Factor vii (blood clotting factor vii). Clotting factors

Blood clotting is a key process in stopping bleeding when the walls of blood vessels are damaged. If bleeding occurs at the first stage, blood loss is reduced by...

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Description of the study

Preparing for the study: Special training not required. Blood with EDTA or buccal (cheek) epithelium is analyzed Test material: Taking blood

Blood clotting is a key process in stopping bleeding when the walls of blood vessels are damaged. If bleeding occurs at the first stage, blood loss is reduced by mechanical means - vasospasm occurs and the damage is blocked by platelets. After this healthy person local formation of a so-called fibrin blood clot occurs and the final blockage of the damage occurs. The formation of fibrin from fibrinogen is a complex multi-step process that takes about 10 minutes. The conversion occurs through a cascade of enzymatic reactions in which one activated coagulation factor catalyzes the activation of the next. There are more than a dozen such factors in total.

When a vessel is damaged, a tissue factor that is not normally there enters the bloodstream. In the bloodstream, it interacts with factor F7, and this interaction triggers a further cascade of reactions leading to the formation of a blood clot.

Replacement of guanine with adenine at position 10976 leads to a decrease in F7 gene expression. Reduced level F7 is a protective factor in the development of myocardial infarction and thrombosis. In addition, women with the mutant gene are less likely to experience miscarriage.

A variant of this protein containing glutamine instead of arginine is found in 10-20% of the European population.

Method

Polymerase is used to detect mutations chain reaction in real time. The polymerase chain reaction allows, under correctly selected conditions, to obtain a large number of copies of a given DNA section. Conditions can be selected in such a way that the difference in DNA chains in one nucleotide significantly affects the efficiency of copy formation. In this way, it is possible to determine which nucleotide is contained in a given sequence.

Reference values ​​- norm
(Gene F7 (blood clotting factor 7), identification of polymorphism G10976A (Arg353Gln))

Information regarding the reference values ​​of indicators, as well as the composition of the indicators included in the analysis, may differ slightly depending on the laboratory!

Norm:

Adenine at position 10976 reduces the likelihood of thrombosis, myocardial infarction, death from myocardial infarction, and miscarriage.

Guanine at position 10976 corresponds to the usual probability of thrombosis, myocardial infarction, death from myocardial infarction, and miscarriage.

Indications

Assessment of the risk of developing myocardial infarction and the likelihood of a fatal outcome in myocardial infarction.

Finding out the causes of miscarriage.

Where to get tested

10 laboratories make this analysis in your region. To find your nearest laboratory and compare prices for the test - Blood clotting factor 7 (F7). Detecting the G10976A (Arg353Gln) mutation - click the button.

Clinical and pharmacological group

20.011 (Drug factor VII blood clotting)

Release form, composition and packaging

pharmachologic effect

Pharmacokinetics

With intravenous administration of Factor VII, the increase in its concentration in the patient’s blood plasma is 60-100%; T 1/2 is on average 3-5 hours.

Dosage

Duration replacement therapy and doses depend on the severity of factor VII deficiency, the location and extent of bleeding or hemorrhage, and clinical condition sick. The prescribed dose of factor VII is calculated in international units (IU) according to current WHO standards for preparations containing factor VII. Factor VII activity in plasma can be calculated as a percentage of normal and in international units.

One international unit of factor VII activity is equivalent to the activity of factor VII in 1 ml of normal human plasma.

The required dose is calculated based on the empirical observation that with the introduction of 1 IU of factor VII per 1 kg of body weight, the activity of factor VII in plasma increases by 1.7%.

The required dose is calculated using the following formula:

Required dose (ME) = body weight (kg) x desired increase in factor VII activity (%) x 0.6

When determining the dose and frequency of drug administration in each specific case clinical effect should be taken into account.

When choosing an administration interval, it should be taken into account that T1/2 factor VII is very short - approximately 3-5 hours.

If it is necessary to maintain for a long time high level factor VII in plasma, the drug should be administered at intervals of 8-12 hours.

No dose adjustment is required for liver diseases.

Method of administration

A solution for intravenous administration from factor VII lyophilisate should be prepared immediately before administration. Use only the included administration kit. The solution should be clear or slightly opalescent. Do not use the solution if it is cloudy or contains mechanical impurities. All used materials and unused solution must be disposed of in accordance with established rules.

Preparation of a solution from lyophilized concentrate

1. Heat the closed bottle with the solvent to room temperature (not higher than 37°C).

2. Remove the protective caps from the bottles containing factor VII concentrate and solvent, and disinfect the rubber stoppers on both bottles.

3. Turn and then remove the protective packaging from one end of the adapter needle included in the kit. Pierce the rubber stopper of the solvent bottle with this end of the needle.

4. Carefully remove the protective packaging from the other end of the adapter needle, without touching the needle itself.

