Octanin f 1000 iu

OCTANINE F 500 IU
OCTANINE F 1000 IU

Composition:

active substance: Human Coagulation Factor IX;

1 ml of reconstituted solution contains 100 IU of human factor IX;

total protein content is not less than 1.6 mg (100 IU).

excipients: heparin (0.05–0.15 IU/IU of factor IX), sodium chloride, lysine hydrochloride, sodium citrate, arginine hydrochloride.

Solvent: water for injections.

Pharmaceutical form. Lyophilized powder and solvent for solution for injection in vials together with a set for reconstitution and intravenous administration.

Main physicochemical properties: white or pale yellow powder or brittle mass.

Pharmacotherapeutic group. Antihemorrhagics: coagulation factor IX. ATC code B02BD04.

Pharmacological properties.

Pharmacodynamics.

Factor IX is a single-chain glycoprotein with a molecular weight of approximately 68,000 daltons. This clotting factor is vitamin K-dependent and is synthesized in the liver. Factor IX is activated by factor XIa via the intrinsic coagulation pathway, as well as by the factor VII/tissue factor complex via the extrinsic coagulation pathway. Activated factor IX, in combination with activated factor VIII, activates factor X. Activated factor X converts prothrombin into thrombin. Thrombin then converts fibrinogen into fibrin, thus forming a blood clot.

Hemophilia B is an X-linked inherited bleeding disorder caused by a deficiency of factor IX, leading to severe bleeding into joints, muscles, and internal organs, occurring spontaneously or following trauma or surgery. Replacement therapy increases factor IX plasma levels, temporarily correcting the deficiency and reducing the tendency to bleed.

Pediatric population.

A study was conducted in 25 children under 6 years of age, including 6 previously untreated patients. Recovery (regeneration) after administration of Octanin F at doses >25 IU/kg body weight was evaluated during the first 3 months of treatment and after 12–24 months. Incremental recovery (geometric mean ± SD, one-stage assay, actual potency) was calculated as (0.8 ± 1.4) and (0.9 ± 1.3) %/IU/kg in the first and second assessments, respectively.

Pharmacokinetics.

In a pharmacokinetic study of Octanin F in 13 patients with hemophilia B aged 12 years and older (mean age 28 years, range 12–61 years), the following results were obtained:

*AUC – area under the concentration-time curve

*MRT – mean residence time

*SD – standard deviation

Recovery was also studied in a second trial. A meta-analysis of recovery (n=19) showed a mean recovery of approximately [1.1 IU/dL/IU/kg].

Clinical characteristics.

Indications.

Treatment and prophylaxis of bleeding episodes in patients with hemophilia B (congenital factor IX deficiency).

Contraindications.

Hypersensitivity to the active substance or to any of the excipients.

Known allergy associated with a decrease in platelet count during heparin therapy (heparin-induced thrombocytopenia, type II).

Interaction with other medicinal products and other forms of interaction.

No interactions between human factor IX and other medicinal products have been reported.

Special warnings and precautions for use.

As with any intravenous protein product, hypersensitivity reactions are possible. The product contains trace amounts of human proteins other than factor IX and heparin. Patients should be informed about early signs of hypersensitivity reactions, including urticaria, angioedema, chest tightness, wheezing, hypotension, and anaphylaxis. If such symptoms occur, patients should be advised to discontinue the product immediately and contact their physician. In case of anaphylactic shock, standard treatment measures should be applied.

Pathogens transmitted by the parenteral route

Standard measures to prevent infections from medicinal products derived from human blood or plasma include donor selection, screening of individual blood donations and plasma pools for specific infection markers, and inclusion of effective viral inactivation/removal steps in the manufacturing process. Nevertheless, it is impossible to completely exclude the risk of transmitting infectious agents when administering products derived from human blood or plasma. This also applies to unknown or new viruses and other pathogens. The measures taken are considered effective against enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV), as well as against the non-enveloped hepatitis A virus (HAV).

The measures employed may have limited effectiveness against non-enveloped viruses such as parvovirus B19. Infection with parvovirus B19 may have serious consequences for pregnant women (fetal infection) and patients with immunodeficiency or increased erythropoiesis (e.g., hemolytic anemia).

For patients who regularly or repeatedly receive factor IX derived from human plasma, appropriate vaccination (against hepatitis A and B) should be considered.

After repeated treatment with human factor IX products, patients should be monitored for the development of neutralizing antibodies (inhibitors), the levels of which are determined in Bethesda units (BU) using appropriate biological assays.

Published data demonstrate a correlation between the development of factor IX inhibitors and allergic reactions. Therefore, patients experiencing allergic reactions should be tested for the presence of inhibitors. It should be noted that patients with factor IX inhibitors may have an increased risk of anaphylactic reaction upon subsequent challenge with factor IX. Due to the risk of allergic reactions, initial administration of factor IX should, at the physician's discretion, be performed only under medical supervision with appropriate facilities available for managing allergic reactions.

Since the historical use of complex factor IX concentrates has been associated with thromboembolic complications (higher risk due to lower purity of the product), the use of factor IX-containing products may be potentially hazardous in patients with signs of fibrinolysis and in patients with disseminated intravascular coagulation. Because of the risk of possible thrombotic complications, when the product is administered to patients with liver disease, postoperative patients, neonates, or patients with a risk of thrombotic events or disseminated intravascular coagulation, clinical monitoring for early signs of thrombotic and consumptive coagulopathy should begin with appropriate laboratory testing. In each such case, the benefit of treatment with Octanine F should be weighed against the risk of complications.

To date, sufficient data from ongoing studies on surgery with continuous infusion of Octanine F are not available.

Cardiovascular complications

In patients with risk factors for cardiovascular disease, replacement therapy with factor IX may increase this risk.

Complications associated with catheter use

If a central venous access device (CVAD) is required, the risk of complications associated with CVAD use, including local infections, bacteremia, and catheter thrombosis, should be considered.

It is strongly recommended that each time Octanine F is administered, the product name and batch number be recorded to establish a link between the patient's condition and the product batch.

This medicinal product contains up to 3 mmol (69 mg) of sodium in one vial of Octanine F 500 IU and up to 6 mmol (138 mg) of sodium in one vial of Octanine F 1000 IU. This should be taken into account when administering the product to patients on a controlled sodium diet.

The product is chemically and physically stable for 72 hours at 25 °C. From a microbiological standpoint, the product should be used immediately. If not used immediately, the product may be stored by the user for no more than 24 hours at 2–8 °C, provided it has been prepared under controlled and validated aseptic conditions.

Use during pregnancy or breastfeeding.

Reproductive toxicity studies in animals using factor IX have not been conducted. Due to the rarity of hemophilia B in women, there are no data on the use of factor IX during pregnancy and breastfeeding. Therefore, factor IX should be used during pregnancy and lactation only if clearly indicated.

Ability to affect reaction rate when driving or operating machinery.

No effect on the ability to drive or operate machinery has been observed.

Method of administration and dosage.

Treatment should be initiated under the supervision of a physician experienced in the management of hemophilia.

Previously untreated patients

The safety and efficacy of Octanine in previously untreated patients have not yet been established.

Monitoring of treatment

During the course of treatment, regular monitoring of factor IX levels is recommended to guide dose selection and frequency of repeat infusions. Individual response (pharmacological response) to factor IX administration may vary among patients, including differences in half-life and recovery. The dose calculated according to body weight may require adjustment in patients with underweight or overweight. In particular, during extensive surgical procedures, precise monitoring of replacement therapy by coagulation testing (factor IX activity in plasma) is mandatory and necessary.

The dosage and duration of replacement therapy depend on the severity of factor IX deficiency, the location and severity of bleeding, and the patient's clinical condition.

On-demand treatment

The amount of factor IX administered is expressed in International Units (IU), corresponding to the WHO standard for factor IX preparations. Factor IX activity in plasma is expressed as a percentage (relative to normal human plasma) or in International Units (according to the international standard for factor IX in plasma).

One International Unit (IU) of factor IX activity is equivalent to the amount of factor IX present in 1 mL of normal human plasma. The calculation of the required dose of factor IX is based on empirical data, where 1 IU of factor IX per 1 kg of body weight increases factor IX activity in plasma by 1% of normal activity. The required dose is calculated using the following formula:

Required number of units = body weight (kg) × desired increase in factor IX (%) (IU/dL) × 0.8

The amount of product to be administered and the frequency of administration should always be guided by clinical efficacy in each individual case. Factor IX products are rarely administered more than once daily.

In the bleeding episodes listed below, factor IX activity should not fall below the specified plasma activity level (as % of normal) during the appropriate period. The table below can be used to calculate the dose in cases of bleeding and during surgery.

In the case of major surgical interventions, careful monitoring of replacement therapy by means of coagulation analyses (determination of plasma factor IX activity) is mandatory. Response to factor IX may vary between individual patients: different levels of in vivo recovery and different half-lives may be observed.

Prophylaxis.

For long-term prevention of bleeding in patients with severe haemophilia B, the usual dose is 20–40 IU per kg body weight (BW), administered at intervals of 3 to 4 days. In individual cases, particularly in younger patients, shorter intervals between administrations or higher doses may be required.

In a study involving 25 children under 6 years of age, the average daily dose administered was similar for both prophylaxis and treatment of bleeding episodes, i.e. 35–40 IU/kg BW.

Patients should be monitored for the development of factor IX inhibitors. If expected plasma factor IX activity levels are not achieved, or if the administered dose fails to control bleeding, an assay to detect factor IX inhibitors should be performed. In patients with high inhibitor titres, factor IX therapy may be ineffective and alternative treatment should be considered. Management of such patients should be supervised by a physician experienced in treating haemophilia.

Data to recommend prolonged infusion of Octanine F during surgical procedures are insufficient.

Octanine F should be administered intravenously after reconstitution as described in the relevant section. The recommended infusion rate is not more than 2–3 ml per minute.

Instructions for use, handling and disposal

Carefully read all instructions and strictly follow them!

The procedure described below should be carried out under sterile conditions!

Do not use after the expiry date stated on the label and carton.

The product reconstitutes rapidly at room temperature. The solution should be clear or slightly opalescent. Do not administer cloudy solution or solution containing precipitate.

Reconstitution procedure.

1. Warm the diluent (water for injections) and the concentrate vials to room temperature. Maintain this temperature during reconstitution. If a water bath is used for warming, ensure that water does not come into contact with the rubber stoppers or caps of the vials. The water bath temperature must not exceed 37 °C.
2. Remove the caps from the concentrate and diluent vials and wipe the rubber stoppers with an alcohol swab.
3. Remove the protective cap from the short end of the double-ended needle without touching its tip.

Puncture the centre of the rubber stopper of the diluent vial vertically with the needle. To ensure complete withdrawal of the diluent, insert the needle through the stopper so that it is visible inside the vial.

1. Remove the protective cap from the other, longer end of the double-ended needle without touching its tip.

Hold the diluent vial upside down over the vertically positioned concentrate vial and quickly puncture the centre of the rubber stopper of the concentrate vial. The vacuum inside the concentrate vial will draw the diluent from the diluent vial into the concentrate vial.

1. Remove the double-ended needle with the empty diluent vial from the concentrate vial, then slowly rotate the concentrate vial until the powder is completely dissolved. At room temperature, Octanine F dissolves rapidly to form a clear solution.

Before administration, the reconstituted preparation should be inspected visually for particulate matter or discoloration.

Do not use the product if the concentrate does not fully dissolve or if aggregates form.

The reconstituted solution may only be used once.

Administration technique.

As a precaution, monitor the patient's pulse before and during factor IX administration. If pulse rate increases, reduce the infusion rate or stop administration.

1. After reconstituting the concentrate ( solution preparation) as described above, remove the protective cap from the filter needle and puncture the rubber stopper of the concentrate vial.
2. Remove the cap from the filter needle and attach it to the syringe.
3. Invert the vial with the attached syringe and withdraw the solution into the syringe.
4. Disinfect the injection site with an alcohol swab.
5. Remove the filter needle from the syringe and attach the infusion butterfly needle instead.
6. Insert the butterfly needle into the selected vein.
7. If a tourniquet was used to locate the vein, it must be removed before starting factor IX administration. Monitor pulse rate before and during infusion.
8. Administer the solution intravenously slowly at a rate of 2–3 ml per minute.

For patients requiring more than one vial of Octanine F concentrate for a single therapeutic procedure, the same butterfly needle and syringe may be used for additional vials.

The filter needle may only be used once.

A filter needle must always be used to draw the product into the syringe.

Unused medicinal product and waste material should be disposed of in accordance with local requirements.

Paediatric population. For instructions on use in children, see section "Posology and method of administration".

Overdose.

Symptoms of overdose with human coagulation factor IX have not been reported.

Adverse reactions.

Rare (≥1/10,000 to <1/1,000)

Very rare (<1/10,000), including isolated reports.

Hypersensitivity or allergic reactions (including angioneurotic edema, burning or tingling at the injection site, chills, hot flashes, Quincke's edema, headache, urticaria, hypotension, lethargy, nausea, restlessness, tachycardia, chest tightness, tinnitus, vomiting, wheezing) are infrequently observed in patients receiving factor IX-containing products. In some cases, such reactions progress to severe anaphylaxis and occur temporally close to the emergence of factor IX inhibitors (see also section "Special precautions").

Patients with hemophilia B may develop neutralizing antibodies (inhibitors) to factor IX. If such inhibitors occur, this condition manifests as a poor clinical response. In such cases, consultation with a specialized hemophilia center is recommended. A study was conducted involving 25 children with hemophilia B, including 6 previously untreated patients (mean treatment duration – 38 days, range from 8 to 90). At baseline, factor IX inhibitor levels in all patients were <0.4 BU. Inhibitors were not detected during the study.

Nephrotic syndrome has been reported following failed attempts of immune tolerance induction in patients with hemophilia B and factor IX inhibitors, as well as in patients with a history of allergic reactions.

Increased body temperature has been observed in rare cases.

There is a risk of thromboembolic events when poorly purified factor IX preparations are administered. When using such preparations, cases of myocardial infarction, disseminated intravascular coagulation, venous thrombosis, and pulmonary embolism are also possible. When highly purified factor IX preparations are used, such adverse effects occur very rarely.

Due to the presence of a certain amount of heparin in the product, a sudden, allergy-induced decrease in platelet count to less than 100,000/µL or 50% of the initial count (type II thrombocytopenia) is possible in rare cases. In patients not previously hypersensitive to heparin, this decrease in platelet count may occur 6–14 days after the start of treatment. In patients previously hypersensitive to heparin, this decrease may occur within several hours after treatment initiation.

Such a significant decrease in platelet count may be accompanied by or lead to arterial and venous thrombosis, thromboembolism, severe coagulation disorders (consumptive coagulopathy), skin necrosis at the injection site, flea-bite-like bleeding (petechial hemorrhages), purpura, and melena. If the above-mentioned allergic reactions occur, administration of Octanin F should be immediately discontinued. The patient should be advised not to use medicinal products containing heparin in the future. Due to this rare effect of heparin on platelets, platelet counts should be continuously monitored in patients, especially at the beginning of treatment.

Data on safety regarding infectious agents are provided in the section "Special precautions".

Incompatibility.

Due to the lack of appropriate data, Octanin F must not be mixed with other medicinal products.

Only the provided injection/infusion set should be used, as treatment may fail due to adsorption of human coagulation factor IX onto the inner surface of certain types of injection/infusion equipment.

Shelf life.

3 years.

Biochemical and physical stability during use has been demonstrated for 72 hours at 25 °C.

From a microbiological standpoint, the prepared solution should be used immediately.

If the solution is not used immediately, the time and conditions of storage prior to use are the responsibility of the user.

It is not recommended to store the solution at room temperature (25 °C) for longer than 8 hours.

Storage conditions.

Store at a temperature not exceeding 25 °C in the original packaging to protect from light. Do not freeze.

Keep out of the reach of children.

Packaging.

Octanin F 500 IU.

Carton box No. 1: contains 1 vial made of Type I glass (Eur. Ph.) with a capacity of 30 ml, containing lyophilized powder for solution for injection, and package leaflet.

Carton box No. 2: contains 1 vial made of Type I glass (Eur. Ph.) with solvent (water for injections, 5 ml) and a reconstitution and intravenous administration kit in a bag or blister pack.

Octanin F 1000 IU.

Carton box No. 1: contains 1 vial made of Type I glass (Eur. Ph.) with a capacity of 30 ml, containing lyophilized powder for solution for injection, and package leaflet.

Carton box No. 2: contains 1 vial made of Type I glass (Eur. Ph.) with solvent (water for injections, 10 ml) and a reconstitution and intravenous administration kit in a bag or blister pack.

The reconstitution and intravenous administration kit consists of:

1 single-use syringe,

1 transfer set (1 double-ended needle, 1 filter needle),

1 infusion set (butterfly needle),

2 alcohol-impregnated swabs.

Two boxes are combined with a plastic film.

Prescription status. Prescription only.

Manufacturer.

1. Oberlaaerstrasse 235, 1100 Vienna, Austria / Oberlaaerstrasse 235, 1100 Vienna, Austria.
2. 72 rue du Marechal Foch, 67380 Lingolsheim, France / 72 rue du Marechal Foch, 67380 Lingolsheim, France