Talate

Package leaflet: Information for the user

Talate 250 IU / 190 IU Powder and solvent for injectable solution

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 questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What Talate is and what it is used for

What Talate is
Talate is a coagulation factor VIII/von Willebrand factor complex derived from human plasma.
The coagulation factor VIII in Talate replaces the missing or malfunctioning factor VIII in patients with haemophilia A. Haemophilia A is a sex-linked inherited disorder characterized by a blood coagulation defect caused by reduced levels of factor VIII. This leads to severe bleeding episodes in joints, muscles, or internal organs, occurring either spontaneously or following accidental or surgical trauma. Administration of Talate thus provides temporary correction of factor VIII deficiency and reduces the tendency to bleed.
In addition to its role as a protein protecting factor VIII, von Willebrand factor (VWF) mediates platelet adhesion to sites of vascular injury and plays a role in platelet aggregation.

What Talate is used for
Talate is used for the treatment and prevention of bleeding in patients with congenital (haemophilia A) or acquired factor VIII deficiency.
Talate is also used for the treatment of bleeding in patients with von Willebrand disease associated with factor VIII deficiency, in cases where effective, specific preparations for treating von Willebrand disease are not available and when treatment with desmopressin (DDAVP) alone is ineffective or contraindicated.

2. What you need to know before using Talate

Do not use Talate

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

If in doubt, consult your doctor.
Warnings and precautions
In case of allergic reactions:

• There is a rare possibility of an anaphylactic reaction (a severe and sudden allergic reaction) to Talate. You should be aware of the early signs of allergic reactions, which include flushing, skin rash, hives, wheals, generalized itching, swelling of the lips, eyelids and tongue, shortness of breath, difficulty breathing, chest pain, feeling of tightness in the chest, general malaise, dizziness, rapid heartbeat and low blood pressure. These symptoms may represent the initial signs of anaphylactic shock, which may also include extreme dizziness, loss of consciousness and severe breathing difficulties.
• In such cases, stop the injection/infusion immediately and contact your doctor. In case of severe symptoms, including difficulty breathing or fainting (or near-fainting), emergency medical treatment is required immediately.

When monitoring is required:

• Your doctor may decide to perform certain tests to adjust the dose in order to achieve and maintain the desired levels of factor VIII or von Willebrand factor.

In case of persistent bleeding:

• The development of inhibitors (antibodies) is a known complication that may occur during treatment with any factor VIII-containing medicine. Inhibitors, especially at high levels, may prevent the treatment from working properly, and you or your child will be closely monitored for the development of such inhibitors. If Talate does not control your or your child’s bleeding, inform your doctor immediately.

If you have von Willebrand disease, especially type 3, you may develop neutralizing antibodies (inhibitors) against von Willebrand factor. Your doctor may decide to perform tests to confirm the presence of inhibitors. Von Willebrand factor inhibitors are antibodies in the blood that block the von Willebrand factor you are receiving. This makes the von Willebrand factor less effective in controlling bleeding.

When medicines are manufactured from human blood or plasma, certain safety measures are applied to prevent transmission of infections to patients. These include careful selection of blood and plasma donors to exclude those at risk of transmitting infections, testing of each blood donation and plasma pool for viruses and infections, and inclusion of manufacturing steps that inactivate or remove viruses. Nevertheless, whenever medicines derived from human blood or plasma are administered, the possibility of transmitting infection cannot be completely excluded. This also applies to unknown or emerging viruses and 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, and against non-enveloped viruses such as hepatitis A virus. The measures taken may have limited effectiveness against non-enveloped viruses such as parvovirus B19.
Parvovirus B19 infection may be serious for pregnant women (fetal infection) and for individuals with a weakened immune system or suffering from certain types of anemia (e.g., sickle cell anemia or hemolytic anemia).
Your doctor may recommend vaccination against hepatitis A and B if you receive regular or repeated treatment with factor VIII products derived from human plasma.
It is strongly recommended that whenever Talate is administered to a patient, the name and batch number of the medicine be recorded, in order to maintain a link between the patient and the product batch.
Talate contains blood group isoagglutinins (anti-A and anti-B). If you have blood group A, B, or AB, hemolysis may occur following repeated administrations at short intervals or after administration of very high doses.
Children
This product should be used with caution in children under 6 years of age who have limited prior exposure to factor VIII products, as clinical data available for this patient group are limited.
Other medicines and Talate
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
No interactions between Talate and other medicines have been reported.
Do not use Talate in combination with other medicines or solvents except with sterile water for injections provided in the package, prior to administration, as this may compromise the efficacy and safety of the product. It is recommended to flush implanted venous access devices with an appropriate solution, e.g., isotonic saline solution, before and after Talate infusion.
Talate with food and drink
There are no specific recommendations regarding administration of Talate with meals.
Pregnancy, breastfeeding and fertility
Due to the rarity of hemophilia A in women, data on the use of Talate during pregnancy, breastfeeding, and the fertility period are not available. During pregnancy and breastfeeding, Talate should be used only if clearly indicated. If you are pregnant, suspect you may be pregnant, planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Driving and using machines
There is no information available on the effects of Talate on the ability to drive vehicles or operate machinery.
Talate contains sodium
This medicine contains 9.8 mg of sodium (the main component of table salt) per vial. This corresponds to 0.5% of the maximum daily recommended dietary intake for an adult.

3. How to use Talate

Treatment must be under the supervision of physicians experienced in the management of haemostatic disorders.
Use this medicine exactly as prescribed by your doctor. If you have any doubts, consult your doctor.

Dosage for prevention of bleeding
If you are using Talate for the prevention of bleeding, your doctor will determine the dose appropriate to your individual needs.
The usual dose ranges between 20 IU and 40 IU of factor VIII per kg of body weight, administered at intervals of 2–3 days. However, in some cases, especially in younger patients, shorter intervals or higher doses may be required.
If you feel that the effect of Talate is insufficient, discuss this with your doctor.

Dosage for treatment of bleeding
If you are using Talate for the treatment of bleeding, your doctor will determine the dose appropriate to your individual needs.
If you feel that the effect of Talate is insufficient, discuss this with your doctor.

Monitoring by the doctor
Your doctor will perform appropriate laboratory tests to ensure that your factor VIII levels are adequate. This is particularly important in the case of major surgery.

Dosage in von Willebrand disease
Your doctor will manage bleeding according to the guidelines provided for the treatment of haemophilia A.

