Prospecto: information for the user

IMMUNINE 1200 UI

Powder and solvent for injectable solution or for infusion

human coagulation factor IX

Read this prospect carefully before starting to use this medicine, because it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed only to you and should not be given to other people, even if they have the same symptoms as you, as it may harm them.
• If you experience adverse effects, consult your doctor or pharmacist, even if they do not appear in this prospect. See section 4.

1. What isIMMUNINEand for what it is used

2. What you need to know before starting to useIMMUNINE

3. How to useIMMUNINE

4. Possible adverse effects

5. Conservation ofIMMUNINE

6. Contents of the package and additional information

IMMUNINE is a concentrate of the factor IX of coagulation. It replaces the factor IX that is lacking or does not function correctly in hemophilia B.. Hemophilia B is a hereditary and sex-linked defect in blood coagulation that is due to a decrease in factor IX levels.It causes severe bleeding in joints, muscles, and internal organs, either spontaneously or as a result of accidental or surgical trauma. The administration of IMMUNINE temporarily corrects the deficiency of factor IX and reduces the tendency to suffer bleeding.

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

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

There are not enough data to recommend the use of IMMUNINE in children under 6 years of age.

No use IMMUNINE

• If you areallergicto human coagulation factor IX or to any of the other components of this medication (listed in section 6).

• If you have a known allergy to heparin or have had an abnormal decrease in the number of blood cells involved in blood clotting caused by the administration of heparin (heparin-induced thrombocytopenia).(heparin-induced thrombocytopenia).

After proper treatment of these situations, IMMUNINE should only be used in cases of life-threatening bleeding episodes.

Warnings and precautions

Consult your doctor or pharmacist before starting to use IMMUNINE.

When an allergic reaction occurs:

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

If you detect one or more of the following symptomsimmediately stop administration and seek medical assistance at once. These may be signs of anaphylactic shock and require urgent immediate treatment.

• skin redness
• hives
• skin rash (urticaria)
• itching all over the body
• swelling of the lips and tongue
• difficulty breathing / dyspnea
• difficulty inhaling or exhaling due to constriction of the airways (sibilance)
• chest tightness
• general feeling of illness
• dizziness
• decrease in blood pressure
• loss of consciousness

When monitoring is required::

• Your doctor may wish to perform some 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 closely monitor you to detect possible complications:
• • if you receive high doses of IMMUNINE
  • if you are prone to developing thrombosis. In that case, you will receive lower levels of factor IX, the active ingredient in IMMUNINE.

When bleeding continues::

• If your bleeding does not subside withIMMUNINE,consult your doctor immediately. It is possible that you have developed inhibitors of Factor IX.Inhibitors of factor IX are antibodies present in the blood that counteract the effect of factor IX. This reduces the effectiveness of IMMUNINE in the treatment of bleeding episodes. Your doctor will perform the necessary tests to confirm it.

• There is a possible connection between the appearance of inhibitors of factor IX and allergic reactions. Patients with inhibitors of factor IX may have a higher risk of sudden and severe allergic reactions (anaphylaxis). Therefore, in patients who experience an allergic reaction, the presence of an inhibitor of factor IX should be investigated.

Inform your doctor if you have heart or liver disease or if you have recently undergone major surgery, as there is a higher risk of complications of blood clotting (coagulation).

Information on safety with respect to infectious agents

When administering medications derived from human plasma or blood, certain measures must be taken to prevent the transmission of infections to patients. These measures include:

• a careful selection of donors, excluding those at risk of being carriers of infectious diseases
• analysis of specific infection markers in individual donations and plasma mixes to detect possible viruses or infections
• the inclusion of stages in the manufacturing process to eliminate / inactivate viruses.

Despite this, when administering medications derived from human blood or plasma, the possibility of transmission of infectious agents cannot be ruled out entirely. This also applies to emerging or unknown viruses or other types of infections.

These measures are considered effective for enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus, and hepatitis C virus, and for non-enveloped viruses such as hepatitis A virus.

These measures may have limited value against other non-enveloped viruses such as parvovirus B19 (virus causing skin rash (erythema infectiosum)).

Parvovirus B19 infection can be severe for a pregnant woman (fetal infection) and for people with a weakened immune system or patients with some type of anemia (e.g. sickle cell anemia or hemolytic anemia).

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

It is strongly recommended that each time IMMUNINE is administered, the name of the medication and the batch number administered be recorded in order to maintain a record of the batches used.

Children

There are not enough data to recommend the use of IMMUNINE in children under 6 years old.

Use of IMMUNINE with other medicationsInform your doctor or pharmacist if you are taking or have taken or may need to take another medication.

No interactions of IMMUNINE with other medications are known.

Pregnancy and breastfeeding

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

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

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

Driving and operating machinery

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

IMMUNINE contains sodium chloride and sodium citrate

This medication contains 41 mg of sodium (main component of table salt / for cooking) in each vial. This is equivalent to 2% of the maximum daily sodium intake recommended for an adult.

