FANHDI 250 IU + 300 IU/10 ML Proszek i rozpuszczalnik do roztworu do wstrzykiwań

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1. Fanhdi “250 IU + 300 IU/10 ml Powder and solvent for infusion solution”, “500 IU + 600 IU/10 ml Powder and solvent for infusion solution”, “1000 IU + 1200 IU/10 ml Powder and solvent for infusion solution”, “1500 IU + 1800 IU/15 ml Powder and solvent for infusion solution”
   1. What Fanhdi is and what it is used for
   2. What you need to know before using Fanhdi
   3. How to use Fanhdi
   4. Possible adverse effects
   5. How to store Fanhdi
   6. Package Contents and Other Information

Fanhdi “250 IU + 300 IU/10 ml Powder and solvent for infusion solution”, “500 IU + 600 IU/10 ml Powder and solvent for infusion solution”, “1000 IU + 1200 IU/10 ml Powder and solvent for infusion solution”, “1500 IU + 1800 IU/15 ml Powder and solvent for infusion solution”

Human coagulation Factor VIII complex and human von Willebrand Factor
Read this leaflet carefully before using this medicine as 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 pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If any side effects occur, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

• 1. What Fanhdi is and what it is used for
• 2. What you need to know before you use 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 constituted by lyophilized powder and solvent for infusion solution, containing approximately
250 IU, 500 IU, 1000 IU and 1500 IU of factor VIII (FVIII), and 300, 600, 1200 or 1800 IU of von
Willebrand factor (VWF) per vial. Once reconstituted with the appropriate amount of solvent (water
for injectable preparations), each vial contains approximately 25, 50 or 100 IU of FVIII/ml and 30, 60 or
120 IU of VWF/ml.

Fanhdi belongs to the group of drugs called antihemorrhagics: blood coagulation factors:
von Willebrand factor and factor VIII of blood coagulation in association.
Fanhdi is used for:

• Treatment and prevention of bleeding episodes in subjects with hemophilia A (congenital deficiency of factor VIII).
• Treatment of acquired factor VIII deficiency.
• Treatment of hemophilia A patients with antibodies against factor VIII (inhibitors).
• Treatment and prevention of bleeding episodes in subjects with von Willebrand disease, when treatment with desmopressin (DDAVP) alone is ineffective or contraindicated.

2. What you need to know before using Fanhdi

Do not use Fanhdi

• If you are allergic to human blood coagulation factor VIII and von Willebrand factor in combination or to any of the other ingredients of this medicine (listed in section 6)

If you would like more information, ask your doctor.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before using Fanhdi.

• Rarely, a hypersensitivity reaction may develop, characterised by skin rash, feeling of tightness in the chest, wheezing, dizziness, lightheadedness, nausea or low blood pressure with dizziness when standing up; this reaction can progress to shock (a severe and sudden allergic reaction). If these symptoms occur, you must stop usingthe product immediatelyand call your doctor.
• The doctor must perform tests to ensure that the dose of Fanhdi you are receiving is sufficient to achieve and maintain an appropriate level of factor VIII, thus blocking any bleeding.
• The formation of inhibitors (antibodies) is a known complication that can occur during treatment with all factor VIII-based medicines. Inhibitors, especially at high levels, prevent the treatment from working correctly and you or your child will be closely monitored to check for the development of these inhibitors. If Fanhdi does not control the bleeding in you or your child, inform your doctor immediately.
• If you have already developed an inhibitor to FVIII and change the factor VIII-based medicine, you may still experience the inhibitor.
• During the treatment of von Willebrand disease, there is a risk of blood clots forming, especially if clinical risk factors are known. Therefore, the doctor must perform tests to identify any signs of clots and prescribe treatment, if necessary.
• In the case of using VWF products containing FVIII:C, prolonged treatment may determine an excessive increase in the level of FVIII:C. Plasma levels of FVIII:C must be carefully monitored to avoid persistently elevated levels in the plasma, resulting in an increased risk of thrombotic events.
• Patients with von Willebrand disease, especially type 3, may develop neutralizing antibodies to von Willebrand factor (inhibitors). Von Willebrand factor inhibitors are antibodies

present in the blood that can block the von Willebrand factor you are using. If
the activity of von Willebrand factor does not reach the expected plasma levels, or if the bleeding does not
control with an appropriate dose, an assay must be performed to determine the
presence of von Willebrand factor inhibitor. In patients with a high level of inhibitor, therapy
with effective von Willebrand factor may prove ineffective and other therapeutic options must be considered.

