Octanine 100 IU/ml powder and solvent for solution for injection

Patient Information Leaflet

Introduction

Patient Information Leaflet

Octanine 100 IU/ml, powder and solvent for injectable solution

Human Coagulation Factor IX

Read the entire leaflet carefully before starting to use this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.

• If you have any questions, consult your doctor, pharmacist, or nurse.

• This medicine has been prescribed for you only and must not be given to other people, even if they have the same symptoms as you, because it may harm them.

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

Leaflet contents:

1. What Octanine is and what it is used for
2. What you need to know before using Octanine
3. How to use Octanine
4. Possible side effects
5. How to store Octanine
6. Contents of the pack and other information

1. What Octanine is and what it is used for

Octanine 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 is used for the treatment and prevention of bleeding in patients with bleeding disorders (haemophilia B). This is a condition in which bleeding may last longer than expected. It is caused by an inherited deficiency in the amount of coagulation factor IX in the blood.

Octanine is supplied as a powder and solvent for preparing an injectable solution. After reconstitution, it is administered intravenously (injected into a vein).

2. What you need to know before using Octanine

Do not use Octanine:

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

Warnings and precautions

• Talk to your doctor, pharmacist, or nurse before you start using Octanine.

• Like all medicines containing proteins administered intravenously, allergic-type hypersensitivity reactions may occur. Octanine contains very small amounts of human proteins other than factor IX and heparin. Early signs of hypersensitivity reactions include:

  • rash
  • skin rash (urticaria)
  • tightness in the chest
  • difficulty breathing
  • decrease in blood pressure
  • acute and severe allergic reaction (anaphylaxis when one or more of the above symptoms develop rapidly and are intense)

If these symptoms occur, stop the infusion immediately and consult your doctor. In case of anaphylactic shock, appropriate treatment should be initiated as soon as possible.

• Your doctor may recommend that you consider vaccination against hepatitis A and B if you regularly or repeatedly receive human plasma-derived products containing factor IX.

• It is known that individuals with haemophilia B may develop inhibitors (neutralizing antibodies) to factor IX produced by immune cells. Inhibitors may increase the risk of anaphylactic shock (severe allergic reactions). Therefore, if you experience an allergic reaction, you must be tested for the presence of an inhibitor. Patients with factor IX inhibitors may have an increased risk of anaphylaxis when treated with factor IX. Therefore, your doctor may decide to administer the first dose of factor IX under medical supervision to ensure appropriate care is available in case of allergic reactions.

• Factor IX protein concentrates may cause blood vessel blockage due to clot formation. Because of this risk, which is higher with low-purity products, you should be monitored for symptoms of blood clot formation after administration of factor IX products if you:

  • show signs of fibrinolysis (blood clots that have broken down)
  • have disseminated intravascular coagulation (widespread blood clotting within blood vessels)
  • have been diagnosed with liver disease
  • have documented cardiovascular risk factors
  • have recently undergone surgery
  • are at high risk of clot formation or disseminated intravascular coagulation.

If any of the above conditions apply to you, your doctor will only administer Octanine if the benefit outweighs the risks.

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

Viral safety of blood products

• When medicines derived from human plasma or blood are administered, certain measures are taken to prevent transmission of infections to patients. These measures include careful selection of donors to exclude those at risk of carrying infectious diseases, testing for specific markers of infection in individual donations and plasma pools, and inclusion of manufacturing steps designed to inactivate or remove viruses. Nevertheless, when medicines derived from human blood or plasma are administered, the possibility of transmitting infectious agents cannot be completely ruled out. This also applies to emerging or unknown viruses and other types of infections.

• These measures are considered effective against enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus, and hepatitis C virus, as well as against the non-enveloped hepatitis A virus. However, the measures may have limited effectiveness against other non-enveloped viruses such as parvovirus B19. Parvovirus B19 infection may be severe in pregnant women (fetal infection) and in individuals with weakened immune systems or in patients with certain types of anaemia (e.g. sickle cell anaemia or haemolytic anaemia).

• Your doctor may recommend vaccination against hepatitis A and hepatitis B if you are regularly or repeatedly administered medicines derived from human plasma.

• It is strongly recommended that each time a dose of Octanine is administered, the name of the medicine and the batch number used should be recorded, in order to maintain a record of batches used.

Children

If Octanine is administered to a newborn, careful monitoring for signs of disseminated intravascular coagulation is required.