The treatment should be initiated and supervised by a doctor with experience in the treatment of hemophilia B.

Your doctor will decide what is the appropriate dose for you.Calculate the dose according to your individual needs.Inform your doctor if you feel that the effect ofImmunineis too strong or too weak in you.

Use in children

There are not enough data to recommend the use ofIMMUNINEin children under 6 years old.

Monitoring by your doctor

Your doctor will perform the appropriate laboratory tests at regular intervals to ensure that you have sufficient levels of Factor IX.This is especially important if you are going to undergo a major operation or bleeding that puts your life at risk.

Patients with inhibitors

If the level of Factor IX in the blood does not reach the expected levels, or if bleeding is not controlled after an appropriate dose, it should be suspected that inhibitors of Factor IX are present.Your doctor will check for the presence of inhibitors by performing the appropriate tests.In case of inhibitor development, contact a specialized center for hemophilia.

If you have developed inhibitors of Factor IX, you may need a higher dose ofIMMUNINEto control bleeding.If this dose does not control your bleeding, your doctor may consider the use of an alternative medication.Do not increase the total dose ofIMMUNINEyou use to control bleeding without consulting your doctor.

Frequency of administration

Your doctor will tell you how often and at what intervals you should administer IMMUNINE.He will calculate it for your case in particular, depending on your response to IMMUNINE.

Route and/or form of administration

IMMUNINE is administeredslowlythrough a vein (intravenously) after preparing the solution with the provided solvent.

Before administration, IMMUNINE should not be mixed with other medications.This may affect the efficacy and safety of the product.

Please follow your doctor's instructions strictly.

The administration rate will depend on the discomfort you may feel, without exceeding 2ml per minute.

• Use only the administration equipment provided.If other administration equipment is used, incorrect dosing may occur due to the adsorption of IMMUNINE to the internal surfaces of some infusion equipment.
• If you are also receiving other products through the same venous access,you mustwash the access with an appropriate solution, such as physiological saline solution,before and afterthe administration of IMMUNINE.
• IMMUNINE should only be reconstituted immediately before administration and the solution should be used immediately.The infusion should be completed within 3hours after reconstitution.
• The injectable solution is transparent or slightly milky (opalescent).Do not use turbid or particle-containing solutions.
• Any unused solution must be disposed of correctly.

Reconstitution of the powder to prepare an injectable solution:

Make sure to prepare the solution in the most clean and sterile conditions possible!

1. Heat the closed vial with a rubber stopper containing the solvent (sterile water for injectable preparations) to room temperature (max. 37 °C).
2. Remove the protectors from the vials with rubber stoppers containing the powder and solvent (fig. A) and clean the rubber stoppers of both vials.
3. Remove the cap that covers one end of the transfer needle by turning and pulling it.Insert the needle through the rubber stopper of the solvent vial (fig. B and C).
4. Remove the cap that covers the other end of the transfer needle, being careful not to touch the exposed end.
5. Invert the solvent vial over the powder vial and insert the free end of the water transfer needle into the powder vial, piercing the stopper (fig. D). The vacuum existing in the powder vial will aspirate the solvent.
6. After all the solvent has passed to the powder vial, separate the two vials by removing the transfer needle from the powder vial (fig. E).Agitate the powder vial gently to accelerate dissolution.
7. Once the powder has completely dissolved, insert the included air needle (Fig. F) and the foam that may have formed will disappear.Remove the air needle.

Injection/Infusion:

Make sure to prepare the solution in the most clean and sterile conditions possible!

1. Remove the protective cover from the included air filter needle by turning and pulling it and place it in a sterile disposable syringe.Aspirate the solution with the syringe (fig. G).
2. Separate the syringe from the air filter needle and injectslowly(maximum rate of 2 ml per minute) the solution intravenously with the provided infusion equipment (or with the included disposable needle).

If the product is administered by infusion, use the infusion equipment with a disposable filter with a suitable filter.

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

Duration of treatment

The treatment with IMMUNINE should normally be maintained for life.

If you use more IMMUNINE than you should:

Inform your doctor.The symptoms of factor IX overdose have not been reported.

If you forgot to use IMMUNINE

• Do not take a double dose to compensate for the missed doses.
• Continue with the next administration immediately and follow the regular intervals as indicated by your doctor.

