Immunine 600 Iu

Leaflet accompanying the packaging: information for the user

IMMUNINE 600 IU

Powder and solvent for solution for injection or infusion
human blood coagulation factor IX

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, please tell your doctor or pharmacist. See section 4.

Table of contents of the leaflet

• 1. What is IMMUNINE and what is it used for
• 2. Important information 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 is IMMUNINE and what is it used for

IMMUNINE is a concentrate of human blood coagulation factor IX. It supplements the deficiency
of factor IX, which is lacking or not functioning properly in hemophilia B. Hemophilia B is a
sex-linked, inherited blood clotting disorder caused by a reduced level of factor IX clotting factor.
This leads to severe bleeding into joints, muscles, and internal organs, both spontaneously and
as a result of accidental or surgical trauma.
Administration of IMMUNINE temporarily corrects the deficiency of factor IX and reduces the
tendency to bleed.
IMMUNINE is used to treat and prevent bleeding in patients with congenital hemophilia B.
IMMUNINE is indicated for use in all age groups, from children over 6 years of age to adults.
There is insufficient data to recommend the use of IMMUNINE in children under 6 years of age.

2. Important information before using IMMUNINE

When not to use IMMUNINE

allergicto human factor IX or any of the other ingredients of this medicine (listed in section 6).heparin-induced thrombocytopenia).

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

Warnings and precautions

Before starting treatment with IMMUNINE, discuss it with your doctor or pharmacist.
If allergic reactions occur:
In rare cases, there is a possibility of a severe allergic reaction (anaphylactic reaction) to IMMUNINE.
If any of the following symptoms occur, stop the infusion immediately and contact your doctor. These symptoms may be signs of anaphylactic shock and require immediate treatment as in emergencies:

• redness of the skin,
• rash,
• hives,
• itching all over the body,
• swelling of the lips and tongue,
• difficulty breathing / shortness of breath,
• difficulty inhaling and (or) exhaling due to constriction of the airways (wheezing),
• feeling of pressure in the chest,
• general malaise,
• dizziness,
• drop in blood pressure,
• loss of consciousness.

If treatment monitoring is required:

• Your doctor will regularly perform blood tests to ensure that the current dose is appropriate and that sufficient factor IX is being delivered.
• In order to diagnose possible complications, the doctor will particularly monitor: if the patient is taking high doses of IMMUNINE. if the patient has a tendency to thrombosis. In this case, the patient will also receive smaller doses of factor IX, the active substance of IMMUNINE.

If bleeding persists:

• If bleeding cannot be controlled with IMMUNINE, inform your doctor immediately. The patient may have developed inhibitors of factor IX. Inhibitors of factor IX are antibodies that appear in the blood and counteract the effects of factor IX. This reduces the effectiveness of factor IX in controlling bleeding. The doctor will perform the necessary tests to confirm this.
• There is a likely relationship between the development of inhibitors of factor IX and allergic reactions. Patients with inhibitors of factor IX may be at increased risk of a sudden and severe allergic reaction (anaphylaxis). Therefore, patients who experience allergic reactions should be evaluated for the presence of an inhibitor.

Tell your doctor if you have liver or heart disease, as well as if you have recently undergone major surgery, as there is an increased risk of complications related to blood clotting (coagulation).
Safety information regarding infectious agents
When medicines are manufactured from human blood or plasma, certain measures are taken to prevent the transmission of infections to patients. These include:

• careful selection of blood and plasma donors to ensure that those who are at risk of carrying infections are excluded,
• testing of individual blood donations and plasma pools for viruses/infections,
• incorporation into the manufacturing process of procedures that inactivate or remove viruses.

