Octanine F 500

Package Leaflet: Information for the User

OCTANINE F 500/OCTANINE F 1000, 500 IU / 1000 IU, powder
and solvent for solution for injection

Human Coagulation Factor IX

Read the package leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this package leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including those not listed in this package leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Table of Contents of the Package Leaflet:

• 1. What is OCTANINE F and what is it used for
• 2. Important information before using OCTANINE F
• 3. How to use OCTANINE F
• 4. Possible side effects
• 5. How to store OCTANINE F
• 6. Contents of the pack and other information

1. What is OCTANINE F and what is it used for

OCTANINE F belongs to a group of medicines called coagulation factors and contains
human coagulation factor IX. It is a special protein that increases the blood's ability
to clot.
OCTANINE F is used to treat and prevent bleeding in patients with bleeding disorders (hemophilia B). This is a medical condition in which bleeding is prolonged compared to expected. It results from a congenital deficiency of factor IX in the blood.
OCTANINE F is supplied as a powder and solvent for solution for injection. After reconstitution, it is administered intravenously (injected into a vein).

2. Important information before using OCTANINE F

When not to use OCTANINE F:

• if you are allergic to human coagulation factor IX or any of the other ingredients of this medicine (listed in section 6),
• if you have had heparin-induced type II thrombocytopenia, which is a decrease in platelet count after heparin administration. Platelets are blood cells that help stop bleeding. Heparin is used to prevent blood clots.

Warnings and precautions

Before starting treatment with OCTANINE F, discuss it with your doctor or
pharmacist.

• All medicines containing protein administered intravenously can cause an allergic reaction. OCTANINE F contains very small amounts of other proteins than factor IX and heparin. Early signs of an allergic reaction include:
• hives,
• rash (hives)
• feeling of chest tightness,
• wheezing,
• drop in blood pressure,
• severe, life-threatening allergic reaction (anaphylaxis in case any or all of the above symptoms develop rapidly and are severe).

In case of the above symptoms, stop the injection immediately and contact your doctor. In case of anaphylactic shock, the doctor must start the recommended treatment as soon as possible.

• It is recommended to have appropriate vaccinations against viral hepatitis A and B in case of regular or repeated use of products containing factor IX derived from human plasma.
• It is known that inhibitors (neutralizing antibodies) of factor IX can develop in patients with hemophilia B. Inhibitors can increase the risk of anaphylactic shock (severe allergic reactions). Therefore, it is recommended to perform tests for the presence of inhibitors in patients with allergic reactions. Patients with factor IX inhibitors are at higher risk of anaphylaxis after factor IX administration. Therefore, the first administration of factor IX, according to the doctor's decision, should be performed under medical supervision in a place where appropriate help can be provided in case of an allergic reaction.
• During the use of factor IX concentrates, blood clots can form in the blood vessels. Due to this risk, which is higher in the case of poorly purified products, patients should be monitored for signs of blood clots after factor IX administration, especially:
• in case of symptoms of fibrinolysis (dissolution of a blood clot),
• in patients with disseminated intravascular coagulation (widespread blood clotting in blood vessels),
• in patients with diagnosed liver disease,
• in case of established cardiovascular risk factors
• in patients after recent surgery,
• in patients with an increased risk of blood clots or disseminated intravascular coagulation.

In case of any of the above disorders in a given patient, the doctor will decide on the administration of OCTANINE F after assessing the potential benefits of treatment compared to the risk associated with the use of the medicine.

• After repeated treatment with products containing human coagulation factor IX, patients should be monitored for the development of neutralizing antibodies (inhibitors), the amount of which is determined in Bethesda units (BU), using appropriate biological tests.

Protection of blood-derived medicines against the transmission of infectious agents
The use of appropriate methods to prevent the transmission of infections to patients is applied to medicines derived from human blood or plasma. These include: strict selection of blood and plasma donors to eliminate carriers of infections, testing of individual donations and plasma pools for specific viral markers. Manufacturers of these medicines also include methods in the production process aimed at inactivating or removing viruses.
Despite this, in the case of administration of medicines derived from human blood or plasma, it is not possible to completely rule out the transmission of an infectious agent.
This applies to both unknown or newly emerging viruses and other types of infections.
These methods are considered effective against enveloped viruses, such as the human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV), as well as the non-enveloped hepatitis A virus (HAV). The applied methods may have limited effectiveness against non-enveloped viruses such as parvovirus B19.
Parvovirus B19 infection can be dangerous for pregnant women (fetal infection) and patients with immune deficiencies and certain types of anemia (e.g., sickle cell anemia or hemolytic anemia).
It is strongly recommended that when administering each dose of OCTANINE F, the product name and batch number should be recorded to keep a record of the batches used.

