Wilfactin
Italy
Table of Contents
PACKAGE LEAFLET: INFORMATION FOR THE USER
WILFACTIN 500 IU
powder and solvent for injectable solution
WILFACTIN 1000 IU
powder and solvent for injectable solution
WILFACTIN 2000 IU
powder and solvent for injectable solution
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, pharmacist or nurse.
- 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, pharmacist or nurse. See section 4.
Contents of this leaflet:
- What WILFACTIN is and what it is used for
- What you need to know before using WILFACTIN
- How to use WILFACTIN
- Possible side effects
- How to store WILFACTIN
- Contents of the pack and other information
1. What WILFACTIN is and what it is used for
WILFACTIN is made from human plasma (the liquid part of blood) and contains the active substance called von Willebrand factor (VWF).
VWF is involved in blood clotting. A deficiency of this factor, as occurs in von Willebrand disease, means that blood does not clot as quickly as it should, resulting in an increased tendency to bleed. Restoring VWF levels with WILFACTIN temporarily normalizes blood clotting mechanisms.
WILFACTIN is indicated for the prevention and treatment of surgical or other bleeding in patients with von Willebrand disease when treatment with desmopressin (DDAVP) alone is ineffective or contraindicated.
WILFACTIN can be used in all age groups.
WILFACTIN must not be used in the treatment of haemophilia A.
2. What you should know before using WILFACTIN
Do not take WILFACTIN:
- If you are allergic to human von Willebrand factor or to any of the other excipients in this medicine (listed in section 6)
- If you have haemophilia A
Warnings and precautions:
Treatment with WILFACTIN must always be supervised by a physician experienced in the
treatment of bleeding disorders.
If you experience severe bleeding and blood tests show that your factor VIII level in the blood is low,
you will be given a preparation containing VWF in combination with a factor VIII preparation within
the first twelve hours.
Allergic reactions
As with any intravenous medicinal product derived from human blood or plasma and containing
proteins, hypersensitivity reactions in the form of allergy may occur.
During the infusion, you will be monitored for the appearance of any early symptoms of
hypersensitivity. These include skin rash (urticaria or generalized urticaria), chest tightness, wheezing,
drop in blood pressure (hypotension), and severe allergic reactions (anaphylaxis). Your doctor will
inform you about the early signs of an allergic reaction.
If signs or symptoms of hypersensitivity occur, treatment must be stopped immediately and you must
seek immediate medical assistance.
Viral safety
When medicines are prepared from human blood or plasma, certain measures are taken to prevent the
transmission of infections to patients. These include:
- careful selection of blood and plasma donors to ensure that those at risk of infection are excluded,
- testing of each donation and plasma pool for signs of viruses/infections,
- inclusion during the processing of blood or plasma of steps that can inactivate or remove viruses.
Despite these measures, when medicines prepared from human blood or plasma are administered, the
possibility of transmitting an infection cannot be completely ruled out. This also applies to unknown
or emerging viruses or other types of infections.
The measures taken are considered effective against enveloped viruses such as the human
immunodeficiency virus (HIV/AIDS), hepatitis B virus, and hepatitis C virus.
The measures taken may have limited effectiveness against non-enveloped viruses such as hepatitis A
virus and parvovirus B19. Infection with parvovirus B19 may be serious for pregnant women (as there
is a risk of infection to the unborn child) and for individuals with a weakened immune system or those
with certain types of anaemia (e.g. sickle cell disease or haemolytic anaemia).
Vaccinations
Your doctor may recommend considering vaccination against hepatitis A and B if you receive human
plasma-derived von Willebrand factor regularly or repeatedly.
Lot number registration
It is strongly recommended that the name and lot number of the product be recorded each time a dose
of WILFACTIN is administered, so as to maintain a record of all lots used.
Thrombosis risk
Blood vessels may also become blocked by blood clots (thrombosis).
This risk particularly exists if your medical or laboratory history indicates the presence of certain risk
factors.
In such cases, you will be closely monitored for early signs of thrombosis, and preventive treatment
(prophylaxis) against venous blockage due to blood clots should be initiated.
When using a von Willebrand factor product containing factor VIII, the physician must be aware that
continued treatment may cause an excessive increase in FVIII. If you receive this VWF-containing
product with FVIII, your doctor must regularly monitor your plasma FVIII levels. This ensures that the
plasma FVIII level is not excessively high, as this could otherwise increase the risk of thrombotic
events.