Route and/or method of administration
Talate is administered intravenously (by intravenous infusion) after reconstituting the powder with the solvent supplied.
Follow carefully the instructions provided by your doctor.
For reconstitution, use only the infusion set supplied in the package, as treatment failure may occur due to adsorption of human coagulation factor VIII onto the internal surfaces of certain infusion equipment.
Talate must be reconstituted immediately before administration. The solution should then be used immediately, as it does not contain preservatives.

Reconstitution of the powder for solution for injection
Use aseptic technique!

1. Bring the vial containing the solvent (sterile water for injections) to room temperature (maximum 37 °C).
2. Remove the protective caps from the powder vial and the solvent vial (Fig. A), and clean the rubber stoppers of both vials.
3. Position and press the corrugated edge of the transfer set onto the solvent vial (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 needle through the rubber stopper of the powder vial (Fig. C). The solvent will pass into the powder vial by vacuum action.
6. After approximately one minute, separate the two vials by removing the transfer set with the solvent vial from the powder vial (Fig. D). Since the product dissolves easily, do not shake or do so only gently. DO NOT SHAKE THE CONTENTS OF THE VIAL. DO NOT INVERT THE POWDER VIAL UNTIL READY TO ASPIRATE THE CONTENTS.
7. After reconstitution, visually inspect the prepared solution for particles and abnormal coloration before administration. The solution should be clear to slightly opalescent. However, even when the reconstitution procedure is carefully followed, a few small particles may occasionally be visible. The provided filtration set removes these particles, and the potency indicated on the label will not be reduced. Solutions that appear cloudy or contain deposits must be discarded. The ready-to-use solution must not be stored in the refrigerator.

Administration
Use aseptic technique!
To avoid administration of particles from rubber stoppers (risk of microembolism), use the provided filtration set. To draw up the reconstituted solution, attach the filtration set to the supplied single-use syringe and insert it into the rubber stopper (Fig. E).
Disconnect the syringe from the filtration set momentarily. Air enters the powder vial, allowing any foam to collapse. Then draw the solution into the syringe through the filtration set (Fig. F).
Disconnect the syringe from the filtration set and inject the solution slowly intravenously (maximum injection rate: 2 ml per minute) using the provided butterfly infusion set (or the supplied single-use needle).
Fig. A Fig. B Fig. C Fig. D Fig. E Fig. F
Any unused product and waste materials derived from this medicine must be disposed of in accordance with local regulations.
Administration of Talate must be documented by the physician, and the batch number recorded. An informative detachable label is provided with each vial.

Frequency of administration
Your doctor will determine the frequency and intervals for Talate administration based on efficacy in the individual case.

Duration of treatment
Replacement therapy with Talate is generally lifelong.

If you use more Talate than you should:

• No symptoms of overdose with coagulation factor VIII have been reported. If in doubt, consult your doctor.
• Thromboembolic events may occur.
• Haemolysis may occur in patients with blood group A, B, or AB.

If you forget to use Talate:

• Do not take a double dose to make up for the missed dose.
• Proceed immediately with the next scheduled dose and continue at regular intervals as advised by your doctor.

If you stop treatment with Talate
Do not decide to stop treatment with Talate without consulting your doctor.
If you have any questions about the use of this medicine, consult your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
Serious possible side effects with factor VIII products derived from human plasma:
Allergic reactions have rarely been observed, which may sometimes progress to severe and potentially life-threatening reactions (anaphylaxis). Therefore, it is essential to recognize early signs of allergic reactions, including flushing, skin rashes (rash), urticaria, hives, generalized itching, swelling of the lips and tongue, dyspnea (difficulty breathing), breathlessness (altered inspiration and/or expiration due to airway narrowing), tightness in the chest, low blood pressure, drop in blood pressure, general malaise, and dizziness. These symptoms may represent an early warning sign of anaphylactic shock. In case of allergic or anaphylactic reactions, stop the injection/infusion immediately and contact your doctor. Severe symptoms require immediate emergency treatment.
In children who have not previously been treated with factor VIII medicines, the development of inhibitory antibodies (see section 2) can be very common (more than 1 in 10 patients); however, in patients who have previously received treatment with factor VIII (more than 150 days of treatment), the risk is uncommon (less than 1 in 100 patients). If this occurs, the medicine administered to you or your child may stop working properly, and you or your child may experience persistent bleeding. If this happens, contact your doctor immediately.
The development of neutralizing antibodies (inhibitors) against von Willebrand factor is a known complication in the treatment of patients with von Willebrand disease. If you develop neutralizing antibodies (inhibitors), this may manifest as an inadequate clinical response (bleeding not controlled by an appropriate dose), or as an allergic reaction. In such cases, it is advisable to contact a specialized haemophilia treatment centre.
Haemolysis may occur if you have blood group A, B or AB, following administration of high doses.

Side effects reported with the use of Talate

Very common (may affect more than 1 in 10 individuals)

• Development of factor VIII inhibitors (in children not previously treated with factor VIII medicines).

Uncommon (may affect up to 1 in 100 individuals)

• Hypersensitivity
• Development of factor VIII inhibitors (in patients previously treated with factor VIII (more than 150 days of treatment)).

Not known (frequency cannot be estimated from available data)

• Coagulation disorders (inability to form clots)
• Agitation
• Paraesthesia (tingling or numbness)
• Dizziness
• Headache
• Conjunctivitis (pink eye)
• Tachycardia (rapid heartbeat)
• Palpitations (awareness of heartbeat)
• Hypotension (low blood pressure)
• Flushing
• Pallor (pale appearance)
• Dyspnoea (shortness of breath)
• Cough
• Vomiting
• Nausea
• Urticaria (rash over the body)
• Rash
• Pruritus (itching sensation)
• Erythema (redness of the skin)
• Hyperhidrosis (excessive sweating)
• Neurodermatitis (itching or irritation of the skin)
• Myalgia (muscle pain)
• Chest pain
• Chest discomfort
• Oedema (fluid retention)
• Pyrexia (fever)
• Chills
• Burning and stinging sensation at the injection site, injection site reactions
• Pain.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, consult your doctor. You can also report side effects directly via the national reporting system. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Talate

Keep this medicine out of the sight and reach of children.
Store in a refrigerator (2 °C – 8 °C). Do not freeze.
Keep in the original packaging to protect the medicine from light.
Do not use this medicine after the expiry date stated on the label and packaging following "Exp.".
The expiry date refers to the last day of that month.
During its shelf life, the product may be stored at room temperature (up to 25 °C) for a single period not exceeding 6 months. Record the period of storage at room temperature on the product packaging. After storage at room temperature, Talate must not be returned to the refrigerator, but must be used immediately or discarded.
Do not use this medicine if you notice that the solution of the reconstituted product is cloudy or contains particles.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer used. This will help protect the environment.

