Sanomyl-Sanovel (Tablets) Instructions for Use

Marketing Authorization Holder

Sanovel Pharmaceutical Products Ind., Inc. (Turkey)

ATC Code

B01AC07 (Dipyridamole)

Active Substance

Dipyridamole (Rec.INN registered by WHO)

Dosage Form

Sanomyl-Sanovel

Coated tablets, 75 mg: 90 pcs.

Dosage Form, Packaging, and Composition

Coated tablets yellow in color, round, flat-cylindrical.

Excipients: lactose monohydrate, corn starch, gelatin, sodium starch glycolate (type A), colloidal silicon dioxide, magnesium stearate, hypromellose, talc, titanium dioxide (E171), macrogol 6000, quinoline yellow (E104), simethicone emulsion.

10 pcs. – blisters (5) – carton packs.
20 pcs. – blisters (2) – carton packs.
20 pcs. – blisters (3) – carton packs.
20 pcs. – blisters (5) – carton packs.

Clinical-Pharmacological Group

Antiplatelet agent. Vasodilator of myotropic action

Pharmacotherapeutic Group

Vasodilating agent

Pharmacological Action

Dipyridamole dilates coronary vessels (mainly arterioles) and causes a significant increase in volumetric blood flow velocity.

It increases the oxygen content in the venous blood of the coronary sinus and its uptake by the myocardium.

It promotes the development of collateral coronary circulation, reduces total peripheral vascular resistance, improves microcirculation, and has an angioprotective effect.

These effects are due to the enhancement of endogenous adenosine activity by reducing its uptake by tissues and degradation (adenosine affects vascular smooth muscle and prevents the release of norepinephrine).

It is an antagonist of the endogenous aggregant adenosine diphosphate (ADP), inhibits phosphodiesterase, thereby reducing the release of aggregation activators from platelets – thromboxane, ADP, serotonin, and others, increases the synthesis of prostacyclin Pgh by the vascular tissue endothelium, which prevents platelet aggregation.

It reduces platelet adhesiveness, prevents thrombus formation in vessels and reduced blood flow in the ischemic focus.

The antiplatelet effect occurs at a plasma concentration of 0.1 mcg/ml.

It dose-dependently prolongs the pathologically shortened platelet lifespan.

It dilates coronary arteries, especially unchanged ones, and causes the steal phenomenon.

It is an interferon inducer, has a modulating effect on the functional activity of the interferon system, and increases the reduced production of interferon alpha and gamma by blood leukocytes in vitro.

It increases nonspecific antiviral resistance to viral infections.

It normalizes venous outflow, reduces the frequency of deep vein thrombosis in the postoperative period.

It improves microcirculation in the retina and renal glomeruli.

It reduces the tone of cerebral vessels and is effective in dynamic disorders of cerebral circulation.

Pharmacokinetics

When taken orally, it is rapidly absorbed in the stomach (most part) and small intestine.

Bioavailability is 37-66%.

After oral administration, C_max of dipyridamole in plasma is reached within 40-60 minutes.

It binds to plasma proteins by 80-95%.

It rapidly penetrates into tissues.

It accumulates in large quantities in the heart and erythrocytes.

T_1/2 is 20-30 minutes in the first phase, and about 10 hours in the second phase.

It is metabolized in the liver to form a monoglucuronide, which is excreted in the bile (20% of the drug is included in the enterohepatic circulation).

Cumulation is possible (mainly in patients with impaired liver function).

Indications

• Thrombosis and thromboembolism (prevention of arterial and venous thrombi, including after heart valve replacement surgery);
• Prevention of stent occlusion and aortocoronary bypass grafts (in combination with acetylsalicylic acid);
• Treatment and prevention of cerebral circulation disorders of the ischemic type;
• Dyscirculatory encephalopathy;
• Microcirculation disorders of any genesis (as part of combination therapy).

ICD codes

Dosage Regimen

Orally, on an empty stomach or 1 hour before meals, with a small amount of water or milk.

