OCTAPLEX - instructions for use, dose, side effects, contraindications

Active substanceFactors of blood coagulation II, VII, IX and X in combinationFactors of blood coagulation II, VII, IX and X in combination

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Coaplex

lyophilizate in / in

CESEL Behring GmbH Germany

OCTAPLEX®

lyophilizate in / in

Octapharma Pharmaceuticals Productionsgesb.H. Austria

Prothromplex 600

lyophilizate in / in

Baxter AG Austria

Dosage form: & nbsplyophilizate for the preparation of a solution for intravenous administration

Composition:

1 bottle contains:

active ingredients**: coagulation factor IX 500 ME, clotting factor II (prothrombin) 280-760 ME, coagulation factor VII 180-480 ME, coagulation factor X 360-600 ME, protein C 260-620 ME, protein S 240-640 ME (** equivalent to the total protein content - 260-820 mg);

Excipients: Heparin (in the form of heparin sodium) 100-250 ME, sodium citrate 130 mg.

Description:

Lyophilizate - white or slightly bluish powder or loose mass, very hygroscopic.

The reconstituted solution - Transparent or slightly opalescent, colorless or pale blue.

Pharmacotherapeutic group:Hemostatic agent

ATX: & nbsp

B.02.B.D.01 Factors of blood coagulation IX, II, VII and X in combination

B.02.B.D Coagulation factors

Pharmacodynamics:

The drug is a complex of coagulation factors II, VII, IX and X, which is called the prothrombin complex.All these factors are synthesized in the liver in the presence of vitamin K.

Factor VII is a proenzyme of the active serine protease factor VIIa, which initiates the endogenous way of blood coagulation. Complex "tissue factor factor" VIIa" activates factors X and IX, resulting in the formation of factors Xa and IHa. In the future, activation of the coagulation cascade with activation of prothrombin (factor II) and its transformation into thrombin. Thrombin ensures the transformation fibrinogen into fibrin, resulting in a clot forming. A normal synthesis of thrombin is also vital for the functioning of platelets in primary hemostasis.

With isolated severe factor VII deficiency, thrombin formation is reduced and bleeding is increased as a result of disruption of fibrin formation and disturbance of primary hemostasis.

Isolated deficiency of factor IX is one of the types of classical hemophilia (hemophilia B).

Isolated deficiency of factor II or factor X is extremely rare, but in severe cases can cause bleeding as in classical hemophilia.

Acquired deficiency of vitamin K-dependent clotting factors can be the result of treatment with vitamin K antagonists. When severe deficiency develops, severe bleeding characterized by retroperitoneal or cerebral bleeding rather than bleeding into muscles and joints.

Severe liver failure also leads to a significant decrease in the level of vitamin K-dependent clotting factors and to clinical symptoms of increased bleeding, which, however, is most often the result of a combination of causes: concurrent malignant intravascular coagulation, low platelet count, deficiency of clotting inhibitors, and impaired fibrinolysis. The use of the prothrombin complex leads to an increase in the level of vitamin K-dependent clotting factors in plasma and can temporarily correct coagulation disorders in patients with one or more of these factors being inadequate.

Pharmacokinetics:

The half-life of factor II is 48-60 h, factor VII is 1.5-6 h, factor IX is 20-24 h and factor X is 24-48 h.

Indications:

- Treatment of bleeding and perioperative prevention of bleeding when surgical interventions in patients with acquired deficiency of prothrombin complex factors, developed, in particular, with the treatment of vitamin K antagonists or their overdose, when rapid correction of the deficit is required;

- treatment of bleeding and perioperative bleeding prophylaxis surgical interventions in patients with congenital deficiency of K-dependent clotting factors II and X, when the preparation of the purified specific clotting factor is not available.

Contraindications:

- Hypersensitivity to the components of the drug;

- an allergic reaction to heparin or a history of heparin-induced thrombocytopenia;

- deficit IgA, when the patient has antibodies to immunoglobulin A.

Pregnancy and lactation:

The safety of the use of prothrombin complex preparations in pregnant and breast-feeding women has not been established. Animal studies can not be applied to assessing safety during pregnancy, for fetal / fetal development, labor and postnatal development.Therefore, during pregnancy and during breastfeeding, it is possible to use the prothrombin complex preparation only in those cases when the prospective benefit for the mother exceeds the possible risk for the fetus or the child.

Dosing and Administration:

The drug is administered intravenously.

The drug should be started under the supervision of a doctor with experience in the treatment of blood clotting disorders.

The dose and duration of treatment depend on the severity of the disorders, localization and severity of bleeding, as well as on the clinical condition of the patient.

The dose and frequency of the drug should be calculated individually for each patient. The intervals between drug administration should be adapted to the different half-life periods of various coagulation factors that make up the prothrombin complex. Selection and correction of an individual dose are carried out on the basis of regular determinations of the concentration of specific coagulation factors in the blood plasma or such indicators as prothrombin time and the international normalized ratio (MPS), as well as taking into account the clinical state of the patient evaluated in dynamics.

In the case of massive surgery, careful monitoring of replacement therapy with coagulation tests (determination of the levels of specific clotting factors and / or general tests for evaluation of the prothrombin complex) is mandatory.

Treatment of bleeding and perioperative prophylaxis of bleeding in patients receiving antagonists of vitamin K

The choice of dose is determined by the baseline (before treatment) and the target MPO.

The table shows the calculation of the doses of Octaptlex®, necessary for the normalization of the value MHO (<1.2 within 1 hour), depending on the initial values of MPO.

The initial value of INR	2-2,5	2,5-3,0	3-3,5	>3,5
Dose of Octaptlex® * (ml of the finished solution per 1 kg of body weight)	0,9-1,3	1,3-1,6	1,6-1,9	>1,9

* The administration of repeated doses of the drug is permissible, if the INR has not reached the required value.

Single dose should not exceed 3000 ME (120 ml of Octaptlex® preparation). The value of INR should be determined after each dose is administered.

In patients of this group, the effect of correction of hemostasis disorders with the administration of the drug Octaplex® persists for 6-8 hours. At the same time, the effect of vitamin K with simultaneous administration with the drug is usually achieved within 4-6 hours. Thus, with the joint application of the drug Octaplex^® and vitamin K, the repeated administration of a prothrombin complex is usually not required.

Since these recommendations are empirical, and the severity and duration of the drug can vary significantly, the INR should be monitored during treatment.

Treatment of bleeding and perioperative bleeding prophylaxis in patients with congenital deficiency of K-dependent clotting factors II and X, when the preparation of the purified specific clotting factor is unavailable

The calculation of the dose is based on the fact that approximately 1 ME factor II or factor X per 1 kg of body weight increases the activity of these factors by 0.02 and 0.017 IU / ml, respectively. The administered dose of a specific factor is expressed in international units (ME), which are determined by the WHO standard for each factor. The activity of each clotting factor in plasma is expressed either as a percentage of normal plasma or in ME in relation to the international standard for a specific coagulation factor.

1 ME clotting factor is equivalent to its amount in 1 ml of normal plasma. For example, the calculation of the required dose of factor X is based on empirical evidence that 1 ME factor X per 1 kg of body weight increases the activity of this factor by 0.017 IU / ml.Calculation of the required dose is made by the formula:

Necessary dose = body weight (kg) x desired factor X increase (IU / ml) x 59, where 59 (ml / kg) is the inverse of the set recovery value.

Calculation of the required dose for factor II:

Necessary dose = body weight (kg) x desired increase in factor II (IU / ml) x 50.

If the individual value of recovery is known, then it should be used to calculate the dose.

Preparation of the preparation for administration

In the preparation and administration of the drug, you should follow the rules of asepsis.

1) If necessary, adjust the solvent (water for injections) and lyophilizate in closed vials to room temperature. If a water bath is used to warm the solvent, care should be taken to ensure that water did not come into contact with rubber stoppers or lids of vials. The temperature of the water bath should not exceed 37 ° C.

2) Remove protective caps from vials with lyophilizate and solvent, disinfect the rubber stoppers of vials of one of the disinfecting napkins.

3) The short end of the double-ended needle is released from the plastic package, without touching the needle itself.Then pierce in the center a stopper of a vial or flask with solvent, keeping a needle strictly vertically. It is necessary to pierce the cork so that only the tip of the needle is visible in the vial.

4) Release the long end of the double-ended needle from the plastic package, without touching the needle itself. Flip the vial with the solvent and pierce the free end of the needle in the center of the vial with a lyophilizate. The vacuum in the vial with lyophilizate will draw water for injection from the vial with the solvent.

5) Empty vial from the solvent with the needle in it is separated from the bottle with lyophilizate. To completely dissolve the lyophilisate, the vial is gently rotated. The dissolution time should not exceed 10 minutes. The resulting solution should be clear or slightly opalescent, colorless or pale blue.

Administration of the drug

Ready-to-use drug should be administered immediately after dissolution. However, subject to sterility, the reconstituted solution can be stored for up to 8 hours at a temperature of 20 to 25 ° C. Prior to the introduction of the prepared solution should be carefully examined. The solution should be clear or slightly opalescent.Do not use a turbid solution, as well as a solution containing a precipitate or suspended particles.

With each introduction, it is necessary to register the name and number of the drug series. Before the start of the introduction, it is recommended to determine the patient's heart rate and control it throughout the entire administration. With a marked increase in the heart rate, it is recommended to reduce the rate of administration or interrupt the administration.

1) After preparing the preparation for administration (as described above), remove the protective coating from the filter needle and pierce it with the rubber stopper of the vial with the dissolved lyophilizate.

2) The other end of the needle is connected to a 20 ml disposable syringe.

3) Turn the vial and collect the solution into the syringe.

4) Disinfect the skin at the injection site with a disinfectant wipe.

5) Disconnect the filter needle from the syringe and attach the butterfly needle.

The initial injection rate is 1 ml / min, then 2-3 ml / min. The filter needle is intended for single use only. When typing the solution in a syringe, always use only a filter needle.Carefully avoid getting into the syringe of the blood, as this can lead to the formation of a fibrin clot.

Any unused solution of the drug must be disposed of in accordance with existing regulations.

Side effects:

Frequency of occurrence of undesirable reactions is classified as follows: very often (> 1/10); often (from ≥ 1/100 to <1/10); infrequently (from ≥ 1/1000, to <1/100); rarely (from≥1 / 10,000 to <1/1000); very rarely (from <1/10000).

From the immune system: rarely hypersensitivity or allergic reactions (angioedema, reactions at the injection site, chills, hyperemia, rash, headache, changes in blood pressure, anxiety, nausea, vomiting, sweating, tachycardia, dyspnea, or bronchospasm). In some cases, these reactions can progress to the development of severe anaphylaxis.

From the laboratory indicators: rarely - a transient increase in "liver" transaminases.

The undesirable phenomena registered during post-marketing use of the drug are listed below. Since unwanted events were registered on a voluntary basis, and also because of the uncertain size of the population of patients receiving the drug,the frequency of occurrence of undesirable phenomena can not be estimated reliably.

Table 2. Adverse events registered with post-marketing drug use

From the immune system: anaphylactic reactions, anaphylactic shock, hypersensitivity reactions.

From the nervous system: tremor

From the cardiovascular system: cardiac arrest, tachycardia, thromboembolic episodes *, vascular insufficiency, hypotension, hypertension.

From the respiratory system: shortness of breath, respiratory failure.

From the gastrointestinal tract: nausea.

From the skin: urticaria, rash.

General disorders: fever, chills.

* including myocardial infarction, ischemic stroke, pulmonary embolism, deep vein thrombosis, peripheral vascular thrombosis.

Due to the presence of heparin in the drug, a sudden decrease in the number of platelets (allergic nature) below the value of 100,000 / μL or 50% of the baseline value (type II thrombocytopenia) is possible. In patients who have not previously experienced hypersensitivity to heparin, such a decrease in the number of platelets can develop 6-14 days after the start of treatment.In patients with known sensitivity to heparin, such a decrease can develop within a few hours from the beginning of treatment. Treatment with the drug should be stopped immediately if such an allergic reaction occurs. Such patients should not receive in the future drugs containing heparin.

Substitution therapy in rare cases (from ≥1 / 10000 to <1/1000) can lead to the formation of circulating antibodies that inhibit one or more factors of the prothrombin complex. In such cases, there is a decrease in the clinical effect.

Overdose:The use of large doses of prothrombin complex preparations can lead in some cases to the development of myocardial infarction, ICE, venous thrombosis and pulmonary embolism. In this regard, in case of an overdose, the risk of developing thromboembolic complications or DIC syndrome increases.

Interaction:

Preparations of the prothrombin complex neutralize the action of vitamin K antagonists. There is no information on the interaction with other drugs.

Influence on biological tests: when conducting blood coagulation tests sensitive to heparin, patients who receive high doses of the drug should take into account the presence of heparin in the formulation.

Octaplex® should not be mixed with other medications.

Special instructions:

Precautions for use

Before using the drug should consult a doctor - a specialist in the treatment of blood clotting disorders. Patients with acquired vitamin-K deficiency dependent clotting factors (eg, due to the use of vitamin K antagonists) should be prescribed only if rapid correction of the prothrombin complex level is necessary - with massive bleeding or with emergency surgical interventions. In other cases, it may be sufficient to reduce the dose of a vitamin K antagonist or to prescribe a vitamin K preparation.

Patients receiving vitamin K antagonists may initially have a tendency to hypercoagulable, and the use of a prothrombin complex may aggravate it. Patients with a congenital deficiency of any one vitamin K dependent clotting factor should be prescribed a specific factor drug when this drug is available.

If an allergic or anaphylactic reaction occurs, the drug should be discontinued immediately.In the case of shock development, conventional anti-shock measures are carried out.

Standard measures to prevent infections caused by the use of drugs derived from human blood or plasma include selection of donors, testing of individual portions and pools of plasma for specific markers of infection, and the use of effective methods for inactivation / elimination of viruses in the production process. Nevertheless, when using drugs derived from human blood and plasma, the possibility of transferring pathogens of infectious diseases can not be completely ruled out. This also applies to unknown or newly identified viruses and other pathogenic microorganisms. These measures are considered effective against envelope viruses - HIV, hepatitis B and hepatitis C and to a lesser extent - against the hepatitis A virus and parvovirus B19.

Infection with parvovirus B19 is a hazard for pregnant women (intrauterine fetus infection), for people with immunodeficiency, for patients with increased erythrocyte formation (eg, for hemolytic anemia).

Patients who receive continuous / repeated treatment with prothrombin complex preparations from human blood plasma should receive appropriate vaccination (against hepatitis A and B).

In patients with congenital or acquired deficiency of coagulation factors in the treatment with prothrombin complex preparations, development of thrombosis or disseminated intravascular coagulation (DVS) is possible, especially when they are repeated. In this regard, especially careful observation of patients with symptoms of thrombosis and intravascular coagulation is necessary.

Because of the risk of developing thrombosis with the introduction of prothrombin complex preparations, patients with history of IHD, liver disease, patients in pre- and postoperative periods, newborns, patients at risk of developing thromboembolic complications or ICE are also closely monitored. In each such case it is necessary to correlate the potential benefit from the administration of the drug with the possible risk of developing these complications.

In patients with ICE under certain conditions, it may be necessary to replace clotting factors of the prothrombin complex.Such substitution can be carried out only after relief of coagulopathy of exhaustion.

Patients with concomitant disease who receive vitamin K antagonists, when they are withdrawn, are at risk of developing thromboembolic complications. Therefore, such patients as soon as possible need to resume anti-coagulant therapy.

There is currently no relevant data on the use of Octaptlex® for the treatment of bleeding in newborns with vitamin K deficiency.

The drug contains 75-125 mg of sodium per bottle, which should be taken into account for patients who follow a diet with sodium restriction.

Effect on the ability to drive transp. cf. and fur:

Studies on the impact on the management of vehicles and work with mechanisms were not carried out.

Form release / dosage:Lyophilizate for the preparation of a solution for intravenous administration.

Packaging:

In a vial of colorless glass (type I, Hebrew F.), sealed with a rubber stopper (type I, Hebrew F.), rolled in with an aluminum cap with an identification number on the side of the cap, corresponding to a certain series of lyophilizate,and covered with a plastic cover (the plastic cover can be scrolled).

1 bottle with lyophilizate together with instructions for use in a cardboard pack.

For 20 ml of solvent (water for injection) into a bottle of colorless glass (type I, Hept. F.), sealed with a rubber stopper (type I, Hebrew F.), rolled in with an aluminum cap with an identification number on the side of the cap, corresponding to a certain series of solvent, and covered with a plastic cover (the plastic cover can be scrolled).

Set for dissolution and administration (1 disposable syringe, 1 double-ended needle, 1 filter needle (filter pore size 20 μm), 1 injection system (needle-butterfly), 2 disinfecting wipes in individual sealed packages) in a plastic bag.

1 bottle with a solvent and 1 packet with a kit for dissolution and insertion into a separate cardboard pack.

1 a cardboard packet with lyophilizate and 1 cardboard pack with a solvent and a package with a kit for dissolving and introducing are fastened with a plastic tape.

Storage conditions:

2 of the year.

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

Shelf life:

In the dark place at a temperature of 2 to 25 ° C. Do not freeze.

Keep out of the reach of children.

Terms of leave from pharmacies:On prescription

Registration number:LP-004107

Date of registration:30.01.2017

Expiration Date:30.01.2022

The owner of the registration certificate:Octapharma Pharmaceuticals Productionsgesb.H.Octapharma Pharmaceuticals Productionsgesb.H. Austria

Manufacturer: & nbsp

OCTAPHARMA France

Representation: & nbspOKTAPHARMA NORDIC AB OKTAPHARMA NORDIC AB Sweden

Information update date: & nbsp02.03.2017

Illustrated instructions

Instructions

OCTAPLEX® (Octaplex)