6. Package contents and other information

What Talate contains
Powder

• The active substances are human coagulation factor VIII and human von Willebrand factor. Each vial contains nominally 250 IU of human coagulation factor VIII and 190 IU of von Willebrand factor derived from human plasma. After reconstitution with the solvent supplied, the product contains approximately 50 IU/mL of human coagulation factor VIII derived from plasma and 38 IU/mL of von Willebrand factor derived from plasma.
• The other components are human albumin, glycine, sodium chloride, sodium citrate, lysine hydrochloride, and calcium chloride.

Solvent

• Sterile water for injections

Description of the appearance of Talate and package contents
Powder and solvent for solution for injection.
Powder or fragile solid, white or pale yellow in colour.
The powder and solvent are supplied in single-dose glass vials, EP (powder: hydrolytic type II;
solvent: hydrolytic type I), closed with butyl rubber stoppers, EP.
Each pack contains:
1 vial of Talate 250 IU / 190 IU
1 vial of sterile water for injections (5 mL)
1 transfer/filter set
1 single-use syringe (5 mL)
1 single-use needle
1 butterfly infusion set.
Pack: 1 x 250 IU / 190 IU
Marketing Authorisation Holder
Marketing Authorisation Holder
Baxalta Innovations GmbH, Industriestrasse 67,
A – 1221 Vienna
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, Cyprus, Malta, Poland, Portugal, Romania, Slovak Republic, Slovenia: Immunate
Hungary: Immunate S/D
Italy: Talate
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Other sources of information
The following information is 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 site and
extent of bleeding, and the patient's clinical condition.
The number of factor VIII units administered is expressed in International Units (IU), which correlate with
the current WHO standard for factor VIII products. Factor VIII activity in plasma is expressed as a percentage
(relative to normal human plasma) or in International Units (relative to an international standard for factor VIII in plasma).
One International Unit (IU) of factor VIII activity is equivalent to the amount of factor VIII contained in 1 mL of normal human plasma.
The required dose of factor VIII is calculated based on the empirical observation that 1 International Unit (IU) of factor VIII per kg of body weight raises plasma factor VIII activity by approximately 2% of normal activity.
The required dose can be calculated using the following formula:
Required units = body weight (kg) x desired factor VIII increase (%) x 0.5
The amount to be administered and the frequency of administration should always be guided by clinical efficacy in the individual case.
Haemorrhage and surgical procedures
In the case of the following haemorrhagic events, factor VIII activity must not fall below the specified plasma activity level (in % of normal or IU/dL) during the corresponding period.
The following table may be used to guide dosing in bleeding episodes and surgical procedures:

Under certain circumstances (e.g. presence of a low-titre inhibitor), doses higher than those calculated using the formula may be required.
Long-term prophylaxis
For long-term prophylaxis against bleeding in patients with severe haemophilia A, the usual doses are 20 to 40 IU of factor VIII per kg of body weight administered at intervals of 2–3 days. In some cases, particularly in younger patients, shorter dosing intervals or higher doses may be necessary.
Dosing in von Willebrand disease
Replacement therapy with Talate for the control of bleeding follows the guidelines provided for haemophilia A.
Since Talate contains a relatively high amount of factor VIII in relation to vWF, the treating physician should be aware that continuous treatment may cause excessive increase in factor VIII:C, which may lead to an increased risk of thrombosis.
Paediatric population
This product should be used with caution in children under 6 years of age, who have limited exposure to factor VIII-containing products, due to limited available data in this patient group.
Dosing in haemophilia A in children and adolescents under 18 years of age is based on body weight and therefore generally follows the same guidelines as in adults. The dose amount and frequency of administration should always be guided by clinical efficacy in the individual case. In some cases, particularly in younger patients, shorter dosing intervals or higher doses may be necessary.

Package leaflet: Information for the user

Talate 500 IU / 375 IU Powder and solvent for injectable solution

human coagulation factor VIII / human von Willebrand factor
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 questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What Talate is and what it is used for
2. What you need to know before using Talate
3. How to use Talate
4. Possible side effects
5. How to store Talate
6. Package contents and other information

1. What Talate is and what it is used for

What Talate is
Talate is a complex of coagulation factor VIII/von Willebrand factor derived from human plasma.
The coagulation factor VIII in Talate replaces the missing or malfunctioning factor VIII in patients with haemophilia A. Haemophilia A is a hereditary, sex-linked disorder characterized by a blood coagulation disorder caused by reduced levels of factor VIII. This leads to severe bleeding into joints, muscles, or internal organs, either spontaneously or following accidental or surgical trauma. Administration of Talate thus enables temporary correction of the factor VIII deficiency and reduces the tendency to bleed.
In addition to its role as a protein protecting factor VIII, the von Willebrand factor (VWF) mediates platelet adhesion to sites of vascular injury and plays a role in platelet aggregation.

What Talate is used for
Talate is used for the treatment and prevention of bleeding in patients with congenital (haemophilia A) or acquired factor VIII deficiency.
Talate is also used for the treatment of bleeding in patients with von Willebrand disease who have factor VIII deficiency, in cases where effective, specific preparations for treating von Willebrand disease are not available and when treatment with desmopressin (DDAVP) alone is ineffective or contraindicated.

2. What you should know before using Talate

Do not use Talate

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

If in doubt, consult your doctor.
Warnings and precautions
In case of allergic reactions:

• There is a rare possibility of an anaphylactic reaction (a severe and sudden allergic reaction) to Talate. You should be aware of the early signs of allergic reactions, which include flushing, skin rash, urticaria, hives, generalized itching, swelling of the lips, eyelids and tongue, dyspnea, shortness of breath, chest pain, feeling of tightness in the chest, general malaise, dizziness, rapid heartbeat and low blood pressure. These symptoms may represent the initial signs of anaphylactic shock, which may also include extreme dizziness, loss of consciousness and severe breathing difficulties.
• In such cases, immediately stop the injection/infusion and contact your doctor. In case of severe symptoms, including difficulty breathing or fainting (or feeling faint), emergency medical treatment is required immediately.