Despite these measures, when medicines made from human blood or plasma are administered, it is not possible to completely exclude the possibility of transmitting an infection. This includes unknown or newly discovered viruses and other types of infections.
The measures taken are considered effective against enveloped viruses, such as human immunodeficiency virus (HIV), hepatitis B virus, and hepatitis C virus, as well as non-enveloped hepatitis A virus.
The measures taken may have limited value against non-enveloped viruses, such as parvovirus B19 [a virus that causes erythema infectiosum (fifth disease)].
Parvovirus B19 infection can be serious in pregnant women (fetal infection) and in people with weakened immune systems or with certain types of anemia (e.g. congenital spherocytosis or hemolytic anemia).
For patients who regularly or repeatedly receive products derived from human plasma, the doctor may recommend considering vaccination against hepatitis A and B.
It is strongly recommended that each administration of IMMUNINE be recorded, including the name and batch number of the product, in order to maintain a record of the batches used.

Children

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

IMMUNINE and other medicines

Tell your doctor or pharmacist about all medicines you are taking, or have recently taken, or that you plan to take.
No interactions between IMMUNINE and other medicinal products are known.

Pregnancy and breastfeeding

Hemophilia B is very rare in women. Therefore, data on the use of IMMUNINE during pregnancy and breastfeeding are not available.
If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine. The doctor will decide whether you can take IMMUNINE during pregnancy or while breastfeeding.

Driving and using machines

No effect on the ability to drive and use machines has been observed.

IMMUNINE contains sodium chloride and sodium citrate.

IMMUNINE 600 IU contains 20 mg of sodium (the main component of common salt) in each vial.
This corresponds to 1% of the maximum recommended daily intake of sodium in the diet for adults.

3. How to use IMMUNINE

Treatment should be started and supervised by a doctor experienced in the treatment of hemophilia B.
The doctor will determine the appropriate dose for the patient. He will calculate it taking into account the individual needs. If the patient feels that the effect of IMMUNINE is insufficient or too strong, they should inform their doctor.

Administration in children

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

Monitoring of treatment by the doctor

The doctor will perform appropriate laboratory tests at regular intervals to ensure that there is a sufficient amount of factor IX in the patient's blood. This is especially important in the case of major surgical procedures or life-threatening bleeding.

Patients with inhibitors

If factor IX does not reach the expected level in the blood despite the administration of the appropriate dose or if bleeding does not stop, inhibitors may be present. The doctor will check for the presence of inhibitors using appropriate tests. If an inhibitor is detected, contact a specialized hemophilia treatment center.
If the patient has developed inhibitors of factor IX, they will likely require larger amounts of IMMUNINE to control bleeding. If bleeding still cannot be controlled, the doctor may consider using an alternative product. Without consulting a doctor, do not increase the dose of IMMUNINE to control bleeding.

Frequency of administration

The doctor will explain to the patient how often and at what intervals IMMUNINE should be administered. The doctor will determine this individually, depending on the patient's response to IMMUNINE.

Route and/or method of administration

IMMUNINE should be administered slowlyinto a vein (intravenously) after preparing the solution using the supplied solvent.
IMMUNINE must not be mixed with other medicines before administration. This may have an adverse effect on the efficacy and safety of the medicine.
Follow the doctor's instructions carefully.
The rate of administration should be adjusted to the patient's level of comfort and should not exceed 2 ml per minute.

• Only the supplied administration sets should be used. If other injection sets are used, IMMUNINE may adhere to the inner surfaces of the set, which may lead to incorrect dosing.
• If other medicines are administered through a common venous access, before and afterthe infusion of IMMUNINE, flushthe common venous access with an appropriate solution, e.g. physiological saline solution.
• IMMUNINE should be reconstituted immediately before administration, and the solution should be used immediately (the product does not contain preservatives). The infusion should be performed within 3 hours of reconstitution.
• The injection solution is clear or slightly cloudy (opalescent). Do not use if the solution is more turbid or contains visible particles.
• Any remaining unused reconstituted product should be disposed of in accordance with local regulations.

Reconstitution of the powder to prepare the solution for injection

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

• 1. Heat the closed vial with a rubber stopper containing the solvent (water for injection) to room temperature (max. 37°C).
• 2. Remove the protective caps from the vials with rubber stoppers containing the powder and solvent (fig. A) and clean the surfaces of the rubber stoppers of both vials.

