Immunine 1200 IU powder and solvent for solution for injection or for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: Information for the user

IMMUNINE 1200 IU

Powder and solvent for solution for injection or infusion

human blood coagulation factor IX

Read all of this leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• 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 or pharmacist, even if they are effects not listed in this leaflet. See section 4.

Contents of this leaflet

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

1. What IMMUNINE is and what it is used for

IMMUNINE is a concentrate of coagulation factor IX. It replaces the missing or non-functioning factor IX in haemophilia B. Haemophilia B is an inherited, sex-linked coagulation disorder caused by reduced levels of factor IX. It causes severe bleeding into joints, muscles, and internal organs, either spontaneously or following accidental or surgical trauma. Administration of IMMUNINE temporarily corrects the factor IX deficiency and reduces the tendency to bleed.

IMMUNINE is used for the treatment and prophylaxis of bleeding episodes in patients with congenital haemophilia B.

IMMUNINE is indicated for all age groups, from children over 6 years of age to adults.

There are insufficient data to recommend the use of IMMUNINE in children under 6 years of age.

2. What you need to know before using IMMUNINE

Do not use IMMUNINE

• 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 a known allergy to heparin or have previously experienced an abnormal drop in blood cells involved in blood clotting caused by heparin administration (heparin-induced thrombocytopenia).

After appropriate treatment of these conditions, IMMUNINE should only be used in life-threatening bleeding episodes.

Warnings and precautions

Talk to your doctor or pharmacist before using IMMUNINE.

When allergic reactions occur:

There is a rare possibility that you may experience a sudden and severe allergic reaction (anaphylactic reaction) to IMMUNINE.

If you notice one or more of the following symptoms, stop administration immediately and seek medical help right away. These may be signs of anaphylactic shock and require immediate emergency treatment.

• Skin redness
• Rash
• Hives (urticaria)
• Itching all over the body
• Swelling of lips and tongue
• Difficulty breathing / dyspnea
• Difficulty inhaling or exhaling due to constriction of the airways (wheezing)
• Chest tightness
• General malaise
• Dizziness
• Drop in blood pressure
• Loss of consciousness

When monitoring is required:

• Your doctor may wish to perform certain tests to ensure that the dose you receive is sufficient to achieve and maintain adequate levels of factor IX in the blood.
• Your doctor will monitor you closely to detect possible complications:
  • If you receive high doses of IMMUNINE
  • If you are prone to developing thrombosis. In such cases, you will receive lower levels of factor IX, the active substance in IMMUNINE.

When bleeding continues:

• If your bleeding does not stop with IMMUNINE, contact your doctor immediately. You may have developed inhibitors to Factor IX. Factor IX inhibitors are antibodies present in the blood that counteract the effect of factor IX. This reduces the effectiveness of IMMUNINE in treating bleeding episodes. Your doctor will perform the necessary tests to confirm this.

• There may be a link between the development of factor IX inhibitors and allergic reactions. Patients with factor IX inhibitors may have an increased risk of sudden and severe allergic reactions (anaphylaxis). Therefore, in patients experiencing an allergic reaction, the presence of a factor IX inhibitor should be investigated.

Inform your doctor if you have heart or liver disease or if you have recently undergone major surgery, as there is an increased risk of complications related to blood clot formation (coagulation).

Safety information regarding transmissible agents

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 to detect possible viruses or infections
• Incorporation of manufacturing steps designed to eliminate/inactivate viruses.

Despite these measures, the possibility of transmitting infectious agents cannot be completely ruled out when administering medicines derived from human blood or plasma. This also applies to emerging viruses or those of unknown nature, as well as 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.

The measures taken may have limited effectiveness against other non-enveloped viruses such as parvovirus B19 (the virus causing skin redness (infectious erythema)).

Infection with parvovirus B19 may be serious for a pregnant woman (fetal infection) and for individuals with weakened immune systems or patients with certain types of anemia (e.g., sickle cell anemia or hemolytic anemia).

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 IMMUNINE is administered, the name of the medicine and the batch number used should be recorded to maintain traceability of the batches.

Children

There are insufficient data to recommend the use of IMMUNINE in children under 6 years of age.

Use of IMMUNINE with other medicines
Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

No interactions between IMMUNINE and other medicines are known.

Pregnancy and breastfeeding

Haemophilia B is rare in women. Therefore, there is currently no experience regarding the use of IMMUNINE during pregnancy and breastfeeding.

