Prospect: information for the user

Fanhdi 25 UI FVIII/30 UI FVW per ml, powder and solvent for injectable solution

Fanhdi 50 UI FVIII/60 UI FVWper ml, powder and solvent for injectable solution

Fanhdi 100 UI FVIII/120 UI FVWper ml, powder and solvent for injectable solution

human coagulation factor VIII and von Willebrand factor complex

Read this prospect carefully before starting to use the medication, as it contains important information for you.

• Keep this prospect as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medication has been prescribed only to you, and you must not give it to other people even if they have the same symptoms as you, as it may harm them.
• Ifyou experience adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this prospect. See section 4.

1.What isFanhdiand for what it is used

2.What you need to know before starting to useFanhdi

3.How to useFanhdi

4.Possible adverse effects

5.Storage ofFanhdi

6.Contents of the package and additional information

Fanhdi belongs to the group of medications known as antihemorrhagics: blood coagulation factors: factor von Willebrand and factor VIII of blood coagulation in combination.

This medication is used for:

Hemophilia A

Fanhdi is indicated for the treatment and prophylaxis (prevention) of bleeding in patients with hemophilia A (congenital deficiency of factor VIII). These patients do not have enough functional factor VIII. Fanhdi serves to increase the amount of factor VIII in the blood, thus allowing the blood to clot.

This product may be useful in the management of acquired factor VIII deficiency.

Von Willebrand disease

Fanhdi is indicated for the treatment of bleeding and surgical bleeding prophylaxis in patients with von Willebrand disease (VWD) when treatment with desmopressin (DDAVP) alone is not effective or contraindicated.

Patients may suffer from different types of VWD.All types of VWD are congenital diseases where bleeding can last longer than expected. This may be due to a lack of FVW in the blood or because FVW does not function as it should.

No use Fanhdi

If you are allergic to the human coagulation factor VIII complex and factor von Willebrand or any of the other components of this medication (listed in section 6).

If you have any doubts about the above, consult your doctor.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to use Fanhdi.

• There is a remote possibility that you may experience anaphylactic reaction (severe allergic reaction). If you observe skin eruptions or generalized urticaria, feel chest oppression, dizziness, or nausea, or feel dizzy while standing, you may be experiencing an anaphylactic reaction to Fanhdi. If this occurs, stop administering the product immediately and seek medical assistance.

• Your doctor may wish to perform some tests to ensure that the dose you receive of Fanhdi is sufficient to achieve and maintain adequate levels of factor VIII.

The formation of inhibitors (antibodies) is a known complication that may occur during treatment with all factor VIII composite medications. These inhibitors, especially in large quantities, prevent the treatment from working correctly, so you and your child will be closely monitored for the development of these inhibitors. If your bleeding or your child's bleeding is not being controlled with Fanhdi, consult your doctor immediately.

• If you have previously developed factor VIII inhibitors and have changed from one factor VIII product to another, you may develop inhibitors again.

• In the case of von Willebrand disease treatment, there is a risk of thrombotic effects, particularly in patients with clinical risks. Therefore, your doctor will perform some tests to detect early signs of thrombosis and initiate anticoagulant treatment according to current recommendations.

• Patients with von Willebrand disease, especially those with type 3, may develop neutralizing antibodies (inhibitors) to factor von Willebrand. Factor von Willebrand inhibitors are antibodies present in the blood that block the factor von Willebrand being used. If the expected plasma factor von Willebrand activity levels are not achieved, or if bleeding is not controlled with the appropriate dose, your doctor will perform tests to determine the presence of factor von Willebrand inhibitor. This makes factor von Willebrand less effective in controlling bleeding.

• If you are going to need a central venous access device (CVAD) for Fanhdi administration, your doctor should consider the risk of complications related to CVAD, including local infections, presence of bacteria in the blood (bacteremia), and the formation of a blood clot in the blood vessel (thrombosis) where the catheter is inserted.

• When medications are prepared from blood or human plasma, a number of measures must be taken to prevent possible transmission of infections to patients. These measures include a careful selection of blood and plasma donors to ensure exclusion of donors at risk of infection, analysis of each donation and plasma mixtures to detect possible viruses or infections, and inclusion of a series of steps in the blood or plasma processing that can inactivate or eliminate viruses.