• 3. Twist and pull off the protective cap from the shorter end of the double-ended needle (fig. B). Insert the exposed needle into the rubber stopper of the vial with the solvent (fig. C).
• 4. Remove the protective cap from the other end of the double-ended needle, being careful not to touch the exposed end of the needle.
• 5. Invert the vial with the solvent over the vial with the powder and puncture the rubber stopper of the vial with the powder with the needle (fig.D). The vacuum will draw the solvent into the vial with the powder.
• 6. When all the solvent has passed into the vial with the powder, separate the two vials by pulling out the double-ended needle from the vial with the powder (fig. E). Gently rotate the vial with the powder to speed up the dissolution of the powder.
• 7. After the powder has completely dissolved, insert the vent needle (fig. F), the foam will settle. Then remove the vent needle.

Administration of the solution by injection/infusion

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

• 1. Twist and pull off the protective cap from one end of the supplied needle with a filter and attach the needle to a sterile single-use syringe. Draw the solution from the vial into the syringe (fig. G)
• 2. Detach the needle with a filter from the syringe and slowly (maximum administration rate 2 ml/min) inject the solution intravenously using the supplied infusion set (or the supplied single-use needle).

When administering as an infusion, use a single-use infusion set with an appropriate filter.
fig.A fig.B fig.C fig.D fig.E fig.F fig.G

Duration of treatment

IMMUNINE is usually required for life.

Overdose of IMMUNINE

Inform your doctor. No symptoms of overdose of factor IX have been reported.

Missed dose of IMMUNINE

• Do not take a double dose to make up for a missed dose.
• Take the next dose as soon as possible and continue administration at regular intervals as recommended by your doctor.

Stopping treatment with IMMUNINE

Do not stop treatment with IMMUNINE without consulting your doctor.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, IMMUNINE can cause side effects, although not everybody gets them. If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

In case of the following serious side effects, seek medical attention immediately:

• severe allergic reactions (anaphylactic reactions). If any of the following symptoms occur, stop the infusion immediately and contact your doctor. Be particularly careful if an inhibitor is detected in the blood.
• redness of the skin
• rash
• hives
• itching all over the body
• swelling of the lips and tongue
• difficulty breathing / shortness of breath
• difficulty inhaling and (or) exhaling due to constriction of the airways (wheezing)
• feeling of pressure in the chest
• 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, deep vein thrombosis, arterial thrombosis, cerebral artery thrombosis)
• sudden redness of the face
• difficulty breathing and (or) exhaling due to constriction of the airways (wheezing)
• breathing difficulties (dyspnea)
• kidney disorder with symptoms such as swelling of the eyelids, face, and lower limbs, along with weight gain and loss of protein in the urine (nephrotic syndrome)

In patients who have developed inhibitors in the blood, there is a particularly increased risk of developing a condition called serum sickness. If any of the following symptoms occur, stop the infusion immediately and contact your doctor:

• rash
• itching
• joint pain (arthralgia), especially of the fingers and toes
• fever
• swelling of the lymph nodes (lymphadenopathy)
• drop in blood pressure (hypotension)
• enlargement of the spleen (splenomegaly)

Other side effects

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

• irritation of the throat and sore throat and cough (dry)
• rash and itching (hives)
• fever

Rare side effects (frequency not known, cannot be estimated from the available data)

• headache
• restlessness
• tingling
• nausea (nausea)
• vomiting
• hives all over the body
• chills
• allergic reactions
• burning and stinging at the injection site
• drowsiness
• sudden redness of the face
• feeling of pressure in the chest

The following side effects have been observed with the use of products from the same group:

Abnormal or decreased sensation (paresthesia).