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

Your doctor will decide whether you can use IMMUNINE during pregnancy and breastfeeding.

Driving and use of machines

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

IMMUNINE contains sodium chloride and sodium citrate

This medicine contains 41 mg of sodium (main component of table/cooking salt) per vial. This corresponds to 2% of the maximum daily recommended sodium intake for an adult.

3. How to use IMMUNINE

Treatment must be initiated and supervised by a physician experienced in the management of haemophilia B.

Your doctor will determine the appropriate dose for you. The dose will be calculated according to your individual needs. Inform your doctor if you feel that the effect of Immunine is too strong or too weak.

Use in children

There are insufficient data to recommend the use of IMMUNINE in children under 6 years of age.

Monitoring by your doctor

Your doctor will perform appropriate laboratory tests at regular intervals to ensure that you have sufficient levels of Factor IX. This is especially important if you are undergoing major surgery or experiencing life-threatening bleeding episodes.

Patients with inhibitors

If Factor IX levels in the blood do not reach the expected levels, or if bleeding is not controlled after an adequate dose, the presence of Factor IX inhibitors should be suspected. Your doctor will check for inhibitors by performing appropriate tests. In case an inhibitor develops, contact with a specialized haemophilia centre should be established.

If you have developed Factor IX inhibitors, you may require higher amounts of IMMUNINE to control bleeding. If this dose fails to control your bleeding, your doctor may consider using an alternative medication. Do not increase the total dose of IMMUNINE used to control your bleeding without consulting your doctor.

Frequency of administration

Your doctor will instruct you on how often and at which intervals IMMUNINE should be administered. This will be calculated specifically for your case, depending on your response to IMMUNINE.

Route and/or method of administration

IMMUNINE is administered slowly into a vein (intravenously) after reconstituting the solution with the solvent provided.

Before administration, IMMUNINE must not be mixed with other medicines. This may affect the product's efficacy and safety.

Please follow your doctor's instructions strictly.

The rate of administration will depend on your tolerance, but must not exceed 2 ml per minute.

• Use only the administration equipment supplied. If other administration devices are used, incorrect dosing may occur due to adsorption of IMMUNINE onto the internal surfaces of certain infusion sets.
• If you are also receiving other products through the same venous access, the line must be flushed with an appropriate solution, such as physiological saline, before and after administration of IMMUNINE.
• IMMUNINE should be reconstituted only immediately before use, and the solution must be used immediately. (The solution contains no preservatives.) Infusion should be completed within 3 hours after reconstitution.
• The injectable solution should be clear or slightly milky (opalescent). Do not use solutions that are cloudy or contain visible particles.
• Any unused solution must be properly discarded.

Reconstitution of the powder for preparing an injectable solution:

Ensure that you prepare the solution under the cleanest and most sterile conditions possible!

1. Warm the closed vial with rubber stopper containing the solvent (sterile water for injection) to room temperature (max. 37 °C).
2. Remove the protectors from the vials with rubber stoppers containing the powder and the solvent (fig. A), and clean the rubber stoppers of both vials.
3. Remove the seal covering one end of the transfer needle by twisting and pulling it off. Insert the needle through the rubber stopper of the solvent vial (fig. B and C).
4. Remove the seal covering the other end of the transfer needle, taking care not to touch the exposed end.
5. Invert the solvent vial over the powder vial and insert the free end of the transfer needle into the powder vial, piercing the stopper (fig. D). The vacuum in the powder vial will draw in the solvent.
6. After all the solvent has passed into the powder vial, separate the two vials by removing the transfer needle from the powder vial (fig. E). Gently swirl the powder vial to accelerate dissolution.
7. Once the powder is completely dissolved, insert the included air vent needle (Fig. F) to dissipate any foam that may have formed. Remove the air vent needle.

Injection / Infusion:

Ensure that you prepare the solution under the cleanest and most sterile conditions possible!

1. Remove the protector from the included filter needle by twisting and pulling it off, and attach it to a sterile disposable syringe. Draw up the solution into the syringe (fig. G).
2. Detach the syringe from the filter needle and inject the solution slowly (maximum rate of 2 ml per minute) intravenously using the provided infusion set (or the included disposable needle).

If the product is administered by infusion, use the disposable winged infusion set with an appropriate filter.

fig.A fig.B fig.C fig.D fig.E fig.F fig.G

Duration of treatment

Treatment with IMMUNINE is normally intended to be lifelong.

If you use more IMMUNINE than you should:

Inform your doctor. Symptoms of overdose with Factor IX have not been reported.

