Vessel Due F
SulodexideAntithrombotic
drugs
Vessel Due F ampoules: Each ampoule contains: Sulodexide 600 LSU Excipients:
sodium chloride, water for injection.
Vessel Due F capsules: Each capsule contains: Sulodexide 250 LSU
Excipients: Sodium lauryl sarcosinate, Precipitated silica,
Triglycerides, gelatine, glycerol, sodium ethyl p-oxybenzoate, sodium propyl
p-oxybenzoate, titanium dioxide E171 and red iron oxide E172.
Mechanisms of action
Sulodexide has a relevant antithrombotic activity both in rats and rabbits.
In the case of rats, Sulodexide is able to prevent the formation of venous
and arterial thrombus; it is also effective in reducing the weight of
pre-formed thrombi both by parenteral and oral administration.
The antithrombotic activity is related to:
a) A block of thrombin and cathepsin G platelet aggregation;
b) Inhibitory effect on platelet adhesives;
c) A block in platelet function;
d) Anticoagulant and pro-fibrinolytic activity shown both in vivo and in
vitro in animals and in humans.
The mechanism of action of the antithrombotic activity is due to the
simultaneous inhibition of circulating thrombin through its affinity for
anti-thrombin III and the thrombin bound to surfaces, such as the surface of
the thrombus, as well as through affinity for heparin cofactor II. This
simultaneous action which catalyses the thrombin inhibition reaction seems
to be better than that observed with heparin and increases the
antithrombotic potential of Sulodexide. Furthermore, Sulodexide causes less
bleeding than conventional heparin at doses which are active on thrombosis.
Affinity for fibrin both in vitro and in vivo, both after intravenous and
oral administration has been shown; in fact, Sulodexide labeled with
fluorescent binds to the fibrin of the thrombus and it is found to be still
bound even several hours after administration. This observation could mean
that Sulodexide is able to carry out its antithrombotic action locally on
the thrombus. Sulodexide shows an anti-atherosclerotic activity in
experimental models in rabbits.
The pharmacological profile of Sulodexide described up to now is
completed by normalisation of altered lipid levels which occurs through the
activation of lipoprotein lipase.
Pharmacology
Sulodexide carries out a marked antithrombotic action both on arteries and
veins.
Several clinical studies carried out by administering the product
parenterally and orally, demonstrated that the antithrombotic activity of
Sulodexide is due to the dose-dependent inhibition of some coagulation
factors, especially activated factor X; interference with thrombin remains
instead at levels of low significance and the consequences of an
anticoagulative action are generally avoided. Antithrombotic action is
sustained even by the inhibition of platelet aggregation and by the
activation of circulatory and wall fibrinolytic system.
Sulodexide also normalises the viscosity parameters which are usually
altered in patients with vascular pathologies with thrombotic risk; this
action mainly takes place through the reduction of fibrinogen levels.
Sulodexide pharmacological profile described so far is completed with the
normalization of altered lipidic values by the activation of lipoprotein
lipase.
Studies carried out to show other possible effects in addition to the
above mentioned, primary to therapeutic efficacy, confirmed that the
administration of VESSEL DUE F has no anticoagulant effects.
Pharmacokinetics
Sulodexide is characterised by absorption through the gastrointestinal
barrier which may be demonstrated based on pharmacodynamic effects of the
drug after oral, intraduodenal, intraileal and rectal administration in rats
of Sulodexide labeled with fluoresceine. Dose-effect and dose-time
correlations in rats and rabbits have been shown following administration by
the routes indicated above. The labeled substance is initially accumulated
in the intestinal cells and then is released by the serum pole in the
systemic circulation.
The concentration of radioactive substance significantly increases in
time at the level of brain, kidney, heart, liver, lung, testicle and plasma.
Pharmacological tests carried out on man with i.m. and i.v. administration
of the product revealed linear dose-effect relationship. The metabolism was
mainly hepatic and the excretion mainly urinary.
Absorption after oral administration in man studied with labeled product,
showed that a first blood level peak occurred after 2 hours and a second
between the 4th and the 6th hour, after which the drug is no longer
detectable in plasma; it reappears at about the 12th hour and then remains
constant until about the 48th hour. The constant blood level found after the
12th hour is probably due to slow release of the drug by the uptake organs
and in particular vessel endothelia. Urinary excretion: using the labeled
product, 55.23% of the administered radioactivity is excreted through urine
during the first 96 hours. This elimination shows a peak after about 12
hours, and an average urinary value of 17.6% of the administered dose in
0-24 hour interval; a second peak at around the 36th hour and urinary
elimination of 22% from the 24th to the 48th hour and a third peak at around
the 78th hour and a urinary elimination of about 14.9% in the 48-96 hour
period. After 96 hours, radioactivity is no longer detectable in the
collected samples.
Faecal excretion: the total radioactivity recuperated from the faeces is
23% in the first 48 hours, after which no labeled substance can be detected.
Indications
Vascular pathologies with thrombotic risk.
Contraindications
Individual hypersensitivity towards the product, heparin, or heparin-like
drugs. Diathesis and haemorrhagic diseases.
Undesirable effects
Occasionally occur.
Capsules: disturbances of the gastroenteric system with nausea, vomiting and
epigastralgia.
Ampoules: pain, burning sensation
and haematoma at the site of the injection. Also, in rare case,
sensitization may occur with cutaneous reactions or reactions on other
sites.
Precautions/Warnings
Given the low toxicity of the substance, there are no particular precautions
for use. However, when treatment with anticoagulants is under way,
haemocoagulative parameters should be monitored periodically.
Drug interactions
As Sulodexide is a heparin-like molecule, it may increase the anticoagulant
effects of heparin itself and of oral anticoagulants if administered at the
same time.
Use in pregnancy
As a precaution, the use of the substance is not advisable during pregnancy
even though studies on fetal toxicity have not revealed any embryo-fetotoxic
effects.
Pharmaceutical precautions
As Sulodexide is an acid polysaccharide, if administered in extemporaneous
association, it may react by forming complexes with all the base substances.
The incompatible substances commonly used for extemporaneous associations
for phleboclysis are: vitamin K, vitamins of the B complex, hydrocortisone,
jaluronidase, calcium gluconate, quaternary ammonium salts, chloramphenicol,
tetracycline, streptomycin.
Dosage
Capsules: 1 capsule twice a day, far from meals.
Ampoules: 1 ampoule a day, i.m. or i.v.
Generally it is advisable to start the therapy with the ampoules and
after 15-20 days, continue the treatment with capsules for 30-40 days. The
complete therapeutic cycle should be repeated at least twice a year. The
posology may be varied in quantity and frequency at the discretion of the
doctor.
Symptoms and treatment for overdosage
Haemorrhage is the only effect which may occur with an overdosage. In the
case of a haemorrhage, it is necessary to inject 1% protamine sulphate (3
ml i.v. = 30 mg) as it is used in "heparin haemorrhages".
Packing
Ampoules: Type I yellow glass weak-point 2 ml ampoule containing a clear
light-yellow to yellow liquid. Each cardboard box containing a polystyrene
tray with 10 dark glass ampoules with injectable solution.
Capsules: 50 capsules (cardboard box containing 2 blisters of 25 soft
capsules each).
Storage conditions
Store below 30 °C.
Expiry period
5 years from the date of
manufacture. |
