Immunine 1200 iu

Patient Information Leaflet

IMMUNINE 1200 IU
powder and solvent for solution for injection or infusion
human coagulation factor IX
Please read this leaflet carefully before using this medicine because it contains important information for you.

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

Leaflet Contents

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 human coagulation factor IX. It replaces deficient or malfunctioning factor IX in haemophilia B. Haemophilia B is an X-linked inherited blood clotting disorder caused by reduced levels of blood coagulation factor IX. This leads to severe bleeding into joints, muscles, and internal organs, occurring spontaneously or following accidental or surgical trauma. Administration of IMMUNINE temporarily corrects the deficiency of factor IX and reduces the tendency to bleed. IMMUNINE is used for the treatment and prevention of bleeding episodes in patients with congenital haemophilia B.
IMMUNINE is indicated for use in all age groups, from children older than 6 years to adults.
There are 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

• if the patient is allergic to human coagulation factor IX or to any of the other ingredients of this medicine (listed in section 6).
• if the patient has an allergy to heparin or has an abnormally low platelet count associated with blood clot formation caused by heparin administration ( heparin-induced thrombocytopenia ).

After appropriate treatment of these conditions, IMMUNINE should be administered only
in life-threatening bleeding episodes.
Warnings and precautions
Before starting treatment with IMMUNINE, discuss this with your doctor or pharmacist.
If allergic reactions occur:
In rare cases, there is a possibility of a sudden severe allergic reaction (anaphylactic reaction) to IMMUNINE.
If any of the following symptoms occur, infusion must be stopped immediately
and medical advice must be sought without delay . These symptoms may indicate anaphylactic shock and require immediate emergency treatment:

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

If monitoring of treatment is required:

• The treating physician will regularly perform blood tests to ensure that the current dose is appropriate and that sufficient factor IX is being provided.
• To detect possible complications, the physician will pay particular attention to:
  • if the patient is receiving high doses of IMMUNINE.
  • if the patient has a predisposition to thrombosis. In such cases, the patient will also receive lower doses of factor IX, the active substance in IMMUNINE.

When bleeding persists:

• If bleeding cannot be controlled with IMMUNINE, the physician must be informed immediately . The patient may have developed factor IX inhibitors. Factor IX inhibitors 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 physician will perform necessary tests to confirm this.
• There is a probable association between the development of factor IX inhibitors and allergic reactions. Patients with factor IX inhibitors may be at increased risk of sudden and severe allergic reactions (anaphylaxis). Therefore, patients experiencing allergic reactions should be evaluated for the presence of inhibitors.

Tell your doctor if you have liver or heart disease, or have recently undergone major
surgical procedures, as there is an increased risk of complications related to blood
coagulation.
Information on safety regarding infectious agents
When medicines are manufactured from human blood or plasma, specific measures are taken
to prevent transmission of infections to patients. These include:

• careful selection of blood and plasma donors to ensure that individuals at risk of carrying infections are excluded,
• testing of individual blood samples and pooled plasma for viruses/infections,
• inclusion of virus inactivation or removal steps during the blood or plasma processing.

Despite these measures, when administering medicines derived from human blood or plasma,
it cannot be completely ruled out that infection transmission may occur. This also applies to unknown or newly emerging viruses and other types of infections.
These measures are considered effective against enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus, hepatitis C virus, and non-enveloped hepatitis A virus.
These measures may have limited effectiveness against non-enveloped viruses such as
parvovirus B19 [a virus that causes skin rash (erythema infectiosum)].
Parvovirus B19 infection may be dangerous for pregnant women (fetal infection) and for individuals
with weakened immune systems or certain types of anemia (e.g. congenital spherocytosis or hemolytic anemia).
For patients receiving products derived from human plasma regularly or repeatedly,
the physician may recommend considering vaccination against hepatitis A and B.
It is strongly recommended to record the name and batch number of the product each time IMMUNINE is administered, to maintain traceability of the batches used.
Children
There are insufficient data to recommend the use of IMMUNINE in children under 6 years of age.
IMMUNINE and other medicines
Inform your doctor or pharmacist about all medicines currently used or recently used, as well as any medicines you plan to take.
No interactions between IMMUNINE and other medicinal products are known.
Pregnancy and breastfeeding
Hemophilia B occurs very rarely in women. Therefore, data on the use of IMMUNINE during
pregnancy and breastfeeding are not available.
If you are pregnant or breastfeeding, suspect you may be pregnant, or plan to have a child,
you should consult your doctor before using this medicine. The doctor will decide whether
IMMUNINE can be used during pregnancy or while 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.
IMMUNINE 1200 IU contains 41 mg of sodium (main component of table salt) in each vial.
This corresponds to 2% of the maximum recommended daily dietary sodium intake for adults.

3. How to use IMMUNINE

Treatment should be initiated and supervised by a physician experienced in the management of haemophilia B.
The physician will determine the appropriate dose for the patient, based on individual requirements. If the patient feels that the effect of IMMUNINE is insufficient or too strong, they should inform the physician.

