Fanhdi
Poland
Table of Contents
1.3.1. SPC, labelling and package leaflet
PACKAGE LEAFLET: INFORMATION FOR THE USER
FANHDI
1000 IU FVIII + 1200 IU VWF
Powder and solvent for solution for injection and infusion
Human coagulation factor VIII and human von Willebrand factor complex
Please read all of this leaflet carefully before using this medicine, because it contains important information for the patient.
- Keep this leaflet, as you may need to read it again.
- If you have any further questions, ask your doctor or pharmacist.
- This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm them, even if their symptoms are the same.
- If the patient experiences any adverse effects, including any not listed in this leaflet, inform the doctor or pharmacist. See section 4.
Contents of this leaflet:
- What FANHDI is and what it is used for
- Important information before using FANHDI
- How to use FANHDI
- Possible side effects
- How to store FANHDI
- Contents of the pack and other information
1. WHAT FANHDI IS AND WHAT IT IS USED FOR
FANHDI is available as a powder and solvent for solution for injection and infusion in vials containing nominally 1000 IU of human blood coagulation factor VIII (FVIII) and 1200 IU of human von Willebrand factor (VWF).
After reconstitution with the appropriate volume of solvent (water for injection), the product contains 100 IU/mL FVIII and 120 IU/mL VWF.
Pharmacotherapeutic group: Antihemorrhagics, combination of blood coagulation factor VIII and von Willebrand factor.
FANHDI is used for the prevention and treatment of bleeding episodes in patients with haemophilia A (congenital factor VIII deficiency).
1.3.1. SPC, labelling and package leaflet
FANHDI is also indicated for the prevention and treatment of bleeding episodes (including bleeding during surgical procedures) in patients with von Willebrand disease (VWD) when treatment with desmopressin (DDAVP) is ineffective or contraindicated.
The product may be used in the treatment of acquired deficiency of human factor VIII.
2. IMPORTANT INFORMATION BEFORE USING FANHDI
When not to use FANHDI
- Do not use FANHDI if the patient is allergic (hypersensitive) to the human factor VIII and von Willebrand factor complex or to any of the other ingredients of this medicine (listed in section 6).
Consult your doctor if you need advice or additional information.
Warnings and precautions
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In rare cases, anaphylactic reactions (sudden, severe allergic reactions) may occur. Allergic reactions to FANHDI may manifest as rash, generalized urticaria, feeling of chest tightness, dizziness, even in the upright position. If such symptoms occur, discontinue administration of the medicine and inform the doctor immediately.
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To determine the FANHDI dose required to achieve and maintain adequate factor VIII levels, the doctor may order a series of tests.
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If bleeding does not stop despite administration of FANHDI, inform the doctor. This may be due to the development of factor VIII inhibitors, which must be confirmed by laboratory testing. Factor VIII inhibitors are antibodies that neutralize the administered factor VIII, resulting in reduced effectiveness in controlling bleeding.
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If a patient has previously developed factor VIII inhibitors and subsequently switched to another factor VIII-containing product, there is an increased risk of recurrence of this complication.
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In patients with von Willebrand disease and known clinical or laboratory risk factors for thrombosis, there is a risk of thrombotic events. Therefore, appropriate monitoring is necessary to detect early signs of such events, and current recommended treatments for thromboembolic complications should be applied.
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In von Willebrand disease, particularly type 3, neutralizing antibodies (inhibitors) against von Willebrand factor may develop. Von Willebrand factor inhibitors are antibodies present in blood that may block the administered factor. In cases where expected plasma von Willebrand factor activity levels are not achieved or bleeding is not controlled despite appropriate dosing, tests should be performed to detect the presence of von Willebrand factor inhibitors. Treatment with von Willebrand factor may be ineffective in patients with high inhibitor titres.
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If central venous access is required for administration of FANHDI, the doctor should consider the risk of local infection, bacteremia (blood infection by bacteria), and development of venous thrombosis at the catheter insertion site.
During the manufacturing process of medicinal products derived from human blood or plasma, the following measures are implemented to minimize the risk of transmission of infectious agents:
- Careful selection of donors to exclude carriers of infectious agents,
- Testing of each donation and plasma pool for the presence of viruses,
- Application of virus inactivation/removal procedures during manufacturing.
Despite these measures, the possibility of transmitting infectious agents with products derived from human blood or plasma cannot be completely excluded, including unknown or newly emerging viruses and other pathogens.
The methods used are considered effective against enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and non-enveloped hepatitis A virus. However, the effectiveness of these methods against non-enveloped viruses such as parvovirus B19 may be limited.
Parvovirus B19 infection may be particularly dangerous for pregnant women (risk of fetal infection) and for individuals with compromised immunity or certain types of anemia (e.g., sickle cell anemia or hemolytic anemia).
For patients receiving regular repeated doses of plasma-derived products containing factor VIII, the treating physician may recommend appropriate vaccinations (against hepatitis A and B viruses).
It is strongly recommended that, with each administration of FANHDI, the patient's name and the product batch number be recorded, to allow traceability between the patient and the medicine batch.
See also section 4.
Children and adolescents
The above warnings and precautions apply to both adults and children.
1.3.1. SPC, labelling and package leaflet
FANHDI and other medicines
Inform the doctor about all medicines currently taken, recently taken, or planned for use.
Interactions between the human factor VIII and von Willebrand factor complex and other medicinal products are not known.
Pregnancy and breastfeeding
Due to the rarity of haemophilia A in women, there is limited experience regarding the use of FVIII/VWF complex during pregnancy and breastfeeding.
Consult your doctor or pharmacist before using any medicine.
Driving and using machines
FANHDI has no influence on the ability to drive or operate machinery.
3. HOW TO USE FANHDI
The medicine must be administered intravenously. The infusion rate must not exceed 10 ml/min.
You should follow the instructions provided by your doctor or healthcare professional at the haemophilia treatment centre. If you have any doubts, consult your doctor or pharmacist.
The dose of FANHDI to be administered depends on several factors such as body weight, clinical condition, and the type and extent of bleeding. To achieve the appropriate blood levels of factor VIII and von Willebrand factor, your doctor will determine the dose of FANHDI and the frequency of administration.
Your doctor will also decide on the duration of treatment with FANHDI.
Do not store any unused portion for later use, even if it is kept refrigerated.
Preparation of the solution:
Ensure that all procedures are carried out under conditions preventing contamination.
- Warm the vials to a temperature not exceeding 30°C (Figure 1).
- Insert the plunger into the diluent syringe (Figure 2).
- Remove the filter from its packaging. Remove the plastic cover from the tip of the syringe and attach the filter (Figure 3).
1.3.1. SPC, labelling and package leaflet
- Remove the vial adapter and connect the syringe with the filter (Figure 4).
- Remove the plastic cap from the vial and disinfect the exposed rubber stopper with an antiseptic (Figure 5).
- Pierce the vial stopper with the needle of the connector (Figure 6).
- Inject the entire diluent into the vial (Figure 7).
- Gently swirl the vial until the powder is completely dissolved (Figure 8). As with other intravenous products, do not use if the product is not fully dissolved or if particles are visible.
- Disconnect the syringe with the filter from the vial briefly to allow air entry (Figure 9).
- Invert the vial and draw the solution into the syringe (Figure 10).
- Prepare the injection site, disconnect the syringe, and administer the product through the attached butterfly needle or another sterile needle. Infuse slowly intravenously at a rate of 3 ml/min, and never exceed 10 ml/min to avoid vasomotor reactions (Figure 11).
1.3.1. SPC, labelling and package leaflet
1.3.1. SPC, labelling and package leaflet
Do not reuse the administration set.
Any unused product and other waste materials must be disposed of in accordance with local regulations.
OVERDOSE OF FANHDI
There have been no reported symptoms in cases of overdose with human factor VIII and von Willebrand factor complex. However, significant overdose may lead to thromboembolic complications. Regardless, any instance of exceeding the recommended dose of FANHDI should be immediately reported to a pharmacist or doctor.
MISSING A DOSE OF FANHDI
- If a dose is missed, administer the next dose as soon as possible and continue treatment regularly as directed by your doctor.
- Do not administer a double dose to make up for a missed dose.
4. POSSIBLE ADVERSE REACTIONS
Like all medicines, this medicine can cause adverse reactions, although they do not occur in all individuals.
Hypersensitivity or allergic reactions (angioedema, burning or pricking sensation at the injection site, chills, facial flushing, generalized urticaria, headache, rash, drop in blood pressure, lethargy, nausea, anxiety, tachycardia, chest tightness, itching, vomiting, wheezing) have been observed rarely and in only some cases led to the development of severe anaphylactic reactions (including shock).
In rare cases, an increase in body temperature has been observed.
In the event of an anaphylactic or allergic reaction, administration of the medicine must be discontinued and a physician must be notified immediately.
The possibility of allergic reactions occurring after administration of this medicine cannot be completely ruled out.
Patients with haemophilia A may develop neutralizing antibodies (inhibitors) against factor VIII. When such inhibitors occur, an inadequate clinical response to treatment is observed.
In very rare cases, patients with von Willebrand disease, particularly type 3, may develop neutralizing antibodies (inhibitors) against von Willebrand factor. If such inhibitors appear, an inadequate clinical response to treatment is observed.
Inhibitors may increase the risk of allergic reactions (anaphylactic shock). In the event of allergic reactions, testing for the presence of inhibitors should be performed.
In such cases, contact with a specialized center for the treatment of bleeding disorders is recommended.
When using the medicine in patients with von Willebrand disease who have known clinical or laboratory risk factors, there is a risk of thrombotic complications.
Maintaining excessively high levels of F:VIII during treatment with a factor VIII-containing product that also contains von Willebrand factor increases the risk of thrombotic complications.
During several clinical trials involving 164 patients, a total of 7000 infusions of FANHDI were administered. Results from both studies indicate good drug tolerance and a low frequency of adverse reactions. Only 2 cases of adverse reactions related to the medicinal product were observed. In these cases, elevated body temperature was reported.
Tabulated list of adverse reactions
The table below lists system organ classes (SOC) and preferred terms according to the MedDRA classification.
Frequency of occurrence was assessed using the following criteria:
- very common (≥ 1/10)
- common (≥ 1/100 to < 1/10)
- uncommon (≥ 1/1000 to < 1/100)
- rare (≥ 1/10,000 to < 1/1000)
- very rare (< 1/10,000)
- not known (frequency cannot be estimated from available data)
Within each frequency category, adverse reactions are listed in descending order of severity, starting with the most severe.
| System organ classes | Adverse reactions | Frequency |
| General disorders and administration site conditions | Increased body temperature. | Rare |
1.3.1. SPC, labelling and package leaflet
Children and adolescents
The frequency, type, and severity of adverse reactions expected in children do not differ from those occurring in adults.
Reporting suspected adverse reactions
After authorisation of the medicinal product, it is important to report suspected adverse reactions. This enables continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reactions via:
Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Tel.: +48 222 49 21 301
Fax: +48 222 49 21 309
e-mail: [email protected]
Thanks to reporting adverse reactions, more information on the safety of the medicinal product can be collected.
Information on precautions against transmission of infectious agents, see section 2.
5. HOW TO STORE FANHDI
Keep this medicine out of the sight and reach of children.
Do not store at temperatures above 30°C. Do not freeze.
Do not use this medicine after the expiry date stated on the label.
The solution should be clear and slightly opalescent.
Do not use solutions in which flakes or precipitate are present.
Do not use if particles are visible in the reconstituted product or if the solution has changed colour.
After reconstitution, the chemical and physical stability of the product remains for up to 12 hours at 25°C. From a microbiological point of view, the product should be used immediately. If the reconstituted product is not used immediately, it may be stored for no longer than 24 hours at 2°C – 8°C, provided that
1.3.1. SPC, labelling and package leaflet
responsibility for the preparation of the solution lies with the user and was carried out under aseptic conditions.
Medicines must not be disposed of via wastewater. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.
Shelf life
3 years.
Do not use this medicine after the expiry date stated on the label.
6. CONTENTS OF THE PACKAGE AND OTHER INFORMATION
What FANHDI contains
Active substance: a complex of human coagulation factor VIII and von Willebrand factor.
Each vial contains 1000 IU of human factor VIII and 1200 IU of von Willebrand factor.
After reconstitution with 10 ml of water for injections, the product contains 100 IU/ml FVIII and 120 IU/ml VWF.
Other components: Human albumin, histidine, and arginine.
Each pre-filled syringe contains 10 ml of water for injections.
What FANHDI looks like and contents of the pack
A vial containing a white or slightly yellow powder and a pre-filled syringe with water for injections.
Each FANHDI pack contains one vial with 1000 IU human factor VIII and 1200 IU von Willebrand factor (powder for solution for injection and infusion) and one pre-filled syringe with 10 ml of water for injections (solvent).
The kit for preparation and administration supplied with the FANHDI pack includes: a vial adapter, filter, and infusion set.
Available pack sizes:
FANHDI 250 IU FVIII + 300 IU VWF
FANHDI 500 IU FVIII + 1200 IU VWF
Not all pack sizes may be marketed.
1.3.1. SPC, labelling and package leaflet
Marketing Authorisation Holder and Manufacturer
Instituto Grifols, S.A.
Can Guasc, 2 - Parets del Vallès
08150 Barcelona, Spain
For further information, please contact the local representative of the Marketing Authorisation Holder:
Grifols Polska Sp. z o.o.