Other medicines and Octanine

• To the best of current knowledge, human coagulation factor IX products do not interact with any other medicines.

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

Pregnancy and breastfeeding

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

If you are pregnant or breastfeeding, think you might be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Driving and using machines

No effects on the ability to drive or operate machinery have been observed.

Octanine contains sodium

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

This should be taken into account when treating patients on low-sodium diets.

3. How to use Octanine

Follow exactly the instructions given by your doctor for administering this medicine. If in doubt, consult your doctor or pharmacist again.

Octanine must be administered intravenously (injected into a vein) after reconstitution with the solvent supplied.

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

Treatment should be initiated under the supervision of a physician experienced in the treatment of hemophilia. The amount of Octanine you need and the duration of replacement therapy depend on the severity of your factor IX deficiency, as well as on the site and extent of bleeding and your clinical condition.

Dose calculation:

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

The dose of factor IX is expressed in International Units (IU). Factor IX activity in plasma refers to the amount of factor IX present in plasma. It is expressed either as a percentage (relative to normal human plasma) or in International Units (relative to an 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 one milliliter of normal human plasma. The calculation of the required dose of factor IX is based on the observation that 1 IU of factor IX per kilogram of body weight increases factor IX activity in plasma 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 needs to be increased.

The required dose is calculated using the following formula:

Units required = body weight (kg) × desired increase in factor IX (%) (IU/dL) × 0.8

The amount of your dose and how often it should be administered will depend on your response to the medication and will be determined by your doctor. Factor IX products rarely need to be administered more than once a day.

Your response to factor IX products may vary. Therefore, factor IX levels must be measured during treatment to determine the correct dose and infusion frequency. Especially during surgical procedures, your doctor will use blood tests (factor IX plasma activity) to closely monitor replacement therapy.

Prevention of bleeding:

If you have severe hemophilia B, you should inject 20 to 40 IU of factor IX per kilogram of body weight (BW). This dose should be administered twice weekly for long-term prophylaxis. Your dose should be adjusted according to your response. In some cases, particularly in younger patients, shorter intervals or higher doses may be required.

Use in children:

In the study conducted in children under 6 years of age, the mean dose administered per exposure day was 40 IU/kg BW.

If your bleeding cannot be stopped due to inhibitors:

If the expected factor IX activity is not achieved after an injection or if bleeding does not stop after administration of the correct dose, you must inform your doctor. Your doctor will test your blood plasma to determine whether you have developed inhibitors (antibodies) against factor IX protein. These inhibitors may reduce factor IX activity. In such a case, a different treatment may be necessary. Your doctor will discuss this with you and recommend another treatment if needed.

If you use more Octanine than you should

Symptoms of overdose with human coagulation factor IX have not been observed. However, the recommended dose should not be exceeded.

For "Instructions for home treatment", see the package kit container.

4. Possible adverse effects

Like all medicines, Octanine may produce adverse effects, although not everyone experiences them.

• Hypersensitivity or allergic reactions have been observed infrequently in patients treated with factor IX-containing products. These reactions may include:
  • Involuntary contraction of blood vessels (spasms) with swelling of the face, mouth, and throat
  • Burning and stinging at the infusion site
  • Chills
  • Flushing
  • Skin rash
  • Headache
  • Hives
  • Decreased blood pressure
  • Fatigue
  • Malaise
  • Restlessness
  • Rapid heartbeat
  • Chest tightness
  • Tingling
  • Vomiting
  • Difficulty breathing

In some cases, these allergic reactions may progress to a serious 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 listed above, inform your doctor immediately.

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

A study was conducted in 25 children with haemophilia B, including 6 previously untreated patients. No inhibitors were observed during the study. The tolerability of all infusions was rated as "very good" or "good".

• Some patients with haemophilia B who have factor IX inhibitors and are undergoing immune tolerance therapy, and who have a history of allergic reactions, have developed nephrotic syndrome (a serious kidney disease).
• Fever may occur in rare cases.
• Low-purity factor IX products may rarely cause blood clots to form within blood vessels. This may lead to one or more of the following complications:
  • Heart attack
  • Widespread clotting in blood vessels (disseminated intravascular coagulation)
  • Blood clots in veins (venous thrombosis)
  • Blood clots in the lungs (pulmonary embolism)

These side effects are more common when using low-purity factor IX products and are rare when using high-purity products such as Octanine.