If you forget to use IMMUNINE

• Do not take a double dose to make up for missed doses.
• Continue with the next scheduled dose as soon as possible, and then continue at regular intervals as directed by your doctor.

If you stop treatment with IMMUNINE

Do not decide to stop treatment with IMMUNINE without consulting your doctor.

If you have any further questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

Seek urgent medical help if any of the following serious adverse effects occur

• Severe allergic reaction (anaphylactic reaction). Immediately stop administration and seek medical assistance immediately if you experience any of the following symptoms. Pay special attention if your doctor detects inhibitors in your blood:

  • Skin redness
  • Skin rash
  • Hives (urticaria)
  • Itching all over the body
  • Swelling of lips and tongue
  • Breathing difficulties (dyspnea)
  • Difficulty inhaling or exhaling due to narrowing of the airways (wheezing)
  • Chest tightness
  • General malaise
  • Dizziness
  • Drop in blood pressure

• Loss of consciousness

• Sudden swelling of the skin or mucous membranes, with or without difficulty swallowing or breathing (angioedema)

• Formation of blood clots in small blood vessels throughout the body (disseminated intravascular coagulation, DIC)

• Heart attack (myocardial infarction)

• Rapid heartbeat (tachycardia)

• Drop in blood pressure (hypotension)

• Blood clots (thromboembolic events)

• Blockage of a blood vessel by a blood clot (e.g., pulmonary embolism, venous thrombosis, arterial thrombosis, cerebral artery thrombosis)

• Skin redness

• Difficulty inhaling or exhaling due to narrowing of the airways (wheezing)

• Difficulty breathing (dyspnea)

• A type of kidney disorder with symptoms such as swelling of the lips, face, and lower legs, weight gain, and protein in the urine (nephrotic syndrome)

If your doctor detects inhibitors in your blood, you may have a specific risk of developing a condition called serum sickness. Immediately stop administration and seek medical assistance immediately if you experience any of the following symptoms:

• Skin rash
• Itching
• Joint pain (arthralgia), especially in the fingers of the hands and feet
• Fever
• Swelling of lymph nodes (lymphadenopathy)
• Drop in blood pressure (hypotension)
• Enlargement of the spleen (splenomegaly)

Other adverse effects

Uncommon adverse effects (may affect up to 1 in 100 people)

• Throat irritation, sore throat, and dry cough
• Skin rash and itching (pruritus)
• Fever (pyrexia)

Adverse effects with frequency not known (cannot be estimated from available data)

• Headache
• Restlessness
• Tingling
• Dizziness (nausea)
• Vomiting
• Whole-body rash (urticaria)
• Chills
• Hypersensitivity reactions
• Burning and stinging sensation at the injection site
• Lethargy
• Skin redness
• Chest tightness

The following adverse effects have been observed with other medicines in the same class: Reduced or abnormal sensation (paresthesia).

Reporting of adverse effects

If you experience any adverse effect, consult your doctor, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through the national reporting system included in the Spanish Pharmacovigilance System for Human Medicines: www.notificaRAM.es.

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

5. Storage of IMMUNINE

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

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.

Store in a refrigerator (2°C–8°C). Do not freeze.

Keep the vial in the outer packaging to protect it from light.

During its shelf life, IMMUNINE may be stored at room temperature up to 25°C for a period not exceeding 3 months only. Record on the product container the start and end dates of the room temperature storage period (up to 25°C). IMMUNINE must be used within these three months. After the end of this period, IMMUNINE must not be refrigerated, but used immediately or discarded.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of IMMUNINE

Powder

• The active substance is human coagulation factor IX. One vial of lyophilized powder for injectable solution contains 1200 IU of human coagulation factor IX. One ml of solution contains approximately 120 IU of human coagulation factor IX when reconstituted with 10 ml of sterile water for injectable preparations.
• The other components are sodium chloride and sodium citrate.

Solvent

• Sterile water for injectable preparations

Appearance of the product and contents of the pack

Immunine is a white or slightly yellow powder for preparing an injectable solution. After reconstitution with the provided solvent (sterile water for injectable preparations), a clear or slightly milky (opalescent) solution is obtained. If particles are observed, discoloration occurs, or the solution is cloudy, do not use the product and please contact Shire's Customer Service Department.