When monitoring is necessary:

• Your doctor may decide to perform certain tests to adjust the dose in order to achieve and maintain the desired levels of factor VIII or von Willebrand factor.

In case of persistent bleeding:

• The development of inhibitors (antibodies) is a known complication that may occur during treatment with all factor VIII medicines. Inhibitors, especially at high levels, may prevent the treatment from working properly, and you or your child will be closely monitored for the development of such inhibitors. If Talate does not control your or your child's bleeding, inform your doctor immediately.

If you have von Willebrand disease, especially type 3, you may develop neutralizing antibodies (inhibitors) against von Willebrand factor. Your doctor may decide to perform tests to confirm the presence of inhibitors. Von Willebrand factor inhibitors are antibodies present in the blood that block the von Willebrand factor you are receiving. This makes the von Willebrand factor less effective in controlling bleeding.
When medicines are produced from human blood or plasma, certain safety measures are applied to prevent transmission of infections to patients. These include careful selection of blood and plasma donors to exclude those at risk of transmitting infections, testing of each donation and plasma pool for viruses and infections, and inclusion of manufacturing procedures that inactivate or remove viruses. Nevertheless, whenever medicines derived from human blood or plasma are used, the possibility of transmitting infection cannot be completely excluded. This also applies to unknown or emerging viruses or 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, and against non-enveloped viruses such as hepatitis A virus. The measures taken may have limited effectiveness against non-enveloped viruses such as parvovirus B19.
Parvovirus B19 infection may be severe in pregnant women (fetal infection) and in individuals with weakened immune systems or with certain types of anemia (e.g., sickle cell anemia or hemolytic anemia).
Your doctor may advise you to be vaccinated against hepatitis A and B if you regularly or repeatedly receive factor VIII products derived from human plasma.
It is strongly recommended that, each time Talate is administered to a patient, the name and batch number of the medicine be recorded, to maintain a link between the patient and the product batch.
Talate contains blood group isoagglutinins (anti-A and anti-B). If you have blood group A, B, or AB, hemolysis may occur following repeated administrations at short intervals or after administration of very high doses.
Children
This product should be used with caution in children under 6 years of age who have limited prior exposure to factor VIII products, as clinical data available for this patient group are limited.
Other medicines and Talate
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
No interactions between Talate and other medicines have been reported.
Do not use Talate in combination with other medicines or solvents except with sterile water for injections provided in the package, prior to administration, as this may compromise the efficacy and safety of the product. It is recommended to flush implanted venous access devices with an appropriate solution, e.g., isotonic saline solution, before and after infusion of Talate.
Talate with food and drink
There are no specific recommendations regarding administration of Talate with meals.
Pregnancy, breastfeeding and fertility
Due to the rarity of hemophilia A in women, data on the use of Talate during pregnancy, breastfeeding, and the fertility period are not available. During pregnancy and breastfeeding, Talate should be used only if clearly indicated. If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or pharmacist before taking this medicine.
Driving and using machines
There is no information available on the effects of Talate on the ability to drive vehicles or operate machinery.
Talate contains sodium
This medicine contains 9.8 mg of sodium (a main component of table salt) per vial. This corresponds to 0.5% of the maximum daily dietary intake recommended for an adult.

3. How to use Talate

Treatment must be under the supervision of physicians experienced in the management of haemostatic disorders.
Use this medicine exactly as prescribed by your doctor. If you have any doubts, consult your doctor.

Dosage for prevention of bleeding
If you are using Talate for the prevention of bleeding, your doctor will determine the dose appropriate to your individual needs.
The usual dose ranges between 20 IU and 40 IU of factor VIII per kg of body weight, administered at intervals of 2–3 days. However, in some cases, particularly in younger patients, shorter intervals or higher doses may be required.
If you feel that the effect of Talate is insufficient, discuss this with your doctor.

Dosage for treatment of bleeding
If you are using Talate for the treatment of bleeding, your doctor will determine the dose appropriate to your individual needs.
If you feel that the effect of Talate is insufficient, discuss this with your doctor.

Monitoring by the doctor
Your doctor will perform appropriate laboratory tests to ensure that your factor VIII levels are adequate. This is particularly important in the case of major surgery.

Dosage in von Willebrand disease
Your doctor will manage bleeding according to the guidelines provided for the treatment of haemophilia A.

Route and/or method of administration
Talate is administered intravenously (by intravenous infusion) after reconstituting the powder with the solvent provided.
Follow carefully the instructions given by your doctor.
For reconstitution, use only the set provided in the package, as treatment may fail due to adsorption of human coagulation factor VIII onto the internal surfaces of certain infusion equipment.
Talate must be reconstituted immediately before administration. The solution should then be used immediately, as it does not contain preservatives.

Reconstitution of the powder for solution for injection
Use an aseptic technique!

8. Bring the vial containing the solvent (sterile water for injections) to room temperature (up to 37 °C).
9. Remove the protective caps from the powder vial and the solvent vial (Fig. A), and clean the rubber stoppers of both vials.
10. Place and press the fluted edge of the transfer set onto the solvent vial (Fig. B).
11. Remove the protective cover from the other end of the transfer set, taking care not to touch the exposed end.
12. Invert the transfer set with the attached solvent vial over the powder vial and insert the needle through the rubber stopper of the powder vial (Fig. C). The solvent will transfer into the powder vial by vacuum action.
13. After approximately one minute, separate the two vials by removing the transfer set with the attached solvent vial from the powder vial (Fig. D). Since the product dissolves readily, do not shake or agitate the concentrate vial. DO NOT SHAKE THE CONTENTS OF THE VIAL. DO NOT INVERT THE POWDER VIAL UNTIL READY TO ASPIRATE THE CONTENT.
14. After reconstitution, visually inspect the prepared solution for particles and abnormal colour before administration. The solution should be clear to slightly opalescent. However, even when the reconstitution procedure is carefully followed, a few small particles may occasionally be visible. The provided filter set removes these particles, and the titre indicated on the label will not be reduced. Solutions that appear cloudy or contain deposits must be discarded. The ready-to-use solution must not be stored in the refrigerator.

Administration
Use an aseptic technique!
To prevent administration of particles from the rubber stoppers (risk of microembolism), use the provided filter set. To aspirate the dissolved preparation, attach the filter set to the provided single-use syringe and insert it into the rubber stopper (Fig. E).
Disconnect the syringe from the filter set momentarily. Air enters the powder vial, allowing any foam to collapse. Then aspirate the solution into the syringe through the filter set (Fig. F).
Disconnect the syringe from the filter set and inject the solution slowly intravenously (maximum injection rate: 2 mL per minute) using the provided butterfly infusion set (or the provided single-use needle).

