Instructions for Vessel Due F capsules 250 LO No. 50
Composition
active ingredient: sulodexide;
1 capsule contains 250 LO (lipoprotein lipase units) of sulodexide;
excipients: sodium lauryl sarcosinate, colloidal anhydrous silicon dioxide, triacetin, gelatin, glycerin, sodium ethyl parahydroxybenzoate (E 215), sodium propyl parahydroxybenzoate (E 217), titanium dioxide (E 171), red iron oxide (E 172).
Dosage form
Soft capsules.
Main physicochemical properties: brick-red capsules containing a homogeneous suspension of grayish-white color.
Pharmacotherapeutic group
Antithrombotic agents. Sulodexide. ATC code B01A B11.
Pharmacological properties
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, anticoagulant, profibrinolytic, and angioprotective effects.
The anticoagulant effect of sulodexide is due to its affinity for heparin cofactor II, which inhibits thrombin.
The antithrombotic effect of sulodexide is mediated by inhibition of Xa activity, promotion of the synthesis and secretion of prostacyclin (PGI2), and reduction of fibrinogen levels in blood plasma.
The profibrinolytic effect is due to an increase in the activity of 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 negative charge density of vascular basement membranes.
In addition, sulodexide normalizes the rheological properties of blood by reducing triglyceride levels (which is associated with the activation of lipoprotein lipase, an 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 basement membranes and the production of intercellular matrix by reducing the proliferation of mesangial cells.
Pharmacokinetics
Sulodexide is absorbed in the small intestine. 90% of the administered dose of sulodexide accumulates in the vascular endothelium, where its concentrations are 20-30 times higher than 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 antithrombotic action and a significant acceleration of sulodexide excretion, does not occur. In studies of the distribution of sulodexide, it was shown that it is excreted by the kidneys with a half-life of up to 4 hours.
Indication
Angiopathies with an increased risk of thrombosis, including thrombosis after acute myocardial infarction;
cerebrovascular diseases: stroke (acute ischemic stroke and early rehabilitation period after stroke);
dyscirculatory encephalopathy caused by atherosclerosis, diabetes mellitus, arterial hypertension, and vascular dementia;
occlusive peripheral arterial diseases 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 mellitus;
thrombophilia, antiphospholipid syndrome;
heparin-induced thrombocytopenia.
Contraindication
- Hypersensitivity to the active substance, heparin and heparin-like substances, or to any other components of the drug;
- hemorrhagic diathesis and diseases accompanied by decreased blood clotting.
Interaction with other medicinal products and other types of interactions
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 drug interactions have been identified.
Application features
During the course of treatment with the drug, hemocoagulation parameters should be periodically monitored (coagulogram determination). 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, activated partial thromboplastin time increases approximately 1.5 times.
Vessel Due F capsules contain sodium ethyl parahydroxybenzoate and sodium propyl parahydroxybenzoate, which may cause allergic reactions (possibly delayed).
Use during pregnancy or breastfeeding
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 LO per day for 10 days, after which oral administration of the drug was prescribed at 1 capsule twice a day (500 LO/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 physician.
It is not yet known whether sulodexide or its metabolites are excreted in human breast milk. Therefore, for 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.
Ability to influence reaction speed when driving vehicles or other mechanisms
In general, the drug has no or little effect on the ability to drive or operate machinery. If loss of consciousness occurs during treatment with the drug, you should refrain from driving or operating machinery.
Method of administration and doses
General instructions
Typically used treatment regimens involve parenteral administration of the drug followed by capsules; in some cases, treatment with sulodexide can be started directly with capsules. The treatment regimen and the doses of the drug used can be adapted at the discretion of the physician based on clinical examination and laboratory results.
In general, it is recommended to take the capsules 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, it is recommended to repeat the full course of treatment at least 2 times a year.
Angiopathies with an increased risk of thrombosis, including thrombosis after acute myocardial infarction
During the first month, intramuscular injections of 600 LO 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 LO/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 early rehabilitation period after stroke)
Treatment begins with daily intramuscular administration of 600 LO 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. The duration of infusion is from 60 minutes (rate 25-50 drops/minute) to 120 minutes (rate 35-65 drops/minute). The recommended duration of the course of treatment is 15-20 days. Then therapy should be continued with the use of capsules, which are taken orally 1 capsule twice a day (500 LO/day) for 30-40 days.
Dyscirculatory encephalopathy caused by atherosclerosis, diabetes mellitus, arterial 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 injection of 600 LO of sulodexide per day for 10-30 days.
Occlusive peripheral arterial diseases of both atherosclerotic and diabetic genesis
Treatment is started with intramuscular daily administration of 600 LO of sulodexide and continued for 20-30 days. Then the course is continued by taking 1-2 capsules orally twice a day (500-1000 LO/day) for 2-3 months.
Phlebopathies and deep vein thrombosis
Usually, oral administration of sulodexide capsules is prescribed at a dose of 500-1000 LO/day (2 or 4 capsules) for 2-6 months. The course of treatment can also be started with daily intramuscular administration of 600 LO of sulodexide per day for 10-30 days.
Microangiopathy (nephropathy, retinopathy, neuropathy) and macroangiopathy (diabetic foot syndrome, encephalopathy, cardiopathy) caused by diabetes mellitus
Treatment of patients suffering from micro- and macroangiopathy is recommended to be carried out in two stages. First, 600 LO of sulodexide are administered intramuscularly daily for 15 days, and then the treatment is continued by taking 1-2 capsules twice a day (500-1000 LO/day). Since the results of short-term treatment may be lost to some extent, 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 administration of 500-1000 LO 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.
In case of heparin-induced thrombocytopenia, heparin or low molecular weight heparin is replaced by sulodexide infusion. To do this, the contents of 1 ampoule of the drug (600 LO of sulodexide) are 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 LO of sulodexide are diluted in 100 ml of 0.9% sodium chloride solution and administered as a 60-minute drip infusion (rate 35 drops/minute) every 12 hours, as long as there is a need for anticoagulant therapy.
Children
There is limited experience with the use of sulodexide preparations in the treatment of diabetic nephropathy and glomerulonephritis in adolescents aged 13-17 years. In such cases, 600 LO of sulodexide were administered intramuscularly daily for 15 days, followed by oral administration of 1-2 capsules of the drug twice daily (500-1000 LO/day) for 2 weeks.
There are no data on the efficacy and safety of the drug in children under 12 years of age.
Overdose
Overdose of the drug may lead to the development of hemorrhagic symptoms, such as hemorrhagic diathesis or bleeding. In case of bleeding, a 1% solution of protamine sulfate should be administered. In general, in case of overdose, the drug should be discontinued and appropriate symptomatic therapy should be initiated.
Adverse reactions
Adverse reactions that have been identified in clinical trials and are associated with the use of sulodexide are classified according to system organ class and frequency. The following terminology is used to define the frequency of adverse reactions: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1000 to < 1/100); isolated (≥ 1/10,000 to < 1/1000); rare (< 1/10,000).
From the nervous system
Uncommon: headache.
Rare: loss of consciousness.
From the side of the organ of hearing and inner ear
Common: dizziness.
Gastrointestinal tract
Common: upper abdominal pain, diarrhea, nausea.
Uncommon: abdominal discomfort, dyspepsia, flatulence, vomiting.
Rare: gastric bleeding.
Skin and subcutaneous tissue disorders
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.
Blood and lymphatic system disorders: anemia.
Metabolic and nutritional disorders: disorders of blood plasma protein metabolism.
Gastrointestinal: gastrointestinal disorders, melena.
Skin and subcutaneous tissue disorders: angioedema, ecchymosis.
Reproductive system and breast disorders: genital swelling, genital erythema, polymenorrhea.
Expiration date
5 years.
Do not use after the expiry date stated on the packaging.
Storage conditions
Store at a temperature not exceeding 30 °C.
Keep out of reach of children.
Packaging
25 capsules in a blister; 2 blisters in a cardboard box.
Release category: By prescription.
Producer
Alfasigma S.p.A./Alfasigma SpA,
Catalent Italy SpA
Location of the manufacturer and address of its place of business
Via Enrico Fermi 1, 65020 Alanno (Pescara), Italy.
Via Nettunense km 20, 100, 04011 – Aprilia (Latina), Italy.
