Kogenate FS

Active material: Oktokog alpha
When ATH: B02BD02
CCF: The preparation of blood coagulation factor VIII
ICD-10 codes (testimony): D66
When CSF: 20.01.06
Manufacturer: BAYER HealthCare LLC (United States)

PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING

Lyophilisate for preparing a solution for intravenous administration complete with solvent (water d / and) in the form of a white powder with a yellowish tint; prepared solution is transparent, Colorless to slightly yellowish.

Excipients: sucrose, gistidin, glycine, sodium chloride, calcium chloride, polysorbate 80.

* According to the WHO standard for coagulation factor VIII 1 IU is approximately equal to the level of antihemophilic factor, found in 1.0 ml pool of fresh human plasma.

Glass Bottles (1) complete with glass syringe (1) with water d/i (2.5 ml) in blister, vial adapter (1) in blister, d/iv/injection device (1) in blister – packs cardboard.

Pharmacological action

Hemostatic drug, is a highly purified glycoprotein, consisting of several peptides, including one with molecular weight 80 kD and various extended subunits with molecular weight 90 kd. Made using recombinant DNA technology. Produced by kidney cells of baby hamsters (VNK), into which the gene for human coagulation factor VIII was introduced (FVIII). Cell culture medium contains a solution of human plasma proteins (HPPS) and recombinant insulin, but does not contain proteins, derived from animal sources. Cogenate FS has the same biological activity, like factor VIII, derived from human blood plasma.

The purification process includes a viral inactivation step with an effective solvent/detergent in addition to classical purification methods using ion exchange chromatography, immunoaffinity chromatography with monoclonal antibodies, along with other chromatographic steps, designed to purify recombinant factor VIII and remove infectious components.

Besides, manufacturing process was investigated for its ability to reduce the infectivity of an experimental transmissible spongiform encephalopathy agent (TGE), which was considered as a model of CJD agents (Creutzfeldt-Jakob disease) and variant CJD. It has been shown, that a number of separate stages of production and preparation of raw materials in the process of manufacturing Cogenate FS reduces the infectivity of this experimental model of the agent. The steps to reduce TSE infectivity included the fraction II separation step + III in a solution of human plasma proteins (6.0 log₁₀) and anion exchange chromatography stage (3.6 log₁₀). These studies provide reasonable assurance that, that in the case of the presence of a CJD pathogen/CJD variant with a low degree of infectivity in the source material, it can be eliminated.

Administration of Cogenate FS provides an increase in the content of factor VIII in the blood plasma and temporarily eliminates the coagulation defect in patients with hemophilia A (hereditary bleeding, characterized by insufficient activity of a specific plasma protein, Blood clotting factor VIII).

Each bottle of Cogenate FS contains the amount of recombinant factor VIII indicated on the label in international units (ME). According to the WHO standard for human coagulation factor VIII, 1 ME is approximately equal to the level of factor VIII activity in 1 ml pool of fresh human plasma.

Pharmacokinetics

Average recovery of factor VIII activity , measured through 10 min after infusion of Cogenate FS was 2.1±0.3%/IU/kg. Average biological T_1/2 recombinant factor VIII (rFVIII-FS), containing sucrose, was approximately 13 h and was similar to T_1/2 antihemophilic factor (FMG), derived from human blood plasma. Cogeneate FS shortened ACTV. Restoration of rFVIII-FS factor activity and its T_1/2 haven't changed since then 24 weeks of treatment with this drug alone, which indicates continued effectiveness and the absence of formation of antibodies to factor VIII. Average recovery of factor VIII activity, measured through 10 min after rFVIII-FS dose administration 37 patients (through 24 weeks of rFVIII-FS treatment), amounted to 2.1%/IU/kg, which was no different from the rate of restoration of factor VIII activity, which was determined at baseline, and through 4 and 12 weeks of treatment.

Testimony

- prevention and treatment of bleeding episodes in hemophilia A.

Dosage regimen

The doses indicated below are approximate. The dose of Cogeneate FS, necessary to restore hemostasis, should be selected individually, depending on the intensity of bleeding, availability of inhibitors and desired level of factor VIII. Factor VIII levels may need to be monitored during treatment.. The clinical effect of factor VIII is most important in assessing the effectiveness of treatment. A higher dose of factor VIII may be required to achieve satisfactory clinical results., what was calculated. If, after administering the calculated dose, the expected concentration of factor VIII or bleeding cannot be controlled, then we should assume the presence of an inhibitor to factor VIII in the patient’s blood. Its presence and quantity (caption) must be confirmed by appropriate laboratory tests. In the presence of an inhibitor, the dose of factor VIII may vary significantly between patients., and the optimal treatment regimen is determined only taking into account the clinical response.

Some patients with low titer inhibitors (<10 Bethesda units) can be successfully treated with factor VIII drugs without an anamnestic increase in inhibitor titer. Factor VIII levels and clinical response to treatment must be monitored to ensure an adequate response.. Patients with a history of response to factor VIII treatment and/or higher inhibitor titers may require the use of alternative medications, such as factor IX complex concentrates, antihemophilic factor (pork), recombinant factor VIIa or anti-inhibitory coagulation complex.

The percentage increase in factor VIII levels in vivo can be calculated using the formula: dose of Cogenate FS in IU/kg body weight x 2%/IU/kg. This calculation method is based on clinical data on the use of plasma-derived and recombinant AGP products and is illustrated by the following examples:

Expected % increased factor VIII = (number of units administered x 2%/IU/kg)/weight (kg).

Example of dose calculation for an adult with body weight 70 kg: (1400 ME x 2%/ME/kg)/70 kg = 40%.

Required dose (ME) = (weight (kg) x desired % increase factor VIII)/ 2%/IU / kg.

An example of calculating the dose for a child weighing 15 kg: (15 kg x 100%)/2%/IU/kg = required 750 ME.

Dose, necessary to achieve complete hemostasis, determined by the type and severity of the hemorrhagic episode, according to the following recommendations:

AGF concentrates can also be administered regularly to bleeding prevention.

The drug is administered only by intravenous injection or infusion. After preparation, the solution should be administered within 3 no. It is recommended to use the supplied system for insertion.

The rate of administration is determined in accordance with the individual response of the patient. Usually, administration of the entire dose over 5-10 min and even faster, well tolerated.

Terms of preparation of the solution

Preparation of the drug, its administration and all manipulations with the administration system should be performed with the utmost care. Cogenate FS with bottle adapter is a needle-free system, which allows you to prevent injuries resulting from needle pricks during the preparation of the solution. If the skin is damaged by a needle, contaminated blood, viruses of various infections can be transmitted, including HIV (AIDS) and hepatitis. In case of injury, seek immediate medical attention. Needles should be placed in the provided containers immediately after use, all equipment for preparing and administering the drug, including the remains of the prepared solution of Cogenate FS, should be disposed of in an appropriate container.

1. Wash your hands thoroughly with warm water and soap.

2. Warm the closed vial and syringe in your hands to room temperature (no higher than 37°C).

3. Remove the protective cap from the bottle (A). Disinfect the rubber stopper with alcohol, being careful not to touch the rubber plug with your hands.

4. Place the bottle with the drug on a hard, non-slip surface. Remove the paper cover from the plastic vial adapter cartridge. Do not remove the adapter from the plastic cartridge. Take a cartridge with an adapter, place it on the bottle with the drug and press firmly. The adapter will snap onto the bottle cap.
Do not remove the cartridge from the adapter at this stage.

5. Carefully open the syringe blister pack, folding the paper backing to the middle. Remove the pre-filled solvent syringe. Holding the piston rod by the upper nozzle, take it out of the package. Do not touch the sides and threads of the piston rod. Holding the syringe straight, take the piston by the upper nozzle and attach the rod, screwing it tightly clockwise into the threaded plug.

6. He took the syringe by the body, break off the cap from the tip of the syringe. Care should be taken, so that the tip of the syringe does not come into contact with your hand or any other surface. Put the syringe aside until the next procedure.

7. Remove the adapter cartridge and throw it away.

8. Attach pre-filled syringe, turning it clockwise, to bottle thread adapter.

9. Introduce solvent, slowly pressing the piston rod.

10. Carefully rotate the bottle, until all the substance dissolves. Do not shake the bottle. Make sure that, that the powder has completely dissolved. Do not use solution, if it is cloudy or contains visible particles.

11. Draw the solution into a syringe, holding the vial by the edge over the vial adapter and syringe, and then slowly and smoothly pull back the piston rod. You need to make sure, that the entire contents of the bottle are drawn into the syringe.

12. Without changing the position of the piston, remove the syringe from the vial adapter (the latter must remain attached to the bottle). Attach the syringe to the supplied system for administering the drug and inject the solution intravenously. Instructions for use of the included infusion set must be followed..

13. If the patient needs to administer more than one vial, then you should prepare a solution in each bottle using the supplied syringe with solvent, and then combine the solutions in a larger syringe (not included) and administer the drug as usual.

14. Parenteral medicinal products should be carefully inspected for foreign particles or discoloration before administration., if the solution and container allow it.

Side effect

CNS: in a few cases – dizziness, depersonalization.

Dermatological reactions: in a few cases – rash, itch.

From the digestive system: in a few cases – unusual taste in the mouth, nausea.

Other: in a few cases – a moderate increase in blood pressure, rhinitis, injection site reactions.

Contraindications

- Hypersensitivity to the drug;

- hypersensitivity to mice or hamster proteins.

Pregnancy and lactation

There is no data on the use of Cogenate FS during pregnancy. Unknown, whether the drug can cause fetal harm or affect fertility when administered to a pregnant woman.

The use of the drug during pregnancy and lactation is possible only if there are absolute indications.

Experimental studies the effects of Cogenate FS on reproductive functions in animals have not been carried out.

Cautions

Cases of arterial hypotension have been described in the literature., hives and chest tightness due to hypersensitivity reactions in patients, treated with antihemophilic factor concentrates. If serious anaphylactic reactions develop, immediate emergency treatment with resuscitation is required, such as administering epinephrine and oxygen.

Cogenate FS is indicated for the treatment of bleeding episodes, caused by factor VIII deficiency. The presence of this deficiency must be established before the introduction of Cogenate FS.

Cogenate FS does not contain von Willebrand factor, therefore not indicated for the treatment of von Willebrand's disease.

During treatment of patients with hemophilia A, the formation of circulating neutralizing antibodies is possible (inhibitors) Factor VIII. Inhibitors appear especially often in the first years of treatment in young children., suffering from severe hemophilia, or in those patients, who have previously received a limited amount of factor VIII. However, the appearance of inhibitors is possible at any time during the treatment of a patient with hemophilia A. Sick, receiving treatment with any AGF drug, incl. Kogenate FS, need to be closely monitored for factor VIII antibodies through appropriate clinical monitoring and laboratory testing as recommended by the Hemophilia Center. During clinical trials in pretreated patients, 109 adverse events on 4160 infusions (2.6%). Availability, at least, remote connection with the study drug was noted by the researcher only in 13 of these phenomena. Yet 7 adverse events could not be assessed. Thus, 20 adverse events in 11 patients were considered either not evaluable, or how, at least, remotely associated with the use of Cogenate FS with a frequency 0.5% relative to the number of infusions performed. In 72 pre-treated patients with severe hemophilia A, who received Cogenate FS, average, during 54 days, No factor VIII inhibitors were detected.

During clinical trials, all patients were tested for seroconversion against mouse and hamster proteins. After the start of treatment, specific antibodies to these proteins did not develop in any of the patients., and no serious allergic reactions, related to animal proteins, against the background of rFVIII infusions – No FS noted. Despite this, patients should be informed of the possibility of developing a hypersensitivity reaction to mice and/or hamster proteins and warned of early signs of such a reaction (eg, hives, localized or generalized urticaria, wheezing and hypotension). Patients should be advised to stop using the drug if such symptoms occur and contact their physician..

Clinical studies of Cogenate FS did not include a sufficient number of patients aged 65 and older, so that we can determine, whether their response to treatment differs from that of younger patients. As for any patient, receiving Cogenate FS, the dose for elderly patients must be selected individually.

Use in Pediatrics

Cogenate FS can be used to treat children. Safety and efficacy studies have been conducted in children (n =62), pre-treated and minimally treated.

Effects on ability to drive vehicles and management mechanisms

No information, that administration of the drug Cogenate FS may reduce the ability to drive a car or operate machines.

The results of experimental studies

In vitro analysis of the mutagenic potential of rFVIII at doses, значительно превышающих максимальную терапевтическую дозу, не выявил обратной мутации или хромосомных аберраций. Исследование rFVIII in vivo на животных с использованием доз, in 10-40 раз превышающих ожидаемый терапевтический максимум, также показало, что rFVIII не обладает мутагенным потенциалом. Долгосрочных исследований на предмет канцерогенного потенциала у животных не проводилось.

Overdose

Симптомы передозировки препарата Когенэйт ФС неизвестны.

Drug Interactions

Лекарственное взаимодействие препарата Когенэйт ФС не изучено.

Conditions of supply of pharmacies

The drug prescription.

Conditions and terms

The drug should be stored out of reach of children, dark place at a temperature of 2 ° to 8 ° C; Do not freeze. Shelf life of lyophilisate – 30 Months, Solvent – 48 Months.

Разрешается хранение препарата при температуре не выше 25°С не более 3 months, eg, при лечении в домашних условиях.