Fanhdı

1.3.1. SPC, labelling and package leaflet

PACKAGE LEAFLET: INFORMATION FOR THE USER

FANHDI
500 IU FVIII + 600 IU VWF
Powder and solvent for solution for injection and infusion
Complex of human coagulation factor VIII and human von Willebrand factor
Please read carefully this leaflet before using the medicine, as it contains important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any doubts, 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 someone else, even if their symptoms are the same.
• If the patient experiences any adverse reactions, including any not listed in this leaflet, inform the doctor or pharmacist. See section 4.

Contents of the 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 500 IU of human coagulation factor VIII (FVIII) and 600 IU of human von Willebrand factor (VWF).
After reconstitution with the appropriate volume of solvent (water for injection), the product contains 50 IU/mL FVIII and 60 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).
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 desmopressin (DDAVP) treatment is ineffective or contraindicated.
The product may be used in the treatment of acquired deficiency of human coagulation 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 complex of coagulation factor VIII and von Willebrand factor or to any of the other components of this medicine (listed in section 6).

Consult your doctor if you need advice or further information.
Warnings and precautions

• In rare cases, anaphylactic reactions (sudden severe allergic reactions) may occur. Hypersensitivity to FANHDI may manifest as rash, generalized urticaria, feeling of chest tightness, dizziness, even in the upright position. If these symptoms occur, discontinue administration of the medicine and inform the doctor immediately.
• To determine the FANHDI dose required to achieve and maintain 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 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. As a result, the effectiveness of factor VIII in controlling bleeding is reduced.
• 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.
• During treatment of von Willebrand disease, especially in patients with known clinical or laboratory risk factors, there is a risk of thrombosis. Therefore, appropriate monitoring is necessary to detect early signs of thrombotic events, and current recommended treatments for thromboembolic complications should be applied.
• In von Willebrand disease, particularly type 3, neutralizing antibodies (inhibitors) against von Willebrand factor may develop. Inhibitors of von Willebrand factor 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 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 possibility of local infection, bacteraemia (blood infection by bacteria), or venous thrombosis at the catheter insertion site.

In the manufacturing process of medicinal products derived from human blood or plasma, the following measures are taken to ensure protection against transmission of infectious agents:

• careful donor selection 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.

Nevertheless, it cannot be completely excluded that the use of medicinal products derived from human blood or plasma may transmit infectious agents. This applies also 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, 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 (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, with each administration of FANHDI, the patient's name and the product batch number be recorded, to allow traceability between patient and 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 your doctor about all medicines currently used or recently used, as well as any medicines the patient plans to take.
Interactions between human coagulation factor VIII/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 operating machinery
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.
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 depends on several factors such as body weight, clinical condition, and the type and severity 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. Attach the plunger into the diluent syringe (Figure 2).
3. Remove the filter from its packaging. Remove the plastic cover from the tip of the diluent syringe and attach the filter (Figure 3).
4. Remove the vial adapter and connect the syringe with filter (Figure 4).
5. Remove the plastic cap from the vial and disinfect the exposed rubber stopper with a suitable antiseptic (Figure 5).
6. Pierce the vial stopper with the needle of the adapter (Figure 6).
7. Inject the entire 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 to enter (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 through the attached butterfly needle or another sterile needle. Administer 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
Do not reuse the administration set.
Any unused product and waste materials must 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 instance of exceeding the recommended FANHDI dose should be immediately discussed with a pharmacist or doctor.

Missed 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 any medicine, this medicine may cause adverse reactions, although not everyone experiences them.

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 should be discontinued immediately and a physician should 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. 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 occur, an inadequate clinical response to treatment is 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 centre 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 von Willebrand factor increases the risk of thrombotic complications.

In several clinical trials involving 164 patients, a total of 7000 infusions of FANHDI were administered. Results from both studies indicate good tolerability of the medicine and a low incidence 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 class (SOC) and preferred term level categories 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 order of severity, from most severe to least severe.

Children and adolescents
The frequency, type, and severity of adverse reactions expected in children do not differ from those occurring in adults.

1.3.1. SPC, labelling and package leaflet
Reporting suspected adverse reactions
Following marketing authorization 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]

Reporting of adverse reactions enables the collection of further information on the safety of using the medicinal product.

For information regarding precautions against transmission of infectious agents, see section 2.

5. HOW TO STORE FANHDI

Keep this medicine out of 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 in which clumps or precipitate are present.
Do not use if, after reconstitution, particles are visible 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 not used immediately after reconstitution, it may be stored for no longer than 24 hours at 2°C–8°C, provided that the responsibility for preparation under aseptic conditions lies with the user.
1.3.1. SPC, labelling and package leaflet
Medicines should not be disposed of via wastewater. Ask your pharmacist how to dispose of medicines no longer in use. Such practices help protect the environment.
Expiry date
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
The active substance is a complex of human coagulation factor VIII and von Willebrand factor.
Each vial of powder contains 500 IU of human coagulation factor VIII and 600 IU of von Willebrand factor.
After reconstitution with 10 ml of water for injection, the product contains 50 IU/ml of FVIII and 60 IU/ml of VWF.
Other components: Human albumin, histidine, and arginine.
Each ampoule-syringe contains 10 ml of water for injection.

What FANHDI looks like and contents of the pack
A vial containing white or pale yellow powder and an ampoule-syringe containing water for injection.
Each FANHDI pack contains one vial with 500 IU of human coagulation factor VIII and 600 IU of von Willebrand factor (powder for solution for injection and infusion) and one ampoule-syringe with 10 ml of water for injection (diluent).
The kit for preparation and administration included in the FANHDI pack: a vial adapter, filter, and infusion set.

Available pack sizes:
FANHDI 250 IU FVIII + 300 IU VWF
FANHDI 1000 IU FVIII + 1200 IU VWF
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
1.3.1. SPC, labelling and package leaflet
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
Tel: +48 22 378 85 61

…………………………………………………………………………………………………
Information intended exclusively for healthcare professionals:

Dosage
Deficiency of coagulation factor VIII

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 coagulation factor VIII is expressed in International Units (IU), according to current WHO standards applicable to medicinal products containing human coagulation 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 coagulation 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.

Immediate treatment
The calculation of the required dose of coagulation factor VIII is based on the empirical observation 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

The dose level and frequency of administration should always be individually adjusted according to the patient's response to treatment.

1.3.1. SPC, labelling and package leaflet
In the treatment of bleeding episodes, depending on their cause and location, the appropriate level of factor VIII activity (expressed as % of normal or IU/dl) should be maintained throughout the recommended treatment period.

The following table may be used to determine dosage depending on the type of bleeding and surgical procedure:

Prophylactic treatment
For long-term prophylaxis of bleeding in patients with severe haemophilia A, a dose of usually 20 to 40 IU/kg body weight administered every 2 to 3 days is used. 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 measurement of factor VIII levels in plasma is recommended to determine the dose and frequency of infusions. Especially during 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, which is reflected in varying levels of in vivo recovery 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 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, 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 higher doses may be required to maintain adequate factor levels, 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, location and extent of bleeding, and on the 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 levels, after 24–48 hours of treatment, consideration should be given to reducing the dose or prolonging the interval between doses, or using medicinal products containing VWF and lower amounts of factor VIII.
Children and adolescents
For the above indication, clinical trial data in children below 6 years of age are limited, 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 according to clinical efficacy is based, as in adults, on dose calculation according to body weight.