO-Dipyridamole SC
• Adezan
• Anaplate
• Anginal
• Anti-Plate 75
• Antiplate
• Atrombin
• Biocardin
• Cardiwell
• Cardoxin Forte
• Cleridium
• Curantil
• Curantyl
• Dipantin
• Dipyrol
• Efosin
• Novo-Dipiradol
• Novodil
• Parotin
• Perazodin
• Persantin
• Persantin 75
• Persantin Depot
• Persantin Forte
• Persantin PL
• Persantin Prolonguets
• Persantin Retard
• Persantin SR
• Persantine
• Plato
• Pressavein
• Procardin
• Pyritin
• Pytazen SR
• Sandel
• Santinal MR
• Shengda
• Solantin
• Tovincocard
• Vasotin
• Zantin

Dipyridamole Brands in Pakistan: