Fanhdi

1.3.1. SPC, labelling and package leaflet

PACKAGE LEAFLET: INFORMATION FOR THE USER

FANHDI
250 IU FVIII + 300 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 you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What FANHDI is and what it is used for
2. Important information before using FANHDI
3. How to use FANHDI
4. Possible side effects
5. How to store FANHDI
6. 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 250 IU of human coagulation factor VIII (FVIII) and 300 IU of human von Willebrand factor (VWF).
After reconstitution with the appropriate volume of solvent (water for injection), the product contains 25 IU/mL FVIII and 30 IU/mL VWF.
Pharmacotherapeutic group: Haemostatics, 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).
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 desmopressin (DDAVP) treatment 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 has hypersensitivity (allergy) to the human factor VIII and von Willebrand factor complex or to any of the other components of this medicine (listed in section 6).

Consult your doctor if you need advice or additional information.

Warnings and precautions

• In rare cases, anaphylactic reactions (sudden severe allergic reactions) may occur. Hypersensitivity to FANHDI may manifest as rash, generalized urticaria, chest tightness, dizziness, even in the standing position. If such symptoms occur, discontinue administration of the medicine immediately and inform your doctor.
• To determine the appropriate FANHDI dose ensuring achievement and maintenance of adequate factor VIII levels, your doctor may order several tests.
• If bleeding does not stop despite administration of FANHDI, inform your 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 block the activity of administered factor VIII, resulting in reduced effectiveness of factor VIII in controlling bleeding.
• If a factor VIII inhibitor has previously developed and treatment has been switched to another factor VIII-containing product, there is an increased risk of recurrence of this complication.
• In patients with von Willebrand disease, particularly type 3, neutralizing antibodies (inhibitors) against von Willebrand factor may develop. Inhibitors of von Willebrand factor are antibodies present in the blood that may block the administered factor. In such cases, if expected plasma levels of von Willebrand factor activity are not achieved or bleeding cannot be 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.
• 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 venous thrombosis at the catheter insertion site.

During the manufacturing process of medicinal products derived from human blood or plasma, the following measures are taken to prevent 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, transmission of infectious agents cannot be completely ruled out when using medicinal products derived from human blood or plasma. This also applies to 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, effectiveness 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 weakened immunity or certain types of anaemia (e.g. sickle cell anaemia or haemolytic anaemia).
For patients receiving regular repeated doses of plasma-derived products containing factor VIII, the treating physician may recommend vaccination against hepatitis A and B viruses.
It is strongly recommended that, for 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.

FANHDI and other medicines
Tell your doctor about all medicines you are currently taking, have recently taken, or plan to take.
Interactions between the human factor VIII and von Willebrand factor complex and other medicines 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 taking any medicine.

Driving and using machines
FANHDI has no influence on the ability to drive or operate machinery.

3. HOW TO USE FANHDI

FANHDI 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 a
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.

1. Warm the vials to a temperature not exceeding 30°C (Figure 1).
2. Insert the plunger into the diluent syringe (Figure 2).
3. Remove the filter from its packaging. Remove the plastic cover from the tip of the syringe and attach the filter (Figure 3).
4. Remove the vial adapter from its packaging and connect the syringe with filter to the vial (Figure 4).

1.3.1. SPC, labelling and package leaflet

5. Remove the plastic cap from the vial and disinfect the exposed rubber stopper with an antiseptic (Figure 5).
6. Pierce the vial stopper with the needle of the adapter (Figure 6).
7. Inject the entire volume of diluent into the vial (Figure 7).
8. 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.
9. Disconnect the syringe with filter from the vial briefly to allow air entry (Figure 9).
10. Invert the vial and draw the solution into the syringe (Figure 10).
11. Prepare the injection site, disconnect the syringe, and administer the product slowly intravenously through the attached butterfly needle or another sterile needle at a rate of 3 ml/min, never exceeding 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 or waste material should be disposed of in accordance with
local regulations.

Administration of a higher than recommended dose of FANHDI
There have been no reported symptoms associated with overdose of human factor VIII
and von Willebrand factor complex. However, significant overdose may lead to thromboembolic complications. Regardless, any case of exceeding the recommended dose of FANHDI should be immediately reported to a pharmacist or doctor.

Missed dose of FANHDI

• If a dose is missed, administer the next dose immediately 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 stinging sensation at the injection site, chills, facial flushing, generalized urticaria, headache, rash, hypotension, lethargy, nausea, anxiety, tachycardia, chest tightness, pruritus, vomiting, wheezing) have been observed rarely and in only some cases led to the development of severe anaphylactic reactions (including anaphylactic 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 immediately and a physician must be notified without delay.

The possibility of allergic reactions following administration of this medicine cannot be completely ruled out.

Patients with haemophilia A may develop neutralizing antibodies (inhibitors) against factor VIII. If such inhibitors occur, an inadequate clinical response to treatment may be 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 occur, an inadequate clinical response to treatment may be observed.

1.3.1. SPC, labelling and package leaflet
Inhibitors may increase the risk of allergic reactions (anaphylactic shock). If allergic reactions occur, 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 administering the medicine to 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 preparation that also contains von Willebrand factor increases the risk of thrombotic complications.

In several clinical studies 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 presents system organ classes (SOC) and preferred terms (Preferred Term Level) 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 starting with the most severe.

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 ratio 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]
By reporting adverse reactions, additional information regarding the safety of the medicinal product can be collected.
Information concerning safeguards 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 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 containing lumps or precipitate.
Do not use if particles are visible in the product after reconstitution or if the solution has changed colour.
After reconstitution, the chemical and physical stability of the product is maintained for up to 12 hours at 25°C. From a microbiological point of view, the product should be used immediately. If not used immediately after reconstitution, it may be stored for no longer than 24 hours at 2°C – 8°C, but only if the responsibility for the preparation of the solution lies with the end user and the reconstitution was performed 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.
1.3.1. SPC, labelling and package leaflet

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 250 IU of human factor VIII and 300 IU of von Willebrand factor.
After reconstitution with 10 ml of water for injections, the product contains 25 IU/ml FVIII and 30 IU/ml VWF.
Other components: Human albumin, histidine, and arginine.
Each syringe-ampoule contains 10 ml of water for injections.

What FANHDI looks like and contents of the pack
A vial containing white or pale yellow powder and a syringe-ampoule with water for injections.
Each FANHDI pack contains one vial with 250 IU of human factor VIII and 300 IU of von Willebrand factor (powder for solution for injection and infusion) and one syringe-ampoule with 10 ml of water for injections (diluent).
The kit for preparation and administration included in the FANHDI pack: a vial connector, filter, and infusion set.

Available pack sizes:
FANHDI 500 IU FVIII + 600 IU VWF
FANHDI 1000 IU FVIII + 1200 IU VWF
Not all pack sizes may be marketed.

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.
1.3.1. SPC, labelling and package leaflet
Ul. Grzybowska 87, 00-844 Warszawa
Tel: +48 22 378 85 61
…………………………………………………………………………………………………
Information intended exclusively for healthcare professionals:

Dosage
Factor VIII deficiency
Dosage and duration of replacement therapy depend on the severity of factor VIII deficiency, location and extent of bleeding, and the patient's clinical condition.
The administered dose of factor VIII is expressed in International Units (IU), according to current WHO standards applicable to medicinal products containing human factor VIII. Factor VIII activity in plasma may be expressed 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 amount of factor VIII present in one ml of normal human plasma.

Acute treatment
The required dose of factor VIII is calculated based on empirical observations that administration of 1 IU/kg body weight increases plasma factor VIII activity by 1.7% to 2.5% of normal activity. The dose is calculated using the following formula:
Required number of units = body weight (kg) × desired increase in factor VIII activity (%) (IU/dL) × 0.5
Dose levels and frequency of administration should always be individually adjusted depending on the patient's response to treatment.
In the treatment of bleeding episodes, depending on their cause and location, the recommended factor VIII activity level (expressed as % of normal or IU/dL) should be maintained for the recommended treatment period.
The following table may be used to determine dosage according to the type of bleeding and surgical procedure:

1.3.1. SPC, labelling and package leaflet

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 certain cases, particularly in younger patients, it may be necessary to shorten the intervals between injections or to increase the dose.
During treatment, appropriate assay of factor VIII levels in plasma is recommended to determine the dose and frequency of infusions. Especially in the case of major surgical procedures, careful monitoring of replacement therapy using coagulation tests (factor VIII activity in plasma) is essential.
Patients may respond individually to factor VIII treatment, reflected by varying in vivo recovery levels and different half-lives among individual patients.

1.3.1. SPC, labelling and package leaflet
Von Willebrand disease
It is generally accepted that administration of 1 IU VWF:RCo/kg body weight increases circulating VWF:RCo levels by 2%. The aim of treatment is to achieve plasma levels of VWF:RCo > 0.6 IU/mL (60%) and FVIII:C > 0.4 IU/mL (40%).
In most cases, 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 to achieve haemostasis.
Patients with type 3 von Willebrand disease, in whom higher doses may be required to maintain adequate factor levels, may need an initial dose of von Willebrand factor of 80 IU/kg body weight.
The selected dose should be administered every 12–24 hours. Dosing and duration of treatment depend on the patient's clinical condition, location and extent of bleeding, and on plasma levels of both VWF:RCo and FVIII:C.
During treatment with factor VIII-containing medicinal products that also contain 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 data are available in children below 6 years of age, and therefore no recommendations can be made for the use of the medicinal product in this age group.
In children, for the above-mentioned indications, dose adjustment based on clinical efficacy is performed according to body weight, as in adults.