Immunate 500 iu fviii/375 iu vwf

Package leaflet: Information for the user

Immunate 500 IU FVIII/375 IU VWF powder and solvent for solution for injection
human coagulation factor VIII / human von Willebrand factor
Please read all of 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, 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 as yours.
• If you experience any adverse reactions, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Leaflet contents

1. What Immunate 500 IU FVIII/375 IU VWF is and what it is used for
2. Important information before using Immunate 500 IU FVIII/375 IU VWF
3. How to use Immunate 500 IU FVIII/375 IU VWF
4. Possible side effects
5. How to store Immunate 500 IU FVIII/375 IU VWF
6. Contents of the pack and other information

1. What Immunate 500 IU FVIII/375 IU VWF is and what it is used for

What Immunate 500 IU FVIII/375 IU VWF is
Immunate is a coagulation factor VIII/von Willebrand factor complex produced from human plasma. The coagulation factor VIII contained in Immunate replaces the missing or malfunctioning factor VIII in haemophilia A. Haemophilia A is a sex-linked inherited coagulation disorder caused by reduced levels of factor VIII. This leads to severe bleeding into joints, muscles, and internal organs, occurring spontaneously or following trauma or surgical procedures. Administration of Immunate temporarily corrects the deficiency of factor VIII and reduces the tendency to bleed. In addition to its role as a protective protein for factor VIII, von Willebrand factor (VWF) mediates platelet adhesion at the site of vessel injury and plays a role in platelet aggregation.

Why Immunate 500 IU FVIII/375 IU VWF is used
Immunate is used for the treatment and prophylaxis of bleeding in congenital (haemophilia A) or acquired factor VIII deficiency.
Immunate is also used to treat bleeding in patients with von Willebrand disease and factor VIII deficiency when no specific product effective for von Willebrand disease is available and when treatment with desmopressin (DDAVP) alone is ineffective or contraindicated.

2. Important information before using Immunate 500 IU FVIII/375 IU VWF

When not to use Immunate 500 IU FVIII/375 IU VWF

• if the patient is allergic to human coagulation factor VIII or to any of the other ingredients of this medicine (listed in section 6).

If in doubt about whether the medicine can be used, consult a doctor.
Warnings and precautions
In case of allergic reactions:

• There is a small possibility of an anaphylactic reaction (a sudden, severe allergic reaction) to Immunate. The patient should be aware of early signs of allergic reactions, such as sudden flushing of the face, rash, hives, urticarial blisters, generalized itching, swelling of lips, eyelids and tongue, shortness of breath, wheezing, chest pain, feeling of pressure in the chest, general malaise, dizziness, rapid heartbeat, and low blood pressure. These symptoms may be early signs of anaphylactic shock, in which additional symptoms may include extreme dizziness, loss of consciousness, and severely impaired breathing.
• If any of these symptoms occur, administration of the injection/infusion must be stopped immediately and medical advice must be sought. Severe symptoms, including difficulty breathing and (near) fainting, require immediate emergency treatment.

When treatment monitoring is required:

• The doctor may order tests to ensure that the current dose is sufficient to achieve and maintain appropriate levels of factor VIII and von Willebrand factor.

If bleeding continues:

• The development of inhibitors (antibodies) is a known complication that may occur during treatment with any factor VIII-containing medicines. These inhibitors, especially at high concentrations, interfere with effective treatment, and the patient will be closely monitored for their development. If bleeding in the patient is not properly controlled with Immunate, this must be reported to the doctor immediately.

