Octanin f 500 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. Powder and solvent for solution for injection in vials, supplied 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 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 either 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 after administration of Octanin F at doses >25 IU/kg body weight was assessed 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 for 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 efficacy (n=19) showed 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 heparin-induced thrombocytopenia (heparin-induced thrombocytopenia, type II).

Interaction with other medicinal products and other forms of interaction.

No interactions of human factor IX preparations with other medicinal products have been reported.

Special precautions for use.

As with any intravenous protein product, hypersensitivity reactions may occur. The product contains traces 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 these 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 infection 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 not possible to fully exclude the risk of transmission of 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 taken 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 preparations, 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 upon administration of factor IX concentrate, initial administration of factor IX should be performed under medical supervision with appropriate facilities for managing allergic reactions, as determined by the physician.

Since the use of complex factor IX concentrates has historically 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 tests. In each such case, the benefit of treatment with Octanine F should be weighed against the risk of complications.

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

Cardiovascular complications

In patients at risk of 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 risks associated with CVAD use, including local infections, bacteremia, and catheter thrombosis, should be considered.

It is strongly recommended that each time a patient receives Octanine F, 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 reconstituted 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 speed 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 treatment 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 patients may respond differently to factor IX administration, including variations in half-life and recovery. The dose based on body weight may require adjustment in patients with low or high body weight. Particularly during extensive surgical procedures, precise monitoring of replacement therapy through coagulation testing (factor IX activity in plasma) is essential and mandatory.

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 preparations 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 prophylaxis 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 some cases, particularly in young 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 appropriate dose fails to control bleeding, an assay should be performed to determine the presence of factor IX inhibitors. In patients with high levels of inhibitors, factor IX therapy may be ineffective and alternative treatment should be considered. Management of such patients should be supervised by a physician experienced in the treatment of haemophilia.

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

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 solutions or solutions containing particulate matter.

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 vials containing the concentrate and water, 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 the tip.

Puncture the center of the rubber stopper of the water vial vertically with the needle. To ensure complete withdrawal of water, 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 water vial upside down over the vertically positioned concentrate vial and quickly puncture the center of the rubber stopper of the concentrate vial with the needle. The vacuum inside the concentrate vial will draw the water from the water vial into the concentrate vial.

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

Before administration, visually inspect the reconstituted product for the presence of particulate matter or discoloration.

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

The reconstituted solution must be used only once.

Administration technique.

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

1. After reconstituting the concentrate ( preparing the solution ) 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 draw the solution into the syringe.
4. Disinfect the injection site with an alcohol-soaked swab.
5. Remove the filter needle from the syringe and attach an 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 the factor IX infusion. Monitor pulse rate before and during administration.
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 treatment session, the same butterfly needle and syringe may be used for additional vials.

The filter needle may be used only once.

Always use a filter needle to draw the product into the syringe.

Unused medicinal product and waste materials must be disposed of in accordance with local regulations.

Children. For administration instructions in children, see section "Dosage and administration".

Overdose.

There have been no reports of symptoms associated with overdose of human coagulation factor IX.

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 stinging at the injection site, chills, flushing, 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 warnings and precautions for use").

Patients with hemophilia B may develop neutralizing antibodies (inhibitors) against factor IX. If such inhibitors develop, this condition manifests as a poor clinical response. In such cases, consultation with a specialized hemophilia center is recommended. A study was conducted in 25 patients with hemophilia B, including 6 previously untreated patients (mean treatment duration 38 days, range 8 to 90). At baseline, all patients had factor IX inhibitor levels <0.4 BU. During the study, no inhibitors were detected.

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

Increased body temperature has been observed in rare cases.

There is a risk of thromboembolism when poorly purified factor IX preparations are administered. When using such preparations, cases of myocardial infarction, disseminated intravascular coagulation, venous thrombosis, and pulmonary embolism may also occur. When using highly purified factor IX preparations, 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 heparin-induced thrombocytopenia) may occur rarely. In patients who have not previously been hypersensitive to heparin, such a decrease in platelet count may occur 6–14 days after initiation of treatment. In patients with prior hypersensitivity to heparin, this decrease may occur 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 aforementioned allergic reactions occur, administration of Octanin F should be discontinued immediately. Patients should be advised not to use heparin-containing medicinal products in the future. Due to this rare effect of heparin on platelets, platelet counts should be monitored continuously, especially at the beginning of treatment.

Data on safety regarding infectious agents are provided in the section "Special warnings and precautions for use".

Incompatibilities.

Due to 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 be ineffective 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 point of view, 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 more 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.

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.

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 carton boxes are combined with a plastic film.

Prescription status. Prescription only.

Manufacturer.

1. Oberlaaer Strasse 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.