5. Turn the bottle with the solvent over and pierce the rubber stopper of the bottle with factor VII concentrate with the free end of the adapter needle. Due to the vacuum, the solvent will flow into the vial containing the factor VII concentrate.

6. Disconnect the bottles by removing the adapter needle from the bottle with factor VII concentrate. To dissolve the concentrate more quickly, carefully rotate and rock the bottle.

7. To deposit the foam after the concentrate has completely dissolved, insert the supplied air duct needle into the bottle. Remove the air duct needle after the foam has settled.

IV jet injection

1. Turn and then remove the protective packaging from the filter needle and attach it to a sterile disposable syringe. Draw the solution into a syringe.

2. Disconnect the filter needle from the syringe, attach a butterfly needle or a disposable injection needle and inject the IV solution slowly (at a rate of no more than 2 ml/min).

3. When administered at home, the patient must put all used materials in the drug packaging and hand it over to medical institution, where it is observed for control.

IV drip administration

For intravenous drip administration, a disposable transfusion system with a filter should be used.

Overdose

When using large doses of drugs containing factor VII, cases of myocardial infarction, disseminated intravascular coagulation syndrome, venous thrombosis and thromboembolism pulmonary artery. Therefore, in case of overdose in patients with risk factors for thromboembolic complications or disseminated intravascular coagulation syndrome, the likelihood of developing these complications increases.

Drug interactions

INTERACTION WITH OTHER DRUGS

No interactions of human plasma Factor VII with other drugs have been observed.

Before administration, Factor VII should not be mixed with other drugs. When using a venous catheter, it is recommended to flush it with isotonic saline solution before and after the introduction of Factor VII.

Effect on laboratory parameters:

In patients receiving large doses of Factor VII, when performing heparin-sensitive coagulation tests, the presence of heparin in the drug should be taken into account. If necessary, the effect of heparin can be neutralized by adding protamine to the test sample.

Pregnancy and lactation

The safety of Factor VII during pregnancy has not been demonstrated in controlled clinical studies. Therefore, Factor VII can be prescribed during pregnancy and lactation only according to strict indications

Side effects

Rarely development is observed allergic reactions(such as urticaria, nausea, vomiting, bronchospasm, decreased blood pressure), in some cases - severe anaphylaxis (including shock).

In rare cases fever was noted. When treated with prothrombin complex factors, one of which is factor VII, thromboembolic complications are possible, especially in cases where high doses of the drug are prescribed and/or in patients with risk factors for thromboembolism.

Storage conditions and periods

The drug should be stored out of the reach of children at a temperature of 2° to 8°C. Shelf life - 3 years.

Indications

Treatment and prevention of blood clotting disorders caused by hereditary or acquired factor VII deficiency;

- acute bleeding and prevention of bleeding during surgical interventions in patients with congenital factor VII deficiency (hypo- or aproconvertinemia);

— acute bleeding and prevention of bleeding during surgical interventions with acquired factor VII deficiency due to oral anticoagulants;

- vitamin K deficiency (for example, if its absorption in the gastrointestinal tract is impaired, with prolonged parenteral nutrition);

— liver failure(for example, with hepatitis, cirrhosis of the liver, severe toxic damage liver).

Contraindications

— disseminated intravascular coagulation (DIC) syndrome and/or hyperfibrinolysis until the underlying causes are eliminated;

- a history of heparin-induced thrombocytopenia;

- age up to 6 years;

— increased sensitivity to the drug or any of its components.

Due to the risk of developing thromboembolic complications, a drug with special care should be used in patients with a history of coronary artery disease, myocardial infarction, liver disease, as well as in patients with postoperative period, newborns and persons at high risk of developing thromboembolism or disseminated intravascular coagulation syndrome. In these cases it is necessary to correlate possible benefit from the use of Factor VII with the risk of developing these complications.

special instructions

Since Factor VII is a protein preparation, allergic reactions may occur. Patients should be informed about early symptoms allergies, such as urticaria (including generalized), chest tightness, wheezing, drop in blood pressure and anaphylaxis. If these symptoms occur, patients should immediately interrupt treatment and contact their doctor.

If shock develops, you should act in accordance with established regulations. this moment rules for the treatment of shock.

Based on the experience of using human plasma prothrombin complex, we can talk about an increased risk of thromboembolic complications and disseminated intravascular coagulation in patients receiving human plasma factor VII.

Theoretically, factor VII replacement therapy may lead to the development of factor VII inhibitors in the patient. However, until now in clinical practice no such case has been described.

The amount of sodium in the maximum daily dose may exceed 200 mg, which should be taken into account when used in patients on a low-sodium diet.

Factor VII is produced from human plasma. When administering drugs made from human blood or plasma, the possibility of transmission of viruses cannot be completely excluded. This also applies to pathogens whose nature is currently unknown.

The risk of virus transmission is minimized as a result of a number of safety measures, namely:

— donor selection based on data medical examination and screening the blood and plasma of each donor, as well as plasma pools, for HBsAg and antibodies to HIV and hepatitis C viruses;

— testing plasma pools for the presence of genomic material of hepatitis A, B and C viruses, HIV-1 and HIV-2, as well as parvovirus B19;

— application of virus inactivation/removal methods in the production process. Using pathogen viruses and/or model viruses, the effectiveness of these methods against hepatitis A, B and C viruses, HIV-1 and HIV-2 has been established.

However, the effectiveness of current virus inactivation/removal methods may not be sufficient for some non-enveloped viruses, such as parvovirus B19, as well as for currently unknown viruses. Infection with parvovirus B19 can be dangerous for pregnant women (infection of the fetus), as well as for people with immunodeficiency or increased production of red blood cells (for example, hemolytic anemia).

Vaccination against hepatitis A and B is recommended for patients receiving human plasma factor VII.

FACTOR VII (BLOOD CLOTTING FACTOR VII) - description and instructions provided by the Vidal drug reference book.

Blood is one of the most important parts human body. This liquid substance nourishes all organs and tissues of our body. Normally, an adult has from 3500 to 5000 ml of blood in the body. And in order for this amount to be maintained, nature provides for the process of stopping blood in case of wounds. Let's look at blood clotting factors. , and what significance it has for human life.

What is hemostasis

In our body, blood must be maintained in a liquid state in order to provide all organs and tissues with the necessary nutrients and oxygen. At the same time, if necessary, the liquid substance must turn into a jelly-like substance so that the person does not die from blood loss. And after the jelly-like clot has completed its mission, it must again take on a liquid state. This process of regulating the state of the blood is called hemostasis.

Hemostasis is very complex mechanism, which involves dozens of substances. If this process fails, a person may face many diseases that are life-threatening. Hemostasis is influenced by coagulation factors in the blood.

Coagulation

Coagulation or - is it defense mechanism body from heavy blood loss. Today, approximately half of humanity has problems with coagulation. It is because of them that such terrible diseases such as thrombosis, heart attack, stroke, extensive bleeding. Every tenth person dies as a result of untimely treatment of these blood pathologies, and every second person does not even suspect that he has a coagulation disorder.

Coagulation is a sequential series of processes, each of which triggers the next. If there is a failure at any stage of coagulation, a pathology occurs that prevents normal blood clotting. Today, scientists have identified the main phases of blood clotting, these are:

• The appearance of prothrombin.
• The appearance of thrombin.
• Fibrin activation.

The last phase of stopping bleeding is the narrowing and dissolution of the blood clot, which turns into an initially liquid state.

Factors influencing coagulation

Two main categories of molecules are responsible for blood clotting in our body - plasma and platelet. Plasma hemostasis occurs with the participation of proteins that are involved in the formation of a blood clot. How many factors influence hemostasis? The table of plasma factors consists of 13 elements, which are designated in medicine by Roman numerals.

Each of these components plays its role in the formation of fibrin.

In addition to the numbered coagulation factors, there are several additional plasma substances that are responsible for the reaction of all components.

Platelet-derived clotting factors are components of platelets, related to the components that are responsible for the clotting of red blood cells. There are 10 of them in medicine. If there is a deficiency or excess of one of the components, a failure in coagulation occurs and the blood clots more slowly than normal.

13 plasma factors

Additional plasma clotting factors also take part in coagulation.

Coagulation factors in the blood include components: von Willebrand, Fletcher, Fitzgerald. These components are involved in the activation of other factors, and if they are deficient, the coagulation chain may be disrupted.

A deficiency of one or more clotting factors leads to the development of a pathology called coagulopathy, which is a blood clotting disorder. Coagulopathy can be caused by both hereditary and acquired causes. TO hereditary factors development of the disease include:

• Deficiency of components 8 and 9, 10 factors.
• Deficiency of components 5, 7, 10 and 11 factors.
• Deficiency of components of other factors.

Acquired factors:

• DIC syndrome.
• Purchased inhibitors.
• Deficiency of prothrombin factors.
• Heparin preparations, etc.

Platelet factors

Platelet-derived clotting factors in the blood are contained directly in platelets - red blood cells. Today, scientists say that their number exceeds 10, but the exact number is still in question. Medical textbooks today list 12 blood clotting molecules:

• Thrombin protein.
• Fibrin trigger accelerator.
• Phospholipoprotein.
• Heparin inhibitor.
• Agglutinabelin.
• Fibrin breakdown inhibitor.
• Prothrombin breakdown inhibitor.
• Retractosin.
• Serotonin.
• Cothromboplastin.
• Fibrin activator.
• ADP is responsible for platelet aggregation.

Factors affecting blood clotting

In order to maintain their health in order, every person should know the factors that accelerate and slow down blood clotting. This knowledge will help to avoid the development of life-threatening conditions and timely establish the coagulation system. Impaired hemostasis at any stage can lead to either extensive bleeding or the formation of blood clots. Both are life-threatening.

Low blood clotting. This condition is dangerous due to the occurrence of fatal internal bleeding. The reasons for the development of pathology can be:

• Genetic disorders.
• Oncological diseases at a late stage.
• Blood thinning drugs.
• Lack of vitamin K.
• Lack of calcium.
• Liver diseases.

Treatment of this pathology depends on the causes of its development. The drugs are prescribed by a hematologist. If the cause of poor clotting is drug treatment, you need to limit your medications or replace them with gentler drugs.

This pathology is dangerous due to the formation of blood clots in blood vessels, veins and arteries. When an artery becomes blocked, the organs it feeds die. The danger also lies in the possibility of a blood clot breaking off, which can clog the vital arteries of the lungs and heart, this leads to fatal outcome. The main reasons for the development of this disorder are:

• Infectious diseases.
• Low physical activity.
• Atherosclerosis.
• Dehydration.
• Hereditary factors.
• Diabetes.
• Excess weight.
• Pregnancy.
• Autoimmune diseases.
• Stress.
• Oncological diseases.

When treating this pathology main goal doctors is to reduce blood clotting to normal level. For these purposes, special drugs are used - anticoagulants. Their use should be under the strict supervision of the attending physician. First, the patient is prescribed a course of heparin, and then aspirin therapy is administered.

For hereditary thrombophelia, aspirin is prescribed in small doses in infancy.

A blood clotting function test must be performed before any surgical intervention, in order to exclude possible complications. This study is also prescribed for pregnant women and for certain patient complaints. Usually increased coagulability observed in elderly patients.

If you have been diagnosed with a blood clotting disorder, there is no need to panic. This means that you need to take more care of your health. Any medicine should be taken only after consulting a doctor. It is also necessary to take all tests to find out the cause of the disorder. If you do not delay treatment and follow all the doctor’s recommendations, the disease will quickly recede and your life will return to a healthy direction.

In contact with

Blood clotting factor VII drug

Active substance

Blood clotting factor VII (human coagulation factor VII)

Release form, composition and packaging

Lyophilisate for preparing a solution for intravenous administration white or slightly colored, in the form of a powder or friable solid.

Excipients: sodium citrate dihydrate, heparin.

Solvent: water for d/i - 10 ml.

Vials (1) complete with solvent (vial), disposable syringe, disposable needle, transfer needle, filter needle, aeration needle and transfusion system - cardboard packs.

pharmachologic effect

Factor VII is one of the vitamin K-dependent factors of normal human blood, a component of the extrinsic pathway of the blood coagulation system. It is a zymogen of the serine protease factor VIla, which initiates the extrinsic coagulation pathway. Administration of human factor VII concentrate increases the concentration of factor VII in plasma and provides temporary correction of a defect in the blood coagulation system in patients with factor VII deficiency.

Pharmacokinetics

With intravenous administration of Factor VII, the increase in its concentration in the patient’s blood plasma is 60-100%; T 1/2 is on average 3-5 hours.

Indications

Treatment and prevention of blood clotting disorders caused by hereditary or acquired factor VII deficiency;

— acute bleeding and prevention of bleeding during surgical interventions in patients with congenital deficiency of factor VII (hypo- or aproconvertinemia);

- acute bleeding and prevention of bleeding during surgical interventions with acquired factor VII deficiency due to oral administration;

— vitamin K deficiency (for example, if its absorption in the gastrointestinal tract is impaired, with long-term parenteral nutrition);

- liver failure (for example, with hepatitis, cirrhosis of the liver, severe toxic damage to the liver).

Contraindications

— disseminated intravascular coagulation (DIC) syndrome and/or hyperfibrinolysis until the underlying causes are eliminated;

- a history of heparin-induced thrombocytopenia;

- age up to 6 years;

- hypersensitivity to the drug or to any of its components.

Due to the risk of developing thromboembolic complications, a drug with special care should be used in patients with a history of coronary artery disease, liver disease, as well as in patients in the postoperative period, newborns and persons at high risk of developing thromboembolism or disseminated intravascular coagulation syndrome. In these cases, it is necessary to balance the possible benefits of using Factor VII with the risk of developing these complications.

Dosage

The duration of replacement therapy and dose depend on the severity of factor VII deficiency, the location and extent of bleeding or hemorrhage, and the clinical condition of the patient. The prescribed dose of factor VII is calculated in international units (IU) according to current WHO standards for preparations containing factor VII. Factor VII activity in plasma can be calculated as a percentage of normal and in international units.

One international unit of factor VII activity is equivalent to the activity of factor VII in 1 ml of normal human plasma.

Calculation of the required dose is based on the empirical observation that 1 International Unit (IU) of factor VII per kilogram of body weight increases plasma factor VII activity by approximately 1.9% (0.019 IU/mL) relative to the normal level of activity.

The required dose is determined using the following formula:

Required dose (IU) = body weight (kg) x desired increase in Factor VII activity (IU/ml) x 53* (unit divided by observed recovery (ml/kg))

*(since 1: 0.019 = 52.6)

When determining the dose and frequency of drug administration in each specific case, the clinical effect should be taken into account.

When choosing an administration interval, it should be taken into account that T1/2 factor VII is very short - approximately 3-5 hours.

If it is necessary to maintain a high level of factor VII in plasma for a long time, the drug should be administered at intervals of 8-12 hours.

No dose adjustment is required for liver diseases.

Method of administration

A solution for intravenous administration from factor VII lyophilisate should be prepared immediately before administration. Use only the included administration kit. The solution should be clear or slightly opalescent. Do not use the solution if it is cloudy or contains mechanical impurities. All used materials and unused solution must be disposed of in accordance with established rules.

Preparation of a solution from lyophilized concentrate

1. Heat the closed bottle with the solvent to room temperature (not higher than 37°C).

2. Remove the protective caps from the bottles containing factor VII concentrate and solvent, and disinfect the rubber stoppers on both bottles.

3. Turn and then remove the protective packaging from one end of the adapter needle included in the kit. Pierce the rubber stopper of the solvent bottle with this end of the needle.

4. Carefully remove the protective packaging from the other end of the adapter needle, without touching the needle itself.

5. Turn the bottle with the solvent over and pierce the rubber stopper of the bottle with factor VII concentrate with the free end of the adapter needle. Due to the vacuum, the solvent will flow into the vial containing the factor VII concentrate.

6. Disconnect the bottles by removing the adapter needle from the bottle with factor VII concentrate. To dissolve the concentrate more quickly, carefully rotate and rock the bottle.

7. To deposit the foam after the concentrate has completely dissolved, insert the supplied air duct needle into the bottle. Remove the air duct needle after the foam has settled.

IV jet injection

1. Turn and then remove the protective packaging from the filter needle and attach it to a sterile disposable syringe. Draw the solution into a syringe.

2. Disconnect the filter needle from the syringe, attach a butterfly needle or a disposable injection needle and inject the IV solution slowly (at a rate of no more than 2 ml/min).

3. When administered at home, the patient must put all used materials in the drug packaging and hand it over to a medical institution where he is observed for control.

IV drip administration

For intravenous drip administration, a disposable transfusion system with a filter should be used.

Side effects

Rarely the development of allergic reactions is observed (such as urticaria, nausea, vomiting, bronchospasm, decreased blood pressure), in some cases - severe anaphylaxis (including shock).

In rare cases fever was noted. When treated with prothrombin complex factors, one of which is factor VII, thromboembolic complications are possible, especially in cases where high doses of the drug are prescribed and/or in patients with risk factors for thromboembolism.

Overdose

When using large doses of drugs containing factor VII, cases of myocardial infarction, disseminated intravascular coagulation syndrome, venous thrombosis and pulmonary embolism have been reported. Therefore, in case of overdose in patients with risk factors for thromboembolic complications or disseminated intravascular coagulation syndrome, the likelihood of developing these complications increases.

Drug interactions

INTERACTION WITH OTHER DRUGS

No interactions of human plasma Factor VII with other drugs have been observed.

Before administration, Factor VII should not be mixed with other drugs. When using a venous catheter, it is recommended to flush it with isotonic saline before and after administration of Factor VII.

Effect on laboratory parameters:

In patients receiving large doses of Factor VII, when conducting coagulation tests sensitive to , the presence of heparin in the drug should be taken into account. If necessary, the effect of heparin can be neutralized by adding protamine to the test sample.

special instructions

Since Factor VII is a protein preparation, allergic reactions may occur. Patients should be informed about early symptoms of allergy, such as urticaria (including generalized), chest tightness, wheezing, drop in blood pressure and anaphylaxis. If these symptoms occur, patients should immediately interrupt treatment and contact their doctor.

If shock develops, you should act in accordance with the currently established rules for the treatment of shock.

Based on the experience with the use of human plasma prothrombin complex, we can talk about an increased risk of thromboembolic complications and disseminated intravascular coagulation in patients receiving human plasma factor VII.

Theoretically, factor VII replacement therapy may lead to the development of factor VII inhibitors in the patient. However, to date, not a single similar case has been described in clinical practice.

The amount of sodium in the maximum daily dose may exceed 200 mg, which should be taken into account when used in patients on a low-sodium diet.

Factor VII is produced from human plasma. When administering drugs made from human blood or plasma, the possibility of transmission of viruses cannot be completely excluded. This also applies to pathogens whose nature is currently unknown.

The risk of virus transmission is minimized as a result of a number of safety measures, namely:

— selection of donors based on medical examination data and screening of the blood and plasma of each donor, as well as plasma pools for HBsAg and antibodies to HIV and viruses;

— testing plasma pools for the presence of genomic material of hepatitis A, B and C viruses, HIV-1 and HIV-2, as well as parvovirus B19;

— application of virus inactivation/removal methods in the production process. Using pathogen viruses and/or model viruses, the effectiveness of these methods has been established against viruses , B and C, HIV-1 and HIV-2.

However, the effectiveness of current virus inactivation/removal methods may not be sufficient for some non-enveloped viruses, such as parvovirus B19, as well as for currently unknown viruses. Infection with parvovirus B19 can be dangerous for pregnant women (infection of the fetus), as well as for people with immunodeficiency or increased production of red blood cells (for example, hemolytic anemia).

Vaccination against hepatitis A and B is recommended for patients receiving human plasma factor VII.

There is currently insufficient evidence to recommend the use of Factor VII in children under 6 years of age.

Impact on the ability to drive vehicles and operate machinery

No effect on the ability to drive a car or operate moving machinery was noted.

Pregnancy and lactation

The safety of Factor VII during pregnancy has not been demonstrated in controlled clinical studies. Therefore, Factor VII can be prescribed during pregnancy and lactation only according to strict indications

Use in childhood

Contraindicated in children under 6 years of age.

For liver dysfunction

The drug should be prescribed with caution for liver diseases.

Conditions for dispensing from pharmacies

The drug is available with a prescription.

Storage conditions and periods

The drug should be stored out of the reach of children at a temperature of 2° to 8°C. Shelf life - 3 years.

Filterable list

Active substance:

Instructions for medical use

Factor VII (Blood Clotting Factor VII)
Instructions for medical use- RU No. P N016158/01

date last change: 10.05.2016

Dosage form

Lyophilisate for the preparation of solution for intravenous administration

Compound

Composition (per 1 bottle):

Active Ingredient:

Factor VII 600 IU

As protein contained in plasma 50-200 mg/vial

Auxiliary ingredients:

Sodium citrate dihydrate 40 mg

Sodium chloride 80 mg

Heparin sodium 250 ME

Solvent:

Water for injections 10 ml

Description of the dosage form

Lyophilisate: white or slightly colored powder or friable solid mass.

Solvent: transparent colorless liquid.

Reconstituted solution: clear or slightly opalescent, colorless to yellowish solution.

Pharmacological group

Hemostatic agent

Pharmacodynamics

Factor VII is one of the vitamin K-dependent factors of normal human plasma, a component of the extrinsic pathway of the blood coagulation system. It is a single chain glycoprotein with molecular weight about 50,000 Dalton. Factor VII is a zymogen of the serine protease factor Vila (an active serine protease), which initiates the extrinsic coagulation pathway. The tissue factor-factor VIIa complex activates coagulation factors IX and X, resulting in the formation of factors IXa and Xa. With further deployment of the coagulation cascade, thrombin is formed, fibrinogen is converted to fibrin, and a clot is formed. Normal thrombin generation is also extremely important for platelet function as part of the hemostatic system. Hereditary factor VII deficiency is an autosomal recessive disorder. The use of human factor VII increases plasma concentrations of factor VII and may temporarily correct the coagulation defect in patients with factor VII deficiency.

Pharmacokinetics

When factor VII is administered intravenously, its concentration in the patient's blood plasma increases to 60-100%.

The half-life is approximately 3-5 hours.

Indications

The drug Factor VII is indicated:

• in the treatment of blood coagulation disorders caused by isolated hereditary deficiency of factor VII;
• for the prevention of blood coagulation disorders caused by isolated hereditary deficiency of factor VII, with a history of bleeding and a residual concentration of factor VII below 25% (0.25 IU/ml).

The drug does not contain significant amounts of factor VIIa and should not be used in hemophilia patients with inhibitors.

Contraindications

• increased sensitivity to active substance or any component of the drug;
• high risk of thrombosis or disseminated intravascular coagulation (DIC);
• known allergy to heparin or history of heparin-induced thrombocytopenia;
• children under 6 years of age (currently available data are insufficient to recommend the use of medicinal product Factor VII for children under 6 years of age).

Use during pregnancy and breastfeeding

The effect of Factor VII on fertility has not been studied in controlled clinical trials.

Human Factors Safety coagulation VII for use during pregnancy has not been confirmed by controlled clinical studies.

Data obtained from animal experiments do not allow us to assess the safety of the drug for pregnant women, the effect on the development of the embryo and fetus, childbirth or postnatal development. The physician must carefully evaluate the expected benefit and possible risk and prescribe the drug Factor VII during pregnancy and during breastfeeding only under strict indications.

See the "Special Instructions" section for information regarding the risks associated with potential danger infection of pregnant women with parvovirus B19.

Directions for use and doses

Treatment with Factor VII should only be carried out by a physician experienced in the use of clotting factor replacement therapy.

The drug Factor VII is administered intravenously in the form of intermittent injections or infusions.

Reconstitution of the Factor VII drug must be carried out immediately before use. When used as an infusion, use only the included infusion set.

Recovery of lyophilisate

1. Warm the unopened bottle of solvent to room temperature, but not more than 37°C.

2. Remove the protective discs from the bottles with lyophilisate and solvent (Fig. A) and wipe the stoppers of both bottles.

3. Remove, by rotating and peeling, the protective coating from one end of the supplied transfer needle (Figure B). Insert the open needle through the rubber stopper into the bottle with the solvent (Fig. B).

4. Remove the protective coating from the other end of the transfer needle without touching the surface of the needle.

5. Turn the bottle with the solvent vertically over the bottle with the concentrate and insert the free end of the needle to transfer it through the rubber stopper of the bottle with the concentrate (Fig. D). The solvent will flow into the concentrate vial under vacuum.

6. Separate the two bottles by removing the needle from the stopper of the bottle with the concentrate (Fig. D). Gently shake and rotate the bottle of concentrate to speed up dissolution.

7. Once the product has been reconstituted, insert the supplied aeration needle (Fig. E) and allow the foam to settle completely. Remove the aeration needle.

8. Before administration, the resulting concentrate should be carefully examined for the presence of foreign particles and color changes (the concentrate may be colorless or yellowish).

If foreign particles, color changes or turbidity are detected, the drug should not be administered!

The drug must be used immediately after recovery.

Method of administration

1.Remove, by rotating and peeling, the protective coating from one end of the supplied filter needle, and attach it to a sterile disposable syringe. Draw the solution into a syringe (Fig. G).

2.Disconnect the filter needle from the syringe and perform a slow intravenous administration solution using the transfusion system (or the disposable needle provided).

Do not exceed the injection rate of 2 ml/min!

The dose and duration of replacement therapy depend on the severity of factor VII deficiency, the location and severity of bleeding episodes, and the clinical condition of the patient. The relationship between residual factor VII concentrations and bleeding tendency is less clear in some patients than in classical hemophilia.

The number of Factor VII units administered is expressed in International Units (IU), corresponding to the existing WHO standard for Factor VII preparations. Factor VII activity in plasma is expressed either as a percentage (relative to normal plasma) or in International Units (relative to the International Standard for Factor VII plasma).

One International Unit (IU) of factor VII activity is equivalent to the amount of factor VII activity in 1 ml of normal human plasma.

Calculation of the required dose is based on the empirical observation that 1 International Unit (IU) of factor VII per kilogram of body weight increases plasma factor VII activity by approximately 1.9% (0.019 IU/ml) relative to the normal level of activity.

The required dose is determined using the following formula:

Required dose (IU) = body weight (kg) × desired increase in factor VII activity (IU/ml) × 53* (unit divided by observed recovery (ml/kg))

*(since 1: 0.019 = 52.6)

In each individual case, the amount of drug to be administered and the frequency of application should always be related to clinical effectiveness. This is especially important in the treatment of factor VII deficiency, since individual bleeding susceptibility is not strictly dependent on plasma factor VII activity measured using laboratory tests. Individual dosing recommendations for Factor VII should be made based on regular measurements of factor VII plasma concentrations and long-term monitoring of the patient's clinical condition. Intervals between doses should take into account the short half-life of factor VII from the circulation, ranging from 3 to 5 hours.

When using Factor VII in the form of intermittent injections/infusions, it is advisable to interval between doses from 6 to 8 hours. Typically, treatment of factor VII deficiency requires (depending on activity in normal plasma) lower doses of the deficient factor compared to classical hemophilia (hemophilia A and B). The table below shows sample recommendations on the use of intermittent injections/infusions, developed based on the limited clinical experience available.

* 1 IU/ml=100 IU/dl=100% normal plasma. Factor VII activity in plasma is expressed either as a percentage (relative to the normal plasma content, taken as 100%) or in International Units (relative to the international standard for factor VII in plasma).

** Based clinical assessment in each case, provided that adequate hemostasis is achieved towards the end of treatment, lower doses may be sufficient. Intervals between doses should be adjusted taking into account short period the half-life of factor VII from the circulation is approximately 3 to 5 hours. If necessary, maintain high concentrations of factor VII for a period of time. long period Doses should be administered at intervals of 8-12 hours.

Unused drug and waste material must be destroyed in accordance with local requirements.

Side effects

Adverse effects observed in clinical studies

Adverse reactions encountered during the procedure clinical trials, are listed according to the following gradation: according to the following gradation: very often (> 1/10); often (> 1/100<1/10); нечасто (>1/1000<1/100); редко (> 1/10 000<1/1000); очень редко (<1/10 000, включая единичные сообщения).

The table below summarizes the adverse reactions observed in a clinical study of 57 adult and pediatric patients with hereditary factor VII deficiency who were administered Factor VII for the control of acute bleeding events, as part of surgery, and for long-term bleeding prophylaxis. In this study, Factor VII was administered for 8,234 days.

a - The rate per patient was determined based on the number of patients who experienced a given adverse event assessed by the investigator as at least possibly related to the administration of the drug, and assessed in the same way by Baxter Healthcare Corporation.

b - Frequency per day of administration was determined based on the total number of observations of a given adverse event assessed by the investigator as at least possibly related to the administration of the drug, and thus assessed by Baxter Healthcare Corporation.

c - “Impaired state of health” is the term used, implying unclear perception.

Adverse effects observed during post-registration use

During post-marketing use, the following adverse effects were observed, listed according to the MedDRA organ system classification in order of increasing severity, where applicable.

Blood and lymphatic system disorders: Factor VII inhibition*.

*-Coded under the MedDRA preferred term for the presence of antibodies to factor VII.

Immune system disorders: hypersensitivity reactions.

Mental disorders: confusion, insomnia, restlessness.

Nervous system disorders: cerebral vein thrombosis, dizziness, sensory disturbance, headache.

Cardiovascular system disorders: arrhythmia, hypotension, deep vein thrombosis, superficial vein thrombosis, flushing of the facial skin.

Disorders of the respiratory system, chest and mediastinal organs: bronchospasm, shortness of breath.

Gastrointestinal disorders: diarrhea, nausea.

Skin and subcutaneous tissue disorders: itching.

General disorders and reactions at the injection site: chest discomfort.

Class-specific reactions

When using factor VII preparations and prothrombin complex preparations containing factor VII, the following adverse events were observed: stroke, myocardial infarction, arterial thrombosis, pulmonary embolism, disseminated intravascular coagulation, allergic or anaphylactic reactions, urticaria, vomiting, increased body temperature.

Precautionary measures

When performing heparin-sensitive clotting tests in patients receiving high doses of Factor VII, the presence of heparin in the drug should be taken into account.

special instructions

When using drugs containing factor VII, the development of hypersensitivity reactions, including anaphylactic reactions, was observed. Patients and their loved ones should be informed about the early signs of hypersensitivity reactions. If such symptoms occur, patients should be advised to immediately stop using the drug and contact their doctor.

If allergic and/or anaphylactic reactions occur, administration should be stopped immediately. In case of shock, standard medical measures should be taken.

Standard interventions to prevent infections resulting from the use of medicinal products derived from human blood or plasma include donor selection, screening of individual donors and plasma pools for specific markers of infection, and implementation of effective virus inactivation/removal steps into production. . Despite this, when using medicinal products prepared from human blood or plasma, the risk of transmitting infectious diseases, including those caused by unknown viruses or other pathogens, cannot be completely eliminated.

The technologies used to remove and inactivate pathogens may have limited effectiveness against some non-enveloped viruses, in particular parvovirus B19. Parvovirus B19 infection can be dangerous for pregnant women (infection of the fetus) and patients with immunodeficiency or increased breakdown of red blood cells (particularly hemolytic anemia).

Appropriate vaccination (against hepatitis A and B) may be recommended for patients regularly receiving plasma-derived Factor VII therapy.

Each time Factor VII is administered, it is strongly recommended that the name and batch number of the drug be recorded to ensure that the relationship between the drug administration and the patient's condition can be traced.

When treated with drugs containing factor VII, there is a risk of developing thromboembolic complications and disseminated intravascular coagulation. Thrombosis, including deep vein thrombosis, and thrombophlebitis have been observed during treatment with Factor VII. Patients receiving Factor VII therapy should be closely monitored due to the possibility of developing signs and symptoms of thromboembolic complications and disseminated intravascular coagulation.

Due to the risk of thromboembolic complications and disseminated intravascular coagulation, particularly strict monitoring should be carried out when administering human coagulation factor VII to patients with coronary heart disease, liver disease, before surgery, neonates or other patients.

Human factor VII replacement therapy may result in the formation of circulating antibodies that inhibit factor VII. If such inhibitors appear, this condition manifests itself as an insufficient clinical response.

Impact on the ability to drive vehicles and other mechanisms

There is no information on the effect of Factor VII on the ability to drive a car and use complex equipment that requires increased attention.

Release form

Lyophilisate for the preparation of solution for intravenous administration 600 ME

600 IU of the drug in a glass vial (type II, EP) and 10 ml of solvent in a glass vial (type I, EP) in a cardboard box along with a dissolution and administration kit (disposable syringe, disposable needle, transfer needle, filter needle , aeration needle, transfusion system) and instructions for use

Storage conditions

At temperatures from 2 to 8°C.

Keep out of the reach of children.

Best before date

Do not use after the expiration date stated on the package.

Conditions for dispensing from pharmacies

By doctor's prescription.

Factor VII (Blood Clotting Factor VII) - instructions for medical use - RU No. P N016158/01 dated 2009-12-15

Synonyms of nosological groups