Haemate p 1000 units fviii/2400 units vwf
Poland
Table of Contents
PACKAGE LEAFLET - INFORMATION FOR THE USER
Haemate P 250 i.u. FVIII/600 i.u. VWF
Haemate P 500 i.u. FVIII/1200 i.u. VWF
Haemate P 1000 i.u. FVIII/2400 i.u. VWF
Powder and solvent for solution for injection or infusion
Human blood coagulation factor VIII (FVIII) / Human von Willebrand factor (VWF)
Please read carefully the entire leaflet before using this medicine, as it contains important information for the patient.
- Keep this leaflet, as you may need to read it again.
- If you have any questions, please consult your doctor or pharmacist.
- This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
- If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.
Table of contents:
- What Haemate P is and what it is used for
- Important information before using Haemate P
- How to use Haemate P
- Possible side effects
- How to store Haemate P
- Contents of the pack and other information
1. WHAT HAEMATE P IS AND WHAT IT IS USED FOR
What Haemate P is
Haemate P is supplied as a powder and solvent. The prepared solution is administered intravenously by injection or infusion.
Haemate P is manufactured from human plasma (the liquid component of blood) and contains human von Willebrand factor and human blood coagulation factor VIII.
What Haemate P is used for
Haemate P contains both human blood coagulation factor VIII (FVIII) and von Willebrand factor (VWF). It is very important to know which factor the patient requires more. If the patient has haemophilia A, the doctor will prescribe Haemate P specifying the number of units of factor VIII. If the patient has von Willebrand disease, the doctor will prescribe Haemate P specifying the number of units of factor VWF.
Von Willebrand disease (VWD)
Haemate P is used for the prevention and treatment of bleeding episodes, including bleeding during surgical procedures, caused by a deficiency of von Willebrand factor, when therapy with desmopressin (DDAVP) alone is ineffective or contraindicated.
Haemophilia A (congenital factor VIII deficiency)
Haemate P is used for the prevention or control of bleeding episodes caused by a lack of factor VIII in the blood.
It may also be used in the treatment of acquired factor VIII deficiency and in patients who have developed inhibitors (antibodies) against factor VIII.
2. IMPORTANT INFORMATION BEFORE USING HAEMATE P
The following sections contain information that should be considered before using Haemate P.
When NOT to use Haemate P:
- In case of hypersensitivity (allergy) to human von Willebrand factor or human factor VIII, or to any of the other components of this medicine (listed in section 6). If you are allergic to any medicine or food, inform your doctor.
Warnings and precautions
Traceability
It is especially recommended to record the name and batch number of Haemate P each time it is administered to a patient, in order to maintain a registry of batches used.
Before starting treatment with Haemate P, discuss the following with your doctor or pharmacist:
- In case of allergic or anaphylactic-type reactions (serious allergic reactions causing severe breathing difficulties or dizziness). As with any protein injection, allergic hypersensitivity reactions may occur. Your doctor should inform you about early signs of hypersensitivity reactions such as hives, generalized skin rash, chest tightness, wheezing, drop in blood pressure, and anaphylaxis (a serious allergic reaction causing severe breathing problems or dizziness). If such symptoms occur, stop administering the medicine immediately and contact your doctor.
- Formation of inhibitors (antibodies) is a known complication that may occur during treatment with any factor VIII-containing product. These inhibitors, especially at high titres, may interfere with effective treatment, and the patient will be closely monitored for their development. If bleeding is not adequately controlled with Haemate P, inform your doctor immediately.
- If you have existing heart disease or are at risk of developing it, inform your doctor or pharmacist.
- If a central venous access device (CVAD) is required for administration of Haemate P, your doctor should consider the risk of complications associated with CVAD, including local infections, bloodstream infections (bacteraemia), and thrombosis (blood clots) at the catheter site.
