Product Information for the User

Octanine 100 UI/ml, Powder and Solvent for Injectable Solution

Human Coagulation Factor IX

Read this entire product information carefully before starting to use this medication, as it contains important information for you.

• Keep this product information, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.

• This medication has been prescribed only to you and should not be given to others, even if they have the same symptoms as you, as it may harm them.

• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this product information. See section 4.

1. What is Octanine and how is it used

2. What you need to know before starting to use Octanine

3. How to use Octanine

4. Possible adverse effects

5. Storage of Octanine

6. Contents of the package and additional information

Octanine belongs to a group of medications called coagulation factors and contains human coagulation factor IX. It is a special protein that increases the blood's ability to clot.

Octanine is used for the treatment and prevention of bleeding in patients with blood disorders (hemophilia B). It is a condition where bleeding can last longer than expected. This is due to a congenital deficiency in the amount of coagulation factor IX in the blood.

Octanine is supplied in the form of powder and solvent to prepare an injectable solution. After reconstitution, it is administered intravenously (injected into a vein).

No use Octanine:

Warnings and precautions

If these symptoms appear, stop the injection immediately and consult your doctor. In case of anaphylactic shock, you should initiate the recommended treatment as soon as possible.

If any of the above symptoms are true for you, your doctor will only administer Octanine if the benefits outweigh the risks.

Viral safety of blood products

Children

If Octanine is administered to a newborn, you should closely monitor the child for signs of disseminated intravascular coagulation.

Other medications and Octanine

Inform your doctor or pharmacist if you are using or have used recently or may need to use other medications, including those obtained without a prescription.

Pregnancy and breastfeeding

No data are available on the use of factor IX during pregnancy and lactation. Therefore, factor IX should be used during pregnancy and lactation only if clearly indicated.

If you are pregnant or breastfeeding, or think you may be pregnant, or intend to become pregnant, consult your doctor or pharmacist before using this medication.

Driving and operating machinery

No effects have been observed on driving and operating machinery.

Octanine contains sodium

This medication contains up to 69 mg of sodium (main component of table salt) in 1 vial of Octanine 500 IU, equivalent to 3.45% of the maximum daily recommended sodium intake for an adult, and up to 138 mg of sodium in 1 vial of Octanine 1000 IU, equivalent to 6.9% of the maximum daily recommended sodium intake for an adult.

You should be aware of this in the treatment of patients with low-sodium diets.

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

Octanine must be administered intravenously (injected into a vein) after reconstituting it with the solvent provided.

Use only the infusion equipment provided. The use of other injection/infusion equipment may cause additional risks and treatment failure.

Treatment should begin under the supervision of an experienced doctor in the treatment of hemophilia. The amount of Octanine to be used and the duration of the substitution therapy depend on the severity of your factor IX deficiency. It also depends on the location and severity of the bleeding, as well as your clinical condition.

Dosage calculation:

Your doctor will tell you how often and how much Octanine you need to be injected.

The factor IX dose is expressed in International Units (UI). The activity of Factor IX in plasma refers to the amount of Factor IX present in plasma. It is expressed either as a percentage (with respect to normal human plasma) or in International Units (with respect to an international standard for Factor IX in plasma).

One International Unit (UI) of Factor IX activity is equivalent to the amount of Factor IX in one milliliter of normal human plasma. The calculation of the required dose of Factor IX is based on the observation that 1 UI of Factor IX per kilogram of body weight increases plasma Factor IX activity by 1% of normal activity. To calculate the dose you need, the level of Factor IX activity in your blood plasma is measured. This will indicate how much activity is needed to be increased.

The required dose is calculated using the following formula:

Required Units = body weight (kg) x desired increase in Factor IX (%) (UI/dl) x 0.8

The amount of your dose and how often you should administer it will depend on how you respond to the medication and will be decided by your doctor. Factor IX products occasionally require administration more than once a day.