Children

When administering OCTANINE F to newborns, they should be closely monitored for signs of disseminated intravascular coagulation.

OCTANINE F and other medicines

• No interactions between human coagulation factor IX and other medicines are known.

Tell your doctor or pharmacist about all medicines you are taking, have recently taken, or might take.

Pregnancy and breastfeeding

There is no experience with the use of factor IX during pregnancy and breastfeeding.
Therefore, factor IX should be used during pregnancy and breastfeeding only if strictly necessary.
Before using any medicine, consult your doctor or pharmacist.

OCTANINE F contains sodium

The medicinal product contains up to 69 mg of sodium (the main component of common salt) in one vial of OCTANINE F 500 IU, which is equivalent to 3.45% of the recommended maximum daily intake for adults, and
up to 138 mg of sodium in one vial of OCTANINE F 1000 IU, which is equivalent to 6.9% of the maximum daily intake of 2 g of sodium for adults.
This should be taken into account in patients on a low-sodium diet.

Driving and using machines

No effect on the ability to drive and use machines has been observed.

3. How to use OCTANINE F

OCTANINE F should always be used according to the doctor's instructions. In case of doubts, consult your doctor or pharmacist.
OCTANINE F should be administered intravenously (injected into a vein) after reconstitution in the supplied solvent.
Only use the supplied infusion set. Using other infusion/ injection sets may cause additional risks and treatment failure.
Treatment should be started under the supervision of a doctor experienced in the treatment of hemophilia B. The dosage of OCTANINE F and the duration of treatment depend on the degree of factor IX deficiency. It also depends on the location and extent of bleeding and the patient's clinical condition.

Dose calculation:

The dose and frequency of administration of OCTANINE F will be determined by your doctor.
The number of units of factor IX administered is expressed in international units (IU). The activity of factor IX in plasma corresponds to the factor IX content in plasma. It can be expressed as a percentage (compared to normal human plasma) or in international units (compared to the international standard for factor IX in blood).
One international unit (IU) of factor IX activity corresponds to the amount of factor IX in 1 ml of normal human plasma. The calculation of the required dose of factor IX is based on empirical evidence that 1 international unit (IU) of factor IX per kilogram of body weight increases the plasma factor IX activity by 1% of normal activity. To calculate the required dose, the activity of factor IX in the patient's plasma should be determined. This will determine how much the activity should be increased.
The required number of units is calculated using the following formula:

Required number of units = body weight (kg) x required increase in factor IX activity (%) (IU/ml) x 0.8

The dose to be administered and the frequency of administration should always depend on the clinical efficacy in the individual patient. Factor IX-containing products are rarely required to be administered more frequently than once a day.
The response to factor IX may vary between patients, so it is necessary to determine the factor IX level during treatment to establish the administered dose and infusion frequency. Especially in the case of major surgical procedures, it is necessary to monitor factor IX activity in plasma during substitution therapy.

Bleeding prophylaxis:

In long-term bleeding prophylaxis in patients with severe hemophilia B, factor IX should be administered at a dose of 20 to 40 IU/kg body weight twice a week. The dose should be adjusted according to individual response to treatment. In some cases, especially in younger patients, it may be necessary to administer the product at shorter intervals or in higher doses.

Use in children:

In a clinical study in children under 6 years of age, the average daily dose was 40 IU/kg body weight.

Lack of bleeding cessation due to the presence of inhibitors:

If the desired factor IX activity cannot be achieved after injection or bleeding does not stop after injection of the appropriate dose, inform your doctor. In this case, the doctor will recommend tests to detect inhibitors (antibodies) of factor IX. Inhibitors can cause a decrease in factor IX activity. In this case, it may be necessary to choose a different treatment method. The doctor will decide on this if further treatment is necessary.

Use of a higher dose of OCTANINE F than recommended

No symptoms of overdose of human coagulation factor IX are known.
However, do not exceed the recommended dose.