Pack size: 1 x 1200 IU

Each box contains:

• 1 vial of IMMUNINE 1200 IU
• 1 vial containing 10 ml of sterile water for injectable preparations
• 1 transfer needle
• 1 venting needle
• 1 filter needle
• 1 disposable needle
• 1 disposable syringe (10 ml)
• 1 infusion set

Marketing Authorization Holder and Manufacturer:

Marketing Authorization Holder:

Baxalta Innovations GmbH
Industriestrasse 67
1221 Vienna, Austria

Manufacturer:

Takeda Manufacturing Austria AG
Industriestrasse 67
A-1221 Vienna, Austria

Local representative:

Takeda Farmacéutica España S.A.
Calle Albacete, 5, 9th floor
Edificio Los Cubos
28027 Madrid, Spain
Tel: +34 91 790 42 22

Marketing Authorization Number: 69603

This medicinal product is authorized in the European Economic Area member states under the following names:

Austria, Bulgaria, Czech Republic, Estonia, Germany, Latvia, Lithuania, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden: Immunine
Italy: Fixnove

Date of the most recent review of this summary: August 2022

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS): http://www.aemps.gob.es/

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This information is intended for healthcare professionals only:

Dosage and method of administration

Treatment should be initiated under the supervision of a physician experienced in the management of hemophilia.

Dosage

The dose and duration of replacement therapy depend on the severity of factor IX deficiency, the location and extent of bleeding, and the patient's clinical condition.

The number of factor IX units administered is expressed in International Units (IU), corresponding to the current WHO standard for factor IX products. Factor IX activity in plasma is expressed either as a percentage (relative to normal human plasma) or in International Units (relative to an international standard for factor IX concentrates 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.

On-demand treatment

The calculation of the required factor IX dose is based on the empirical finding that 1 International Unit (IU) of factor IX per kg of body weight increases factor IX activity in plasma by 1.1% of normal activity in patients aged 12 years and older.

The required dose can be calculated using the following formula:

IU required = body weight (kg) × desired factor IX increase (%) (IU/dL) × 0.9

The amount to be administered and the frequency of administration should always be adjusted according to the individual clinical response. Factor IX products rarely need to be administered more than once daily.

In the following bleeding episodes, factor IX activity should not fall below the specified plasma activity level (expressed as % of normal or in IU/dL) during the corresponding time period.

In surgery and bleeding episodes, the following table may be used as a dosage guideline:

Degree of bleeding/Surgical procedure	Required factor IX level (% of normal) (IU/dL)	Dosing frequency (hours)/Duration of treatment (days)
Bleeding
Early hemarthrosis or muscle or oral bleeding	20–40	Repeat every 24 hours for at least 1 day, until resolution of the bleeding episode as indicated by pain or healing.
More extensive hemarthrosis, muscle bleeding, or hematoma	30–60	Repeat infusion every 24 hours for 3–4 days or longer, until pain and acute disability resolve.
Life-threatening bleeding	60–100	Repeat infusion every 8–24 hours until the danger has passed.
Surgery
Minor surgery including dental extractions	30–60	Every 24 hours, for at least 1 day, until healing.
Major surgery	80–100 (pre- and postoperative)	Repeat infusion every 8–24 hours until adequate wound healing is achieved, and continue therapy for at least another 7 days to maintain factor IX activity between 30% and 60%

Prophylaxis

For long-term prophylaxis against bleeding episodes in patients with severe hemophilia B, the usual doses are 20 to 40 IU of factor IX per kg of body weight administered at intervals of 3 to 4 days.

In some cases, particularly in younger patients, shorter dosing intervals or higher doses may be required.

During the course of treatment, appropriate monitoring of factor IX levels is recommended to guide both the dose administered and the frequency of repeated infusions. Particularly in the case of major surgical procedures, accurate monitoring of replacement therapy by means of coagulation analyses (plasma factor IX activity) is essential. Individual patient response to factor IX may vary, with different in vivo recovery levels and different half-lives observed.

Pediatric population

Based on available clinical data, dose recommendations can be established for pediatric patients aged 12 to 18 years. There are insufficient clinical data to provide a dose recommendation for patients between 6 and 12 years of age.

Adverse reactions

Special population

The use of IMMUNINE has been studied in pediatric patients with hemophilia B. The safety profile was similar to that observed in adults receiving IMMUNINE.

The use of IMMUNINE was evaluated in two observational studies in children up to 6 years of age and in patients aged 0–64 years with hemophilia B, respectively. The safety profile in children up to 6 years of age was similar to that in children over 6 years of age and in adults receiving IMMUNINE.