Atenativ (antithrombin i) 500 IU antithrombus i №1 vial + solvent 10 ml.

Description

Ingredients

active substance: antithrombin III;

1 ml contains 50 IU of antithrombin III;

1 vial contains 500 IU (70–100) mg or 1000 IU (140–200) mg of antithrombin III;

excipients:sodium chloride, albumin stabilized (100 mg (500 IU) or 200 mg (1000 IU), containing acetyltryptophan, caprylic acid.

Solvent: water for injections.

Medicinal form

Powder and solvent for solution for infusion.

The main physical and chemical properties:

powder: white or almost white, hygroscopic brittle mass or powder;

solvent (water for injections): clear, colorless liquid, without particles.

Pharmacotherapeutic group

Antithrombotic agents, heparin group. Antithrombin III. Code АТХВ01АВ02.

Pharmacological properties

Pharmacodynamics.

Antithrombin, molecular weight 58 kDa, consisting of 432 amino acids, belongs to the serpin subfamily (inhibitors of serine proteases). It is one of the most important natural blood clotting inhibitors. The factors most inhibited are thrombin and cofactor Xa, as well as contact activation factors, the intrinsic system, and the factor VIIa/tissue factor complex. The activity of antithrombin is significantly enhanced by heparin, and the anticoagulant effect of heparin depends on the presence of antithrombin. Antithrombin contains two functionally important domains. The first one contains a reactive center and provides cleavage of such proteinases as thrombin and promotes the formation of a stable proteinase-inhibitor complex. The second is a glycosaminoglycan-binding domain responsible for interaction with heparin and related substances involved in the acceleration of thrombin inhibition. Coagulation inhibitor-enzyme complexes are removed by the reticuloendothelial system. The activity of antithrombin in adults is 80–120%, and in newborns it is about 40–60%.

There are several smaller studies in consumption syndrome (Disseminated Intravascular Coagulation, DIC), sepsis, pre-eclampsia, L-asparaginase treatment of acute lymphoblastic leukemia, veno-occlusive disease, surgical interventions with an artificial circulatory device, where the use of antithrombin has shown a positive effect on coagulation parameters. A conclusive effect on morbidity and mortality has not been documented in these cases. In the so-called KyberSept trial, which involved more than 2,300 patients with sepsis, there was no difference in mortality in those treated with antithrombin compared to those treated with a placebo.

Indications

Patients with congenital deficiency of antithrombin III for:

1. a) prevention of deep vein thrombosis and thromboembolism in situations of clinical risk (especially during surgical interventions or in the perinatal period), in combination with heparin, if it is prescribed;
2. b) prevention of progression of deep vein thrombosis and thromboembolism together with heparin, as indicated.

Atenativ is indicated for use by adults.

Contraindications

Hypersensitivity to the active substance or to any of the auxiliary substances or to the residues of substances used in the production process.

Method of application and dosage

Treatment should be initiated under the supervision of a physician experienced in treating patients with antithrombin deficiency.

With congenital deficiency, the dose should be selected individually for each patient, taking into account the family history of thromboembolic complications, existing clinical risk factors, as well as laboratory test results.

The number of units of antithrombin prescribed is expressed in international units (IU) corresponding to the current WHO standard for antithrombin. The activity of antithrombin in blood plasma is expressed as a percentage (relative to normal human blood plasma) or in international units (IU) (according to the international standard for antithrombin in blood plasma).

One international unit (IU) of antithrombin activity corresponds to the amount of antithrombin in 1 ml of normal human blood plasma. The calculation of the required dose of antithrombin is based on empirical data that 1 international unit (IU) of antithrombin per 1 kg of body weight increases the activity of antithrombin in blood plasma by approximately 1%.

The initial dose is determined by the following formula:

Number of units = body weight (kg)× (target level – available antithrombin activity [%])× 1.

The initial target activity of antithrombin depends on the clinical situation. When antithrombin replacement therapy is indicated, the dose should be sufficient to achieve the target antithrombin activity and maintain an effective level. The dose should be determined and controlled by laboratory measurements of antithrombin activity, which should be carried out at least twice a day until a stable concentration is reached in the patient, then once a day, preferably immediately before the next intravenous administration of the drug. When adjusting the dose, signs of an increase in the renewal of antithrombin should be taken into account in accordance with the verification of laboratory indicators and the clinical course of the disease. Antithrombin activity should be maintained at a level above 80% throughout the treatment period, unless clinical data indicate a different effective level.

Usually, the initial dose for congenital deficiency of antithrombin III is 30–50 IU/kg.

Next, the dose and frequency, as well as the duration of treatment, should be selected according to biological data and the clinical situation.

Application method

The powder is diluted in sterile water for injection.

After dilution, Atenativ can be mixed with isotonic sodium chloride solution (9 mg/ml) and/or isotonic glucose solution (50 mg/ml) in glass infusion bottles and plastic containers.

Atenativ cannot be used after the expiration date indicated on the package.

Usually the solution is clear or slightly opalescent. Do not use solutions that are cloudy or that contain sediment.

The drug dissolves within no more than 5 minutes. After dissolution, the drug should be used as soon as possible and within 12 hours, if it was stored at a temperature of 15 to 25 °C.

Any unused solution should be disposed of.

Any unused product or waste material should be disposed of in accordance with local requirements.

The drug should be administered intravenously.

The infusion rate for adults should not exceed 300 IU/min.

Children.

There are no data.

The safety and effectiveness of Atenativ for children have not been established.