Patients with von Willebrand disease, particularly type 3 patients, may develop neutralizing antibodies (inhibitors) against von Willebrand factor. The doctor may order tests to confirm their presence. Inhibitors against von Willebrand factor are antibodies in the blood that block the administered von Willebrand factor. As a result, von Willebrand factor is less effective in controlling bleeding.
For medicines prepared from human blood or plasma, appropriate precautions are taken to prevent transmission of infection to patients. These include careful selection of blood and plasma donors to ensure that individuals at risk of carrying infections are excluded, testing of each blood donation and plasma pool for viruses/infections, and inclusion of virus inactivation or removal steps during the manufacturing process. Despite these measures, it cannot be completely ruled out that administration of medicines derived from human blood or plasma may transmit infection, including unknown or newly emerging viruses and other types of infections.
The measures used are considered effective against enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus, hepatitis C virus, and non-enveloped hepatitis A virus. The measures may have limited effectiveness against non-enveloped viruses such as parvovirus B19. Parvovirus B19 infection may have serious consequences for pregnant women (fetal infection) and for patients with immunodeficiency or certain types of anemia (e.g. hereditary spherocytosis or hemolytic anemia).
For patients receiving regular or repeated doses of factor VIII products derived from human plasma, the doctor may recommend vaccination against hepatitis A and B.
It is especially recommended that the name and batch number of the medicinal product be recorded each time a dose of Immunate is administered, to maintain traceability of the batch used.
Immunate contains blood group isohemagglutinins (anti-A and anti-B). Hemolysis may occur in patients with blood group A, B, or AB following repeated administration in a short time or administration of very high doses.
Children
This product should be used with caution in children under 6 years of age who have had limited prior exposure to factor VIII-containing products, as clinical data in this patient group are limited.
Immunate 500 IU FVIII/375 IU VWF and other medicines
Inform the doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.
No interactions between Immunate and other medicines have been reported.
Immunate must not be mixed with other medicines or solvents prior to administration, except with the water for injection provided, as they might adversely affect the efficacy and safety of the product. It is recommended to flush the intravenous line with an appropriate solution, e.g. saline, before and after administration of Immunate.
Immunate 500 IU FVIII/375 IU VWF with food and drink
There are no special instructions regarding administration of Immunate in relation to meals.
Pregnancy, breastfeeding and fertility
As hemophilia A is rare in women, experience with the use of Immunate during pregnancy, breastfeeding, and its effect on fertility is lacking. Immunate should be used during pregnancy and breastfeeding only if clearly indicated. If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor or pharmacist before using this medicine.
Driving and using machines
There is no information available on the influence of Immunate on the ability to drive and use machines.
Immunate 500 IU FVIII/375 IU VWF contains sodium
The medicine contains 9.8 mg of sodium (the main component of table salt) in each vial. This corresponds to 0.5% of the maximum recommended daily intake of sodium in adults' diets.

3. How to use Immunate 500 IU FVIII/375 IU VWF

Treatment must be supervised by a physician experienced in the management of bleeding disorders.
This medicine should always be used exactly as prescribed by the doctor. If in doubt, consult your doctor.

Dosing for prophylaxis of bleeding
If Immunate is used to prevent bleeding, the doctor will determine the dose based on the individual patient's needs. The usual dose is between 20 and 40 IU of factor VIII per kilogram of body weight, administered every 2–3 days. However, in certain cases, especially in younger patients, shorter intervals between doses or higher doses may be necessary.
If the patient feels that the effect of Immunate is too weak, they should consult their doctor.

Dosing for treatment of bleeding
If Immunate is used to treat bleeding episodes, the doctor will calculate the dose according to the individual needs of the patient.
If the patient feels that the effect of Immunate is too weak, they should consult their doctor.

Monitoring of treatment by the physician
To ensure adequate factor VIII levels, the doctor will perform appropriate laboratory tests. This is particularly important during major surgical procedures.

Dosing in von Willebrand disease
The physician will manage bleeding episodes according to guidelines for hemophilia A.

Route and (or) method of administration
Immunate is administered intravenously after reconstitution with the solvent provided.
Strictly follow the doctor’s instructions.
Only use the infusion set supplied in the package for reconstitution, as adsorption of human coagulation factor VIII onto internal surfaces of certain infusion sets may lead to treatment failure.
Immunate should be reconstituted immediately before use. The solution should be used immediately, as it contains no preservatives.

Reconstitution of powder for injection solution
Use aseptic technique!

1. Warm the unopened vial containing the solvent (water for injection) to room temperature (up to a maximum of 37 °C).
2. Remove the protective caps from both the powder and solvent vials (Fig. A) and disinfect the rubber stoppers of both vials.
3. Place the flared end of the transfer set onto the solvent vial and press firmly (Fig. B).
4. Remove the protective cover from the other end of the transfer set, taking care not to touch the exposed end.
5. Invert the transfer set with the attached solvent vial over the powder vial and insert the free needle through the rubber stopper of the powder vial (Fig. C). The solvent will be drawn under vacuum into the powder vial.
6. After approximately one minute, disconnect the vials by removing the transfer set with the solvent vial from the powder vial (Fig. D). Since dissolution occurs easily, gently swirl the concentrate vial or not at all. DO NOT SHAKE THE CONTENTS OF THE VIAL. DO NOT INVERT THE POWDER VIAL UNTIL READY TO TRANSFER THE CONTENTS.
7. After reconstitution, inspect the prepared solution for insoluble particles or discoloration before administration. The solution should be clear or slightly opalescent. However, even when the reconstitution procedure is strictly followed, a small amount of fine particles may occasionally be observed. The provided filter set will remove these particles, and the labeled potency of the product will not be reduced. Discard any solution that is cloudy or contains sediment. Do not refrigerate the reconstituted solution.

