SINTROM ® Acenocumarol

SINTROM ® is a drug based on Acenocumarol.

THERAPEUTIC GROUP: Antithrombotics.

IndicationsAction mechanismStudies and clinical effectiveness Usage and dosage instructionsWarnings Pregnancy and lactationInteractionsContraindicationsUndesirable effects

Indications SINTROM ® Acenocumarol

SINTROM® is useful as a preventive and therapeutic pharmacological intervention against thromboembolic disorders.

Mechanism of action SINTROM ® Acenocumarol

The acenocumarol, taken orally by SINTROM ® is rapidly absorbed in the intestine, reaching the maximum plasma concentration, which is dose dependent, in about 2-3 hours. Despite the high first-pass metabolism - which involves reducing the pharmacologically active portion of the drug in favor of non-functioning alcohol and hydroxylated metabolites - the bioavailability of the active ingredient reaches about 60%.

Linked to plasma proteins, mainly albumin, acenocoumarol is able to inhibit the functionality of vitamin K, making the coagulation process difficult.

Although the activity of coumarin derivatives in antagonizing the coagulant effect of vitamin K has not yet been fully characterized, it is possible that these substances reduce the biologically active form of this molecule (ie the reduced form) involved as a cofactor. in the reaction of carboxylation of glutamic acid residues, necessary to start the coagulation process.

The inhibiting action on the coagulation process is realized with the sought antithrombotic effect.

The acenocumarol and its inactive metabolites, after about 10 hours, are eliminated for about 2/3 through the urine and for the remainder through the faeces.

Studies carried out and clinical efficacy

COMBINED THERAPY IN VENOUS THROMBOSIS

The study shows that the concomitant administration of acenocoumarol and heparin can guarantee an important reduction in the symptoms related to venous thrombosis. In fact, in the group treated with acenocumarol alone, the incidence of venous thrombosis symptoms was 40%; decidedly higher value compared to the 8% observed in patients receiving combined therapy.

2. INTER-INDIVIDUAL VARIABILITY OF ACENOCUMAROL EFFECTIVENESS

The pharmacokinetic characteristics of acenocumarol are strongly influenced by some polymorphisms involving CYP2C9 and VKORC1 (enzymes involved in the metabolism of the active ingredient and vitamin K) which are very frequent in the population, and which generally require a further adjustment of the dosage of this drug. These assumptions make it necessary to monitor the coagulation framework before and during the therapeutic intervention, in order to avoid clinically serious side reactions.

3. ACENOCUMAROL, DIFFICULTY OF PRESCRIPTION

The relevant metabolic and hemodynamic effects of anticoagulants subject the physician to an important task, which is the formulation of the correct dosage, useful for reducing the potentially dangerous side effects of the therapy. To simplify the work of the doctor on the one hand, and to standardize the therapeutic protocol on the other hand, new algorithms based on the physio-pathological characteristics of the patient could guide the practitioner towards the correct formulation of the dosage.

Method of use and dosage

SINTROM ® quadrisechable tablets of 1 - 4 mg of acenocumarol: given the enormous individual variability to the anticoagulant therapeutic action, it is not possible to suggest a clinically safe and effective standard dosage.

The choice of the therapeutic procedure should be made by the doctor, after a careful evaluation of the patient's coagulation and hematological picture, in order to avoid the occurrence of side effects and at the same time maximize the therapeutic result.

The customization of the dosage is simplified by the possibility of easily dividing the tablets, allowing a fine modulation of the dose taken, which should be adequate, even during therapy, to the hematological values found.

IN ANY CASE, BEFORE TAKING SINTROM ® Acenocumarol - THE REQUIREMENT AND CHECK OF YOUR DOCTOR IS NECESSARY.

Warnings SINTROM ® Acenocumarol

Before starting treatment with SINTROM ® it would be necessary to carefully examine the coagulation parameters (in order to correctly address the therapeutic protocol), repeating them periodically with the therapy in progress.

Particular attention should be paid in the case of patients suffering from alterations of the coagulation picture or in case of reduced liver function, for which significant alterations of the pharmacokinetic properties of the drug could be more frequent. Such alterations could also occur in the case of altered binding to plasma proteins, which can be documented in cases of thyrotoxicosis, tumors, renal disorders, infections and inflammatory pathologies.

In all the aforementioned states, careful monitoring of the haematological picture would be advisable, as well as a gradual suspension of therapy in order to avoid rebound hypercoagulability.

Even metabolic alterations affecting the absorption and synthesis of vitamin K could interfere with the normal therapeutic capacity of SINTROM ®, thus requiring an adjustment of the dosage.

The reduced coagulative capacity induced by the acenocumarol, could determine the onset of hematomas in case of intramuscular injections.

In case of surgery or first aid, it would be advisable to remind health personnel of the intake of an anticoagulant drug.

PREGNANCY AND BREASTFEEDING

The important hemodynamic effects induced by SINTROM ® could cause haemorrhages in the fetus, spontaneous abortions, death and preterm labor; therefore its intake is strongly contraindicated in case of pregnancy.

This contraindication should also be extended during lactation, given the important secretion of acenocoumarol in breast milk.

Interactions

Acenocoumarol, as a coumarin derivative, is particularly subject to interactions with other active ingredients; from the clinical point of view, however, the relevant ones are with:

Allopurinol, anabolic steroids, antiarrhythmic androgens, antibiotics, fibrates and derivatives, glucagon, antihistamines, oral antidiabetic agents, thyroid hormones and cimetidine.
Heparin, salicylic acid and derivatives, with enhancement of the anticoagulant effect and greater risk of hemorrhage;
barbiturates, cholestyramines, oral contraceptives, corticosteroids, diuretics and rifampicin, may instead decrease the anticoagulant effect.

Therefore, given the multiple interactions, it would be appropriate to monitor the coagulation framework in case of concomitant administration of other drugs.

Contraindications SINTROM ® Acenocumarol

SINTROM ® is contraindicated in case of known hypersensitivity to coumarin derivatives, in patients at risk of hemorrhage (suffering from peptic ulcer, hemorrhagic cysts, cerebrovascular haemorrhages, parenchymal lesions of internal organs ...).

The need for adequate and constant monitoring requires active patient participation; therefore therapy with SINTROM ® is contraindicated in case of uncooperative patients.

Undesirable effects - Side effects

The side effects described following therapy with SINTROM ® essentially concern the coagulation picture, with a greater incidence of hemorrhages in different parts of the body, especially against the gastro-intestinal, cerebral and genito-urinary tract.

These manifestations are decidedly more evident in all those patients predisposed to the development of such diseases.

More rarely have been described alopecia, fever, gastro-intestinal reactions and urticaria.