Limited efficacy
In patients with von Willebrand disease, especially in patients with type 3, it is possible that proteins
develop which neutralize the effect of VWF. These proteins are called neutralizing antibodies or
inhibitors. If laboratory results show that your VWF levels are not being restored, or if bleeding does
not stop despite an adequate dose of WILFACTIN, your doctor will check whether VWF inhibitors
have developed in your body. If these inhibitors are present in high concentrations, treatment with VWF
may not be effective and alternative treatment options must be considered. The new treatment will be
provided by a physician experienced in the management of bleeding disorders.
Other medicines and WILFACTIN
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other
medicines.
Pregnancy and breastfeeding
WILFACTIN should be used during pregnancy and breastfeeding only if clearly indicated.
The safety of WILFACTIN during pregnancy and breastfeeding has not been evaluated in clinical
studies.
Animal studies are insufficient to establish safety with respect to fertility, pregnancy, and fetal
development during pregnancy and after birth.
If you are pregnant or breastfeeding, or if you think you may be pregnant or are planning a pregnancy,
consult your doctor or pharmacist before taking this medicine.
Driving and use of machines
No effects on the ability to drive vehicles or use machinery have been observed.
WILFACTIN contains sodium
A 5 mL vial (500 IU) of WILFACTIN contains 0.15 mmol (3.4 mg) of sodium.
This corresponds to 0.17% of the maximum daily dietary intake recommended for an adult.
A 10 mL vial (1,000 IU) of WILFACTIN contains 0.3 mmol (6.9 mg) of sodium.
This corresponds to 0.35% of the maximum daily dietary intake recommended for an adult.
A 20 mL vial (2,000 IU) of WILFACTIN contains 0.6 mmol (13.8 mg) of sodium.
This corresponds to 0.69% of the maximum daily dietary intake recommended for an adult.
3. How to use WILFACTIN
Your treatment must be initiated and monitored by a physician experienced in the management of bleeding disorders. If your doctor considers that administration can be performed at home, appropriate instructions will be provided.
Dose
Always take this medicine exactly as prescribed by your doctor. Consult your doctor if you are unsure.
WILFACTIN should preferably be administered by a doctor or nurse. However, if WILFACTIN has been prescribed for you to use at home, your doctor will ensure that you are shown how to inject it and how much to use. Follow the instructions given by your doctor and seek help if you have any difficulties handling the syringe; the syringe must always be used by someone trained in its use.
Your doctor will calculate the appropriate dose of WILFACTIN (in international units or IU).
The dose depends on:
- body weight,
- site of bleeding,
- severity of bleeding,
- your clinical condition,
- required surgical procedure,
- von Willebrand factor (VWF) activity levels in the blood after surgery,
- severity of the disease.
This dose ranges between 40 and 80 IU/kg.
Your doctor will prescribe blood tests during treatment to monitor:
- factor VIII levels (FVIII:C),
- von Willebrand factor levels (VWF:RCo),
- presence of inhibitors,
- early signs of clot formation, if you are at risk of such complications.
Based on the results of these tests, your doctor will decide whether dose adjustments or changes in injection frequency are needed.
In some cases, a factor VIII-containing preparation (another clotting protein) may also be required in addition to WILFACTIN to treat or prevent bleeding more rapidly (in emergency situations or acute bleeding episodes).
WILFACTIN may also be administered as long-term prophylaxis; in this case, the dose level is individually determined. WILFACTIN doses of 40 to 60 IU/kg administered two to three times per week reduce the number of bleeding episodes.
Use in children and adolescents
Dosing in children and adolescents is based on body weight. In some cases, especially in younger patients (under 6 years of age), higher doses may be required (up to 100 IU/kg).
Talk to your doctor if you think that the effect of WILFACTIN is too strong or too weak.
Method of administration
Detailed instructions for reconstitution and administration of the medicine are provided at the end of this leaflet.
If you use more WILFACTIN than you should
Symptoms of overdose with WILFACTIN have not been reported.
However, the risk of thrombosis cannot be excluded in the case of severe overdose.
If you forget to use WILFACTIN
If you forget to use WILFACTIN, speak with your doctor.
Do not take a double dose to make up for a missed dose.
If you have any further questions about the use of this medicine, please consult your doctor, pharmacist, or nurse.
4. Possible side effects
Like all medicines, WILFACTIN can cause side effects, although not everyone experiences them.
Contact your doctor immediately if:
- you notice symptoms of hypersensitivity or allergic reactions (observed "uncommonly": may affect up to 1 in 100 people). In some cases, these reactions may progress to a severe allergic reaction (anaphylaxis), including anaphylactic shock (frequency not known).