Fig. A  Fig. B  Fig. C  Fig. D  Fig. E  Fig. F

Any unused product and waste material derived from this medicine must be disposed of in accordance with local regulations.
The administration of Talate must be documented by the doctor, and the batch number recorded. An informative removable label is provided with each vial.

Frequency of administration
Your doctor will determine the frequency and intervals for administration of Talate based on efficacy in the individual case.

Duration of treatment
Replacement therapy with Talate is generally lifelong.

If you use more Talate than you should

• No symptoms of factor VIII coagulation factor overdose have been reported. If in doubt, consult your doctor.
• Thromboembolic events may occur.
• Haemolysis may occur in patients with blood group A, B, or AB.

If you forget to use Talate:

• Do not take a double dose to make up for the missed dose.
• Administer the next dose immediately and continue at regular intervals as advised by your doctor.

If you stop using Talate
Do not decide to stop treatment with Talate without consulting your doctor.
If you have any doubts about using this medicine, consult your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Serious possible side effects with factor VIII products derived from human plasma:

Allergic reactions have rarely been observed, which may sometimes progress to severe and potentially life-threatening reactions (anaphylaxis). Therefore, it is important to be aware of the early signs of allergic reactions, which include flushing, skin rashes (rash), hives, wheals, generalized itching, swelling of the lips and tongue, dyspnea (difficulty breathing), breathlessness (impaired inspiration and/or expiration due to airway constriction), chest tightness, low blood pressure, drop in blood pressure, general malaise, and dizziness. These symptoms may be early signs of anaphylactic shock. In case of allergic or anaphylactic reactions, stop the injection/infusion immediately and contact your doctor. Severe symptoms require immediate emergency treatment.

In children who have not previously been treated with factor VIII medicines, the development of inhibitory antibodies (see section 2) can be very common (more than 1 in 10 patients). However, in patients who have previously received factor VIII treatment (more than 150 days of treatment), the risk is uncommon (less than 1 in 100 patients). If this occurs, the medicine administered to you or your child may stop working properly, and you or your child may experience persistent bleeding. If this happens, contact your doctor immediately.

The development of neutralizing antibodies (inhibitors) against von Willebrand factor is a known complication in the treatment of patients with von Willebrand disease. If you develop neutralizing antibodies (inhibitors), this may manifest as an inadequate clinical response (bleeding is not controlled with an appropriate dose) or as an allergic reaction. In such cases, it is advisable to contact a specialized haemophilia treatment centre.

Haemolysis may occur if you have blood group A, B or AB, following administration of high doses.

Side effects reported with the use of Talate

Very common (may affect more than 1 in 10 people)

• Development of factor VIII inhibitors (in children not previously treated with factor VIII medicines).

Uncommon (may affect up to 1 in 100 people)

• Hypersensitivity
• Development of factor VIII inhibitors (in patients previously treated with factor VIII (more than 150 days of treatment)).

Not known (frequency cannot be estimated from the available data)

• Coagulation disorders (inability to form clots)
• Agitation
• Paraesthesia (tingling or numbness)
• Dizziness
• Headache
• Conjunctivitis (pink eye)
• Tachycardia (rapid heartbeat)
• Palpitations (awareness of heartbeat)
• Hypotension (low blood pressure)
• Flushing
• Pallor (pale appearance)
• Dyspnoea (shortness of breath)
• Cough
• Vomiting
• Nausea
• Urticaria (rash all over the body)
• Rash
• Pruritus (itching sensation)
• Erythema (redness of the skin)
• Hyperhidrosis (excessive sweating)
• Neurodermatitis (itching or irritation of the skin)
• Myalgia (muscle pain)
• Chest pain
• Chest discomfort
• Oedema (fluid retention)
• Pyrexia (fever)
• Chills
• Burning and stinging sensation at the injection site, injection site reactions
• Pain

Reporting of side effects

If you experience any side effects, including those not listed in this leaflet, please talk to your doctor. You can also report side effects directly via the national reporting system. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Talate

Keep this medicine out of the sight and reach of children.
Store in the refrigerator (2 °C – 8 °C). Do not freeze.
Keep in the original packaging to protect the medicine from light.
Do not use this medicine after the expiry date which is stated on the label and on the packaging after
“Exp.”.
The expiry date refers to the last day of that month.
During the shelf life, the product may be stored at room temperature (up to 25 °C) for a single period not exceeding 6 months. Record the period of storage at room temperature on the product packaging. After storage at room temperature, Talate must not be returned to the refrigerator, but must be used immediately or disposed of.
Do not use this medicine if you notice that the reconstituted solution is cloudy or contains particles.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Talate contains
Powder

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

Solvent

• Sterile water for injections

Description of the appearance of Talate and contents of the pack
Powder and solvent for injectable solution.
White or pale yellow powder or friable solid.
The powder and solvent are supplied in single-dose glass vials, EP (powder: hydrolytic type II; solvent: hydrolytic type I), closed with butyl rubber stoppers, EP.
Each pack contains:
1 vial of Talate 500 IU / 375 UI
1 vial of sterile water for injections (5 ml)
1 transfer/filter set
1 single-use syringe (5 ml)
1 single-use needle
1 butterfly infusion set.
Pack: 1 x 500 IU / 375 UI
Marketing Authorisation Holder
Baxalta Innovations GmbH, Industriestrasse 67,
A – 1221 Vienna
Manufacturer
Takeda Manufacturing Austria AG
Industriestrasse 67
1221 Vienna
Austria
This medicinal product is authorised in the European Economic Area Member States under the following
names:
Austria, Bulgaria, Croatia, Cyprus, Estonia, Germany, Latvia, Lithuania, Malta, Poland, Portugal, Romania,
Slovak Republic, Slovenia: Immunate
Czech Republic: Immunate Stim Plus
Hungary: Immunate S/D
Italy: Talate
<--------------------------------------------------------------------------------------
--------------------------------------->
Other sources of information
The following information is 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 number of factor VIII units administered is expressed in International Units (IU), which correlate with
the current WHO standard for factor VIII products. Factor VIII activity in plasma is expressed as a percentage
(relative to normal human plasma) or in International Units (relative to an international standard for factor VIII in plasma).
One International Unit (IU) of factor VIII activity is equivalent to the amount of factor VIII contained in 1 ml of normal human plasma.
The calculation of the required factor VIII dose is based on the empirical observation that 1 International Unit (IU) of factor VIII per kg of body weight increases plasma factor VIII activity by approximately 2% of normal activity.
The required dose is determined using the following formula:
Required units = body weight (kg) x desired increase in factor VIII (%) x 0.5
The amount to be administered and the frequency of administration should always be guided by clinical efficacy in the individual case.
Bleeding episodes and surgical procedures
In the case of the following bleeding events, factor VIII activity must not fall below the specified plasma activity level (in % of normal or IU/dl) during the corresponding period.
The following table may be used to guide dosing in bleeding episodes and surgical procedures:

