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
Please read all of this leaflet carefully before this medicine is administered,
because it contains important information for you.

• Keep this 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 a specific individual. Do not pass it on to others. It may harm them, even if their symptoms are the same.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of the leaflet:

1. What OCTANINE F is and what it is used for
2. Before you use 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 OCTANINE F is and what it is used for
OCTANINE F belongs to a group of medicines called coagulation factors and contains human coagulation factor IX. This is a special protein that enhances the blood's ability to clot.
OCTANINE F is used in the treatment and prevention of bleeding in patients with a bleeding disorder (haemophilia B). This is a medical condition characterized by prolonged bleeding compared to what is expected. It results from an inherited deficiency in the amount of factor IX in the blood.
OCTANINE F is supplied as a powder and solvent for reconstitution into a solution for injection. After reconstitution, it is administered intravenously (injected into a vein).

2. Before you use OCTANINE F

Do not use OCTANINE F:

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

Warnings and precautions
Talk to your doctor or pharmacist before using OCTANINE F.

• All medicines containing proteins administered intravenously may cause allergic-type hypersensitivity reactions. OCTANINE F contains very small amounts of proteins other than factor IX and heparin. Early signs of hypersensitivity reactions include:
  • urticaria,
  • rash (urticaria),
  • feeling of chest tightness,
  • wheezing,
  • drop in blood pressure,
  • acute, severe allergic reaction (anaphylaxis, if any or all of the above symptoms develop rapidly and are severe).

If any of the above symptoms occur, administration must be stopped immediately and your doctor should be contacted. In case of anaphylactic shock, the doctor must initiate appropriate treatment as quickly as possible.

• Vaccination against hepatitis A and B is recommended for patients receiving regular or repeated treatment with factor IX products derived from human plasma.
• The development of inhibitors (neutralizing antibodies) against factor IX, produced by immune cells in patients with haemophilia B, is known. Inhibitors may increase the risk of anaphylactic shock (severe allergic reactions). Therefore, testing for the presence of inhibitors is recommended in patients experiencing allergic reactions. Patients with factor IX inhibitors are at higher risk of anaphylaxis after administration of factor IX. Therefore, the first administration of factor IX, according to the treating physician's decision, should be performed under medical supervision in a setting where appropriate emergency treatment can be provided in case of allergic reactions.
• Thrombotic events (blood vessel blockage by clots) may occur during treatment with protein concentrates containing factor IX. Due to this risk, which is higher with poorly purified products, patients should be monitored for signs of blood clots after administration of factor IX-containing products in the following cases:
  • presence of signs of fibrinolysis (clot dissolution),
  • patients with disseminated intravascular coagulation (widespread clotting in blood vessels),
  • patients diagnosed with liver disease,
  • documented cardiovascular risk factors,
  • patients who have recently undergone surgery,
  • patients at increased risk of thrombosis or disseminated intravascular coagulation.

If any of the above conditions are present in a given patient, the doctor will decide whether to administer OCTANINE F after evaluating the potential benefits of treatment against the risks associated with its use.

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

Viral safety of medicines derived from human blood
o Appropriate measures are applied in the production of medicines derived from human blood or plasma to prevent transmission of infections to patients. These include: strict selection of blood and plasma donors to exclude carriers of infection, testing of individual donations and plasma pools for specific viral markers. Manufacturers of these medicines also include in the production process methods intended to inactivate or remove viruses. Despite these measures, when administering medicines derived from human blood or plasma, transmission of infectious agents cannot be completely ruled out. This includes unknown or newly emerging viruses and other types of infections.
o These methods are considered effective against enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and non-enveloped hepatitis A virus (HAV). The methods used may have limited effectiveness against non-enveloped viruses such as parvovirus B19. Infection with parvovirus B19 may be dangerous for pregnant women (fetal infection) and for immunocompromised patients and certain types of anaemia (e.g. sickle cell anaemia or haemolytic anaemia).
It is strongly recommended that the name and batch number of the OCTANINE F product be recorded each time a dose is administered, to maintain a record of batches used.

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

OCTANINE F with other medicines

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

Tell your doctor or pharmacist about all medicines you are currently 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 indicated.
Consult your doctor or pharmacist before taking any medicine.

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

Driving and using machines
No effects on the ability to drive and use machines have been observed.

3. How to use OCTANINE F

OCTANINE F should always be used as directed by the physician. If in doubt, consult a doctor or pharmacist.
OCTANINE F should be administered intravenously (injected into a vein) after reconstitution with the provided solvent.
Only use the infusion set supplied. Using other injection/infusion sets may pose additional risks and lead to treatment failure.
Treatment should be initiated under the supervision of a physician experienced in the management of hemophilia B. The dosage and duration of therapy depend on the severity of factor IX deficiency, as well as the site 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 the physician.
The number of units of factor IX administered is expressed in international units (IU). Plasma factor IX activity corresponds to the concentration of factor IX in plasma. It may be expressed as a percentage (relative to normal human plasma) or in international units (relative to the international standard for blood plasma factor IX).
One international unit (IU) of factor IX activity corresponds to the amount of factor IX present in 1 ml of normal human plasma. The required dose of factor IX is calculated based on empirical data showing that 1 international unit (IU) of factor IX per kilogram of body weight raises plasma factor IX activity by 1% of normal activity. To calculate the required dose, determine the patient's plasma factor IX activity level to establish by how much it needs to be increased.

The required dose is calculated using the following formula:
Required number of units = body weight (kg) × required increase in factor IX activity (%) (IU/dl) × 0.8

The dose and frequency of administration should always be adjusted according to the individual patient's clinical response. Factor IX-containing products rarely require administration more than once daily.
Individual patient response to factor IX may vary; therefore, factor IX levels should be monitored during treatment to determine the appropriate dose and infusion frequency. Monitoring of plasma factor IX activity is especially necessary during major surgical procedures while undergoing substitution therapy.

Prophylaxis of bleeding:
For long-term prophylaxis of bleeding in patients with severe hemophilia B, factor IX should be administered at a dose of 20 to 40 IU per kilogram of body weight twice weekly. The dose should be adjusted according to individual response to treatment. In some cases, especially in younger patients, more frequent administration or higher doses may be required.

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

Lack of bleeding control due to presence of inhibitors:
If the desired factor IX activity level is not achieved after injection, or if bleeding does not resolve despite administration of an appropriate dose, inform the physician. In such cases, the physician will order tests to detect inhibitors (antibodies) against factor IX. Inhibitors may reduce factor IX activity. In such cases, an alternative treatment approach may be necessary. The physician will decide on further management if additional treatment is required.

Administration of a higher than recommended dose of OCTANINE F
There are no known symptoms of overdose with human coagulation factor IX. However, the recommended dose should not be exceeded.

Instructions for home treatment are provided in the package box with the equipment.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although
they do not occur in everyone.

• Hypersensitivity or allergic reactions have not been frequently observed in patients treated with products containing factor IX. These included:

reflex vasoconstriction (spasms) with facial, oral cavity and throat swelling,
burning and stinging pain at the infusion site,
chills,
facial flushing,
rash,
headache,
urticaria,
hypotension,
feeling of fatigue,
nausea,
restlessness,
rapid heartbeat,
feeling of chest tightness,
tingling sensation,
vomiting,
wheezing.

In some cases, these reactions may 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 any
of these symptoms occur.

• In patients with haemophilia B, neutralizing antibodies (inhibitors) against factor IX may occur. These antibodies may be responsible for reduced treatment efficacy. Your doctor should discuss this with you and determine further treatment if necessary. A clinical trial was conducted in 25 children with haemophilia B, including 6 who had not been previously treated. No development of inhibitors was observed during the study. Tolerance to all injections was rated as "very good" and "good".

• Some patients with haemophilia B and factor IX inhibitors, who underwent immune tolerance induction, developed nephrotic syndrome (a serious kidney disease).

• Fever may occur rarely.

• Factor IX-containing products of low purity may rarely lead to thrombosis in blood vessels. This may result in the following complications:

myocardial infarction,
disseminated intravascular coagulation (DIC),
venous thrombosis,
pulmonary embolism.

These complications are more common when using low-purity factor IX products and occur rarely 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 known as "heparin-induced thrombocytopenia type II". Rarely, in patients without prior hypersensitivity to heparin, this drop in platelet count may occur between days 6 and 14 after starting treatment. In patients with prior hypersensitivity to heparin, this change may appear within several hours after starting treatment. This serious drop in platelets may cause or be associated with:

arterial and venous blood clots,
vessel occlusion by thrombus occurring elsewhere,
a severe coagulation disorder called consumption coagulopathy,
skin necrosis at the injection site,
petechial bleeding,
bruising,
tarry stools.

If these allergic reactions occur, administration of OCTANINE F must be immediately discontinued and heparin-containing medicines must not be used in the future. Due to this rare effect of heparin on platelets, platelet count should be frequently monitored, especially at the beginning of treatment.

Information regarding protection against transmissible infectious agents, see section 2 (special caution should be exercised when using OCTANINE F).