Despite these measures, when administering medications prepared from blood or human plasma, the possibility of transmission of infections cannot be completely ruled out. This also applies to unknown or emerging viruses and other types of infections.

The measures taken are considered effective for enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus, and hepatitis C virus, and for non-enveloped viruses such as hepatitis A virus. The measures taken may have limited value for non-enveloped viruses such as parvovirus B19.

Parvovirus B19 infection can be severe for a pregnant woman (fetal infection) and for individuals with a weakened immune system or those with some type of anemia (e.g., with sickle cell anemia or hemolytic anemia).

Your doctor may recommend that you consider hepatitis A and B vaccination if you regularly/repeatedly receive human plasma-derived factor VIII concentrates.

Each time you are administered a dose of Fanhdi, it is recommended to record the name and batch number of the medication to maintain a record of the batches used.

See also section 4.

Children and adolescents

The warnings and precautions indicated apply to both adults and children.

Use of Fanhdi with other medications

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication.

No interactions have been observed between the human coagulation factor VIII complex and factor von Willebrand and other medications.

Pregnancy and breastfeeding

Consult your doctor or pharmacist before using any medication.

During pregnancy and breastfeeding, the FVIII/FVW complex may be used only if clearly indicated.

Driving and operating machinery

No indication exists that Fanhdi may affect the ability to drive vehicles or operate machinery.

Sodium content

The residual sodium content in Fanhdi, resulting from the manufacturing process, does not exceed 23 mg per vial in the 250, 500, and 1000 UI presentations, and 34.5 mg per vial in the 1500 UI presentation. This is equivalent to 1.15% and 1.72% respectively of the maximum daily sodium recommended for an adult. However, depending on the patient's weight and dosage, the patient may receive more than one vial.

The product must be administered intravenously. The administration rate must not exceed 10 ml/min.

Follow exactly the administration instructions indicated by your doctor or by the healthcare staff at the hemophilia center. If you have any doubts, consult your doctor or pharmacist.

The amount of Fanhdi you should use depends on many factors, such as your weight, your clinical condition, and the location and importance of the bleeding. Your doctor will calculate the dose of Fanhdi and how often and at what intervals it should be administered to achieve the necessary level of factor VIII or factor von Willebrand in your blood.

Your doctor will inform you of the duration of your treatment with Fanhdi.

Preparation of the solution:

Ensure that you work in the most suitable conditions at all stages of the process to avoid contamination of the product.

1. Warm the vial and the syringe of the solvent without exceeding 30 °C.
2. Attach the plunger to the syringe of the solvent.
3. Remove the filter seal. Separate the cap from the cone of the syringe of the solvent and attach it to the filter.
4. Remove the vial adapter seal and attach it to the filter-syringe assembly.
5. Remove the vial seal, disinfecting the cap with one of the alcohol wipes.
6. Insert the needle of the adapter into the vial.
7. Transferring all the solvent from the syringe to the vial.
8. Gently rotate the vial to ensure complete dissolution without agitation. Do not use if the solution is incomplete or contains particles.
9. Separate the filter-syringe assembly from the rest to facilitate subsequent aspiration of the solution and immediately reattach the filter-syringe assembly to the vial.
10. Invert the vial and aspirate the contents into the syringe.

Administration

Prepare the patient's injection site, separate the syringe from the rest, and inject the product using the butterfly needle provided at a rate of 3ml/min intravenously. The administration rate must not exceed 10 ml/min to avoid vasomotor reactions.

It is recommended to use the injection equipment provided with the medication. In the event that medical perfusion equipment is used, check the compatibility of the system with the pre-loaded syringe. It may be necessary to use an adapter to ensure proper administration of the product.

The administration equipment must not be reused. In no case should the unused fraction be stored in the refrigerator.

If you use more Fanhdi than you should

No cases of overdose with human coagulation factor VIII and factor von Willebrand complex have been reported. However, if you have used Fanhdi more than you should, consult your doctor or pharmacist immediately.

In case of overdose or accidental administration, consult the Toxicological Information Service. Phone 91 562 04 20.