Your response to Factor IX products may be variable. Therefore, your Factor IX levels should be measured during treatment to calculate the correct dose and infusion frequency. Especially during surgical procedures, your doctor will use blood tests (plasma Factor IX activity) to closely monitor substitution therapy.

Bleeding prevention:

If you have severe hemophilia B, you should inject20 to 40 UI of Factor IX per kilogram of body weight (PC). This dose should be administered twice a week for long-term prevention. Your dose should be adjusted based on your response. In some cases, especially in young patients, shorter administration intervals or higher doses may be necessary.

Use in children:

In the study conducted in children under 6 years of age, the mean daily dose of exposure was 40 UI/kg PC.

If bleeding cannot be stopped due to inhibitors:

If the expected Factor IX activity is not achieved after an injection or bleeding does not stop after administering the correct dose, you should inform your doctor. They will examine your blood plasma to see if you have developed inhibitors (antibodies) against the Factor IX protein. These inhibitors can reduce Factor IX activity. In this case, alternative treatment may be necessary. Your doctor will discuss this with you and recommend another treatment if necessary.

If you use more Octanine than you should:

No symptoms of overdose have been observed with human coagulation Factor IX. However, do not exceed the recommended dose.

For "Home Treatment Instructions", see the package insert of the equipment.

Like all medicines, Octanine may cause side effects, although not everyone will experience them.

•Infrequently, hypersensitivity or allergic reactions have been observed in patients treated with products containing factor IX. These reactions may include:

• Spasms with swelling in the face, mouth, and throat
• Burning and stinging at the injection site
• Chills
• Flush
• Skin rash
• Headache
• Hives
• Decreased blood pressure
• Fatigue
• Malaise
• Anxiety
• Fast heart rate
• Chest tightness
• Prickling
• Vomiting
• Difficulty breathing

In some cases, these allergic reactions may lead to a severe reaction called anaphylaxis, which may include shock. These reactions are generally associated with the development of factor IX inhibitors. If you experience any of the symptoms mentioned above, inform your doctor.

•If you have hemophilia B, you may develop neutralizing antibodies (inhibitors) against factor IX. These antibodies can interfere with the proper functioning of your medicine.Your doctor will discuss this with you and recommend alternative treatment if necessary.

A study was conducted in 25 children with hemophilia B, of whom 6 patients had not been previously treated. No inhibitors were observed during the study. The tolerability of all injections was estimated as “very good” or “good”.

•Patients with hemophilia B and factor IX inhibitors who have undergone immunotolerance therapy and have a history of allergic reactions may develop nephrotic syndrome (a severe kidney disease).

•In rare cases, it may cause fever.

•Low-purity factor IX products may, in rare cases, cause blood clots to form within blood vessels. This may lead to some of the following complications:

• Heart attack
• Widespread blood clotting in blood vessels (disseminated intravascular coagulation)
• Blood clots in veins (thrombosis)
• Blood clots in the lungs (pulmonary embolism)

These side effects are more common with low-purity factor IX products and are rare with high-purity products like Octanine.

•The heparin in the preparation may cause a sudden drop in platelet count below 100,000 per microliter or less than 50% of the initial count. This is an allergic reaction called “heparin-induced thrombocytopenia type II”. In rare cases, in patients who are not previously hypersensitive to heparin, this drop in platelet count may occur 6-14 days after starting treatment. In patients with previous hypersensitivity to heparin, this alteration may develop a few hours after starting treatment. This severe form of platelet reduction may be accompanied by or result in:

• Blood clots in arteries and veins
• Obstruction of a blood vessel by a clot from another area
• A severe coagulation disorder called consumption coagulopathy
• Skin gangrene at the injection site
• Bleeding with a mosquito bite appearance
• Hematomas
• Black stools

If you observe these allergic reactions, stop injecting Octanine immediately and do not use in the future any medicines containing heparin.Due to this rare effect on blood platelets, your doctor will closely monitor your platelet count, especially when starting treatment.

For safety regarding transmissible agents, see section 2.