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

When medicines are produced from human plasma or blood, precautionary measures are taken to
prevent the possibility of transmitting infections to patients. These measures include:

• careful selection of plasma and blood donors, to ensure that donors at risk of carrying infections are excluded,
• testing of each donation and plasma pools for signs of viruses/infections,
• inclusion of processes during the processing of blood or plasma that can inactivate or remove viruses.

Despite these measures, when medicines produced from human plasma or blood are administered,
the possibility of transmitting an infection cannot be completely excluded. This applies to all viruses
of still unknown origin, emerging viruses or other types of infections.
The measures taken are considered effective for enveloped viruses, such as the human immunodeficiency virus (HIV), hepatitis B virus, hepatitis C virus and for the non-
enveloped hepatitis A virus. The measures taken may be of limited value against non-enveloped
viruses such as parvovirus B19.
Infections with parvovirus B19 can be severe for pregnant women (fetal infection) and for
individuals with immunodeficiency or with certain types of anemia (for example: sickle cell anemia or hemolytic anemia).
The doctor may recommend vaccination against hepatitis A and B if you infuse
regularly/repeatedly factor VIII concentrates derived from human plasma.
It is recommended that the name and batch number of the
product be recorded each time Fanhdi is administered, to maintain traceability of the batches used.
See also section 4.
Children and adolescents
The warnings and precautions listed apply to both adults and children.

Other medicines and Fanhdi
Tell your doctor or pharmacist if you are taking, have recently taken or might take
any other medicines.
No interactions of FVIII/FVW with other medicines are known.

Pregnancy and breastfeeding
If you are pregnant, suspect you are pregnant or are planning to become pregnant, or if you are breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.
FVIII/VWF should be used during pregnancy and breastfeeding only if clearly indicated.

Driving and using machines
Fanhdi does not affect the ability to drive and operate machinery.

Sodium content
The residual sodium content in Fanhdi, from the manufacturing process, does not exceed 23 mg per
vial (0.1 mmol/ml or 2.3 mg/ml) in the 250, 500 and 1000 IU presentations, and 34.5 mg per
vial (0.1 mmol/ml or 2.3 mg/ml) in the 1500 IU presentation. This corresponds to 1.15% and 1.72%,
respectively, of the recommended maximum daily intake of sodium for an adult. However, depending on the patient's body weight and dosage, the patient may receive more than one
vial.

3. How to use Fanhdi

The product must be injected intravenously. The administration rate should not exceed
10 ml/min.
Use this medicine exactly as your doctor or healthcare professional at the
hemophilia center has instructed. If you have any doubts, ask your doctor, pharmacist, or nurse.
The amount of Fanhdi you need to use depends on various factors, such as weight, clinical condition, type and
severity of bleeding. The doctor will calculate the dose, frequency, and intervals of administration
of Fanhdi, to achieve the necessary level of factor VIII or von Willebrand factor in the blood.
The doctor will decide the duration of treatment with Fanhdi.
To prepare the solution:
Make sure to work under the most appropriate conditions at all stages of the process, to avoid
contamination of the product.

• 1. Warm the vial and syringe, without exceeding 30 °C.
• 2. Insert the plunger into the syringe containing the solvent.
• 3. Remove the filter from its packaging. Remove the cap from the syringe connector and connect it to the filter.
• 4. Remove the vial adapter from its packaging and connect it to the filter on the syringe.
• 5. Remove the plastic protector from the vial and clean the stopper with the disinfectant wipes provided.
• 6. Puncture the vial stopper with the needle of the adapter.
• 7. Transfer all the solvent from the syringe to the vial.
• 8. Rotate the vial without shaking, until all the product is dissolved. Since this is a solution for parenteral use, do not use the product if it has not dissolved completely or if particles are visible.
• 9. Quickly separate the syringe with the filter from the vial with the adapter, to eliminate the vacuum.

• 10. With the vial held high, draw the solution into the syringe.
• 11. Prepare the injection site, disconnect the syringe and inject the product using the butterfly needle set provided. The injection rate should be 3 ml/min into the vein and in any case not exceeding 10 ml/min, to avoid vasomotor reactions.

Do not reuse the administration sets. The remaining product should never be used at a
later time, nor stored in the refrigerator.
It is important to use the infusion set provided with the medicine. If other
medical infusion systems are used, the compatibility of these systems with the prefilled
syringe must be verified. Adapters must be used if necessary to ensure correct
administration of the product.

Use in children and adolescents
Data from clinical studies are insufficient to recommend the use of Fanhdi in children under the age of
6 years.

If you use more Fanhdi than you should
No cases of overdose with factor VIII and von Willebrand factor have been reported in association.
In the event of a severe overdose, thromboembolic events may occur.
However, if you have taken more Fanhdi than you should, inform your doctor or pharmacist immediately.

