NovoSeven

Active material: Eptakog alpha
When ATH: B02BD08
CCF: The preparation of Factor VIIa clotting
ICD-10 codes (testimony): D66, D67, D68.2, D68.4, D69
When CSF: 20.01.06
Manufacturer: NOVO NORDISK A/S (Denmark)

Pharmaceutical form, composition and packaging

Valium for drug of a solution for / in white, homogeneous.

Excipients: sodium chloride, Calcium chloride dihydrate, Glycylglycine, polysorbate 80, mannitol, nitrogen (to fill the void volume of the bottle).

* 1 CUD matches 1000 ME (International units).

Solvent: water d / and.

Bottles of colorless glass (1) together with the solvent (fl.), vial adapter, disposable polypropylene syringe for dilution and administration, system for transfusion, alcohol swabs (2 PC.) – packs cardboard.

Pharmacological action

Recombinant coagulation factor VIIa, weight of about 50000 Dalton, obtained by genetic engineering from hamster kidney cells. The mechanism of action of the drug is to bind factor VIIa with tissue factor Liberate. The resulting complex activates factor IX, active form of factor IXa and factor X to form active factor Xa, which leads to a small amount of primary conversion of prothrombin to thrombin. Thrombin activates platelets and factors V and VIII in the lesion and by converting fibrinogen into fibrin provides a haemostatic plug formation.

At therapeutic doses, the drug NovoSeven^® directly, regardless of factors tkanevogo, activates factor X on the surface of activated platelets, localized to the site of injury. This leads to the formation of thrombin from prothrombin in large amounts independent of tissue factor. Thus, pharmacodynamic effect of factor VIIa is to strengthen local education factor Xa, thrombin and fibrin.

Theoretically, we can not completely eliminate the risk of systemic activation of the blood clotting in patients, suffering from diseases, predisposing to the development of DIC.

Pharmacokinetics

Inhibitory hemophilia A and B

Using the method of determining the activity of the coagulation factor VII, pharmacokinetic properties of NovoSeven^® studied in 25 cases is bleeding and conditions 5 cases of bleeding.

It was analyzed coagulation factor VII activity in the plasma before and during 24 hours after administration of NovoSeven^®.

Pharmacokinetics preparation NovoSэven^® a single administration at a dose 17.5, 35 and 70 micrograms per kg of body weight was of linear. Average apparent V_d in equilibrium and elimination phase totaled 106 and 122 ml / kg in terms of bleeding and is 103 and 121 ml / kg at a bleeding.

The average clearance of the two groups was 31.0 ml / hr x kg 32.6 ml / h × kg, respectively. Withdrawal was described by the average residence time in the blood plasma, and T_1/2, which respectively accounted for 3.44 and h 2.89 no (averages) for conditions and is bleeding 2.97 and 2.3 h for bleeding. The median plasma recovery was 45.6% patients is bleeding and conditions 43.5% patients during bleeding.

Factor VII deficiency

Pharmacokinetics preparation NovoSэven^® a single administration at a dose 15 and 30 ug per kg of bodyweight had no significant difference in parameters dozonezavisimym: total clearance (70.8-79.1 ml / h × kg), V_d at equilibrium (280-290 ml / kg), the average residence time in the plasma (3.74-3.8 no) and T_1/2 (2.82 – 3.11 no). The median in vivo plasma recovery was approximately 20%.

Glanzmann thrombasthenia

Pharmacokinetics preparation NovoSэven^® in patients with thrombasthenia Glantsmana has not been studied, but it is assumed, it is similar to the pharmacokinetics of the drug in patients with hemophilia A and B.

Testimony

To stop the bleeding and prevent their development during surgery and invasive procedures in patients with the following disorders:

- Hereditary hemophilia with a titer inhibitors of coagulation factors VIII or IX more 5 WAS (Bethesda units);

- Hereditary hemophilia with the expected immune response to infusion of factor VIII or factor IX on the basis of history;

- Acquired haemophilia;

- Congenital factor VII deficiency;

- Thrombasthenia Glantsmana the presence of antibodies to glycoprotein IIb-IIIa and refractory (in the present or past) to platelet transfusions.

