Vessel Due F- action, indications, use, side effects

active substance : sulodexide;

1 capsule contains 250 LO (lipoprotein lipase units) of sulodexide;

auxiliary substances: sodium lauryl sarcosinate, silicon dioxide colloidal anhydrous, triacetin, gelatin, glycerin, sodium ethyl parahydroxybenzoate (E 215), sodium propyl parahydroxybenzoate (E 217), titanium dioxide (E 171), iron oxide red (E 172).

Capsules are soft.

Main physicochemical properties: brick-red capsules containing a grayish-white homogenous suspension.

Antithrombotic agents. Sulodexide. ATX code B01A B11.

Pharmacodynamics.

Vessel Due F is a preparation of sulodexide, a natural mixture of glycosaminoglycans isolated from the intestinal mucosa of pigs. Sulodexide consists of a heparin-like fraction with a molecular weight of about 8000 Da (80%) and dermatan sulfate (20%).

Sulodexide has antithrombotic, anticoagulation, profibrinolytic and angioprotective effects.

The anticoagulant effect of sulodexide is due to its affinity with the cofactor of heparin II, which inhibits thrombin.

Antithrombotic effect of sulodexide is mediated by inhibition of Xa activity, promotion of synthesis and secretion of prostacyclin (PGI2) and reduction of fibrinogen level in blood plasma.

The profibrinolytic action is due to an increase in the activity of the tissue plasminogen activator and a decrease in the activity of its inhibitor.

The angioprotective effect is associated with the restoration of the structural and functional integrity of endothelial cells and the normalization of the density of the negative charge of the basal membranes of vessels.

In addition, sulodexide normalizes the rheological properties of blood by reducing the level of triglycerides (which is associated with the activation of lipoprotein lipase – the enzyme responsible for the hydrolysis of triglycerides).

The effectiveness of the drug in diabetic nephropathy is determined by the ability of sulodexide to reduce the thickness of the basement membranes and the production of the intercellular matrix by reducing the proliferation of mesangium cells.

Pharmacokinetics.

Sulodexide is absorbed in the small intestine. 90% of the administered dose of sulodexide accumulates in the endothelium of blood vessels, where its concentrations are 20-30 times higher than those in the tissues of other organs. Sulodexide is metabolized mainly by the liver and excreted mainly by the kidneys. Unlike unfractionated and low-molecular-weight heparin, desulfation, which would lead to a decrease in the antithrombotic effect and a significant acceleration of the elimination of sulodexide, does not occur. In studies of the distribution of sulodexide, it has been shown that it is excreted by the kidneys with a half-life of up to 4 hours.

• Angiopathies with an increased risk of thrombosis, including thrombosis after an acute myocardial infarction;
• cerebrovascular diseases: stroke (acute ischemic stroke and the period of early rehabilitation after a stroke);
• dyscirculatory encephalopathy caused by atherosclerosis, diabetes, hypertension, and vascular dementia;
• occlusive diseases of peripheral arteries of both atherosclerotic and diabetic genesis;
• phlebopathy and deep vein thrombosis;
• microangiopathy (nephropathy, retinopathy, neuropathy) and macroangiopathy (diabetic foot syndrome, encephalopathy, cardiopathy) caused by diabetes;
• thrombophilia, antiphospholipid syndrome;
• heparin-induced thrombocytopenia.

• Hypersensitivity to the active substance, heparin and heparin-like substances, or to any other components of the drug;
• hemorrhagic diathesis and diseases accompanied by a decrease in blood coagulation.

Since sulodexide is a heparin-like molecule, when used simultaneously, it may increase the anticoagulant effect of heparin and oral anticoagulants. No other clinically significant interactions of the drug with medicinal products were found.

During the course of treatment with the drug, hemocoagulation parameters should be periodically monitored (determination of the coagulogram). At the beginning and after the end of therapy, the following laboratory parameters should be determined: activated partial thromboplastin time, bleeding time/clotting time and antithrombin III level. During the use of the drug, the activated partial thromboplastin time increases approximately 1.5 times.

Vessel Due F capsules contain sodium ethyl parahydroxybenzoate and sodium propyl parahydroxybenzoate, which can cause allergic reactions (possibly delayed).

Use during pregnancy or breastfeeding.

Since there is no experience with the use of the drug in the first trimester of pregnancy, it should be avoided to prescribe the drug to women during this period, except in cases where, in the opinion of the doctor, the expected benefit of the treatment for the mother exceeds the possible risk to the fetus.

There is limited experience with the use of sulodexide in the II and III trimesters of pregnancy for the treatment of vascular complications caused by type I and II diabetes and late toxicosis. In such cases, sulodexide was administered daily intramuscularly at a dose of 600 IU per day for 10 days, after which oral administration of the drug was prescribed for 1 capsule twice a day (500 IU/day) for 15-30 days. In case of toxicosis, this treatment regimen can also be combined with traditional methods of treatment.

During the II and III trimesters of pregnancy, the drug should be used with caution, under the close supervision of a doctor.

It is not yet known whether sulodexide or its metabolites pass into human breast milk. Therefore, based on safety reasons, it is not recommended to prescribe the drug to women during breastfeeding.

Animal studies have not shown direct or indirect harmful effects of sulodexide on male or female fertility.

The ability to influence the speed of reaction when driving vehicles or other mechanisms.In general, the drug does not affect or almost does not affect the ability to drive vehicles or work with mechanisms. If there is a loss of consciousness during treatment with the drug, you should refrain from driving vehicles and working with mechanisms.

General instructions

Commonly used treatment regimens involve parenteral administration of the drug followed by capsules; in some cases, treatment with sulodexide can be started directly by taking capsules. The treatment regimen and applied doses of the drug can be adapted at the discretion of the doctor based on the clinical examination and the results of the determination of laboratory parameters.

In general, capsules are recommended to be taken between meals; if the daily dose of capsules is divided into several doses, it is recommended to maintain a 12-hour interval between doses of the drug.

In general, the full course of treatment is recommended to be repeated at least 2 times a year.

Angiopathies with an increased risk of thrombosis, including thrombosis after an acute myocardial infarction

During the first month, intramuscular injections of 600 IU of sulodexide (contents of 1 ampoule) are administered daily, after which the course of treatment is continued by taking 1-2 capsules orally twice a day (500-1000 IU/day). The best results can be obtained if treatment is started within the first 10 days after an episode of acute myocardial infarction.

Cerebrovascular diseases: stroke (acute ischemic stroke and the period of early rehabilitation after a stroke)

Treatment begins with daily intramuscular administration of 600 IU of sulodexide or intravenous bolus or drip infusion, for which the contents of 1 ampoule of the drug are dissolved in 150-200 ml of saline. Duration of infusion – from 60 minutes (speed 25-50 drops/minute) to 120 minutes (speed 35-65 drops/minute). The recommended duration of the treatment course is 15-20 days. Then the therapy should be continued with the use of capsules taken orally, 1 capsule twice a day (500 IU/day) for 30-40 days.

Dyscirculatory encephalopathy caused by atherosclerosis, diabetes, hypertension, and vascular dementia

It is recommended to take 1-2 capsules of the drug twice a day (500-1000 LO/day) orally for 3-6 months. The course of treatment can also be started with intramuscular administration of 600 IU of sulodexide per day for 10-30 days.

Occlusive diseases of peripheral arteries of both atherosclerotic and diabetic genesis

Treatment begins with daily intramuscular administration of 600 IU of sulodexide and continues for 20-30 days. Then the course is continued by taking orally 1-2 capsules twice a day (500-1000 IU/day) for 2-3 months.

Phlebopathies and thrombosis of deep veins

Oral intake of sulodexide capsules is usually prescribed at a dose of 500-1000 IU/day (2 or 4 capsules) for 2-6 months. The course of treatment can also be started with daily intramuscular administration of 600 IU of sulodexide per day for 10-30 days.