If you forget to use Fanhdi

• Proceed immediately with the next administration and continue at regular intervals, following your doctor's instructions.
• Do not use a double dose to make up for the missed dose.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everybody gets them.
Rarely, some of the following side effects may develop after the administration of
Fanhdi. Call your doctor immediately if you feel:

• itching, localised reactions at the injection site (e.g. burning and temporary redness),
• allergic reactions (e.g. oppression of the chest or feeling unwell, dizziness, nausea and low blood pressure, which can cause lightheadedness when standing up, chills, flushing, widespread urticaria, headache, drowsiness, agitation, tingling, vomiting, wheezing),
• fever,
• fast heartbeat (tachycardia).

Rarely, anaphylactic shock may occur. If you feel any of the following symptoms during the
administration

• oppression of the chest or feeling unwell
• dizziness
• low blood pressure which can cause dizziness when standing up
• chills
• flushing, widespread urticaria
• headache, drowsiness, agitation
• tingling
• wheezing
• nausea, vomiting

may be an early sign of hypersensitivity and anaphylactic reaction. In case of anaphylactic or
allergic reaction, stop the administration and call your doctor immediately.
Haemophilia A
Allergic reactions to the excipients of the product cannot be ruled out. In children not previously treated
with factor VIII-based medicines, the formation of inhibitor antibodies (see paragraph

• 2) may be very common (more than 1 patient in 10); however, in patients who have received previous treatment with factor VIII (more than 150 days of treatment) the risk is uncommon (less than 1 patient in 100). If this happens, the medicine for you or your child may stop working properly and you or your child may experience persistent bleeding. If this happens, you should contact your doctor immediately.

Von Willebrand Disease
When using a VWF-containing product with FVIII, for the treatment of VWD (von Willebrand disease), prolonged treatment may cause an excessive increase in FVIII in the blood. This
can increase the risk of thrombotic events.
If you are a patient with known clinical or laboratory risk factors, you should be monitored for
the early signs of thrombosis. Your doctor will need to establish preventive measures (prophylaxis) against
venous thromboembolism, according to current recommendations.
Especially if you are a patient with type 3 von Willebrand disease, you may rarely
develop neutralising antibodies (inhibitors) to von Willebrand factor. If these inhibitors develop, the von Willebrand factor is less effective in controlling bleeding. If your bleeding
does not stop, the presence of inhibitors in your blood should be checked. These antibodies
may be associated with anaphylactic reactions. Therefore, in those patients who develop reactions
anaphylactic reactions, the presence of inhibitors should be evaluated. In these cases, contact your doctor immediately.
For information on viral safety, see paragraph 2.
Paediatric population
The frequency, type and severity of adverse reactions in children are expected to be the same as in
adults.

Reporting of adverse reactions
If you get any side effects, even if not listed in this leaflet, tell your
doctor or pharmacist or nurse. You can also report side effects directly
through the national reporting system, at the address: www.agenziafarmaco.gov.it/content/come-
segnalare-una-sospetta-reazione-avversa ”.
By reporting side effects you can help provide more information on the safety of
this medicine.

5. How to store Fanhdi

Keep this medicine out of the sight and reach of children.
Do not store at a temperature above 30°C.
Do not freeze. Protect from light.
Do not use this medicine after the expiry date which is stated on the label and the carton after
“Exp.”.
Do not use this medicine if you notice that the solution is cloudy or contains deposits. The solution must
be clear or slightly opalescent. If the solution is cloudy or shows changes in colour, discard it.
The product after reconstitution has a validity of 12 hours if stored at a temperature of 25 °C.
From a microbiological point of view, the product must be used immediately; if not used
immediately, the time and conditions of storage before use are the responsibility of
the user and, as a rule, do not exceed 24 hours at (+2 - +8) °C, unless the reconstitution has been
carried out under controlled and validated aseptic conditions.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Package Contents and Other Information

What Fanhdi contains
The active ingredient is human blood coagulation factor VIII and von Willebrand factor in
association.
Fanhdi is supplied as a lyophilized powder and solvent for solution for infusion, containing approximately
250 IU, 500 IU, 1000 IU or 1500 IU of human blood coagulation factor VIII, and 300 IU, 600 IU,
1200 IU or 1800 IU of von Willebrand factor per vial. The product is reconstituted with 10 ml (for the
250 IU, 500 IU and 1000 IU sizes) or 15 ml (for the 1500 IU size) of water for injections.
The other ingredients are histidine, human albumin, arginine.

