Vessel^® Due F (Capsules, Solution) Instructions for Use

ATC Code

B01AB11 (Sulodexide)

Active Substance

Sulodexide (Rec.INN registered by WHO)

Clinical-Pharmacological Group

A drug with antithrombotic and angioprotective action

Pharmacotherapeutic Group

Antithrombotic agents; heparin group

Pharmacological Action

Vessel^® Due F (Sulodexide) is a biological medicinal product representing a natural mixture of glycosaminoglycans (GAGs): a heparin-like fraction with a molecular weight of 8000 daltons (80%) and dermatan sulfate (20%).

The mechanism of action of sulodexide is due to two main properties: the fast-acting heparin-like fraction has an affinity for antithrombin III (ATIII), and the dermatan fraction has an affinity for heparin cofactor II (HCII).

After oral administration at the recommended dose, the amount of sulodexide and its derivatives after the first-pass effect is sufficient to induce antithrombotic action without affecting the usual coagulation parameters (APTT, thrombin time, activated factor X). Thus, it can be assumed that Sulodexide, when administered orally, does not have an anticoagulant effect.

It has angioprotective, profibrinolytic, and antithrombotic effects.

Angioprotective action is associated with the restoration of the structural and functional integrity of vascular endothelial cells and the restoration of the normal density of the negative electric charge of the pores of the vascular basement membrane. Furthermore, the drug normalizes the rheological properties of blood by reducing triglyceride levels (it stimulates the lipolytic enzyme lipoprotein lipase, which hydrolyzes triglycerides that are part of LDL).

The efficacy of the drug in diabetic nephropathy is determined by the ability of sulodexide to reduce the thickness of the basement membrane and the production of extracellular matrix by reducing the proliferation of mesangial cells.

Profibrinolytic action is due to an increase in the blood level of tissue plasminogen activator and a decrease in the content of its inhibitor.

Antithrombotic activity of orally administered sulodexide is mainly the result of all types of action that Sulodexide exerts on the vascular wall (angioprotective action), fibrinolysis (profibrinolytic action), and inhibition of platelet adhesion.

Pharmacokinetics

Absorption

Sulodexide is absorbed from the small intestine. After oral administration of the labeled drug, the first peak of sulodexide in plasma is observed after 2 hours, the second – from 4 to 6 hours, after which the drug is no longer detected in plasma; the concentration is restored after approximately 12 hours and then remains constant until about the 48th hour.

Distribution, Metabolism and Excretion

A constant plasma level is detected after 12 hours, probably due to the slow release of the drug from the uptake organs and, in particular, from the vascular endothelium. Sulodexide is distributed in the vascular endothelium at a concentration 20-30 times higher than the concentration in other tissues.

It is metabolized in the liver and excreted mainly by the kidneys. In a study with a radioactive labeled drug, 55.23% of sulodexide was excreted in the urine within the first 96 hours.

Indications

• Angiopathies with an increased risk of thrombosis, including after myocardial infarction;
• Cerebrovascular accident, including the acute period of ischemic stroke and the early recovery period;
• Dyscirculatory encephalopathy due to atherosclerosis, diabetes mellitus, arterial hypertension;
• Vascular dementia;
• Occlusive lesions of peripheral arteries of both atherosclerotic and diabetic origin;
• Phlebopathies, deep vein thrombosis;
• Microangiopathies (nephropathy, retinopathy, neuropathy);
• Macroangiopathies in diabetes mellitus (diabetic foot syndrome, encephalopathy, cardiopathy);
• Thrombophilic conditions, antiphospholipid syndrome (prescribed together with acetylsalicylic acid, as well as following low molecular weight heparins);
• Treatment of heparin-induced thrombotic thrombocytopenia, since the drug does not cause or aggravate it).

ICD codes

Dosage Regimen

Solution

It is administered parenterally – intramuscularly or intravenously.

1 ampoule/day for 15-20 days. For intravenous administration, bolus or drip, the drug is pre-dissolved in 150-200 ml of saline.

Then therapy should be continued with the drug in capsule form – 1-2 capsules twice a day, before meals, for 30-40 days.

The full course of treatment should be repeated at least 2 times a year.

Depending on the results of the clinical and diagnostic examination of the patient, the dosage regimen may be changed at the doctor’s discretion.