Instructions for home treatment are included in the package with the administration kit.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

• Allergic reactions or hypersensitivity were not commonly observed in patients treated with products containing factor IX. These included:

reflexive blood vessel spasm with facial, oral, and pharyngeal edema,
burning and stinging pain at the injection site,
chills,
flushing of the face,
rash,
headache,
hives,
drop in blood pressure,
feeling of fatigue,
nausea,
anxiety,
rapid heartbeat,
feeling of chest tightness,
tingling sensation,
vomiting,
wheezing.
In some cases, these reactions can lead to a severe reaction called anaphylaxis, including shock. These reactions are mainly associated with the development of factor IX inhibitors. Inform your doctor if you experience any of these symptoms.

• In patients with hemophilia B, neutralizing antibodies (inhibitors) against factor IX may develop. These antibodies can be responsible for reduced treatment efficacy. The doctor should discuss this with the patient and determine further treatment if necessary. A clinical study was conducted in 25 children with hemophilia B, 6 of whom had not been previously treated. No inhibitor development was observed during the study. Tolerance to all injections was rated as "very good" and "good".
• Some patients with hemophilia B and factor IX inhibitors who underwent immune tolerance induction developed nephrotic syndrome (severe kidney disease).
• Fever may occur in rare cases.
• Products containing factor IX with low purity may rarely lead to the development of blood clots in blood vessels, which can lead to the following complications:

myocardial infarction,
disseminated intravascular coagulation (DIC),
venous thrombosis (phlebothrombosis),
pulmonary embolism (pulmonary embolism).
These complications occur more frequently in the case of low-purity factor IX products and rarely occur with high-purity products such as OCTANINE F.

• Heparin contained in the product may cause a sudden drop in platelet count below 100,000/μl or by 50% compared to the initial count. This is an allergic reaction called "heparin-induced thrombocytopenia type II". In rare cases, in patients without prior hypersensitivity to heparin, this decrease in platelet count may occur between 6 and 14 days after the start of treatment. In patients with prior hypersensitivity to heparin, this change may occur after a few hours after the start of treatment. This significant drop in platelet count can cause or be associated with:

blood clots in arteries and veins,
closure of a blood vessel by a clot formed in another location,
severe coagulation disorder called consumption coagulopathy,
skin necrosis at the injection site,
petechiae (small red or purple spots on the skin),
bruising,
black stools.

In case of these allergic reactions, stop the OCTANINE F injection immediately and do not use heparin-containing products in the future.

Due to this rare effect of heparin on platelets, the platelet count in the patient should be frequently monitored, especially when starting treatment.
Information related to protection against transmissible infectious agents, see section 2 (special precautions should be taken when using OCTANINE F).

Reporting side effects

If you experience any side effects, including those not listed in this package leaflet, tell your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products
Urząd Rejestracji Produktów Leczniczych, Wyrobów Medycznych i Produktów Biobójczych
Al. Jerozolimskie 181C

• 02 - 222 Warsaw Tel.: + 48 22 49 21 301 Fax: + 48 22 49 21 309 e-mail: ndl@urpl.gov.pl

Side effects can also be reported to the marketing authorization holder.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store OCTANINE F

Keep the medicine out of the sight and reach of children.
Do not store above 25°C.
Do not freeze.
Store the vial in the outer packaging to protect from light.
Do not use this medicine after the expiry date stated on the label and carton. The expiry date refers to the last day of the month.
It is recommended to use the reconstituted product immediately, but no later than 8 hours after storage at room temperature (25°C).
OCTANINE F should only be used for a single administration. Do not use this medicine if you notice that the solutions are cloudy or not fully dissolved.
Medicines should not be disposed of via wastewater or household waste.
Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What OCTANINE F contains

The active substanceis human coagulation factor IX.
The other ingredientsare: heparin, sodium chloride, sodium citrate, arginine hydrochloride, and lysine hydrochloride.

What OCTANINE F looks like and contents of the pack

OCTANINE F is available in 2 pack sizes with the following strengths:

• OCTANINE F 500 is available as a powder and solvent for solution for injection containing nominally 500 IU of human coagulation factor IX in a vial.

After reconstitution in 5 ml of water for injection, the product contains approximately 100 IU/ml of human factor IX.

