Emoclot

Patient Information Leaflet

EMOCLOT, 500 IU, powder and solvent for solution for injection and infusion
EMOCLOT, 1000 IU, powder and solvent for solution for injection and infusion
Human Coagulation Factor VIII
Please read all of 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 further questions, please consult your doctor.
• 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 you experience any adverse effects, including any not listed in this leaflet, inform your doctor. See section 4.

Table of contents:

1. What EMOCLOT is and what it is used for
2. Important information before using EMOCLOT
3. How to use EMOCLOT
4. Possible side effects
5. How to store EMOCLOT
6. Contents of the pack and other information

1. What EMOCLOT is and what it is used for

EMOCLOT is a highly purified concentrate of coagulation factor VIII derived from human plasma. Factor VIII is a protein with antihemorrhagic activity. EMOCLOT is used:

• for the treatment and prophylaxis of bleeding episodes in patients with congenital factor VIII deficiency (hemophilia A);
• for the treatment of bleeding episodes in patients with acquired factor VIII deficiency;
• for the treatment of patients with hemophilia who have developed inhibitors (antibodies) against factor VIII.

This medicine does not contain a pharmacologically effective amount of von Willebrand factor; therefore, it is not indicated for the treatment of von Willebrand disease.

2. Important information before using EMOCLOT

When not to use EMOCLOT
if the patient is allergic to human factor VIII or any of the other components of this
medication (listed in section 6).

Warnings and precautions
Before starting treatment with EMOCLOT, discuss this with your doctor.

Hypersensitivity
Allergic-type hypersensitivity reactions associated with EMOCLOT may occur.
EMOCLOT contains trace amounts of other human proteins besides factor VIII. Patients should be
informed about early signs of hypersensitivity reactions. Administration of the medicine should be
immediately discontinued if the patient develops symptoms suggesting an allergic reaction, such as:
rash, generalized urticaria, chest tightness, wheezing, low blood pressure, or acute allergic reaction.
In case of shock, administration must be stopped immediately and treatment should follow shock management guidelines.

Antibodies
Development of inhibitors (antibodies) is a known complication that may occur during treatment with any factor VIII-containing medication. These inhibitors, especially at high titres, may interfere with proper treatment, and the patient will be closely monitored for their development. If bleeding is not adequately controlled after administration of Emoclot, inform your doctor immediately.

Cardiovascular events
In patients with existing cardiovascular risk factors, factor VIII replacement therapy may increase the risk of cardiovascular disorders.

Complications related to central venous catheter use
If a central venous access device is required, consider the risks associated with its use, including local infection, bacteremia, and catheter site thrombosis.

Viral safety
For medications manufactured from human blood or plasma, appropriate preventive measures are taken to avoid transmission of infection to patients. These include:

• careful selection of blood and plasma donors to ensure exclusion of individuals at risk of carrying infections;
• testing of each donation and plasma pool (a collection of donations) for viruses and infectious agents;
• inclusion in the manufacturing process of procedures that inactivate or remove viruses.

Despite these precautions, it cannot be completely excluded that a medicine prepared from human blood or plasma might transmit infectious agents, including unknown or newly identified viruses and other pathogens. These measures are considered effective against enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and non-enveloped viruses such as hepatitis A virus (HAV). However, their effectiveness may be limited against non-enveloped viruses such as parvovirus B19. Parvovirus B19 infection may be harmful to pregnant women (fetal infection) and to patients with immunodeficiency or certain types of anemia (e.g. sickle cell anemia or hemolytic anemia).

It is strongly recommended that each time EMOCLOT is administered to a patient, the product name and batch number be recorded to allow future identification of the batch used.
For patients receiving regular or repeated administration of plasma-derived factor VIII, appropriate vaccinations (against hepatitis A and B) should be considered.

Children and adolescents
The above warnings and precautions apply to both adults and children.
Further information is provided at the end of this leaflet in the section intended for healthcare professionals.

EMOCLOT with other medicines
Inform your doctor or pharmacist about all medicines the patient is currently taking, has recently taken, or plans to take.
No interactions between factor VIII and other medicines have been reported.
There are no specific data on use in children.

Pregnancy and breastfeeding

• If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor before using this medicine.
• Animal reproductive studies with factor VIII have not been conducted. Due to the rarity of hemophilia A in women, there is limited experience with factor VIII use during pregnancy and breastfeeding. Therefore, factor VIII should be used during pregnancy and lactation only if strictly indicated.

Driving and operating machinery
EMOCLOT has no influence on the ability to drive or operate machinery.

EMOCLOT contains sodium
The medicine contains up to 41 mg of sodium (the main component of table salt) per 10 ml vial. This corresponds to 2.05% of the maximum daily recommended sodium intake in the adult diet.