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

Monitoring of treatment by the physician
The physician will perform appropriate laboratory tests at regular intervals to ensure that sufficient levels of factor IX are present in the patient's blood. This is particularly important in the case of major surgical procedures or life-threatening bleeding episodes.

Patients with developed inhibitors
If factor IX does not reach the expected blood level despite administration of an appropriate dose, or if bleeding does not stop, inhibitors may be present. The physician will check for the presence of inhibitors using appropriate tests. If inhibitors have developed, contact should be made with a specialized haemophilia treatment centre.
If a patient develops inhibitors to factor IX, they will likely require higher amounts of IMMUNINE to control bleeding. If bleeding cannot be controlled despite this, the physician may consider using an alternative product. Do not increase the dose of IMMUNINE to control bleeding without consulting a physician.

Frequency of administration
The physician will explain to the patient how often and at what intervals IMMUNINE should be administered. This will be determined individually, depending on the patient's response to IMMUNINE.

Route and (or) method of administration
IMMUNINE must be administered slowly intravenously after reconstitution using the solvent provided.
IMMUNINE must not be mixed with other medicinal products prior to administration, as this may adversely affect the efficacy and safety of the product.
Strictly follow the physician's instructions.
The infusion rate should be adjusted according to the patient's comfort level and must not exceed 2 ml per minute.

• Use only the infusion sets provided. If other injection sets are used, IMMUNINE may adhere to the internal surfaces of the set, which could lead to incorrect dosing.
• If other medicinal products are administered through the same intravenous line, the line must be flushed before and after IMMUNINE infusion with an appropriate solution, e.g. physiological saline.
• IMMUNINE should be reconstituted immediately before use, and the solution should be used promptly (the product does not contain preservatives). The infusion should be completed within 3 hours after reconstitution.
• The injection solution should be clear or slightly opalescent (milky). Do not use if the solution is cloudy or contains visible particles.
• Any unused reconstituted product must be disposed of in accordance with local regulations.

Reconstitution of the powder to prepare the injection solution
Ensure that the solution is prepared under conditions as clean and sterile as possible!

1. Warm the vial containing the solvent (water for injections) with its rubber stopper to room temperature (max. 37°C).
2. Remove the protective caps from the vials containing the powder and solvent (fig. A) and disinfect the rubber stoppers of both vials.
3. Twist and remove the protective cover from the shorter end of the double-ended needle. Insert the exposed needle into the rubber stopper of the solvent vial (fig. C).
4. Remove the cover from the other end of the double-ended needle, taking care not to touch the exposed needle end.
5. Invert the solvent vial over the vial containing the powder and pierce the rubber stopper of the powder vial with the needle end (fig. D). The vacuum will draw the solvent into the powder vial.
6. Once all the solvent has transferred into the powder vial, disconnect the two vials by removing the double-ended needle from the powder vial (fig. E). Gently rotate the powder vial to accelerate dissolution of the powder.
7. After complete dissolution of the powder, insert the venting needle (fig. F); the foam formed will subside. Then remove the venting needle.

Administration of the solution by injection / infusion
Ensure that the solution is prepared under conditions as clean and sterile as possible!

1. Twist and remove the protective cover from one end of the provided filter needle and attach the needle to a sterile single-use syringe. Draw the solution from the vial into the syringe (fig. G).
2. Disconnect the filter needle from the syringe and slowly (maximum infusion rate 2 ml/min) administer the solution intravenously using the provided infusion set (or the provided single-use needle).

When administering by 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
Treatment with IMMUNINE is usually required for life.

Use of a higher than recommended dose of IMMUNINE
Inform the physician. No symptoms of factor IX overdose have been reported.

Missed dose of IMMUNINE

• Do not administer 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 directed by the physician.

Discontinuation of IMMUNINE
Do not discontinue IMMUNINE without consulting the physician.
If you have any further questions about the use of this medicinal product, consult your physician or pharmacist.

4. Possible adverse reactions

Like all medicines, IMMUNINE may cause adverse reactions, although not everyone will experience them. If any of the adverse symptoms worsen or if any adverse reactions not listed in this leaflet occur, inform your doctor or pharmacist.

In the event of the following severe adverse reactions, seek immediate medical advice:

• Severe allergic reactions (anaphylactic reactions). If any of the symptoms listed below occur, the infusion must be stopped immediately and medical advice sought without delay. Particular caution is required in patients with known presence of inhibitor in the blood.
• Skin redness
• Rash
• Skin welts (urticaria)
• Itching all over the body
• Swelling of lips and tongue
• Breathing difficulties / apnoea
• Difficulty inhaling and (or) exhaling due to airway constriction (wheezing)
• Feeling of 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 arterial blood pressure (hypotension)
• Blood clots (thromboembolic episodes)
• Vessel blockage by a blood clot (e.g. pulmonary artery embolism, venous thrombosis, arterial thrombosis, cerebral artery thrombosis)
• Sudden facial redness
• Difficulty inhaling and (or) exhaling due to airway constriction (wheezing)
• Breathing difficulties (dyspnoea)
• Kidney disorder with symptoms such as eyelid, facial and lower limb swelling, together with weight gain and loss of protein in urine (nephrotic syndrome)