Administration
Use aseptic technique!
Use the provided filter set to prevent administration of rubber particles from the stopper (risk of microembolism). To withdraw the reconstituted product, attach the filter set to the provided single-use syringe and insert it through the rubber stopper (Fig. E).
Briefly disconnect the syringe from the filter set. Air will enter the powder vial, allowing any foam inside to dissipate. Withdraw the solution into the syringe through the filter set (Fig. F).
Disconnect the syringe from the filter set and slowly administer the solution intravenously (maximum infusion rate: 2 ml per minute) using the provided infusion set – butterfly needle (or provided single-use needle).

Fig. A Fig. B Fig. C Fig. D Fig. E Fig. F
Any unused medicinal product or waste material should be disposed of in accordance with local regulations.
Administration of Immunate should be documented, and the batch number recorded. A detachable label is provided with each vial for inclusion in the patient’s records.

Frequency of administration
The doctor will inform the patient how often and at what intervals Immunate should be administered, based on the treatment response in each individual patient.

Duration of treatment
Replacement therapy with Immunate is usually required for life.

Use of a higher than recommended dose of Immunate 500 IU FVIII/375 IU VWF

• No symptoms of factor VIII overdose have been reported. In case of doubt, consult the doctor.
• Thromboembolic events may occur.
• Hemolysis may occur in patients with blood group A, B, or AB.

Missed dose of Immunate 500 IU FVIII/375 IU VWF

• Do not administer a double dose to make up for a missed dose.
• Take the next regular dose as soon as possible and continue treatment at the intervals prescribed by the doctor.

Discontinuation of Immunate 500 IU FVIII/375 IU VWF
Do not discontinue treatment with Immunate without consulting the doctor.
In case of any further doubts regarding the use of this medicine, consult the doctor.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Serious adverse reactions that may occur after administration of factor VIII products derived from human plasma
Allergic reactions have been observed rarely, which in some cases may lead to severe and life-threatening reactions (anaphylaxis). Therefore, it is important to be aware of early signs of allergic reactions, such as: sudden redness of the face, rash, urticaria, blistering rash, generalized itching, swelling of lips and tongue, shortness of breath (breathing difficulties), wheezing (difficulty inhaling/exhaling due to narrowing of the airways), chest tightness, low blood pressure, drop in blood pressure, general malaise, and dizziness. These symptoms may be early signs of anaphylactic shock. If any allergic or anaphylactic reaction occurs, administration (injection/infusion) must be stopped immediately and the physician must be informed. Severe symptoms require immediate emergency treatment.
In previously untreated children receiving factor VIII-containing medicines, inhibitory antibodies (see section 2) may develop very commonly (more than 1 in 10 patients). However, in patients who have previously been treated with factor VIII (more than 150 days of treatment), the risk is uncommon (less than 1 in 100 patients). If this occurs, the patient's medication may no longer work properly and persistent bleeding may occur. If this happens, contact the physician immediately.
Development of neutralizing antibodies against von Willebrand factor is a known complication in the treatment of patients with von Willebrand disease. If neutralizing antibodies (inhibitors) develop, this may manifest as inadequate clinical response to treatment (bleeding is not controlled despite appropriate dosing) or as an allergic reaction. In such cases, consultation with a specialized hemophilia treatment center is recommended.
Hemolysis may occur following administration of high doses in patients with blood group A, B, or AB.
Adverse reactions reported after use of Immunate
Very common (may affect more than 1 in 10 patients)

• factor VIII inhibition (in children who have not been previously treated with factor VIII-containing medicines).

Uncommon (may affect not more than 1 in 100 patients)

• hypersensitivity;
• factor VIII inhibition [in patients previously treated with factor VIII (treatment lasting longer than 150 days)].

Frequency not known (frequency cannot be estimated from the available data)

• coagulation disorders (inability to form blood clots);
• anxiety;
• paresthesia (tingling or prickling sensation);
• dizziness;
• headache;
• conjunctivitis;
• tachycardia (rapid heartbeat);
• palpitations;
• hypotension (low blood pressure);
• sudden redness of the face;
• pallor (pale appearance);
• dyspnea (breathing difficulties);
• cough;
• vomiting;
• nausea;
• urticaria (widespread itchy rash);
• rash;
• pruritus (itching sensation);
• erythema (redness of the skin);
• excessive sweating;
• neurodermatitis (itchy or rough skin);
• muscle pain;
• chest pain;
• discomfort in the chest;
• edema (fluid retention);
• fever;
• chills;
• burning and stinging at the site of administration (local reactions);
• pain.