If you forgot to use Fanhdi

• Proceed immediately with the next administration and continue at regular intervals following your doctor's instructions.
• Do not administer a double dose to compensate for the missed doses.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

In rare cases, you may notice some of these side effects after the administration of Fanhdi:

• Itching, local reactions at the injection site (e.g. burning sensation or tingling and transient redness)
• Allergic reactions (e.g. chest tightness/general feeling of discomfort, difficulty breathing, dizziness, nausea, and mild drop in blood pressure that can cause dizziness when standing)
• Unusual taste in the mouth
• Fever
• Tachycardia
• Restlessness
• Headache
• Drowsiness
• Vomiting
• Chills

It is also impossible to completely rule out the possibility of anaphylactic shock. If you notice any of the following symptomsduring administration:

• Chest tightness/general feeling of discomfort
• Dizziness
• Mild hypotension (mild decrease in blood pressure with dizziness when standing)
• Nausea

may be an early sign of hypersensitivity and anaphylactic reaction. If an allergic or anaphylactic reaction occurs, administration should be interrupted and your doctor should be consulted immediately.

Hemophilia A

In children who have not received prior treatment with factor VIII-containing medications, the production of inhibitor antibodies (see section 2) may occur very frequently (more than 1 in 10 patients); however, in patients who have received prior treatment with factor VIII (more than 150 days of treatment), the risk is infrequent (less than 1 in 100 patients). If this happens, the medications you or your child take may not work properly, and you or your child may experience persistent bleeding. In that case, contact your doctor immediately.

Von Willebrand disease

When using a FVW product containing FVIII to treat EVW, continued treatment may cause excessive increases in FVIII levels in the blood. This may increase the risk of altered blood flow (thrombosis).

If you are a patient with known clinical or laboratory risk factors, your doctor should monitor the first signs of thrombosis. Your doctor should establish a prevention (prophylaxis) of thrombotic episodes, in accordance with current recommendations.

Especially if you are a patient with type 3 von Willebrand disease, in very rare cases, you may develop neutralizing antibodies (inhibitors) to factor von Willebrand. If these inhibitors appear, the factor von Willebrand is less effective in controlling bleeding. In the case of continued bleeding, the presence of these inhibitors in your blood should be analyzed. These antibodies may appear associated with anaphylactic reactions. Therefore, in patients who experience anaphylactic reactions, the presence of inhibitors should be evaluated. In such cases, consult your doctor immediately.

For information on viral safety, see section 2.

Reporting of adverse reactions

If you experience any type of adverse reaction, consult your doctor, pharmacist, or nurse, even if it is a possible adverse reaction that does not appear in this prospectus. You can also report them directly through theSpanish System for Pharmacovigilance of Medicinal Products for Human Use:www.notificaRAM.es

By reporting adverse reactions, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not store at a temperature above 86°F (30°C). Do not freeze.

Do not use this medication after the expiration date that appears on the packaging after “CAD”.

Do not use this medication if you observe that the solution is cloudy or has sediment. The solution is usually clear or slightly opalescent.

Once reconstituted, the solution must be discarded if particles are observed inside or any type of discoloration.

After reconstitution, the product is chemically and physically stable for 12 hours at 77°F (25°C). From a microbiological standpoint, the product must be used immediately. If not used immediately, the time and storage conditions before use are the responsibility of the user and, normally, will not be more than 24 hours at 36°F - 46°F (2°C - 8°C) unless reconstitution was performed in controlled and validated aseptic conditions.

All unused product and waste material must be disposed of in accordance with local requirements.

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of empty containers and unused medications. This will help protect the environment.

Composition of Fanhdi

• The active principle is the human coagulation factor VIII and von Willebrand factor complex. Once reconstituted, Fanhdi contains 25 UI FVIII/30 UI FVW per ml, 50 UI FVIII/60 UI FVW per ml or 100 UI FVIII/120 UI FVW per ml. See below “Fanhdi presentations”.

• The other components are albumin, histidine and arginine.

Appearance of the product and contents of the package

Pre-filled vial containing white or pale yellow powder and syringe with water for injectable preparations (solvent).

Package contents: 1 lyophilized vial, 1 pre-filled syringe with solvent and accessories (vial adapter, filter, 2 alcohol wipes and butterfly needle).