• OCTANINE F 1000 is available as a powder and solvent for solution for injection containing nominally 1000 IU of human coagulation factor IX in a vial.

After reconstitution in 10 ml of water for injection, the product contains approximately 100 IU/ml of human factor IX.
The OCTANINE F product is manufactured from human plasma.
Activity (in IU) is determined using a one-stage coagulation test, according to the European Pharmacopoeia, compared to the World Health Organization (WHO) international standard. The specific activity of OCTANINE F is approximately 100 IU/mg protein.

Pack description:

OCTANINE F is sold in a pack containing two boxes connected by a plastic strip.
One box contains a vial with powder for solution for injection and a patient information leaflet.
The other box contains a vial with solvent (water for injection); 5 ml for OCTANINE F 500 or 10 ml for OCTANINE F 1000.
The pack also includes the following medical devices:

• 1 package with administration kit (1 transfer set, 1 infusion set, 1 single-use syringe),
• 2 alcohol swabs.

Marketing authorization holder and manufacturer

For more information about this medicine, contact your local representative of the marketing authorization holder.
Octapharma (IP) SPRL
Allée de la Recherche 65
1070 Anderlecht
Belgium

Manufacturer:

Octapharma S.A.S
70-72 Rue du Maréchal Foch
67380 Lingolsheim
France
Octapharma Pharmazeutika Produktionsges.m.b.H.
Oberlaaer Strasse 235
1100 Vienna
Austria
Date of last revision of the package leaflet: March 2021

Instructions for use at home

Read all instructions carefully and follow them!

During the procedure described below, maintain aseptic conditions!

Do not use the OCTANINE F product after the expiry date stated on the label.

Before administration, check the prepared solution visually for particulate matter or discoloration.

The solution should be clear or slightly opalescent. Do not use solutions that are cloudy or contain particulate matter.

Use the reconstituted product immediately to prevent microbial contamination.

Use only the supplied infusion set. Using other infusion/injection sets may cause additional risks and treatment failure.

Instructions for preparing the solution:

• 1. Do not use the product directly after removal from the refrigerator. Leave the solvent and powder in closed vials until they reach room temperature.
• 2. Remove the caps from both vials and clean the rubber stoppers with one of the enclosed alcohol swabs.
• 3. The transfer set is shown in Fig. 1. Place the vial with solvent on a flat surface and hold it firmly. Take the transfer set and turn it upside down. Place the blue part of the transfer set on top of the vial with solvent and press firmly until it clicks (Fig. 2 + 3). Do not rotate during connection.

• 4. Place the vial with powder on a flat surface and hold it firmly. Take the vial with solvent with the attached transfer set and turn it upside down. Place the white part of the transfer set on top of the vial with powder and press firmly until it clicks (Fig. 4). Do not rotate during connection. The solvent flows automatically into the vial with powder.

• 5. With both vials still connected, gently rotate the vial with powder until the product is dissolved. Dissolution will occur within 10 minutes at room temperature. Some foam may form during preparation. Unscrew the transfer set into two parts (Fig. 5). The foam will disappear.

Discard the empty vial with solvent along with the blue part of the transfer set.

Instructions for injection:

As a precaution, check your pulse before and during injection. If you experience a significant increase in heart rate, reduce the injection rate or pause the administration for a short time.

• 1. Connect the syringe to the white part of the transfer set. Turn the vial upside down and draw the solution into the syringe (Fig. 6).

The solution in the syringe should be clear or slightly opalescent.
After transferring the solution, firmly hold the syringe plunger (with the syringe pointing downwards) and remove the syringe from the transfer set (Fig. 7). Discard the empty vial along with the white part of the transfer set.

• 2. Clean the selected injection site with one of the enclosed alcohol swabs.
• 3. Connect the supplied infusion set to the syringe.

• 4. Insert the needle into the selected vein. If a tourniquet is used to make the vein visible, loosen it before starting the injection of OCTANINE F. Blood must not enter the syringe due to the risk of forming fibrin clots.
• 5. Inject the solution slowly into the vein, no faster than 2-3 ml per minute.

In case of using more than one vial of OCTANINE F powder for one treatment cycle, it is possible to reuse the same needle and syringe.
The transfer set is intended for single use only.
Any unused product or waste material should be disposed of in accordance with local regulations.