3. How to use EMOCLOT
This medicine should always be used exactly as prescribed by the doctor. Treatment should be initiated under the supervision of a physician experienced in the management of hemophilia.

Recommended dose
The dosage and duration of replacement therapy depend on the severity of factor VIII deficiency, the site and extent of bleeding, and the patient's clinical condition.

On-demand treatment
The required amount and frequency of administration should be based on clinical efficacy in the individual case.

Prophylaxis
For long-term prophylaxis of bleeding episodes in patients with severe hemophilia A, doses of 20 to 40 IU of factor VIII per kg body weight are usually administered every 2 to 3 days.
In certain cases, especially in younger patients, more frequent administration or higher doses may be necessary.

Patients treated with factor VIII should be closely monitored and tested for the development of antibodies.
During treatment, the appropriate factor VIII level should be assessed to adjust dosage and frequency of infusions. Particularly during major surgical procedures, precise monitoring of replacement therapy using coagulation tests (factor VIII activity in plasma) is essential.

Children and adolescents
EMOCLOT is not recommended for use in children under 12 years of age due to insufficient data on safety and efficacy.

Further information on dosing and duration of treatment is provided at the end of this leaflet in the section intended for physicians and healthcare professionals.

Method of administration
The medicine is administered intravenously by injection or slow infusion.

For intravenous injection, administration over 3 to 5 minutes is recommended. Monitor the patient's pulse rate and discontinue or slow down the infusion if the pulse rate increases. The infusion rate should be individually adjusted for each patient.

Only the provided infusion or injection sets should be used, as adsorption of human factor VIII clotting factor onto the internal surfaces of certain medical infusion or injection devices may lead to therapeutic failure.

Incompatibilities: Due to lack of compatibility studies, this medicine must not be mixed with other medicinal products.

Reconstitution of powder with solvent:

1. Bring the vial of powder and the vial of solvent to room temperature;
2. Maintain room temperature throughout the reconstitution process (maximum 10 minutes);
3. Remove protective caps from both the powder vial and the solvent vial;
4. Clean the rubber stoppers of both vials with alcohol;
5. Open the medical reconstitution kit by carefully removing the cover without touching the device inside (Fig. A);
6. Do not remove the device from the packaging;
7. Invert the packaging with the device and insert the plastic spike through the stopper into the solvent vial, connecting the blue part of the device to the solvent vial (Fig. B);
8. Holding the edge of the packaging, remove it from the device without touching the device (Fig. C);
9. Ensure the powder vial is placed on a stable surface. Invert the connected device and solvent vial so that the solvent vial is on top. Press the transparent/white adapter onto the stopper of the powder vial so that the plastic spike of the device pierces the stopper. The solvent will automatically flow into the powder vial (Fig. D);
10. After the solvent has flowed in, unscrew the blue part of the reconstitution device with the attached solvent vial and discard it (Fig. E);
11. Gently mix by rotating the vial until the powder is completely dissolved. Do not shake vigorously to avoid foaming (Fig. F). Ensure the powder is completely dissolved; otherwise, the product may lose its effectiveness.

Fig. A	Fig. B
Fig. C	Fig. D
Fig. E	Fig. F

Administration of the solution
After reconstitution, the solution may contain a few small flakes or particles.
The reconstituted product should be visually inspected for the presence of particulate matter or discoloration before administration.
The solution should be clear or slightly opalescent. Do not use solutions that are cloudy or contain precipitate.

1. Fill the syringe with air by pulling back the plunger, connect the syringe to the device, and by pushing the plunger inject air into the vial containing the dissolved solution (Fig. G);
2. Keeping the syringe plunger stationary, invert the vial and syringe so that the vial containing the reconstituted solution is on top, and slowly pull back the plunger to draw the solution into the syringe (Fig. H);
3. Disconnect the syringe by turning it counterclockwise;
4. Inspect the solution in the syringe, which should be clear or slightly opalescent and free of particles;
5. Attach a butterfly needle to the syringe and administer via infusion or slow intravenous injection.

Fig. G

Fig. H

Use of a higher than recommended dose of EMOCLOT
Symptoms of overdose with human coagulation factor VIII are not known.
In case of accidental ingestion or overdose of EMOCLOT, seek immediate medical attention at the nearest hospital.
If you have any further doubts regarding the use of this medicine, consult your doctor.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
If any of the adverse reactions listed below occur, immediately inform your doctor or the nearest hospital:

• Serious allergic reactions (hypersensitivity): rapidly progressing swelling of the skin and mucous membranes around the mouth and face (angioedema). This reaction has been observed rarely, but in some cases may worsen and lead to acute allergic reactions, including anaphylactic shock.
• In patients with haemophilia A, neutralizing antibodies (inhibitors) against factor VIII may develop, resulting in a poor clinical response to treatment. In such cases, consultation with a specialized haemophilia treatment center is recommended.