• The heparin in the preparation may cause a sudden drop in platelet count below 100,000 per microliter or a reduction of more than 50% from baseline. This is an allergic reaction known as "heparin-induced thrombocytopenia type II." Rarely, in patients not previously hypersensitive to heparin, this drop in platelet count may occur 6–14 days after starting treatment. In patients previously hypersensitive to heparin, this condition may develop within hours of starting treatment. This severe form of thrombocytopenia may be accompanied by, or result in:
  • Blood clots in arteries and veins
  • Blockage of a blood vessel by a clot originating elsewhere
  • A serious coagulation disorder known as consumption coagulopathy
  • Skin gangrene at the injection site
  • Bleeding resembling mosquito bites
  • Bruising
  • Tar-colored stools

If you experience these allergic reactions, stop Octanine infusions immediately and do not use any medicines containing heparin in the future. 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 effects

If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are possible adverse effects not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicinal Products: www.notificaRAM.es.

By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Octanine

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

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

Do not use this medicine after the expiry date stated on the label and the carton. The expiry date refers to the last day of the month indicated.

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

Do not use this medicine if you observe cloudy solutions or if the contents are not completely dissolved. Discard any unused portion. Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging that you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Octanine

The active substance is human coagulation factor IX.

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

Appearance of Octanine and contents of the pack

Octanine is available in 2 pack sizes with the following strengths:

• Octanine 100 IU/ml presentation for reconstitution with 5 ml of water for injections, supplied as powder and solvent for injection with a nominal content of 500 IU of human coagulation factor IX per vial.
• Octanine 100 IU/ml presentation for reconstitution with 10 ml of water for injections, supplied as powder and solvent for injection with a nominal content of 1000 IU of human coagulation factor IX per vial.

Octanine is produced from human donor plasma.

The potency (IU) is determined using the one-stage clotting assay of the European Pharmacopoeia, referenced against the World Health Organization (WHO) international standard. The specific activity of Octanine is approximately 100 IU/mg protein.

Pack description:

Octanine is supplied as a combination pack containing two boxes joined by a plastic seal:

One box contains 1 vial of powder for injectable solution and the package leaflet.

The other box contains the vial with solvent (water for injections, 5 ml for the 500 IU presentation and 10 ml for the 1000 IU presentation).

This pack also contains the following medical devices:

• 1 box of intravenous infusion equipment (1 transfer device, 1 infusion set, 1 disposable syringe)

• 2 alcohol swabs

Marketing Authorisation Holder and Manufacturer

For any information about this medicine, please contact the Marketing Authorisation Holder.

Octapharma S.A.

Parq. Em. S. Fernando,

Avda. Castilla 2 - Edif. Dublin - 2ª Planta,

San Fernando de Henares (Madrid) 28830

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

Date of the most recent review of this leaflet: November 2020.

Detailed and up-to-date information on this medicine is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS)

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

Instructions for outpatient treatment

• Please read all instructions carefully and follow them exactly.
• Do not use Octanine after the expiry date stated on the label and on the carton.
• Sterility must be maintained throughout the procedure described below.
• Visually inspect the reconstituted medicine before administration to check for particles or discoloration.
• The solution should be clear or slightly opalescent. Do not use turbid solutions or those containing sediment.
• Use the prepared solution immediately to avoid microbial contamination.
• Use only the infusion equipment provided. The use of other injection/infusion equipment may result in additional risk and treatment failure.

Instructions for preparing the solution:

Injection Instructions:

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

1. Attach the syringe to the white part of the transfer device. Turn the vial upside down and draw the solution into the syringe (Fig. 6). The solution should be clear or slightly opalescent.

Once the solution has been transferred, firmly hold the syringe plunger (keeping it depressed) and remove the syringe from the transfer device (Fig. 7). Discard the empty vial together with the white part of the transfer device.

1. Clean the injection site with one of the alcohol swabs provided.
2. Attach the infusion set provided to the syringe.
3. Insert the injection needle into the selected vein. If a tourniquet was used to make the vein more visible, it must be released before starting to inject Octanine.

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

1. Inject the solution into the vein slowly, at a rate not exceeding 2–3 mL per minute.

If more than one vial of Octanine powder is used for one treatment, the same injection needle and syringe may be used.

The transfer device is for single use only.

Any unused medicine and all materials that have come into contact with it must be disposed of in accordance with local regulations.