Reporting of adverse reactions

If you experienceany type of adverse reaction, consult your doctor, pharmacist, or nurse, even if it is apossibleadverse reaction that does not appear in this leaflet.You can also report them directly through theSpanish System for the Pharmacovigilance of Medicines for Human Use:www.notificaRAM.es.

By reporting adverse reactions, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Store the vial in the outer packaging to protect it from light and below +25°C. Do not freeze.

Do not use this medication after the expiration date that appears on the label and on the box. The expiration date is the last day of the month indicated.

It is recommended to use the reconstituted product immediately, and, otherwise, at least within 8 hours stored at room temperature (25°C). Use Octanine on a single occasion.

Do not use this medication if you observe cloudy solutions or those that are not completely dissolved. Discard the unused content. Medications should not be thrown down the drain or in the trash. Ask your pharmacist how to dispose of the containers and medications that you do not need. This will help protect the environment.

Composition of Octanine

The active principle is human coagulation factor IX.

The other components are heparin, sodium chloride, sodium citrate, arginine hydrochloride, and lysine hydrochloride.

Appearance of Octanine and packaging contents

Octanine is presented in 2 packaging sizes with the following doses:

•Octanine 100 UI/ml presentation to reconstitute with 5 ml of injectable water, presented as a powder and injection solvent with a nominal content of 500 UI of human coagulation factor IX per vial.

•Octanine 100 UI/ml presentation to reconstitute with 10 ml of injectable water, presented as a powder and injection solvent with a nominal content of 1000 UI of human coagulation factor IX per vial.

Octanine is produced with human donor plasma.

The potency (UI) is determined using the single-stage coagulation test of the European Pharmacopeia, compared to the international standard of the World Health Organization (WHO). The specific activity of Octanine is approximately 100 UI/mg protein.

Description of the packaging:

Octanine is supplied as a combined package containing two connected cases with a plastic seal:

One case contains 1 vial with injectable solution powder and the leaflet.

The other case contains the vial with the solvent(injectable water, 5 ml for the 500 UI presentation and 10 ml for the 1000 UI presentation).

This packaging also contains the following medical devices:

•1 case of intravenous injection equipment (1 transfer set, 1 perfusion set, 1 disposable syringe)

•2 alcohol wipes

Marketing authorization holder and responsible manufacturer

For any information about this medication, please contact the marketing authorization holder.

Octapharma S.A.

Parq. Em. S. Fernando,

Avda. Castilla 2 - Edif. Dublin - 2nd Floor,

San Fernando de Henares (Madrid) 28830

Responsible manufacturer:

Octapharma Pharmazeutika Produktionsges.m.b.H.

Oberlaaer Strasse 235

A-1100 Vienna

Austria

or

Octapharma S.A.S.

70-72 Rue du Maréchal Foch

67380 Lingolsheim

France

Last review date of this leafletNovember 2020.

Detailed and updated information about this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)

http://www.aemps.gob.es/

Treatment instructions for outpatient use

Instructions for preparing the solution:

Instructions for injection:

As a precaution, measure your pulse rate before and during injection. If your pulse rate increases significantly, reduce the injection rate or interrupt administration for a brief period.

1. Attach the syringe to the white part of the transfer set. Turn the vial over and extract the solution into the syringe (Fig.6). The solution must be clear or slightly opalescent.

Once the solution has been transferred, hold the syringe plunger firmly in place (keeping it down) and remove the syringe from the transfer set (Fig. 7). Dispose of the empty vial along with the white part of the transfer set.

1. Clean the area where the injection will be administered with one of the alcohol wipes included.
2. Attach the included perfusion equipment to the syringe.
3. Insert the injection needle into the selected vein. If you used a tourniquet to make the vein more visible, this tourniquet must be released before starting the injection.

Blood should not flow into the syringe due to the risk of fibrin clot formation.

1. Inject the solution into the vein at a slow rate, not exceeding 2-3 ml per minute.

If you use more than one powder vial ofOctaninefor a treatment, you can use the same injection needle and syringe.

The transfer set is for single use.

The disposal of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations.