Dipyridamole

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DIPYRIDAMOL (DIPYRIDAMOL)

Composition:

Active ingredient: dipyridamole;

1 ml of solution contains 5 mg of dipyridamole;

Excipients: tartaric acid, propylene glycol, water for injections.

Pharmaceutical form. Solution for injection.

Main physicochemical properties: clear yellow liquid.

Pharmacotherapeutic group.

Antithrombotic agents. ATC code B01AC07.

Pharmacological properties.

Pharmacodynamics.

Dipyridamole dilates coronary vessels, increases volumetric velocity of coronary blood flow, improves oxygen supply to the myocardium, and enhances its resistance to hypoxia. It promotes improvement of blood circulation in the collateral vascular network in case of disturbances in the main coronary vessels. Dipyridamole reduces total peripheral vascular resistance, slightly decreases systemic arterial pressure, and improves cerebral circulation. Dipyridamole is a competitive inhibitor of adenosine deaminase – an enzyme that breaks down adenosine and promotes increased formation of adenosine, which participates in autoregulation of coronary blood flow. The drug inhibits platelet aggregation and prevents thrombus formation. This effect is apparently due to stimulation of prostacyclin synthesis and inhibition of thromboxane biosynthesis. The effect of the drug on arachidonic acid metabolism is associated with increased prostacyclin production in the vascular wall. The antiaggregatory activity of dipyridamole is similar to that of acetylsalicylic acid.

Pharmacokinetics.

The bioavailability of the drug is 37–66 %. Time to reach maximum plasma concentration – 40–60 minutes. Plasma protein binding – 80–95 %. It rapidly penetrates into tissues. It is metabolized in the liver with the formation of monoglucuronide, which is excreted with bile.

Clinical characteristics.

Indications.

For prevention of postoperative thrombosis and cerebrovascular disorders.

Contraindications.

Hypersensitivity to the components of the drug. Widespread atherosclerosis of coronary arteries. Acute myocardial infarction. Decompensated heart failure. Arrhythmias. Arterial hypotension (collapse). Unstable angina. Subaortic stenosis. Renal failure. Bronchial asthma. Obstructive lung diseases. Severe hepatic insufficiency. Hemorrhagic diatheses. Diseases associated with bleeding (peptic ulcer of the stomach and duodenum).

Interaction with other medicinal products and other types of interactions.

Dipyridamole is incompatible with xanthine derivatives.

Concomitant use of Dipyridamole with cholinesterase inhibitors may worsen the course of disease in patients with myasthenia gravis.

Use of the drug with heparin increases the risk of hemorrhagic complications.

When used concomitantly with anticoagulants, acetylsalicylic acid, heparin, as well as with β-lactam antibiotics (penicillins, cephalosporins), tetracyclines, and chloramphenicol, an enhanced anti-aggregation effect is observed. Administration of dipyridamole with heparin may be accompanied by a risk of developing hemorrhagic complications. Xanthine derivatives reduce the coronary-dilating effect of the drug. Antacids, sorbents, and coating agents decrease dipyridamole absorption, leading to reduced maximum plasma concentration and decreased efficacy.

Dipyridamole enhances the hypotensive effect of antihypertensive agents and reduces the anticholinergic properties of cholinesterase inhibitors.

Dipyridamole increases plasma adenosine levels and its cardiovascular effects. Therefore, dosage adjustment of adenosine may be required.

Special precautions for use

When administered parenterally, care must be taken to avoid injecting the drug into the subcutaneous tissue (irritant effects may occur).

Coronary artery disease. High doses of the drug may cause the "steal syndrome," i.e., reduced blood supply to ischemic areas of the myocardium. Dipyridamole has a vasodilatory effect; therefore, it should be used with caution in patients with severe coronary artery disease (e.g., unstable angina or recent myocardial infarction). In such patients, dipyridamole may exacerbate substernal chest pain.

Hepatic impairment. Administration of high doses of dipyridamole may lead to increased levels of liver enzymes and hepatic failure.

There are no data on the use of the drug in elderly patients with hepatic or renal impairment; therefore, it should be used with caution in these cases.

Arterial hypotension. Dipyridamole should be used with caution in patients with arterial hypotension due to its potential to cause peripheral vasodilation.

Use during pregnancy or breastfeeding.

The drug should not be used during pregnancy.

The drug passes into breast milk; therefore, breastfeeding should be discontinued during treatment with this drug.

Ability to affect reaction speed when driving vehicles or operating machinery.

Caution should be exercised when driving vehicles or operating machinery during treatment with this drug.

Method of Administration and Dosage.

For adults and children aged 12 years and older: administer 1–2 mL of 0.5% solution daily by intramuscular or slow intravenous injection. The duration of treatment is determined individually and depends on the degree of risk of thromboembolic complications.

Children.

Not recommended for children under 12 years of age.

Overdose.

Symptoms: sensation of warmth in the body, facial skin flushing, increased sweating, irritability, general weakness and dizziness, arterial hypotension, tachycardia, angina attacks.

Treatment: use of adsorbents; symptomatic treatment with vasopressor agents is recommended. Administration of xanthine derivatives (e.g., aminophylline) inhibits the vasodilatory effect of dipyridamole.

Due to the high degree of protein binding of dipyridamole, dialysis is ineffective.

The vasodilatory effect of dipyridamole can be reversed by intravenous administration of aminophylline (50–100 mg over 1 minute). In case of angina attacks, sublingual nitroglycerin should be administered.

Adverse reactions.

Cardiovascular system: palpitations, bradycardia, arrhythmias, arterial hypotension, sensation of warmth and tachycardia, especially in patients receiving vasodilators, exacerbation of ischemic heart disease (angina and arrhythmia), coronary "steal" syndrome, decreased arterial pressure with rapid intravenous administration.

Gastrointestinal tract: nausea, vomiting, diarrhea, epigastric pain, dyspepsia.

Blood system: thrombocytopenia, changes in platelet functional properties, bleeding; very rarely, increased tendency to bleeding during or after surgical procedures has been observed.

Nervous system: headache, weakness, vascular dizziness, loss of consciousness, tremor.

Skin and subcutaneous tissue: allergic reactions, including transient skin rashes, urticaria.

Immune system: possible severe bronchospasm and Quincke's edema.

Musculoskeletal system: muscle pain, arthritis, myalgia.

Hepatobiliary system: there have been reports that dipyridamole is found as a component of gallbladder stones.

General disorders: general weakness, sensation of ear fullness, tinnitus, facial skin hyperemia, rhinitis, injection site reactions.

Shelf life. 3 years.

Storage conditions.

Store in original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Incompatibility.

The drug solution must not be mixed in the same syringe with other medicinal products.

Packaging.

2 ml in an ampoule; 5 ampoules per blister; 1 or 2 blisters per carton;

2 ml in an ampoule; 5 or 10 ampoules per cardboard carton with partitions.

Prescription category. By prescription only.

Manufacturer.

JSC "Lubnifarm".

Manufacturer's address and location of its business activity.

16 Barvinkova St., Lubny, Poltava region, 37500, Ukraine.