Von Willebrand disease
- In patients with known risk of thrombosis (blood clots), including cases of thromboembolism such as pulmonary embolism, particularly in patients with clinical or morphological risk factors (e.g. perioperative periods without antithrombotic prophylaxis, prolonged immobilization, obesity, overdose, malignancy). In such cases, patients must be monitored for early signs of thrombosis. Prophylaxis against venous thromboembolism should be initiated according to current guidelines.
Your doctor will carefully weigh the benefits of Haemate P treatment against the risk of these complications.
Viral safety
For medicines prepared from human blood or plasma, precautions are taken to prevent transmission of infections. These include:
- Careful selection of blood and plasma donors to exclude those at risk of transmitting infections.
- Testing of each donation and plasma pools for the presence of viruses/infections.
- Inclusion in the manufacturing process of procedures capable of inactivating or removing viruses.
Despite these measures, it cannot be completely excluded that treatment with medicines derived from human blood or plasma may result in transmission of infection, including currently unknown or newly emerging viruses and other infectious agents.
The procedures used are considered effective against enveloped viruses such as human immunodeficiency virus (HIV, the virus causing AIDS), hepatitis B virus, and hepatitis C virus (liver inflammation), as well as against the non-enveloped hepatitis A virus (liver inflammation).
For non-enveloped viruses such as parvovirus B19, the effectiveness of the procedures may be limited.
Parvovirus B19 infection may be dangerous:
- For pregnant women (risk of infection to the unborn child), and
- For individuals with impaired immune systems or increased red blood cell production due to certain types of anaemia (e.g. sickle cell anaemia or haemolytic anaemia).
With regular/repeated administration of products derived from human plasma containing von Willebrand factor and factor VIII, your doctor may recommend considering vaccination against hepatitis A and B.
Haemate P and other medicines
Inform your doctor or pharmacist about all medicines you are currently taking, have recently taken, or plan to take, including over-the-counter medicines.
- Haemate P must not be mixed with other medicines, solvents, or diluents.
Pregnancy, breastfeeding and fertility
- If you are pregnant, breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medicine.
- Since haemophilia A is rare in women, data on the use of factor VIII during pregnancy and breastfeeding are not available.
- In von Willebrand disease, women are more affected than men due to the additional risk of bleeding associated with menstruation, pregnancy, childbirth, and gynaecological complications. Based on post-marketing experience, von Willebrand factor (VWF) replacement therapy is recommended for the prevention and treatment of acute bleeding episodes. Clinical studies on VWF replacement therapy in pregnant and lactating women are not available.
- During pregnancy and breastfeeding, Haemate P should only be administered if there is a clear medical need.
Driving and operating machinery
There are no reports indicating that Haemate P impairs the ability to drive or operate machinery.
Haemate P contains sodium
Haemate 250 i.u. FVIII/600 i.u. VWF contains less than 1 mmol of sodium (23 mg) per vial and may therefore be considered essentially "sodium-free".
Haemate 500 i.u. FVIII/1200 i.u. VWF contains 26 mg of sodium (main component of table salt) per vial, equivalent to 1.3% of the recommended maximum daily intake of sodium for an adult.
Haemate 1000 i.u. FVIII/2400 i.u. VWF contains 52.5 mg of sodium (main component of table salt) per vial, equivalent to 2.6% of the recommended maximum daily intake of sodium for an adult.
3. HOW TO USE HAEMATE P
Treatment should be initiated and managed under the supervision of a physician experienced in the treatment of this type of disorder.
Dosage
The required amount of von Willebrand factor and factor VIII, as well as the duration of treatment, depend on several factors such as body weight, severity of the disorder, location and intensity of bleeding, or the need to prevent bleeding during surgery or a procedure (see section “Information intended exclusively for medical professionals”). If Haemate P has been prescribed for home use, the patient will be trained by a physician in the method of administering the injection and dosage.
Follow the instructions provided by your physician or nurse at the hemophilia treatment center.
Use of a higher than recommended dose of Haemate P
Symptoms of overdose with VWF or FVIII are currently unknown. However, the risk of blood clot formation (thrombosis) cannot be excluded when exceptionally high doses are administered, particularly with VWF products containing high levels of FVIII.