Description of the appearance of Fanhdi and contents of the pack
Vial containing a white or pale yellow powder and a syringe with water for
injections (solvent).
Pack: 1 vial, 1 pre-filled syringe of solvent and accessories (a vial adapter, a
filter, 2 disinfectant wipes and an infusion set).

Marketing Authorisation Holder and Manufacturer
Instituto Grifols S.A.
Can Guasc, 2 – Parets del Vallès
08150 Barcelona - SPAIN
…………………….........................................................................................................................
...........
The following information is intended exclusively for physicians or healthcare professionals:

Dosage and Administration
Hemophilia A
The doses and duration of replacement therapy depend on the severity of the factor VIII deficiency, the
location and extent of the bleeding and the patient’s clinical condition.
The number of units of factor VIII administered is expressed in International Units (IU), which are
correlated with current WHO standards for factor VIII-based products. The activity of factor VIII in
plasma is expressed either as a percentage (relative to normal human plasma) or in International
Units (relative to an International Standard for plasma factor VIII).
One International Unit (IU) of factor VIII is equivalent to the amount of factor VIII in 1 ml of
normal human plasma.

On-demand treatment
The calculation of the required dosage of factor VIII is based on empirical evidence that 1 International
Unit (IU) of factor VIII per kg of body weight increases plasma factor VIII activity by 2.1 + 0.4% of
normal activity. The required dose is determined by applying the following formula:

Units required = Body weight xDesired increase in factor VIII x 0.5
(IU)(kg)(%) (IU/dl)
The amount to be administered and the frequency of administrations should always aim to
achieve clinical efficacy in each individual case.
In the case of the following bleeding events, the factor VIII activity should not fall below the activity levels
indicated (as % of normal or IU/dl) within the specified time. The following table can be used to guide
dosage in bleeding episodes and surgery:

Grade of bleeding /
Type of surgical procedure
Required factor
VIII levels
(%) (IU/dl)
Frequency of
administrations
(hours) / Duration of therapy (days)
Bleeding
Recent hemarthrosis, intramuscular or oral cavity bleeding.

• 20 – 40 Repeat every 12 - 24 hours. At least 1 day, until the bleeding episode resolves, or scarring occurs. More extensive hemarthrosis, intramuscular bleeding or hematoma.
• 30 – 60 Repeat the infusion every 12 - 24 hours for 3-4 days or more, until pain and acute disability resolve. Life-threatening bleeding.
• 60 – 100 Repeat the infusion every 8 - 24 hours, until the danger has passed. SurgeryMinor surgery (including dental extractions)
• 30 – 60 Every 24 hours, at least 1 day, until scarring.

Major surgery 80 – 100
(pre- and
postoperative)
Repeat administration every 8 - 24
hours until adequate wound healing, then therapy for at least another 7
days to maintain a factor VIII activity of 30 to 60% (IU/dl).

Prophylaxis
For long-term prophylaxis of bleeding in patients with severe hemophilia A, the usual doses range
from 20 to 40 IU of factor VIII per kg of body weight, at intervals of 2 - 3 days. In some cases,
especially in younger subjects, it may be necessary to reduce the intervals between doses or
administer higher doses.
During the course of treatment, it is advisable to carefully determine factor VIII levels, to
adjust the dose to be administered and the frequency of repeating infusions. Individual patients
may show different responses to factor VIII, exhibiting different half-lives and recoveries. As the dose is based
on body weight, dose adjustment may be necessary in underweight or
overweight patients. In the case of major surgery, in particular, precise
monitoring of replacement therapy by means of coagulation tests (plasma factor VIII activity) is essential.
Von Willebrand Disease
Generally, 1 IU/kg of VWF:RCo increases circulating VWF:RCo levels by 0.02 IU/ml (2%).
Levels of VWF:RCo  0.6 IU/ml (60%) and FVIII:C  0.4 IU/ml (40%) should be achieved.
Normally, to achieve hemostasis, it is recommended to administer 40-80 IU/kg of von
Willebrand factor (VWF:RCo) and 20-40 IU/kg of FVIII:C.
An initial dose of 80 IU/kg of von Willebrand factor may be necessary, especially for patients
with type 3 von Willebrand disease, where maintaining adequate levels may require higher doses
than other types of von Willebrand disease.
Appropriate doses should then be 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 VWF:RCo and FVIII:C.
When using von Willebrand factor preparations containing FVIII, the physician must be informed
that prolonged treatment can lead to an excessive increase in FVIII:C levels. After 24-48
hours of treatment, it is advisable to reduce the dose and/or increase the time interval between
administrations or use a VWF product containing a low FVIII titre to avoid an
excessive increase in FVIII:C levels.

Paediatric population
The safety and efficacy of Fanhdi in children under 6 years of age have not been established.