ArioSeven^® (Lyophilisate) Instructions for Use

ATC Code

B02BD08 (Eptacog alfa activated (blood coagulation factor VIIa))

Active Substance

Eptacog alfa (activated)

Eptacog alfa (activated) (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Blood coagulation factor VIIa preparation

Pharmacotherapeutic Group

Hemostatic agents; vitamin K and other hemostatic agents; blood coagulation factors

Pharmacological Action

Recombinant blood coagulation factor VIIa. In therapeutic doses, it binds to a large amount of tissue factor, forming a complex that enhances the initial activation of factor X.

In the presence of calcium ions and anionic phospholipids, it is capable of activating factor X on the surface of activated platelets, acting “bypassing” the coagulation cascade system.

It acts only at the site of injury and does not cause systemic activation of the coagulation process.

Pharmacokinetics

Pharmacokinetic profiles indicate a directly proportional dose-dependent relationship.

The V_d at steady state ranged from 130 to 165 ml/kg, mean clearance values ranged from 33.3 to 37.2 ml/h x kg, and the mean T_1/2 ranged from 3.9 to 6.0 hours.

Indications

Bleeding and prevention of massive bleeding during surgical operations in patients with hereditary or acquired hemophilia with inhibitors to coagulation factor VIII and coagulation factor IX; hereditary factor VII deficiency; in patients with Glanzmann’s thrombasthenia and refractoriness (current or past) to platelet transfusions in the presence or absence of platelet antibodies or when platelet concentrate is unavailable.

ICD codes

Dosage Regimen

Administer intravenously by bolus injection over 2-5 minutes. Determine the dosage regimen individually based on indication, severity of bleeding, and clinical response.

For hemophilia A or B with inhibitors, the recommended dose for bleeding episodes is 90 mcg/kg initially. Repeat dosing every 2-3 hours until hemostasis is achieved. For minor bleeding, a single dose may be sufficient. For major bleeding, continue treatment for at least 48 hours; the dosing interval may be increased to 4, 6, 8, or 12 hours once hemostasis is secured.

For surgical prophylaxis in hemophilia with inhibitors, administer a dose of 90 mcg/kg immediately before surgery. Monitor for clinical hemostasis. Repeat dosing every 2-3 hours for the duration of the procedure. For major surgery, continue dosing every 2-3 hours for 48 hours, then every 4-6 hours for up to 2-3 weeks until healing is complete.

For congenital Factor VII deficiency, the recommended dose is 15-30 mcg/kg every 4-6 hours until hemostasis is achieved. Adjust dose and interval based on clinical response and Factor VIIa activity levels.

For Glanzmann’s thrombasthenia with refractoriness to platelets, the recommended dose is 90 mcg/kg. Repeat dosing every 1.5-2 hours for mild to moderate bleeding. For severe bleeding, use the same initial dose and interval; the interval may be increased to 3 hours once hemostasis is achieved. Continue treatment until bleeding stops.

Reconstitute the lyophilisate only with the provided sterile water for injection. Use the reconstituted solution immediately, or within 3 hours when stored at room temperature. Do not refrigerate after reconstitution. Discard any unused solution.

Monitor patients for signs of thrombotic events or disseminated intravascular coagulation (DIC), particularly in patients with predisposing conditions. If hemostasis is not achieved with the recommended dosing, test for the presence of inhibiting antibodies.

Adverse Reactions

From the blood coagulation system: disseminated intravascular coagulation and associated changes in laboratory parameters (increased D-dimer levels and decreased antithrombin III activity, coagulopathy).

From the immune system: hypersensitivity reactions, anaphylactic reactions.

From the nervous system: headache.

From the cardiovascular system: arterial thromboembolism (myocardial infarction, cerebral infarction, cerebral ischemia, cerebral artery occlusion, cerebrovascular complications, renal artery thrombosis, peripheral vascular ischemia, peripheral artery thrombosis, and intestinal ischemia), angina pectoris, thromboembolism (deep vein thrombosis, injection site vein thrombosis, pulmonary thromboembolism, hepatic thromboembolism, incl. portal vein thrombosis, renal vein thrombosis, thrombophlebitis, superficial vein thrombophlebitis, and intestinal ischemia), intracardiac thrombus.

From the digestive system: nausea.

From the skin and subcutaneous tissues: skin rash (incl. allergic dermatitis and erythematous rash), skin itching and urticarial rash, skin redness, angioedema.

From laboratory parameters: increased fibrin degradation products, increased ALT activity, ALP, LDH, and prothrombin concentration.

Other: fever, reactions at the injection site, including pain.

Contraindications

Hypersensitivity to proteins of mice, hamsters, and cows.

Use in Pregnancy and Lactation

Use during pregnancy should be avoided.

It is not known whether the active substance is excreted in breast milk. Use with caution during breastfeeding, only if the expected benefit to the mother outweighs the potential risk to the infant.

Use in Hepatic Impairment

Should be used with caution in patients with liver diseases.

Pediatric Use

Can be used in children according to indications, in recommended doses and regimens. Should be used with caution in newborns.

When used in pediatric practice, higher doses may be required to achieve a plasma concentration of eptacog alfa similar to that in adult patients.

Special Precautions

In pathological conditions accompanied by increased release of tissue factor, the use of eptacog alfa may be associated with a potential risk of thrombotic complications or DIC syndrome. Such conditions include severe atherosclerosis, crush injuries, septicemia, or DIC syndrome.

Eptacog alfa should be prescribed with caution to patients with an increased risk of thrombotic complications or DIC syndrome, patients with a history of coronary artery disease and liver diseases, as well as patients in the postoperative period and newborns.

In each case, the potential benefit of using eptacog alfa for treating patients with the listed conditions must be carefully weighed against the risk of developing the described complications. Such patients require careful medical supervision.

In patients with blood coagulation factor VII deficiency, prothrombin time and blood coagulation factor VII activity should be monitored before and after administration of eptacog alfa.

If factor VIIa activity does not reach the expected value, or bleeding continues despite the use of eptacog alfa in recommended doses, antibody formation can be suspected. In this case, an analysis for the presence of antibodies should be performed.

Cases of thrombosis have been reported with the use of eptacog alfa during surgical interventions in patients with blood coagulation factor VII deficiency, but there is no data on the risk of thrombosis in patients with blood coagulation factor VII deficiency during treatment with eptacog alfa.

Drug Interactions

Eptacog alfa should not be mixed with infusion solutions.

Storage Conditions

Store at 2°C (36°F) to 8°C (46°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

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.