Ul. Grzybowska 87, 00-844 Warsaw, Poland
Tel: +48 22 378 85 61
…………………………………………………………………………………………………
Information intended exclusively for healthcare professionals:
Dosage
Factor VIII deficiency
The dosage and duration of replacement therapy depend on the severity of factor VIII deficiency, the location and extent of bleeding, and the patient's clinical condition.
The administered dose of factor VIII is expressed in International Units (IU), in accordance with current WHO standards applicable to medicinal products containing human factor VIII. Factor VIII activity in plasma may be expressed either as a percentage (relative to activity in normal plasma) or in International Units (according to the international standard for factor VIII in plasma).
One International Unit (IU) of factor VIII activity corresponds to the quantity of factor VIII present in one ml of normal human plasma.
Treatment of acute bleeding
The required dose of factor VIII is calculated based on empirical observations showing that administration of 1 IU/kg body weight increases plasma factor VIII activity by 1.7% to 2.5% of normal activity. The dose can be calculated using the following formula:
Required number of units = body weight (kg) x desired increase in factor VIII activity (%) (IU/dL) x 0.5
The dose level and frequency of administration must always be individually adjusted according to the patient's response to treatment.
In the treatment of bleeding episodes, depending on their cause and location, an appropriate level of factor VIII activity (% of normal or IU/dL) should be maintained throughout the recommended treatment period.
The following table may be used when determining dosage according to the type of bleeding or surgical procedure:
| Bleeding severity/Surgical procedure type | Required factor VIII level (%) (IU/dl) | Dosing frequency (hours)/Duration of treatment (days) |
| Bleeding Acute bleeding into joints, muscles or oral cavity. More severe bleeding into joints, muscles or hematoma. Life-threatening bleeding. | 20 – 40 30 – 60 60 – 100 | Repeat every 12–24 hours for at least 1 day, until resolution of pain caused by bleeding or wound healing. Repeat infusions every 12–24 hours for 3–4 days or longer, until resolution of pain or functional impairment. Repeat infusions every 8–24 hours until the life-threatening condition has resolved. |
| Surgical procedures Minor Including dental extractions Major | 30 – 60 80 – 100 (pre- and postoperative period) | Every 24 hours, for at least 1 day, until wound healing. Repeat infusions every 8–24 hours until adequate wound healing is achieved, then continue treatment for an additional 7 days, maintaining factor VIII activity between 30% and 60% (IU/dl). |
Prophylactic treatment
For long-term prophylaxis of bleeding in patients with severe haemophilia A, the usual dose is 20 to 40 IU/kg body weight administered every 2 to 3 days. In some cases, particularly in younger patients, it may be necessary to shorten the intervals between injections or to increase the dose.
1.3.1. SPC, labelling and package leaflet
During treatment, appropriate monitoring of factor VIII plasma levels is recommended to determine the dose and frequency of infusions. Precise monitoring of replacement therapy using coagulation tests (factor VIII activity in plasma) is especially necessary during major surgical procedures.
Patients may respond individually to factor VIII treatment, which is reflected in varying in vivo recovery rates and different half-lives among individual patients.
Von Willebrand disease
It is generally accepted that administration of 1 IU VWF:RCo/kg body weight results in a 2% increase in circulating VWF:RCo. The treatment goal is to achieve a VWF:RCo level > 0.6 IU/mL (60%) and FVIII:C > 0.4 IU/mL (40%) in plasma.
In most cases, to achieve haemostasis, a dose of 40–80 IU/kg body weight of von Willebrand factor and 20–40 IU/kg body weight of factor FVIII:C is recommended.
Patients with type 3 von Willebrand disease, in whom maintaining adequate factor levels may require higher doses, may need an initial dose of 80 IU/kg body weight of von Willebrand factor.
The selected dose should be administered every 12–24 hours. Dosing and duration of treatment depend on the patient's clinical condition, site and extent of bleeding, and levels of both VWF:RCo and FVIII:C.
During treatment with medicinal products containing factor VIII and von Willebrand factor, the treating physician should consider the possibility of excessive increase in FVIII:C levels. To avoid excessive elevation of FVIII:C, after 24–48 hours of treatment, consideration should be given to reducing the dose, extending the interval between doses, or using medicinal products containing VWF and lower amounts of factor VIII.
Children and adolescents
For the above indications, only limited clinical trial data are available in children below 6 years of age, and therefore no recommendations for use of the medicinal product can be made for this age group.
In children, for the above-mentioned indications, dose adjustment based on clinical efficacy, as in adults, involves calculating the dose according to body weight.