In certain circumstances (e.g. presence of a low-titer inhibitor), doses higher than those calculated using the formula may be required.
Long-term prophylaxis
For long-term prophylaxis against bleeding in patients with severe haemophilia A, the usual doses are 20 to 40 IU of factor VIII per kg of body weight administered at intervals of 2–3 days. In some cases, particularly in younger patients, shorter dosing intervals or higher doses may be required.
Dosing in von Willebrand disease
Replacement therapy with Talate for control of bleeding follows the guidelines provided for haemophilia A.
Since Talate contains a relatively high amount of factor VIII in relation to vWF, the treating physician should be aware that continuous treatment may cause excessive increases in factor VIII:C, which could lead to an increased risk of thrombosis.
Paediatric population
This product should be used with caution in children under 6 years of age, who have limited exposure to factor VIII-containing products, as available data in this patient group are limited.
Dosing for haemophilia A in children and adolescents under 18 years of age is based on body weight and therefore generally follows the same guidelines as for adults. The amount and frequency of administration should always be guided by clinical efficacy in the individual case. In some cases, particularly in younger patients, shorter dosing intervals or higher doses may be required.

Package leaflet: information for the user

Talate 1000 IU / 750 IU Powder and solvent for solution for injection

Active substances: human coagulation factor VIII / human von Willebrand factor
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 questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

1. What Talate is and what it is used for
2. What you need to know before using Talate
3. How to use Talate
4. Possible side effects
5. How to store Talate
6. Package contents and other information

1. What Talate is and what it is used for

What Talate is
Talate is a complex of coagulation factor VIII/von Willebrand factor derived from human plasma.
The coagulation factor VIII in Talate replaces the missing or malfunctioning factor VIII in patients with haemophilia A. Haemophilia A is a sex-linked inherited disorder characterized by a blood coagulation disorder caused by reduced levels of factor VIII. This leads to severe bleeding episodes in joints, muscles, or internal organs, occurring either spontaneously or following accidental or surgical trauma. Administration of Talate thus enables temporary correction of the factor VIII deficiency and reduces the tendency to bleed.
In addition to its role as a protein that protects factor VIII, von Willebrand factor (VWF) mediates platelet adhesion to sites of vascular injury and plays a role in platelet aggregation.

What Talate is used for
Talate is used for the treatment and prevention of bleeding in patients with congenital (haemophilia A) or acquired factor VIII deficiency. Talate is also used for the treatment of bleeding in patients with von Willebrand disease who have factor VIII deficiency, in cases where effective specific preparations for treating von Willebrand disease are not available and when treatment with desmopressin (DDAVP) alone is ineffective or contraindicated.

2. What you need to know before using Talate

Do not use Talate

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

If in doubt, consult your doctor.
Warnings and precautions
In case of allergic reactions:

• There is a rare possibility that an anaphylactic reaction (a severe and sudden allergic reaction) may occur towards Talate. You should be aware of the early signs of allergic reactions, which include flushing, skin rash, hives, wheals, generalized itching, swelling of the lips, eyelids and tongue, shortness of breath, difficulty breathing, chest pain, sensation of chest tightness, general feeling of malaise, dizziness, rapid heartbeat and low blood pressure. These symptoms may represent an initial sign of anaphylactic shock, which may also include extreme dizziness, loss of consciousness and severe breathing difficulties.
• In such a case, stop the injection/infusion immediately and consult your doctor. In case of severe symptoms, including difficulty breathing or fainting (or near-fainting), immediate emergency treatment is required.

When monitoring is necessary:

• Your doctor may decide to perform certain tests to adjust the dose in order to achieve and maintain the desired levels of factor VIII or von Willebrand factor.

In case of persistent bleeding:

• The development of inhibitors (antibodies) is a known complication that may occur during treatment with all factor VIII-containing medicines. Inhibitors, especially at high levels, may prevent the treatment from working properly, and you or your child will be closely monitored for the development of such inhibitors. If Talate does not control your or your child's bleeding, inform your doctor immediately.

If you have von Willebrand disease, especially type 3, you may develop neutralizing antibodies (inhibitors) against von Willebrand factor. Your doctor may decide to carry out tests to confirm the presence of inhibitors. Von Willebrand factor inhibitors are antibodies present in the blood that block the von Willebrand factor you are receiving. This makes the von Willebrand factor less effective in controlling bleeding.
When medicines are produced from human blood or plasma, certain safety measures are applied to prevent transmission of infections to patients. These include careful selection of blood and plasma donors to exclude those at risk of transmitting infections, testing of each blood donation and plasma pool for viruses and infections, and inclusion of manufacturing procedures that inactivate or remove viruses. Nevertheless, whenever medicines prepared from human blood or plasma are used, the possibility of transmitting infection cannot be completely ruled out. This also applies to unknown or emerging viruses or 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, and also against non-enveloped hepatitis A virus. The measures taken may have limited effectiveness against non-enveloped viruses such as parvovirus B19.
Parvovirus B19 infection may be severe in pregnant women (fetal infection) and in individuals with a weakened immune system or those affected by certain types of anemia (e.g., sickle cell anemia or hemolytic anemia).
Your doctor may recommend vaccination against hepatitis A and B if you receive regular/repeated factor VIII products derived from human plasma.
It is strongly recommended that each time Talate is administered to a patient, the name and batch number of the medicine be recorded to maintain a traceability link between the patient and the product batch.
Talate contains blood group isoagglutinins (anti-A and anti-B). If you have blood group A, B, or AB, hemolysis may occur following repeated administrations at short intervals or after administration of very high doses.
Children
This product should be used with caution in children under 6 years of age who have limited prior exposure to factor VIII products, as the available clinical data in this patient group are limited.
Other medicines and Talate
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
No interactions of Talate with other medicines have been reported.
Do not use Talate in combination with other medicines or solvents except with sterile water for injections included in the package, prior to administration, as this may compromise the efficacy and safety of the product. It is recommended to flush implanted venous access devices with an appropriate solution, e.g. isotonic saline solution, before and after Talate infusion.
Talate with food and drink
There are no specific recommendations regarding administration of Talate with meals.
Pregnancy, breastfeeding and fertility
Due to the rarity of hemophilia A in women, data on the use of Talate during pregnancy, breastfeeding, and the fertility period are not available. During pregnancy and breastfeeding, Talate should be used only if clearly indicated. If you are pregnant, suspect you may be pregnant, planning a pregnancy, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Driving and using machines
There is no information available on the effects of Talate on the ability to drive vehicles or operate machinery.
Talate contains sodium
This medicine contains 19.6 mg of sodium (the main component of table salt) per vial.
This is equivalent to approximately 1% of the recommended maximum daily dietary intake for an adult.