Dosage regimen

At inhibitor haemophilia A or B, and acquired haemophilia to begin administering the drug NovoSeven^® It should be as soon as possible after the onset of bleeding. The drug is introduced into / jet. 1 dose of 90 ug / kg body weight. The drug should be administered every 2-3 hours until hemostasis. If there are indications for further treatment after the bleeding stops, the intervals between doses of the drug can be successively increased to 4, 6, 8 or 12 h for the entire period of therapy according to indications.

The duration of treatment and the interval between administration of the drug are determined by the nature of the severity of bleeding or invasive procedures or surgery.

At bleeding light to moderate (including outpatient treatment) better early introduction of NovoSeven^®. The recommended dosing regimens: 1) the introduction of 1 to 3 injection at a dose 90 ug / kg body weight via 3 no, for maintenance can be assigned to another 1 injection drug dose 90 mg / kg; 2) a single injection of the drug on the basis of 270 ug / kg body weight. The duration of outpatient treatment should not exceed 24 no.

At severe bleeding The recommended starting dose is 90 ug / kg body weight and can be administered during their transportation to the hospital, which is usually the patient is being treated. Driving further treatment depends on the type and severity of bleeding. At the beginning of the treatment drug is administered every 2 hours before the onset of clinical improvement. If there is evidence to continue treatment intervals between administration of the drug can be increased to 3 h for 1-2 d. In the following intervals between doses of the drug may be increased to 4, 6, 8 or 12 h for the entire treatment period according to indications. Duration of treatment may be severe bleeding 2-3 week, or more if clinically indicated.

At invasive procedures or surgery immediately prior to the initial dose is administered intervention 90 ug / kg body weight. The second dose is administered through 2 no, and then the drug is injected with 2-3 hour intervals during the first 24-48 h depending on the conductivity of the intervention and the clinical condition of the patient. For large operations, treatment continues 6-7 days 2-4 hour intervals between doses. During the treatment in the next 2 week intervals between doses of the drug can be increased to 6-8 no. The total duration of the drug after major surgery may be 2-3 week until healing.

At acquired haemophilia (including outpatient treatment) at the onset of bleeding should be introduced as soon as possible drug. The recommended starting dose is 90 ug / kg body weight / jet. If necessary, administration of NovoSeven^® can be repeated. The duration of treatment and the interval between administration of the drug are determined by the nature of the severity of bleeding or invasive procedures / surgery. With the introduction of the initial dose interval should be 2-3 no. After achieving hemostasis intervals between doses of the drug for the entire period of treatment can be increased to 4, 6, 8 or 12 no.

At congenital deficiency of factor VII to stop the bleeding and the prevention of bleeding during surgery or invasive procedures recommended dose is 15-30 ug / kg body weight. The drug is administered every 4-6 hours until hemostasis. The dosage and frequency of administration are specified individually.

At trombastenii Glancmana to stop the bleeding and the prevention of bleeding during surgery or invasive procedures recommended dose is 90 g (80-120 g) kg body weight. The drug is administered every 2 no (1.5-2.5 no). To ensure a stable hemostasis requires at least 3 doses. It recommended in / bolus, because when drip drug efficacy may be reduced. When trombastenii Glantsmana without refractory drug of choice is a platelet.

Terms of use of NovoSeven^®

Breeding It should be carried out under aseptic conditions. NovoSeven vial^® (liofilizatom) and the solvent (water) It should be warmed to room temperature (but not higher than 37 ° C), hold in their hands. Remove the protective plastic cap from the vial and the vial containing the lyophilisate with the solvent. If the cap is missing or wearing loose, then the vial must not be used. Treat rubber stoppers with a cotton swab with rubbing alcohol and allow to dry. Remove the protective cover from the vial adapter, without taking it out of the package. Attach the adapter to a bottle of water. Do not touch the tip of the vial adapter. After, the adapter is fitted to a bottle, remove his package. Pulling back the plunger, to dial into a syringe in a volume of air, equal to the volume of the vial with water. Carefully screw the syringe to the vial adapter on the water. By pressing the plunger, to introduce air into the bottle until, yet you will not feel strong resistance. Then turn the bottle upside down, completely get water from a bottle into a syringe. Remove empty bottle tipping the syringe with the vial adapter.