Warning signs of allergic reactions include:
- Difficulty breathing and swallowing
- Wheezing
- Chest tightness
- Increased heart rate
- Decrease or drop in blood pressure
- Fainting
- Extreme fatigue
- Restlessness, nervousness
- Headache
- Chills, feeling cold
- Flushing, hot flushes
- Swelling in different parts of the body
- Rash, generalized hives
- Burning or sharp pain at the infusion site
- Tingling
- Vomiting
- Nausea
If any of these effects occur, stop treatment immediately and inform your doctor so that appropriate treatment can be started depending on the type and severity of the reaction.
- You notice that the medicine no longer works properly (bleeding is not controlled). This may be due to inhibition of von Willebrand factor (VWF) (frequency not known).
In patients with von Willebrand disease, particularly those with type 3 disease, proteins may develop that neutralize the effect of VWF. These proteins are called neutralizing antibodies or inhibitors. Patients treated with VWF should be closely monitored by their doctors for the development of inhibitors through appropriate clinical observations and laboratory tests. If such inhibitors develop, this condition may present as an inadequate clinical response or may occur simultaneously with severe allergic reactions.
- You notice symptoms of impaired perfusion in the extremities (e.g. cold, pale extremities) or vital organs (e.g. severe chest pain). This may be due to blood clot formation in blood vessels (frequency not known).
There is a risk of blood clot formation (thrombosis), particularly in patients with known risk factors. After correction of von Willebrand factor deficiency, you should be monitored for early signs of thrombosis or disseminated intravascular coagulation and receive treatment to prevent thrombosis in situations associated with an increased risk of thrombosis (after surgery, during bed rest, or in case of deficiency of a coagulation inhibitor or a fibrinolytic enzyme).
If you receive VWF-containing preparations that also contain FVIII, the risk of thrombosis may be increased due to persistently elevated plasma levels of FVIII.
The following side effects have been observed commonly (may affect up to 1 in 10 people):
- Reactions at the infusion site
The following side effects have been observed uncommonly (may affect up to 1 in 100 people):
- Dizziness
- Paresthesia, hypoesthesia
- Hot flushes
- Itching
- Sensation of pressure
- Chills, feeling cold
Other side effect observed with a frequency not known
- Fever
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects via:
http://www.aifa.gov.it/content/segnalazioni-reazioni-avverse
By reporting side effects, you can help provide more information on the safety of this medicine.
5. How to store WILFACTIN
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the vial label and on the outer carton.
Do not store above 25°C. Store in the original packaging to protect from light.
Do not freeze.
For sterility reasons, the product should be used immediately after reconstitution. However, in-use stability has been demonstrated for 24 hours at +25°C.
Do not use this medicine if you notice that the solution is cloudy or contains particles.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist or nurse how to dispose of medicines no longer required. This will help protect the environment.
6. Package contents and other information
What WILFACTIN contains
- The active substance is: Human von Willebrand factor (500 IU, 1,000 or 2,000 IU), expressed in International Units (IU) of ristocetin cofactor activity (VWF:RCo).
After reconstitution with 5 mL (500 IU), 10 mL (1,000 IU), or 20 mL (2,000 IU) of water for injections, a vial contains approximately 100 IU/mL of human von Willebrand factor.
Prior to the addition of albumin, the specific activity is greater than or equal to 60 IU of VWF:RCo/mg of total protein.
- Excipients:
Powder: human albumin, arginine hydrochloride, glycine, sodium citrate, calcium chloride dihydrate
Solvent: water for injections
Description of the appearance of WILFACTIN and contents of the pack
WILFACTIN is supplied as a white or pale yellow powder or friable solid and solvent for injectable solution, clear or colourless, to be reconstituted using a transfer device.
WILFACTIN is available in pack sizes of 500 IU/5 mL, 1,000 IU/10 mL and 2,000 IU/20 mL.
The reconstituted solution should be clear or slightly opalescent, colourless or slightly yellow.
Marketing Authorisation Holder and Manufacturer
LABORATOIRE FRANÇAIS DU FRACTIONNEMENT ET DES BIOTECHNOLOGIES
Tour W – 102 Terrasse Boieldieu, 19th Floor – 92800 Puteaux – France
Manufacturers:
LFB-BIOMEDICAMENTS
3, Avenue des Tropiques - BP 305 - 91958 Les Ulis, Courtaboeuf Cedex - France
LFB-BIOMEDICAMENTS
59, Rue Trévise – BP 2006 - 59011 Lille Cedex - France
This medicinal product is authorised in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:
Finland: Wilfactin
France: Wilfactin
Greece: Wilfactin
Italy: Wilfactin
Luxembourg: Wilfactin
Netherlands: Wilfactin
This patient information leaflet was last approved on:
INSTRUCTIONS FOR USE
Dosage
Generally, the administration of 1 IU/kg of von Willebrand factor increases circulating
VWF:RCo levels by approximately 0.02 IU/mL (2%).
VWF:RCo levels above 0.6 IU/mL (60%) and FVIII:C levels above 0.4 IU/mL (40%) should be achieved.
Haemostasis cannot be ensured until the coagulant activity of factor VIII (FVIII:C) reaches 0.4 IU/mL (40%).
Injection of von Willebrand factor alone does not induce maximal FVIII:C increase for at least 6–12 hours. The injection cannot immediately correct FVIII:C levels. Therefore, if baseline FVIII:C levels in the patient are below this critical threshold, in all situations requiring rapid correction of haemostasis—such as treatment of bleeding, severe trauma, or emergency surgery—factor VIII must be administered together with the first dose of von Willebrand factor to achieve plasma FVIII:C levels sufficient to ensure haemostasis.
However, when an immediate increase in FVIII:C is not required, such as in the case of scheduled surgery, or when baseline factor VIII:C levels are already sufficient to ensure haemostasis, the physician may decide to avoid co-administration of factor VIII with the first dose of von Willebrand factor.
- Initiation of treatment
The initial dose of Wilfactin is 40 to 80 IU/kg for the treatment of bleeding or trauma, administered concomitantly with the required amount of factor VIII-containing product, calculated according to the patient's baseline plasma FVIII:C levels, in order to achieve appropriate plasma FVIII:C levels immediately before the procedure or as soon as possible after the onset of a bleeding episode or severe trauma. In the case of surgery, the first injection should be administered one hour before the procedure.
An initial dose of 80 IU/kg of WILFACTIN may be required, particularly in patients with type 3 von Willebrand disease, in whom maintaining adequate levels may require higher doses compared to other types of VWD.
In the case of elective surgery, the first injection of WILFACTIN should be administered between 12 and 24 hours before the procedure, and the second injection should be given before surgery. In these cases, co-administration of a factor VIII-containing product is not necessary, as endogenous FVIII:C usually reaches the critical level of 0.4 IU/mL (40%) before surgery. However, this must be confirmed on a case-by-case basis.
- Subsequent injections:
If necessary, treatment should be continued for one or more days by administering WILFACTIN alone at a dose of 40 to 80 IU/kg daily, given in one or two injections. The dose and frequency of injections should be adjusted according to the type of surgical procedure, the patient's clinical and biological status (VWF:RCo and FVIII:C), and the type and severity of the bleeding episode.
- Long-term prophylaxis:
WILFACTIN may be used for long-term prophylaxis, with dosages individually adjusted.
Doses of WILFACTIN ranging from 40 to 60 IU/kg administered two or three times per week reduce the number of bleeding episodes.
- Outpatient treatment:
Treatment may be initiated at home following physician approval, especially in cases of mild to moderate bleeding or during long-term prophylaxis to prevent bleeding.
Paediatric population
For each indication, dosing is based on body weight. The dose and duration of treatment must be adjusted according to the patient's clinical condition and plasma levels of VWF:RCo and FVIII:C.
- Initiation of treatment:
- For children under 6 years of age, the initial dose may be guided by the patient's incremental recovery (IR). If IR data are not available, an initial dose of 60 to 100 IU/kg may be required to increase the patient's VWF:RCo levels to 100 IU/dL.
- For children over 6 years of age and adolescents, the dosage is the same as for adult patients.
- Subsequent injections: For children and adolescents, subsequent doses should be individualized based on clinical condition and VWF:RCo levels, and adjusted according to clinical response.
For elective surgery:
- In children under 6 years of age, after an initial dose administered 12 to 24 hours before the procedure, the dose may be repeated 30 minutes before the procedure.
- For children over 6 years of age and adolescents, the dosage is the same as for adult patients.
- Prophylaxis: For children and adolescents, the dose and frequency of re-administration should be individualized based on the patient's incremental recovery and VWF:RCo levels, and adjusted according to clinical response.
Method and route of administration
Administration by intravenous route
Reconstitution
Current guidelines for aseptic procedures must be followed. The transfer system is used only for reconstituting the medicinal product, as described below. It is not intended for administration of the medicinal product to the patient.
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The powder normally dissolves instantaneously and must dissolve within less than 50 minutes.
The solution should be clear or slightly opalescent, colorless or slightly yellow. Do not use
solutions that appear cloudy or contain deposits. Do not mix with other medicinal products.
Do not dilute the reconstituted product.
Administration
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Storage after reconstitution
For sterility reasons, the product must be used immediately after reconstitution.
However, chemical-physical in-use stability has been demonstrated for 24 hours at 25°C.
Any unused product or waste material should be disposed of in accordance with local requirements.