Reconstitution and method of administration
General information
- The powder must be mixed (reconstituted) with the solvent (liquid component) and withdrawn from the vial under aseptic conditions.
- The solution should be clear or slightly opalescent. After filtration/withdrawal (see below), the reconstituted product should be visually inspected for particles and discoloration prior to administration. Even when reconstitution procedures are strictly followed, the presence of a few small fibres or particles may occasionally occur. The filter included in the Mix2Vial device completely removes these particles. Filtration does not affect dose calculations.
- Do not use solutions that are visibly cloudy or contain fibres or particles after filtration.
- Any unused portions of the product or waste material after administration must be disposed of in accordance with national regulations and physician recommendations.
Reconstitution
Without opening either vial, warm the Haemate P powder and solvent to room temperature by leaving the vials at room temperature for about one hour or by holding them in your hands for several minutes. DO NOT expose vials to direct heat sources. Vials must not be heated above body temperature (37°C).
Carefully remove the protective caps from both the solvent vial and the Haemate P powder vial. Clean the exposed rubber stoppers of both vials with an alcohol swab and allow them to dry. The solvent may then be transferred to the vial containing the powder using the provided Mix2Vial transfer device. Follow the instructions below.
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Collection and administration
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Instructions for Use
For Haemate P injection, plastic disposable syringes are recommended, as solutions of this type tend to adhere to the surfaces of all glass syringes.
The solution should be administered slowly intravenously, at a rate not exceeding 4 ml per minute. Care must be taken to prevent blood from entering the syringe filled with the product. Once the product has been drawn into the syringe, it should be used immediately.
When a larger amount of factor is required, administration may also be performed via infusion. For this purpose, transfer the reconstituted product into an approved infusion system. The infusion should be carried out according to the physician's instructions. Close attention should be paid to the occurrence of any immediate reactions. If any reaction possibly related to the administration of Haemate P occurs, the injection/infusion must be stopped (see also section 2).
If there are any further doubts regarding the use of this medicinal product, consult a physician or pharmacist.
4. POSSIBLE ADVERSE REACTIONS
Like all medicines, Haemate P can cause adverse reactions, although not everyone experiences them.
The following adverse reactions have occurred very rarely (in less than 1 in 10,000 patients):
- Acute allergic reaction (such as angioedema, burning and stinging sensation at the infusion site, chills, facial flushing, generalized urticaria, headache, skin allergic reaction (urticaria), hypotension, lethargy, nausea, restlessness, tachycardia, chest tightness, tingling, vomiting, wheezing), which occurred very rarely and in some cases may lead to acute anaphylaxis (including shock).
- Increase in body temperature (fever).
Von Willebrand disease
- Very rarely, there is a risk of thrombotic / thromboembolic events, including pulmonary embolism (risk of formation and migration of blood clots into the vascular system (veins/arteries) with potential organ involvement).
- In patients receiving VWF-containing products, persistently elevated plasma levels of FVIII:C may increase the risk of thrombosis (see also section 2).
- In patients with von Willebrand disease, inhibitors (neutralizing antibodies) against VWF may very rarely develop. If such inhibitors occur, this will manifest as an insufficient clinical response leading to prolonged bleeding. This is particularly observed in patients suffering from a specific form of von Willebrand disease, so-called type 3. These antibodies may precipitate and may appear in association with anaphylactic reactions. Therefore, patients who have experienced an anaphylactic reaction should be tested for the presence of inhibitors. In such cases, contact with a specialized hemophilia treatment center is recommended.
Hemophilia A
- In previously untreated children receiving factor VIII-containing medicines, blocking 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 cease to work properly and prolonged bleeding may occur. If this happens, immediate contact with a physician is required.
Adverse reactions in children and adolescents
The frequency, type, and severity of adverse reactions in children are comparable to those in adults.
Reporting of adverse reactions
If any adverse symptoms occur, including any adverse symptoms not listed in this leaflet, inform your doctor, pharmacist, or nurse. 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 181C
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 this medicinal product.
5. HOW TO STORE HAEMATE P
- Keep the medicine out of the sight and reach of children.
- Do not use this medicine after the expiry date stated on the label and carton (after EXP abbreviation).
- Do not store above 25 o C.
- Do not freeze.
- Store the vials in the outer packaging to protect from light.
- Haemate P does not contain a preservative, therefore the reconstituted solution should be used immediately.
- If the reconstituted solution is not administered immediately, it should be used within 3 hours.
- After drawing the product into a syringe, it should be used immediately.
- The batch number is stated on the label and carton after the abbreviation (Lot).
6. CONTENTS OF THE PACKAGE AND OTHER INFORMATION
What Haemate P contains
The active substances are:
Human von Willebrand factor and human coagulation factor VIII
Other components (excipients) are:
Human albumin, glycine, sodium chloride, sodium citrate, sodium hydroxide or hydrochloric acid (in small
amounts for pH adjustment)
Solvent: Water for injections
What Haemate P looks like and contents of the pack
Haemate P is supplied as a white or light yellow powder or as a brittle, solid mass, together with water for injections as solvent. The resulting solution should be clear or slightly opalescent (i.e. may shimmer when held to light), but must not contain any visible particles.
Available pack sizes
Pack containing 250 IU FVIII / 600 IU VWF:
1 vial of powder
1 vial containing 5 ml of water for injections
1 transfer system 20/20 with filter
Administration set (inner packaging)
1 single-use syringe with a capacity of 5 ml
1 venipuncture set
2 alcohol-impregnated swabs
1 non-sterile plaster
Pack containing 500 IU FVIII / 1200 IU VWF:
1 vial of powder
1 vial containing 10 ml of water for injections
1 transfer system 20/20 with filter
Administration set (inner packaging)
1 single-use syringe with a capacity of 10 ml
1 venipuncture set
2 alcohol-impregnated swabs
1 non-sterile plaster
Pack containing 1000 IU FVIII / 2400 IU VWF:
1 vial of powder
1 vial containing 15 ml of water for injections
1 transfer system 20/20 with filter
Administration set (inner packaging)
1 single-use syringe with a capacity of 20 ml
1 venipuncture set
2 alcohol-impregnated swabs
1 non-sterile plaster
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
CSL Behring GmbH
Emil-von-Behring-Strasse 76
35041 Marburg
Germany
Information intended exclusively for medical professionals:
Dosage
von Willebrand disease:
It is important to calculate the dose using the stated number of international units (IU) of VWF:RCo.
1 IU/kg of VWF:RCo typically increases circulating VWF:RCo levels by 0.02 IU/mL (2%).
The target should be to achieve VWF:RCo levels > 0.6 IU/mL (60%) and FVIII:C > 0.4 IU/mL (40%).
A dose of 40–80 IU/kg of von Willebrand factor (VWF:RCo) and 20–40 IU FVIII:C/kg body weight is
usually recommended to achieve hemostasis.
An initial dose of 80 IU/kg of von Willebrand factor may be required, especially in patients with type 3 von Willebrand disease, where maintaining adequate levels may require higher doses than in other types of this disease.
Prevention of bleeding during surgical procedures or following severe trauma:
To prevent massive bleeding during or after surgery, the first dose should be administered 1 to 2 hours before the procedure.
The appropriate dose should be administered every 12–24 hours. The dose and duration of therapy depend on the patient's clinical condition, type and severity of bleeding, and levels of VWF:RCo and FVIII:C.
When using von Willebrand factor preparations containing FVIII, the treating physician should be aware that prolonged therapy may lead to excessive increase in FVIII:C levels. After 24–48 hours of treatment, consideration should be given to reducing the dose and/or extending the interval between doses to avoid uncontrolled elevation of FVIII:C levels.
Children and adolescents
Dosing in children is based on body weight; therefore, the dose is determined on the same basis as in adults. The frequency of administration should always be individually adjusted according to clinical efficacy.
Hemophilia A:
Monitoring of treatment
During treatment, appropriate assays of Factor VIII levels should be performed to determine the correct dose and frequency of repeat infusions. Individual patient responses to Factor VIII may vary due to differences in recovery and half-life. Dosing based on body weight may require adjustment in patients who are overweight or underweight. Especially during major surgical procedures, careful monitoring of replacement therapy through coagulation testing (Factor VIII activity levels in plasma) is essential.
Patients should be monitored for the development of Factor VIII inhibitors. See also section 2.
The dosage and duration of replacement therapy depend on the severity of Factor VIII deficiency, location and severity of bleeding, and the patient's clinical condition.
It is important to calculate the dose using the stated number of international units (IU) of FVIII:RCo.
The amount of administered Factor VIII is expressed in international units (IU), referring to the current WHO standard for Factor VIII concentrates. Factor VIII activity in plasma is expressed as a percentage (relative to normal human plasma) or preferably in IU (relative to the International Standard for Factor VIII in plasma).
One IU of Factor VIII activity corresponds to the amount of Factor VIII present in 1 mL of normal human plasma.
On-demand treatment
The calculation of required Factor VIII dosage is based on the empirical observation that 1 IU of Factor VIII per kg of body weight increases plasma Factor VIII activity by approximately 2% (2 IU/dL). The required dose is calculated using the following formula:
Required number of units = body weight [kg] × desired increase in Factor VIII level [% or IU/dL] × 0.5.
The dose and frequency of administration should always be individually adjusted according to clinical efficacy in individual patients.
In the event of the following types of bleeding, Factor VIII activity should not fall below the specified levels (in % or IU/dL) during the corresponding time period.
The table below may be used to determine dosing in cases of bleeding and during surgical procedures:
| Type of bleeding / surgical procedure | Therapeutic level of factor VIII activity in plasma (% or IU/dL) | Dosing frequency (hours) / duration of treatment (days) |
| Spontaneous bleeding | ||
| Minor joint hemorrhage, muscle bleeding, or oral cavity bleeding | 20–40 | Repeat infusion every 12 to 24 hours for at least 1 day until resolution of pain and bleeding or healing |
| Extensive joint hemorrhage; muscle hemorrhage or hematoma | 30–60 | Repeat infusion every 12–24 hours for 3 to 4 days or more until resolution of pain and acute dysfunction |
| Life-threatening hemorrhage | 60–100 | Repeat infusion every 8 to 24 hours until the threat is resolved |
| Surgical procedures | ||
| Minor surgical procedures including tooth extraction | 30–60 | Every 24 hours, for at least 1 day until healing is achieved |
| Major surgical procedures | 80–100 (pre- and postoperatively) | Repeat infusion every 8–24 hours until adequate wound healing is achieved, followed by therapeutic dosing for at least 7 days to maintain factor VIII activity between 30% and 60% (IU/dL) |
Prophylaxis
For long-term prophylactic treatment in patients with severe haemophilia A, a dose of usually 20 to 40 IU of factor VIII per kg body weight is administered every 2 to 3 days.
In some cases, particularly in younger patients, more frequent administration or higher doses may be required.
Children and adolescents
There are no clinical study data available on the dosing of Haemate P in children.
Special warnings and precautions for use
When using VWF preparations, the treating physician should be aware that prolonged therapy may lead to excessive increases in FVIII:C levels. In patients receiving VWF preparations containing FVIII, plasma FVIII:C levels should be monitored to avoid sustained, excessive elevation of FVIII:C, which may increase the risk of thrombotic events; consideration should therefore be given to the use of antithrombotic agents.
Undesirable effects
When very high or frequently repeated doses are required, when inhibitors are present, or during pre- and postoperative care, all patients should be monitored for symptoms of hypervolaemia. Additionally, patients with blood groups A, B, and AB should be monitored for signs of intravascular haemolysis and/or decreasing haematocrit values.