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 Immunate 500 IU FVIII/375 IU VWF
Keep the medicine out of the sight and reach of children.
Store and transport under refrigerated conditions (2 °C – 8 °C). Do not freeze.
Keep in the original packaging to protect from light.
Do not use this medicine after the expiry date stated on the label and carton after EXP. The expiry date refers to the last day of the stated month.
During its shelf life, the product may be stored at room temperature (up to 25 °C) for one period not exceeding 6 months. The date and time when room temperature storage begins must be recorded on the product packaging. After storage at room temperature, Immunate must not be returned to the refrigerator but should be used promptly or discarded.
Do not use this medicine if, after reconstitution, the solution is cloudy or contains particulate matter.
Medicines must 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 Immunate 500 IU FVIII/375 IU VWF contains
Powder:

• The active substances are human coagulation factor VIII and human von Willebrand factor. Each vial contains nominally 500 IU of factor VIII and 375 IU of von Willebrand factor derived from human plasma. After reconstitution with the provided solvent, the product contains approximately 100 IU/mL of factor VIII from human plasma and 75 IU/mL of von Willebrand factor from human plasma.
  • Other components are human albumin, glycine, sodium chloride, sodium citrate, lysine hydrochloride, and calcium chloride.

Solvent:

• Water for injections

What Immunate 500 IU FVIII/375 IU VWF looks like and contents of the pack
Powder and solvent for solution for injection.
White or slightly yellow powder or fragile, amorphous mass.
The powder and solvent are available in single-dose glass vials, Ph. Eur. (powder: type II glass; solvent: type I glass), closed with butyl rubber stoppers, Ph. Eur.
Each pack contains:
1 vial of Immunate 500 IU FVIII/375 IU VWF
1 vial of water for injections (5 ml)
1 transfer or filtration set
1 single-use syringe (5 ml)
1 single-use needle
1 infusion set (butterfly needle).
Pack size: 1 x 500 IU FVIII / 375 IU VWF
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
This medicinal product is authorised in the Member States of the European Economic Area under the following names:
Austria, Bulgaria, Croatia, Cyprus, Estonia, Germany, Latvia, Lithuania, Malta, Poland, Portugal, Romania, Slovakia, Slovenia: Immunate
Czech Republic: Immunate Stim Plus
Hungary: Immunate S/D
Italy: Talate

Other sources of information
Information intended for healthcare professionals only:
Dosing in haemophilia A
The dose and duration of replacement therapy depend on the severity of factor VIII deficiency, the location and extent of bleeding, and the patient's clinical condition.
The administered dose of factor VIII is expressed in International Units (IU), corresponding to the current WHO standard for factor VIII-containing products. Plasma factor VIII activity is expressed as a percentage (relative to normal human plasma) or in IU (relative to the International Standard for plasma factor VIII).
One International Unit (IU) of factor VIII activity corresponds to the amount of factor VIII present in one millilitre of normal human plasma.
The required factor VIII dose has been calculated based on empirical observations that 1 International Unit (IU) of factor VIII per kg body weight raises plasma factor VIII activity by approximately 2% of normal activity.
The required dose is calculated using the following formula:
Required number of units = body weight (kg) x desired increase in factor VIII (%) x 0.5
The administered amount and frequency should always be adjusted according to the clinical response in each individual case.
Bleeding episodes and surgical procedures
In the following types of bleeding, factor VIII activity should not fall below the indicated plasma activity levels (in % of normal or IU/dL) at the appropriate time.
The following table may be used to determine dosing according to the type of bleeding or surgical procedure:

In certain circumstances (e.g., in the presence of a low inhibitor titer), doses higher than those calculated according to the formula may be required.
Long-term prophylaxis
In long-term prophylaxis of bleeding in patients with severe hemophilia A, the usual doses of factor VIII are 20–40 IU/kg body weight administered every 2–3 days.
In some cases, especially in younger patients, shorter intervals between doses or higher doses may be necessary.
Dosing in von Willebrand disease
Substitution therapy using Immunate to control bleeding is based on the guidelines for hemophilia A.
Immunate contains a relatively high amount of factor VIII in relation to von Willebrand factor content; therefore, the treating physician should be aware that continued treatment may lead to excessive increases in FVIII:C, which could result in an increased risk of thrombotic events.
Children and adolescents
The product should be used with caution in children under 6 years of age who have limited exposure to products containing factor VIII, as data in this patient group are limited.
Dosing of factor VIII in children and adolescents under 18 years of age is based on body weight and therefore generally follows the same guidelines as for adult patients.
The dose and frequency of administration should always be adjusted according to the clinical efficacy in the individual case (see section 4.4). In some cases, especially in younger patients, shorter intervals between doses or higher doses may be necessary.