3. How to use Talate

Treatment must be under the supervision of physicians experienced in the management of haemostatic disorders.
Use this medicine exactly as prescribed by your doctor. If you have any doubts, consult your doctor.

Dosage for prevention of bleeding
If you are using Talate for the prevention of bleeding, your doctor will determine the dose appropriate for your individual needs.
The usual dose ranges between 20 IU and 40 IU of factor VIII per kg of body weight, administered at intervals of 2–3 days. However, in some cases, particularly in younger patients, shorter intervals or higher doses may be required.
If you feel that the effect of Talate is insufficient, discuss this with your doctor.

Dosage for treatment of bleeding
If you are using Talate for the treatment of bleeding, your doctor will determine the dose appropriate for your individual needs.
If you feel that the effect of Talate is insufficient, discuss this with your doctor.

Monitoring by the doctor
Your doctor will perform appropriate laboratory tests to ensure that your factor VIII levels are adequate. This is particularly important in the case of major surgery.

Dosage in von Willebrand disease
Your doctor will manage bleeding according to the guidelines provided for the treatment of haemophilia A.

Route and/or method of administration
Talate is administered intravenously after reconstituting the powder with the solvent provided.
Follow carefully the instructions given by your doctor.
For reconstitution, use only the transfer set supplied in the package, as treatment may fail due to adsorption of human coagulation factor VIII onto the internal surfaces of certain infusion equipment.
Talate must be reconstituted immediately before administration. The solution should then be used immediately, as it does not contain preservatives.

Reconstitution of the powder for preparing an injectable solution
Use an aseptic technique!

15. Bring the vial containing the solvent (sterile water for injections) to room temperature (up to a maximum of 37 °C).
16. Remove the protective caps from the powder vial and the solvent vial (Fig. A), and clean the rubber stoppers of both vials.
17. Position and press the fluted edge of the transfer set onto the solvent vial (Fig. B).
18. Remove the protective cover from the other end of the transfer set, taking care not to touch the exposed end.
19. Invert the transfer set with the attached solvent vial over the powder vial and insert the needle through the rubber stopper of the powder vial (Fig. C). The solvent will pass into the powder vial by vacuum action.
20. After approximately one minute, separate the two vials by removing the transfer set with the solvent vial from the powder vial (Fig. D). Since the product dissolves easily, do not shake the concentrate vial, or do so only gently. DO NOT SHAKE THE CONTENTS OF THE VIAL. DO NOT INVERT THE POWDER VIAL UNTIL READY TO ASPIRATE THE CONTENTS.
21. After reconstitution, visually inspect the prepared solution for particles and abnormal coloration before administration. The solution should be clear to slightly opalescent. However, even when the reconstitution procedure is carefully followed, a few small particles may occasionally be visible. The provided filter set will remove these particles, and the labelled potency will not be reduced. Discard solutions that appear cloudy or contain deposits. The ready-to-use solution must not be refrigerated.

Administration
Use an aseptic technique!
To avoid administering particles from rubber stoppers together with the medicine (risk of microembolism), use the filter set provided. To aspirate the dissolved preparation, attach the filter set to the supplied single-use syringe and insert it into the rubber stopper (Fig. E).
Disconnect the syringe momentarily from the filter set. Air enters the powder vial and any foam collapses. Then draw the solution into the syringe through the filter set (Fig. F).
Disconnect the syringe from the filter set and inject the solution slowly intravenously (maximum injection rate: 2 ml per minute) using the provided butterfly infusion set (or the provided single-use needle).
Fig. A Fig. B Fig. C Fig. D Fig. E Fig. F
Any unused product and waste materials derived from this medicine must be disposed of in accordance with local regulations.
Administration of Talate must be documented by the physician, and the batch number recorded. A removable information label is provided with each vial.

Frequency of administration
Your doctor will determine the frequency and intervals for administration of Talate based on efficacy in the individual case.

Duration of treatment
Replacement therapy with Talate is generally lifelong.

If you use more Talate than you should

• No symptoms of overdose with coagulation factor VIII have been reported. If in doubt, contact your doctor.
• Thromboembolic events may occur.
• Haemolysis may occur in patients with blood group A, B, or AB.

If you forget to use Talate

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

If you stop using Talate
Do not decide to stop treatment with Talate without consulting your doctor.
If you have any doubts about using this medicine, consult your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
Serious possible side effects with plasma-derived factor VIII products
Allergic reactions have rarely been observed, which may sometimes progress to severe and potentially life-threatening reactions (anaphylaxis). Therefore, it is important to recognize the early signs of allergic reactions, including flushing, skin rashes (rash), hives, wheals, generalized itching, swelling of the lips and tongue, dyspnea (difficulty breathing), shortness of breath (altered inspiration and/or expiration due to airway narrowing), chest tightness, low blood pressure, drop in blood pressure, general malaise and dizziness. These symptoms may represent an early sign of anaphylactic shock. In case of allergic or anaphylactic reactions, stop the injection/infusion immediately and contact your doctor. Severe symptoms require immediate emergency treatment.
In children who have not previously been treated with factor VIII-containing medicines, the development of inhibitory antibodies (see section 2) may be very common (more than 1 in 10 patients); however, in patients who have previously received factor VIII treatment (more than 150 days of treatment), the risk is uncommon (less than 1 in 100 patients). If this occurs, the medicine administered to you or your child may stop working properly and you or your child may experience persistent bleeding. If this happens, contact your doctor immediately.
The development of neutralizing antibodies (inhibitors) against von Willebrand factor is a known complication in the treatment of patients with von Willebrand disease. If you develop neutralizing antibodies (inhibitors), this may manifest as an inadequate clinical response (bleeding not controlled with an appropriate dose), or as an allergic reaction. In such cases, it is advisable to contact a specialized haemophilia treatment centre.
Haemolysis may occur if you have blood group A, B or AB, following administration of high doses.