For prevention and treatment of thromboembolic complications as monotherapy – 75 mg 3-6 times/day; daily dose – 300-450 mg, if necessary – 600 mg; in combination with oral anticoagulants or with acetylsalicylic acid – 75 mg 3 times/day.

For prevention of thromboembolic syndrome, stent thrombosis, and aortocoronary bypass grafts – on day 1, 50 mg together with acetylsalicylic acid, then – 100 mg, frequency of administration – 4 times/day (discontinued 7 days after surgery provided that acetylsalicylic acid is continued at a dose of 325 mg/day) or 100 mg 4 times/day for 2 days before surgery and 100 mg 1 hour after surgery (if necessary in combination with warfarin).

For coronary insufficiency – 25-50 mg 3 times/day; in severe cases at the beginning of treatment – 75 mg 3 times/day, then the dose is reduced; daily dose – 150-200 mg.

Adverse Reactions

From the cardiovascular system palpitations, tachycardia, bradycardia, flushing, coronary steal syndrome (when using doses above 225 mg/day), decreased BP.

From the digestive system nausea, vomiting, diarrhea, epigastric pain.

From the blood and hemostasis system thrombocytopenia, changes in platelet functional properties, bleeding, increased bleeding tendency.

Others weakness, dizziness, feeling of ear fullness, noise in the head, headache, facial skin hyperemia, arthritis, myalgia, rhinitis, allergic reactions.

Contraindications

• Acute myocardial infarction;
• Widespread sclerosing atherosclerosis of coronary arteries;
• Unstable angina;
• Hypertrophic obstructive cardiomyopathy;
• Decompensated chronic heart failure;
• Arterial hypotension;
• Severe arterial hypertension;
• Severe cardiac rhythm disorders;
• Hemorrhagic diathesis;
• Gastric and duodenal ulcer (tendency to bleeding)
• Chronic obstructive pulmonary disease;
• Renal failure
• Hepatic failure;
• Childhood (under 18 years);
• Hypersensitivity to the drug components.

Use in Pregnancy and Lactation

Dipyridamole may be used during pregnancy only if the expected therapeutic benefit justifies the potential risk to the fetus, which should be particularly considered in the first trimester of pregnancy.

Dipyridamole passes into breast milk, therefore Dipyridamole should not be used during lactation.

Use in Hepatic Impairment

Contraindicated in hepatic failure. Cumulation is possible in patients with impaired liver function.

Use in Renal Impairment

Contraindicated in renal failure.

Pediatric Use

Contraindicated in children under 18 years.

Special Precautions

To reduce dyspeptic phenomena, take with milk.

During treatment, avoid consumption of coffee and tea, which weaken the effect of dipyridamole.

In case of coronary steal syndrome, aminophylline is indicated to improve intracardiac blood flow.

Overdose

Overdose may cause headache, gastrointestinal disorders, decreased BP. In case of decreased BP, short-term use of vasopressor drugs is recommended if necessary. In patients with ischemic heart disease, coronary vasodilation may lead to chest pain. Retrosternal pain and bronchospasm are eliminated by immediate intravenous administration of aminophylline and nitroglycerin.

Symptomatic treatment is provided in case of overdose.

Drug Interactions

The antiplatelet effect is enhanced when taken with indirect anticoagulants, acetylsalicylic acid, penicillin antibiotics, cephalosporins, tetracyclines, chloramphenicol, nicotinic acid.

Xanthine derivatives containing caffeine weaken the antithrombotic effect. It weakens the effect of cholinesterase inhibitors.

Antacids reduce the maximum concentration due to reduced absorption.

Heparin, indirect anticoagulants, thrombolytics increase the risk of hemorrhagic complications.

Storage Conditions

List B.

Store the drug in a dry place at a temperature not exceeding 25°C (77°F). Keep out of reach of children.

Shelf Life

Shelf life 3 years. Do not use after the expiration date printed on the package.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.