If you interrupt the treatment with IMMUNINE

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

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

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

You must seek immediate medical help if any of the following severe side effects occur

• severe allergic reaction (anaphylaxis). Stop administering immediately and seek medical assistance at once if you experience any of the following symptoms. Pay special attention if your doctor detects inhibitors in your blood. skin redness
• • skin rash
  • hives on the skin
  • itching all over the body
  • swelling of the lips and tongue
  • difficulty breathing (dyspnea)
  • difficulty inhaling or exhaling due to constriction of the airways (sibilance)
  • chest tightness
  • general discomfort
  • dizziness
  • decreased 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)
• low blood pressure (hypotension),
• blood clots (thromboembolic episodes)
• blockage of a vessel by a blood clot (e.g. pulmonary embolism, deep vein thrombosis, arterial thrombosis, cerebral artery thrombosis)
• redness.
• difficulty inhaling or exhaling due to constriction of the airways (sibilance)
• difficulty breathing (dyspnea)
• a type of kidney disorder with symptoms such as swelling of the lips, face, and lower legs, with weight gain and protein loss in the urine (nephrotic syndrome)

If your doctor detects inhibitors in your blood, you may have a specific risk of developing a disease calledserum disease. Stop administering immediately and seek medical assistance at once 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 the lymph nodes (lymphadenopathy)
• low blood pressure (hypotension)
• enlargement of the spleen (splenomegaly)

Other side effects

Less common side effects (may affect up to 1 in 100 people)

• sore throat, sore throat, and dry cough
• skin rash and itching (pruritus)
• fever (pyrexia)

Side effects of unknown frequency (cannot be estimated from available data)

• headache
• restlessness
• tingling
• sensation of dizziness (nausea)
• vomiting
• hives all over the body (urticaria)
• chills
• hypersensitivity reactions
• sensation of burning and itching at the injection site
• lethargy
• redness
• chest tightness

The following side effects have been observed with other medications in the same group:reduced or abnormal sensitivity (paresthesia).

Reporting of side effects

If you experience any type of side effect, consult your doctor, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the national notification system included in the Spanish System for Pharmacovigilance of Medicines for Human Use:www.notificaRAM.es.

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

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

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

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

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

During its validity period, IMMUNINE can be stored at room temperature up to 25°C for a period not exceeding3 monthsonly. Note the start and end dates of the room temperature storage period (up to 25°C) on the product packaging. IMMUNINE must be used within those three months. After the end of this period, IMMUNINE should not be refrigerated, but used immediately or discarded.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of unused packaging and medications. By doing so, you will help protect the environment.

Composition of IMMUNINE

Dry powder

•The active principle is human coagulation factor IX. 1 vial with dry powder for injectable solution contains 1200 UI of human coagulation factor IX. 1 ml of solution contains approximately 120 UI 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.

Vehicle

•Sterile water for injectable preparations

Appearance of the product and contents of the package

IMMUNINE is a white or light yellow powder to prepare an injectable solution. After reconstitution with the provided vehicle (sterile water for injectable preparations), a transparent or slightly milky (opalescent) solution is obtained. If particles or coloration are observed or the solution is turbid, please do not use the product and contact the Shire Customer Service department.

Package size:1 x 1200 UI

Each box contains:- 1 vial of IMMUNINE 1200 UI

- 1 vial with 10 ml of sterile water for injectable preparations

-1 transfer needle

-1 air 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 Member States of the European Economic Area with the following names:

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

Italy: Fixnove

Last review date of this leaflet:August 2022.

The detailed and updated information on this medicinal product is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es/

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This information is intended solely for healthcare professionals:

Dosage and administration

The treatment should be initiated under the supervision of a doctor with experience in the treatment of hemophilia.

Dosage

The dose and duration of the substitution therapy depend on the severity of the factor IX deficiency, the location and extent of the hemorrhage, and the patient's clinical status.

The number of factor IX units administered is expressed in International Units (UI), which are related to the current WHO standard for factor IX products.The activity of factor IX 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 (UI) 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 dose of factor IX is based on the empirical finding that 1 International Unit (UI) of factor IX per kg of body weight increases plasma factor IX activity by 1.1% of normal activity in patients aged 12 years and older.

The required dose is determined using the following formula:

UI required = body weight (kg) x desired factor IX increase (%) (UI/dl) x 0.9

The amount to be administered and the frequency of administration should always be guided by clinical efficacy in each individual case.Factor IX products rarely need to be administered more than once a day.

In the case of subsequent hemorrhagic episodes, plasma factor IX activity should not fall below the given activity level (in% of normal or in UI/dl) during the corresponding period.

In surgery and in hemorrhagic episodes, the following table may be used as a dosage guide:

Prophylaxis

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

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

During the course of treatment, it is recommended to determine plasma factor IX levels as a guide to the dose to be administered and the frequency of repeated infusions. In particular, in the case of major surgical interventions, exact monitoring of substitution therapy by means of coagulation analysis (plasma factor IX activity) is indispensable.Response to factor IX may vary in each individual patient, achieving different levels of in vivo recovery and showing different half-lives.

Pediatric population

Based on available clinical data, the recommended posology in the pediatric population can be performed in patients aged 12 to 18 years. There are no sufficient clinical data to provide a posology recommendation in patients aged 6 to 12 years.

Adverse reactions

Special population

The use of IMMUNINE was investigated in pediatric patients with hemophilia B. Safety was similar to that of adults using IMMUNINE.

The use of IMMUNINE was investigated in two observational studies in children up to 6 years of age and in patients aged 0-64 years with hemophilia B, respectively. Safety in children up to 6 years of age was similar to that of older children and adults using IMMUNINE.