Side effects reported with the use of Talate
Very common (may affect more than 1 in 10 individuals)

• Development of factor VIII inhibitors (in children not previously treated with factor VIII-containing medicines).

Uncommon (may affect up to 1 in 100 individuals)

• Hypersensitivity
• Development of factor VIII inhibitors (in patients previously treated with factor VIII (more than 150 days of treatment)).

Not known (frequency cannot be estimated from the available data)

• Coagulation disorders (inability to form clots)
• Agitation
• Paraesthesia (tingling or numbness)
• Dizziness
• Headache
• Conjunctivitis (pink eye)
• Tachycardia (rapid heartbeat)
• Palpitations (awareness of heartbeat)
• Hypotension (low blood pressure)
• Flushing
• Pallor (pale appearance)
• Dyspnoea (shortness of breath)
• Cough
• Vomiting
• Nausea
• Urticaria (rash over the body)
• Rash
• Pruritus (itching sensation)
• Erythema (redness of the skin)
• Hyperhidrosis (excessive sweating)
• Neurodermatitis (itching or irritation of the skin)
• Myalgia (muscle pain)
• Chest pain
• Chest discomfort
• Oedema (fluid retention)
• Pyrexia (fever)
• Chills
• Burning and pricking sensation at the injection site, injection site reactions
• Pain.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor. You can also report side effects directly via the national reporting system. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Talate

Keep this medicine out of the sight and reach of children.
Store in a refrigerator (2 °C – 8 °C). Do not freeze.
Keep in the original packaging to protect the medicine from light.
Do not use this medicine after the expiry date stated on the label and packaging after "Exp.".
The expiry date refers to the last day of that month.
During its shelf life, the product may be stored at room temperature (up to 25 °C) for a single period not exceeding 6 months. Record the period of storage at room temperature on the product packaging. After storage at room temperature, Talate must not be returned to the refrigerator, but should be used immediately or disposed of.
Do not use this medicine if you notice that the solution of the reconstituted product is cloudy or contains particles.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Talate contains
Powder

• The active substances are human coagulation factor VIII and human von Willebrand factor. Each vial contains nominally 1000 IU of human coagulation factor VIII and 750 IU of von Willebrand factor derived from human plasma. After reconstitution with the solvent supplied, the product contains approximately 100 IU/ml of human coagulation factor VIII derived from plasma and 75 IU/ml of von Willebrand factor derived from plasma.
• The other components are human albumin, glycine, sodium chloride, sodium citrate, lysine hydrochloride and calcium chloride.

Solvent

• Sterile water for injections

Description of the appearance of Talate and contents of the pack
Powder and solvent for solution for injection.
White or pale yellow powder or friable solid.
The powder and solvent are supplied in single-dose glass vials, EP (powder: hydrolytic type II; solvent: hydrolytic type I) closed with butyl rubber stoppers, EP.
Each pack contains:
1 vial of Talate 1000 IU / 750 UI
1 vial of sterile water for injections (10 ml)
1 transfer/filtration set
1 single-use syringe (10 ml)
1 single-use needle
1 butterfly infusion set.
Pack: 1 x 1000 IU / 750 IU
Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
Baxalta Innovations GmbH, Industriestrasse 67,
A – 1221 Vienna
Manufacturer
Takeda Manufacturing Austria AG
Industriestrasse 67
1221 Vienna
Austria
This medicinal product is authorized in the Member States of the European Economic Area under the following names:
Austria, Croatia, Cyprus, Estonia, Germany, Latvia, Lithuania, Malta, Poland, Portugal, Romania, Slovak Republic, Slovenia: Immunate
Czech Republic: Immunate Stim Plus
Hungary: Immunate S/D
Italy: Talate
<--------------------------------------------------------------------------------------
--------------------------------------->
Other sources of information
The following information is 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 site and extent of bleeding, and the clinical condition of the patient.
The number of factor VIII units administered is expressed in International Units (IU), which correlate with the current WHO standard for factor VIII-containing products. Factor VIII activity in plasma is expressed as a percentage (relative to normal human plasma) or in International Units (relative to an international standard for factor VIII in plasma).
One International Unit (IU) of factor VIII activity is equivalent to the amount of factor VIII contained in 1 ml of normal human plasma.
The calculation of the required factor VIII dose is based on the empirical observation that 1 International Unit (IU) of factor VIII per kg of body weight raises plasma factor VIII activity by approximately 2% of normal activity.
The required dose can be calculated using the following formula:
Required units = body weight (kg) x desired increase in factor VIII (%) x 0.5
The amount to be administered and the frequency of administration should always be guided by clinical efficacy in the individual case.
Bleeding episodes and surgical procedures
In the case of the following bleeding events, factor VIII activity should not fall below the indicated plasma activity level (in % of normal or IU/dl) during the corresponding period.
The following table may be used to guide dosing during bleeding episodes and surgical procedures:

In certain circumstances (e.g. presence of a low-titer inhibitor), doses higher than those calculated using the formula may be required.

Long-term prophylaxis
For long-term prophylaxis against bleeding in patients with severe haemophilia A, the usual doses are 20 to 40 IU of factor VIII per kg body weight administered at intervals of 2–3 days. In some cases, particularly in younger patients, shorter dosing intervals or higher doses may be necessary.

Dosing in von Willebrand disease
Replacement therapy with Talate for the control of bleeding follows the guidelines provided for haemophilia A.
Since Talate contains a relatively high amount of factor VIII in relation to vWF, the treating physician must be aware that continuous treatment may lead to excessive increases in factor VIII:C, which could increase the risk of thrombosis.

Paediatric population
This product should be used with caution in children under 6 years of age, who have limited exposure to factor VIII-containing products, as available data in this patient group are limited.
Dosing in haemophilia A in children and adolescents under 18 years of age is based on body weight and therefore generally follows the same guidelines as in adults. The dose amount and frequency must always be adjusted according to the clinical efficacy in the individual case. In some cases, particularly in younger patients, shorter dosing intervals or higher doses may be necessary.