Microangiopathy (nephropathy, retinopathy, neuropathy) and macroangiopathy (diabetic foot syndrome, encephalopathy, cardiopathy) caused by diabetes

Treatment of patients suffering from micro- and macroangiopathy is recommended to be carried out in two stages. First, for 15 days, 600 IU of sulodexide are administered intramuscularly daily, and then the treatment is continued by taking 1-2 capsules twice a day (500-1000 IU/day). Since its results may be lost to some extent with short-term treatment, it is recommended to extend the duration of the second stage of treatment to at least 4 months.

Thrombophilia, antiphospholipid syndrome

The usual treatment regimen involves oral intake of 500-1000 IU of sulodexide per day (2 or 4 capsules) for 6-12 months. Sulodexide capsules are usually prescribed after treatment with low-molecular-weight heparin in combination with acetylsalicylic acid, and the dosage regimen of the latter does not need to be changed.

Heparin-induced thrombocytopenia

In the event of the development of heparin-induced thrombocytopenia, the introduction of heparin or low molecular weight heparin is replaced by sulodexide infusion. To do this, the content of 1 ampoule of the drug (600 IU of sulodexide) is diluted in 20 ml of 0.9% sodium chloride solution and administered as a slow infusion lasting 5 minutes (rate 80 drops/minute). After that, 600 IU of sulodexide is diluted in 100 ml of 0.9% sodium chloride solution and administered as 60-minute drip infusions (rate of 35 drops/minute) every 12 hours, while there is a need for anticoagulation therapy.

Children.

There is limited experience with the use of sulodexide drugs in the treatment of diabetic nephropathy and glomerulonephritis in adolescents aged 13-17 years. In such cases, 600 IU of sulodexide was administered intramuscularly daily for 15 days, and then 1-2 capsules of the drug were prescribed orally twice a day (500-1000 IU/day) for 2 weeks.

There are no data on the effectiveness and safety of the drug in children under 12 years of age.

An overdose of the drug can lead to the development of hemorrhagic symptoms, such as hemorrhagic diathesis or bleeding. In case of bleeding, it is necessary to enter a 1% solution of protamine sulfate. In general, in case of overdose, the use of the drug should be discontinued and appropriate symptomatic therapy should be started.

Adverse reactions that have been identified in clinical studies and are associated with the use of sulodexide, are classified according to the classes of system organs and frequency. The following terminology is used to determine the frequency of adverse reactions: very common (≥ 1/10); common (from ≥ 1/100 to < 1/10); uncommon (from ≥ 1/1000 to < 1/100); single (from ≥ 1/10000 to < 1/1000); rare (< 1/10000).

From the side of the nervous system

Uncommon: headache.

Rare: loss of consciousness.

From the side of the organ of hearing and the inner ear

Common: dizziness.

From the gastrointestinal tract

Common: pain in the upper part of the abdominal cavity, diarrhea, nausea.

Uncommon: abdominal discomfort, dyspepsia, flatulence, vomiting.

Rare: gastric bleeding.

From the side of the skin and subcutaneous tissues

Common: skin rash.

Uncommon: eczema, erythema, urticaria.

General disorders and administration site conditions

Rare: peripheral edema.

During post-marketing studies of the use of sulodexide, additional reports of the following adverse reactions were received, the frequency of which cannot be established based on the available data.

From the blood and lymphatic system: anemia.

Disorders of metabolism and nutrition: disorders of the metabolism of blood plasma proteins.

From the gastrointestinal tract: gastrointestinal disorders, melena.

From the side of the skin and subcutaneous tissues: angioneurotic edema, ecchymosis.

On the part of the reproductive system and mammary glands: edema of the genitals, erythema of the genitals, polymenorrhea.

5 years.

Do not use after the expiration date indicated on the package.

Store at a temperature not higher than 30 °C.

Keep out of the reach of children.

25 capsules in a blister; 2 blisters in a cardboard box.

By prescription.

Alfasigma S.p.A./Alfasigma SpA,

Catalent Italy SpA/Catalent Italy SpA