Snap Adapter for bottle, connected to a syringe, on the vial with lyophilisate. Hold the syringe in a slightly tilted state downwardly. Enter the water in a bottle, slowly pushing the plunger of the syringe. The stream of water should not fall directly on the lyophilisate, tk. this may cause the formation of foam. It vial slowly rotated until complete dissolution of lyophilizate. Do not shake the bottle, tk. with the possible formation of foam.

Prior to administration, check the prepared solution of NovoSeven^® for mechanical particles and colorless. Commercially available disposable syringe kit is compatible with the prepared solution, but it is impossible to keep the drug dissolved in plastic syringes. It is recommended to use the drug NovoSeven^® immediately after reconstitution.

Introduction. Make sure that, that the plunger fully into the syringe before, like pulling it (the piston can be pushed under pressure into the syringe). Holding the syringe upside (“upside down”), collect all the prepared solution into a syringe. Unscrew the vial adapter with the empty vial. At this stage of NovoSeven^® ready for administration. Further, the normal procedure should be followed with the introduction of the system applied for transfusion. The drug is administered in / for 2-5 m.

Syringe, adapter for the bottle, bottles, system for transfusion, Any number of unused product and the materials used should be disposed of in accordance with the requirements.

Side effect

Based on experience with the drug in clinical side effects are rare (<1 on 1000 standard dose). In the analysis of organs and systems of the following parameters were obtained in the incidence of side effects.

From the blood coagulation system: rarely (< 1/10 000) – coagulopathies (increase in D-dimer, and the accumulation of coagulopathy), increase in prothrombin. There are cases of bleeding during treatment with the drug NovoSeven^®. Expected, that NovoSeven^® It is not the cause of bleeding, however already emerged bleeding may continue in case of insufficient efficacy or inadequate doses.

Cardio-vascular system: rarely (< 1/10 000) – myocardial infarction, venoznыy thrombosis.

From the digestive system: rarely (< 1/10 000) – nausea, increased ALT, Alkaline phosphatase.

CNS: rarely (< 1/10 000) – cerebrovascular disorders, incl. cerebral infarction and cerebral ischemia.

Dermatological reactions: possible skin rash.

Other: rarely (< 1/1000, > 1/10 000) – lack of effectiveness of the drug; rarely (< 1/10 000) – fever, pain at the injection site, LDH increase.

Side effects, registered postmarketinogovyh studies

From the blood coagulation system and the cardiovascular system: arteryalnыy thrombosis (myocardial infarction or ischemia, cerebrovascular pathology and intestinal infarction) – the vast majority in the predisposition to the development of arterial thrombosis (associated disease, age, atherosclerosis); venoznыy thrombosis (tromboflebit, deep vein thrombosis and complications – pulmonary embolism) – in most cases with the predisposition to the development of venous thrombosis due to the presence of associated risk factors (associated disease, JavaScript thrombosis history, immobilization in the postoperative period or vein catheterization).

Allergic reactions: in some cases – hypersensitivity reactions (including anaphylactic reactions), the appearance of antibodies to factor VII after administration of NovoSeven^® in patients with deficiency of factor VII (these patients previously poured human plasma and / or plasma factor VII, in 2 patients had inhibitory effect of the antibodies in vitro). Factor VII antibodies in patients with hemophilia A and B have been identified. Described 1 cases of angioedema after administration of NovoSeven^® a patient with thrombasthenia Glantsmana.

Contraindications

- Hypersensitivity to mouse proteins, hamster or cow;

- Hypersensitivity to the drug.