Reporting of side effects

If you experience any side effects, including any not listed in this leaflet, please tell your doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products:
Al. Jerozolimskie 181 C
02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store IMMUNINE

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the label after EXP. The expiry date refers to the last day of that month.
Store in a refrigerator (2°C - 8°C). Do not freeze.
Store the vial in the outer packaging to protect from light.
During the shelf life, IMMUNINE can be stored at a temperature not above 25°C for a maximum of 3 months. The start and end dates of storage at room temperature (up to 25°C) should be recorded on the outer packaging of the product.
IMMUNINE must be used within these 3 months. After this period, do not return IMMUNINE to the refrigerator, but use it immediately or discard it.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What IMMUNINE contains

Powder

• The active substance is human blood coagulation factor IX. 1 vial of powder for solution for injection contains 600 IU of human blood coagulation factor IX. After reconstitution in 5 ml of water for injection, 1 ml of solution contains approximately 120 IU of human blood coagulation factor IX.
• The other ingredients are sodium chloride and sodium citrate.

Solvent

• Water for injection

What IMMUNINE looks like and contents of the pack

IMMUNINE is a white or slightly yellow powder for solution for injection. After reconstitution in the supplied solvent (water for injection), the solution is clear or slightly cloudy (opalescent). Do not use the product if you notice the presence of solid particles, color change, or cloudiness of the solution.
Package size: 1 x 600 IU.

Each pack contains:

• 1 vial of IMMUNINE 600 IU
• 1 vial of 5 ml water for injection
• 1 double-ended needle
• 1 vent needle
• 1 needle with a filter
• 1 single-use needle
• 1 single-use syringe (5 ml)
• 1 infusion set

Marketing authorization holder and manufacturer

Marketing authorization holder
Takeda Pharma Sp. z o.o.
ul. Prosta 68
00-838 Warsaw
Manufacturer
Takeda Manufacturing Austria AG
Industriestrasse 67
1221 Vienna
Austria
Marketing authorization number:14541

This medicinal product is authorized in the Member States of the European Economic Area 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 last revision of the leaflet:08/2022
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Information intended for healthcare professionals only:

Dosage and method of administration

Treatment should be started under the supervision of a doctor experienced in the treatment of hemophilia.
Dosage
The dose and duration of substitution therapy depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient's clinical condition.
The number of units of factor IX administered is expressed in international units (IU), which refer to the current WHO standard for factor IX products. Factor IX activity in plasma is expressed either as a percentage (relative to normal plasma) or in international units (relative to the international standard for factor IX concentrates in plasma). One international unit (IU) of factor IX is equivalent to the amount of factor IX in 1 ml of normal human plasma.
Acute treatment
The calculation of the required dose of factor IX is based on empirical data that 1 international unit (IU) of factor IX per kg of body weight increases the factor IX activity in plasma by 1.1% of normal activity in patients over 12 years of age.
The required dose is calculated using the following formula:

Required number of units = body weight (kg) x desired increase in factor IX (%) (IU/ml) x 0.9

The dose and frequency of administration should always be determined based on clinical efficacy in individual cases. Factor IX preparations are rarely required to be administered more than once a day.
In the event of the following types of bleeding, factor IX activity should not fall below the specified level in the blood (as a percentage of normal or IU/ml) in the corresponding time interval.

Prophylactic treatment
In long-term prophylaxis of bleeding in patients with severe hemophilia B, the usual doses are 20 to 40 IU of factor IX/kg body weight at intervals of 3 to 4 days.
In some cases, especially in younger patients, it may be necessary to shorten the interval between doses or administer higher doses.
During treatment, it is recommended to monitor factor IX levels to adjust the dose and frequency of repeated infusions. In particular, during major surgical procedures, precise monitoring of substitution therapy is necessary through coagulation analysis (factor IX activity). Individual patients may differ in their response to factor IX, achieving different recovery levels in vivoand showing different half-lives.
Children and adolescents
Based on available clinical data, recommendations for use in pediatric patients may apply to patients aged 12 to 18 years. In the age group 6 to 12 years, available clinical data are insufficient to provide dosing recommendations.

Side effects

Special patient groups
The use of IMMUNINE has been evaluated in children and adolescents with hemophilia B. The safety profile was similar to that in adults using IMMUNINE.
The use of IMMUNINE was the subject of two observational studies in children under 6 years of age and in individuals aged 0-64 years with hemophilia B. The safety profile in children under 6 years of age was similar to that in children over 6 years of age and adults using IMMUNINE.