In patients with inhibitors detected in the blood, there is an increased risk of developing a condition known as serum sickness. If any of the following symptoms occur, the infusion must be stopped immediately and medical advice sought without delay:

• Rash
• Itching
• Joint pain (arthralgia), particularly in fingers of hands and feet
• Fever
• Swollen lymph nodes (lymphadenopathy)
• Drop in blood pressure (hypotension)
• Enlarged spleen (splenomegalia)

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

• Throat irritation, sore throat and dry cough
• Rash and itching (urticaria)
• Fever

Adverse reactions with unknown frequency (cannot be estimated from available data)

• Headache
• Restlessness
• Tingling sensation
• Nausea
• Vomiting
• Generalized urticaria
• Chills
• Hypersensitivity reactions
• Burning and stinging at the site of administration
• Drowsiness
• Sudden facial redness
• Chest tightness

The following adverse reactions have been observed with products of the same class:
Abnormal or reduced sensation (paraesthesia)

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions 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
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to provide more information on the safety of the 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 stated on the label after EXP. The expiry date refers to the last day of the stated month.
Store in a refrigerator (2°C - 8°C). Do not freeze.
Keep the vial in the outer packaging to protect it from light.
During the stated shelf life, IMMUNINE may be stored at temperatures up to and including 25°C. However, this is limited to a maximum period of 3 months. The start and end dates of the room temperature storage period (up to 25°C) must be recorded on the outer packaging of the product. IMMUNINE must be used within these 3 months. After this period has ended, IMMUNINE must not be returned to the refrigerator, but should be used immediately or discarded.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What IMMUNINE contains
Powder

• The active substance is human coagulation factor IX. One vial of powder for solution for injection contains 1200 IU of human coagulation factor IX. After reconstitution with 10 ml of water for injections, 1 ml of solution contains approximately 120 IU of human coagulation factor IX.
• The other ingredients are sodium chloride and sodium citrate.

Solvent

• Water for injections

What IMMUNINE looks like and contents of the pack
IMMUNINE is a white or slightly yellow powder for solution for injection. After reconstitution with the provided solvent (water for injections), the solution is clear or slightly milky (opalescent). Do not use the product if particulate matter is observed, or if there is any change in colour or turbidity of the solution.
Pack size: 1 x 1200 IU
Each pack contains:

• 1 vial of IMMUNINE 1200 IU
• 1 vial of 10 ml water for injections
• 1 double-ended needle
• 1 venting needle
• 1 filter needle
• 1 single-use needle
• 1 single-use syringe (10 ml)
• 1 infusion set

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Takeda Pharma Sp. z o.o.
ul. Prosta 68
00-838 Warsaw
Manufacturer
Takeda Manufacturing Austria AG
Industriestrasse 67
1221 Vienna
Austria
Marketing Authorisation Number: 14615
This medicinal product is authorised for sale 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

Information intended exclusively for medical professionals:

Dosage and administration
Treatment should be initiated under the supervision of a physician experienced in the treatment of hemophilia.

Dosage
The dosage 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 amount of factor IX administered is expressed in International Units (IU), referenced 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 plasma factor IX concentrates).
One International Unit (IU) of factor IX is equivalent to the amount of factor IX present in one ml of normal human plasma.

On-demand treatment
The calculation of the required factor IX dose is based on empirical data showing that 1 International Unit (IU) of factor IX per kg body weight raises plasma factor IX activity by 1.1% of normal activity in patients aged 12 years and older.
The required dose can be calculated using the following formula:
Required number of units
= body weight (kg) × desired increase in factor IX level (%) (IU/dL) × 0.9

The dose and frequency of administration should always be adjusted according to individual clinical response. Factor IX products rarely require administration more than once daily.

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

The following table may be used as a guide for dosage determination in cases of bleeding or surgical procedures:

Prophylactic treatment
For long-term prevention of bleeding in patients with severe haemophilia B, the usual dose is
20 to 40 IU of factor IX per kg body weight, administered every 3 to 4 days.
In some cases, particularly in younger patients, it may be necessary to shorten the interval
between doses or to administer higher doses.
During treatment, appropriate monitoring of factor IX levels is recommended to adjust the dose and
frequency of repeated infusions. In particular, during major surgical procedures, precise monitoring of
substitution therapy through coagulation analysis (factor IX activity) is essential. Individual patients
may respond differently to factor IX, achieving varying levels of in vivo recovery and exhibiting different half-lives.

Children and adolescents
Based on available clinical data, recommendations for use in paediatric patients apply to individuals aged 12 to 18 years.
For the age group 6 to 12 years, available clinical data are insufficient to provide dosing recommendations.

Adverse reactions
Special patient groups
The use of IMMUNINE has been evaluated in children and adolescents with haemophilia B. The safety profile was similar to that observed in adults treated with IMMUNINE.
The safety of IMMUNINE was assessed in two observational studies involving children up to 6 years of age and individuals aged 0–64 years with haemophilia B. The safety profile in children up to 6 years of age was similar to that in children above 6 years of age and adults treated with IMMUNINE.