Pregnancy and lactation

NovoSeven during pregnancy^® prescribed only under strict indications. Unknown, Can the NovoSeven^® when administered to a pregnant woman or the fetus cause damage to lead to a breach of reproductive function.

Unknown, whether it is allocated an active ingredient of the drug in breast milk. Therefore, if necessary, the appointment of NovoSeven^® lactation should be careful.

IN experimental studies on animals have shown, in / with the introduction of NovoSeven^® no effect on fetal development, fertility and reproductive properties.

Cautions

Therapy with NovoSeven^® It does not require laboratory monitoring. Doses are determined depending on the severity of bleeding and clinical effect. It has been shown, that after the introduction of NovoSeven^® prothrombin time (PV) APTT and reduced, However, the correlation between the PX and aPTT and clinical efficacy of NovoSeven^® There were no.

Under pathological conditions, accompanied by an increased release of tissue factor (severe atherosclerosis, crush injury, septicemia), the use of NovoSeven^® It may be associated with a potential risk of thrombotic complications or disseminated intravascular coagulation (ICE). Such conditions include severe atherosclerosis, crush injury, septicemia. Patients with increased risk of developing DIC requires strict surveillance with laboratory control.

Because the drug NovoSeven^® may contain trace amounts of mouse IgG, bovine IgG and other residual culture proteins (whey proteins hamsters and cows), the introduction of this drug there is very little opportunity to develop hypersensitivity to these proteins.

Patients with allergic history requires careful observation.

Severe bleeding drug is preferably used in clinics, specializing in the treatment of haemophilia with inhibitors to coagulation factors VIII or IX, and if this is not possible, in close collaboration with a physician, specializing in the treatment of hemophilia.

No clinical experience of administration of a single dose of 270 ug / kg body weight elderly patients.

The duration of outpatient therapy should not exceed 24 no. If during this time you can not stop the bleeding, required hospitalization. Patients or persons, taking care of them, should, at the first opportunity, notify your doctor or clinic about every use of NovoSeven^® at home.

Patients with a deficiency of factor VII, prothrombin time must be monitored and factor VII activity before and after administration of NovoSeven^®. If the activity of factor VIIa does not reach the expected level or bleeding continues, despite the use of the drug at the recommended doses, We can assume antibody. In this case, should be analyzed for the presence of antibodies.

Data on the risk of thrombosis in patients with factor VII deficiency on the background of treatment with NovoSeven^® no.

Patients, who have a risk of developing venous thrombosis requires careful observation.

Before use, check the clarity of the solution and the presence of particles. Unused products and waste should be disposed of in accordance with local requirements.

Overdose

Elderly patients (senior 80 years) male Factor VII deficient, the preparation in a dose of, exceeds recommended in 10-20 time, thrombotic complications observed. No other thrombotic complications from overdose have not been observed, incl. in 6-year-old boy with haemophilia A with inhibitors, the preparation in a dose of, exceed the recommended dose 8-10 time.

Drug Interactions

Data on the risk of possible interactions between the drug NovoSeven^® and concentrates of clotting factors are missing. It should not be administered simultaneously prothrombin complex concentrate (activated or not activated) and NovoSeven^®.

According to reports Antifibrinolytics reduce intraoperative blood loss in patients with hemophilia, especially in orthopedic surgery and surgery tissues with high fibrinolytic activity, eg, oral. The experience of the combined use of NovoSeven and antifibrinolytics^® limited.

NovoSeven^® should not be mixed with infusion solutions or nominate a drip.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored in its original packaging (to protect from light) in a refrigerator at 2 ° to 8 ° C.; Do not freeze. Shelf life in commercial package – 3 year.

It has been shown, that the drug retains chemical and physical properties at a temperature of 25 ° C for 24 hours after dilution. From the microbiological point of view, the prepared solution should be used immediately after reconstitution. In that case, if the entire dilute the drug is administered at once, responsible for the duration and conditions of storage (usually, is less than 24 hours at a temperature of from 2 ° to 8 ° C.), own risk, except dilution of the drug in a controlled aseptic conditions. Do not store the diluted drug in plastic syringes.