Other possible adverse reactions:

• Other allergic reactions (hypersensitivity) may include:
• burning and pain at the site of administration;
• chills, sudden flushing of the face, generalized urticaria (hives affecting the entire body), rash;
• headache;
• drop in blood pressure (hypotension), restlessness, rapid heartbeat (tachycardia), chest tightness, wheezing;
• drowsiness (lethargy);
• nausea, vomiting;
• tingling sensation.

The above adverse reactions have been observed rarely after administration of factor VIII-containing medicines, but in some cases may progress to severe allergic reactions, including anaphylactic shock.

The frequency of adverse reactions following the introduction of Emoclot to the market is unknown, meaning it cannot be estimated based on available data.
Fever has also been observed.

In previously untreated children receiving factor VIII-containing medicines, blocking antibodies (see section 2) may develop very commonly (more than 1 in 10 patients). However, in patients who have previously been treated with factor VIII (over 150 days of treatment), the risk is uncommon (less than 1 in 100 patients). If this occurs, the medicine may stop working properly in the patient and persistent bleeding may occur. If this happens, contact your doctor immediately.

Additional adverse reactions in children
Although there are no specific data on the pediatric population, several published studies on efficacy and safety have not shown major differences between adults and children suffering from the same condition.

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor or nurse. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C,
02-222 Warsaw,
tel: 22 4921301,
fax: 22 4921309,
Website: https://smz2.ezdrowie.gov.pl/

Reporting adverse reactions helps to provide more information on the safety of the medicine.
Adverse reactions can also be reported directly to the marketing authorization holder.

For safety information regarding the transmission of infectious agents, see section 2.

5. How to store EMOCLOT

Keep the medicine out of sight and reach of children. Do not use the medicine after
the expiry date stated on the package following EXP. The expiry date refers to the last
day of the stated month.
Store in a refrigerator (2°C - 8°C). Do not freeze. Keep in the outer packaging to protect
from light.
Before use and during the medicine's shelf life, the vial containing the powder may be stored at
room temperature not exceeding 25°C for up to 6 consecutive months. After this period, the
medicine must be discarded. Under no circumstances may the medicine be returned to the
refrigerator after storage at room temperature.
The initial date of room temperature storage should be recorded on the outer packaging (carton).
After opening the vials, the contents should be used immediately. The contents of a vial are
intended for a single administration only.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist
how to dispose of medicines no longer required. Such measures will help protect the
environment.

6. Contents of the package and other information

What EMOCLOT contains
The active substance is human blood coagulation factor VIII.

The potency (IU) of the product has been determined by a chromogenic method in accordance with the European Pharmacopoeia.
The specific activity of the medicinal product is approximately 80 IU/mg of protein.
The medicinal product is manufactured from human plasma derived from donors.
The medicinal product contains: human von Willebrand factor: ristocetin cofactor activity (RCO) not less than
10 IU/ml for the 500 IU/10 ml strength and not less than 20 IU/ml for the 1000 IU/10 ml strength.
Other components of the medicinal product are sodium citrate, sodium chloride, glycine, calcium chloride.
Solvent: water for injections.
What Emoclot looks like and contents of the pack
Powder and solvent for solution for injection and infusion.
After reconstitution, the solution may contain a few small flakes or particles.
The reconstituted solution should be inspected visually for the presence of particulate matter or discoloration.
The solution should be clear or slightly opalescent. Do not use solutions that are cloudy or contain a precipitate.
The Emoclot pack contains one vial of powder, one vial of solvent for preparing the solution for administration, and a sterile set for reconstitution and administration consisting of a reconstitution device, a single-use syringe, and a butterfly needle with PCV tubing.
Emoclot, 500 IU/10 ml
1 vial of powder + 1 vial of solvent + set for reconstitution and administration.
Emoclot, 1000 IU/10 ml
1 vial of powder + 1 vial of solvent + set for reconstitution and administration.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Kedrion S.p.A. - Loc. Ai Conti, 55051 Castelvecchio Pascoli, Barga (Lucca), Italy
Manufacturer
Kedrion S.p.A. - 55027 Bolognana, Gallicano (Lucca), Italy
For further information, please contact the representative of the Marketing Authorisation Holder
MB&S Medical Business and Science, ul. Pilicka 4, 02-629 Warsaw, Poland
e-mail: [email protected]

Information intended exclusively for medical professionals:

Treatment Monitoring
During treatment, the appropriate factor VIII level should be assessed to adjust dosing and frequency of infusion repeats. Response to factor VIII may vary among individual patients in terms of half-life and recovery levels. Dose based on body weight may require adjustment in patients who are underweight or overweight.
Particularly during more serious surgical procedures, precise monitoring of replacement therapy is essential by measuring coagulation factor (factor VIII activity in plasma) to determine accurate dosing and infusion frequency.
When using a one-stage in vitro clotting assay based on activated partial thromboplastin time (aPTT) to determine factor VIII activity in patient blood samples, both the type of aPTT reagent and the reference standard used in the test may significantly influence the results of plasma factor VIII activity measurements.
Significant differences may also occur between results obtained with the one-stage aPTT-based clotting assay and those obtained with a chromogenic assay performed according to the European Pharmacopoeia. This is particularly important when changing laboratories and/or reagents used in testing.

Dosage
The dosage and duration of replacement therapy depend on the severity of factor VIII deficiency, the site and extent of bleeding, and the patient's clinical condition.
The number of units of administered factor VIII is expressed in International Units (IU), corresponding to the current WHO standards for factor VIII products. Factor VIII activity in plasma is expressed either as a percentage (relative to normal human plasma) or in International Units (relative to international standards for factor VIII in plasma).
One International Unit (IU) of factor VIII activity is equivalent to the amount of factor VIII present in 1 ml of plasma from a healthy individual.

On-demand treatment
Calculation of required factor VIII dosage is based on empirical data showing that 1 IU of factor VIII per kg of body weight increases factor VIII activity in plasma by 1.5% to 2%.
The required dosage is determined using the following formula:
Required number of units = body weight [kg] × desired rise in factor VIII activity [%]
[IU/dl] × 0.4

When determining the required amount and frequency of administration, clinical efficacy in the individual case should always be the guiding principle.
In the following bleeding situations, factor VIII activity at the appropriate time should not fall below the indicated plasma level (in % of normal or IU/dl).
The table below may serve as a basis for dosing during bleeding episodes and surgical procedures:

| Bleeding severity / Surgical procedure | Required factor VIII level (%) | (IU/dl) | Dosing frequency (hours) | Treatment duration (days) | |--------------------------------------------|--------------------------------------|-------------|-------------------------------|-------------------------------| | Bleeding: | | | | | | Early joint haemarthrosis, muscle haemorrhage, or oral cavity bleeding | 20 – 40 | | Repeat infusions every 12 to 24 hours for at least 1 day, until cessation of bleeding as assessed by pain relief or wound healing | | | More severe joint haemarthrosis, muscle haemorrhage, or acute haematoma | 30 – 60 | | Repeat every 12–24 hours for 3–4 days or longer until pain or acute disability resolves | | | Life-threatening bleeding | 60 – 100 | | Repeat every 8 to 24 hours until the threat has subsided | | | Surgical procedures: | | | | | | Minor surgical procedures, including tooth extraction | 30 – 60 | | Repeat infusions every 24 hours for at least 1 day, until wound healing | | | Major surgical procedures (pre- and post-operatively) | 80 – 100 | | Repeat every 8 to 24 hours until wound healing, then for at least 7 additional days to maintain factor VIII activity at 30% to 60% (30 IU/dl – 60 IU/dl) | |

Prophylaxis
For long-term prophylaxis of bleeding in patients with severe haemophilia A, doses of 20 to 40 IU of factor VIII per kg of body weight, administered every 2 to 3 days, are typically used.
In certain cases, especially in younger patients, more frequent administration or higher doses may be necessary.

Children and adolescents
EMOCLOT is not recommended for use in children under 12 years of age due to insufficient data on safety and efficacy. Dosing in adolescents (12–18 years) for each indication is calculated based on body weight.

Method of administration
Administer intravenously by injection or slow infusion.
For intravenous injection, it is recommended to administer over 3 to 5 minutes, monitoring the patient's pulse rate and interrupting or slowing the infusion if the pulse rate increases.
The infusion rate should be individually determined for each patient.
For instructions on reconstitution of the medicinal product prior to administration, see section 3. "How to use EMOCLOT".

Inhibitors
The clinical significance of an inhibitor formed will depend on its titre, with low-titre inhibitors posing a lower risk of inadequate clinical response compared to high-titre inhibitors.
In general, all patients treated with factor VIII coagulation products must be closely monitored for inhibitor development through clinical observation and laboratory testing. If, despite appropriate dosing, the expected factor VIII activity level in plasma is not achieved or bleeding cannot be controlled, testing for the presence of factor VIII inhibitors should be performed. In patients with significant inhibitor activity, treatment with factor VIII may be ineffective, and alternative therapeutic options should be considered. The management of such patients should be conducted under the supervision of physicians experienced in the treatment of haemophilia and factor VIII inhibitors.