Capsules

Treatment usually begins with parenteral (intramuscular or intravenous) administration of the drug. The solution for intravenous and intramuscular injection is prescribed at 1 ampoule/day for 15-20 days. Then therapy should be continued with the drug in capsule form.

Take orally, 1-2 capsules twice a day, before meals, for 30-40 days.

The full course of treatment should be repeated at least 2 times a year.

Depending on the results of the clinical and diagnostic examination of the patient, the dosage regimen may be changed at the doctor’s discretion.

Adverse Reactions

Adverse reactions related to gastrointestinal disorders and skin reactions were most frequently reported. They are generally reversible.

Bleeding may occur in various locations, including gastric bleeding, hemoptysis, and polymenorrhea, especially in the presence of other predisposing factors.

The adverse reactions listed below are based on previously conducted clinical studies and post-marketing experience according to the MedDRA System Organ Class (SOC) with an indication of their frequency of occurrence.

Side effects are classified by frequency of occurrence as follows: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10000 to <1/1000), very rare (<1/10000); frequency unknown (cannot be estimated from the available data).

Blood and lymphatic system disorders frequency unknown – anemia.

Metabolism and nutrition disorders frequency unknown – disorder of plasma protein metabolism.

Psychiatric disorders frequency unknown – derealization.

Nervous system disorders : uncommon – loss of consciousness, headache; frequency unknown – convulsions, tremor.

Eye disorders frequency unknown – visual impairment.

Ear and labyrinth disorders common – dizziness.

Cardiac disorders frequency unknown – palpitations.

Vascular disorders frequency unknown – flushing.

Respiratory, thoracic and mediastinal disorders frequency unknown – hemoptysis.

Gastrointestinal disorders common – diarrhea, upper abdominal pain; uncommon – gastric hemorrhage; frequency unknown – melena, vomiting, flatulence, dyspepsia, nausea, abdominal discomfort.

Skin and subcutaneous tissue disorders common – rash; uncommon – urticaria, eczema; frequency unknown – angioedema, erythema, purpura, ecchymoses, pruritus.

Renal and urinary disorders frequency unknown – bladder stenosis, dysuria.

Reproductive system and breast disorders frequency unknown – polymenorrhea, genital edema, genital erythema.

General disorders and administration site conditions uncommon – peripheral edema; frequency unknown – chest pain, pain.

Contraindications

• Hypersensitivity to the active substance or any excipient or to heparin or heparinoids;
• Hemorrhagic diseases and hemorrhagic diathesis;
• First trimester of pregnancy.

With caution when used concomitantly with other anticoagulants, periodic monitoring of blood coagulation parameters should be performed.

Use in Pregnancy and Lactation

Pregnancy

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity.

The drug is prescribed to pregnant women under strict medical supervision in the second and third trimesters of pregnancy. There is positive experience with the use of sulodexide for the treatment and prevention of vascular complications in women with type 1 diabetes in the second and third trimesters of pregnancy and for the treatment of late gestosis.

Breastfeeding period

It is not known whether Sulodexide or its metabolites pass into breast milk.

The risk to the breastfed child cannot be excluded.

Vessel^® Due F should not be used during breastfeeding.

Fertility

Animal studies do not indicate direct or indirect harmful effects on male and female fertility.

Special Precautions

Due to the pharmacotoxicological properties of sulodexide, the use of the drug does not require special precautions. Nevertheless, when used concomitantly with other anticoagulants, periodic monitoring of blood coagulation parameters should be performed.

Vessel^® Due F contains sodium ethylparahydroxybenzoate (E 215) and sodium propylparahydroxybenzoate, which may cause allergic reactions (possibly delayed).

Vessel^® Due F contains less than 1 mmol sodium (23 mg) per 1 capsule, i.e., it is essentially sodium-free.

Effect on ability to drive and operate machinery

Sulodexide has no or negligible influence on the ability to drive and use machines.

Overdose

Symptoms bleeding may occur in case of overdose.

Treatment in case of bleeding development, administration of protamine sulfate, used in the treatment of bleeding caused by heparin, is necessary.

Drug Interactions

Since Sulodexide is a heparin-like molecule, it may enhance the anticoagulant effect of heparin itself and oral anticoagulants when used concomitantly.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 30°C (86°F).

Shelf Life

The shelf life is 5 years. Do not use after the expiration date.

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.