Reporting of adverse reactions

If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse reactions can be reported directly to:

Department of Monitoring Adverse Drug Reactions
Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Tel.: +48 22 49 21 301
Fax: +48 22 49 21 309
e-mail: [email protected]

Adverse reactions can also be reported to the responsible entity.

By reporting adverse reactions, additional information on the safety of the medicine can be collected.

5. How to store OCTANINE F

Keep this 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 specified month.
It is recommended to use the reconstituted product immediately and no later than within 8 hours of storage at room temperature (25°C).
OCTANINE F should be used for a single administration only. Do not use this medicine if the solutions appear cloudy or not completely dissolved.
Medicines must not be disposed of via wastewater or household waste.
Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the package and other information

What OCTANINE F contains
Active substance: human coagulation factor IX.
Other ingredients: 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 two package sizes with the following strengths:

• OCTANINE F 500 is supplied as a powder and solvent for solution for injection, nominally containing 500 IU of human coagulation factor IX per vial.
  After reconstitution with 5 ml of water for injections, the product contains approximately 100 IU/ml of human coagulation factor IX.

• OCTANINE F 1000 is supplied as a powder and solvent for solution for injection, nominally containing 1000 IU of human coagulation factor IX per vial.
  After reconstitution with 10 ml of water for injections, the product contains approximately 100 IU/ml of human coagulation factor IX.

OCTANINE F is manufactured from human plasma.
The activity (in IU) is determined by a one-stage clotting assay, in accordance with the European Pharmacopoeia, using the World Health Organization (WHO) international reference standard. The specific activity of OCTANINE F is approximately 100 IU/mg protein.

Pack description:
OCTANINE F is supplied as a package containing two boxes connected by a plastic strip.
One box contains a vial of powder for solution for injection and a patient leaflet.
The second box contains a vial of solvent (water for injections); 5 ml for OCTANINE F 500 or 10 ml for OCTANINE F 1000.
The package also includes the following medical devices:

• 1 package containing intravenous administration equipment (1 transfer set, 1 infusion set, 1 single-use syringe),
• 2 alcohol-impregnated swabs.

Marketing Authorisation Holder and Manufacturer
For further information on this medicinal product, please contact the local representative of the Marketing Authorisation 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

Instructions for home use

• Read all instructions carefully and follow them exactly!
• Maintain aseptic conditions during the procedure described below!
• Do not use OCTANINE F after the expiry date stated on the label.
• Before administration, visually inspect the prepared solution for the presence of 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 prepared solution immediately to avoid microbiological contamination.
• Use only the provided infusion set. Using other injection/infusion equipment may lead to additional risks and treatment failure.

Instructions for preparing the solution:

1. Do not use the product immediately after removing it from the refrigerator. Allow both the solvent and the powder to reach room temperature while still in their closed vials.
2. Remove the caps from both vials and clean the rubber stoppers with one of the provided alcohol-impregnated swabs.
3. The transfer set is shown in Fig. 1. Place the solvent vial 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 onto the top of the solvent vial and press firmly until it clicks into place (Fig. 2 + 3). Do not rotate while attaching.

Fig. 3
Fig. 1 Fig. 2

4. Place the vial containing the powder on a flat surface and hold it firmly. Take the solvent vial with the attached transfer set and turn it upside down. Place the white part of the transfer set onto the top of the powder vial and press firmly until it clicks into place (Fig. 4). Do not rotate while attaching. The solvent will automatically flow into the vial containing the powder.

5. While keeping both vials connected, gently rotate the powder vial until the product is completely dissolved. Dissolution will occur within less than 10 minutes at room temperature. Slight foaming may occur during preparation. Unscrew the transfer set into two parts (Fig. 5). The foam will disappear.

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

Instructions for administering the injection:
As a precaution, monitor the pulse before and during the injection. If a significant increase in pulse rate occurs, reduce the injection rate or temporarily interrupt administration.

1. Attach 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 (keeping it pointing downward) and remove the syringe from the transfer set (Fig. 7). Discard the empty vial together with the white part of the transfer set.

2. Clean the selected injection site with one of the provided alcohol-impregnated swabs.
3. Connect the provided infusion set to the syringe.
4. Insert the needle into the selected vein. If a tourniquet was used to visualize the vein, loosen it before starting the injection of OCTANINE F. Blood must not enter the syringe due to the risk of fibrin clot formation.
5. Inject the solution slowly into the vein, at a rate no faster than 2–3 ml per minute.

When more than one vial of OCTANINE F powder is used during a single treatment cycle, the same needle and syringe may be reused.
The transfer set is intended for single use only.
Any unused product or waste material should be disposed of in accordance with local regulations.