Fanhdi presentations

Fanhdi 25 UI FVIII/30 UI FVW per ml

Presented as a powder for injectable solution containing 250 UI of human coagulation factor VIII and 300 UI of human von Willebrand factor per vial, which is reconstituted with 10 ml of injectable water.

Fanhdi 50 UI FVIII/60 UI FVW per ml

Presented as a powder for injectable solution containing 500 UI of human coagulation factor VIII and 600 UI of human von Willebrand factor per vial, which is reconstituted with 10 ml of injectable water.

Fanhdi 100 UI FVIII/120 UI FVW per ml

Presented as a powder for injectable solution containing 1000 UI of human coagulation factor VIII and 1200 UI of human von Willebrand factor per vial, which is reconstituted with 10 ml of injectable water.

Or

Presented as a powder for injectable solution containing 1500 UI of human coagulation factor VIII and 1800 UI of human von Willebrand factor per vial, which is reconstituted with 15 ml of injectable water.

Marketing authorization holder and manufacturer

Instituto Grifols, S.A.

Can Guasc, 2 - Parets del Vallès

08150 Barcelona – ESPAÑA

Last review date of this leaflet:

December 2020.

The detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es//

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This information is intended solely for healthcare professionals:

Dosage

Hemophilia A

The dosage and duration of treatment depend on the severity of the factor VIII deficiency, the location and severity of the hemorrhage, and the patient's clinical condition.

The number of factor VIII units administered is expressed in International Units (UI), in relation to the World Health Organization (WHO) standard for factor VIII concentrates. The plasma activity of factor VIII is expressed as a percentage (in relation to normal human plasma) or in International Units (in relation to an international standard for factor VIII in plasma).

One International Unit (UI) of factor VIII activity is equivalent to the amount of factor VIII in 1 ml of normal human plasma.

On-demand treatment

The calculation of the required dose of factor VIII is based on the empirical observation that 1 International Unit (UI) of factor VIII per kg of body weight increases the plasma activity of factor VIII by 2.1 ± 0.4% of normal activity. The required dose is determined using the following formula:

Required units = body weight (kg) x desired increase in factor VIII (%) (UI/dl) x 0.5

The dose and administration frequency must be calculated based on the patient's clinical response.

In the case of hemorrhagic episodes such as those listed below, the factor VIII activity should not be less than the established plasma activity level (in % of normal plasma or UI/dl) in the corresponding period. The following table can be used as a guide for dosing in hemorrhagic episodes and surgery:

Prophylaxis

In long-term prophylaxis to prevent bleeding in patients with severe hemophilia A, doses of 20 to 40 UI of FVIII/kg of body weight should be administered at intervals of 2 to 3 days. In some cases, especially in young patients, it may be necessary to shorten the administration intervals or use higher doses.

Von Willebrand disease (VWD)

Generally, 1 UI of FVW:RCo/kg increases the circulating level of the same by approximately 2%. The levels of FVW:RCo > 0.6 UI/ml (60%) and FVIII:C > 0.4 UI/ml (40%) should be achieved.

Normally, 40 - 80 UI/kg of factor von Willebrand (FVW:RCo) and 20 - 40 UI/kg of FVIII:C are recommended to achieve hemostasis.

A higher initial dose of 80 UI/kg of factor von Willebrand may be needed, especially in patients with type 3 VWD, in which maintaining adequate levels may require higher doses than in other types of VWD.

A suitable dose should be re-administered every 12 - 24 hours. The dose and duration of treatment depend on the patient's clinical condition, the type and severity of the bleeding, and the levels of FVW:RCo and FVIII:C.

In the use of a factor von Willebrand preparation that contains factor VIII, the treating physician should take into account that continued treatment may cause excessive increases in FVIII:C. After 24 - 48 hours of treatment, and to avoid excessive increases in FVIII:C, consideration should be given to reducing the dose and/or prolonging the interval between doses, or using products with factor von Willebrand that contain low levels of factor VIII.

Pediatric population

The safety and efficacy of Fanhdi have not been established in children under 6 years of age for the authorized indications.

The dosage in children 6 years of age or older is not considered different from that of adults, as it is associated with body weight and adjusted to the clinical outcome of the conditions mentioned above.