Emoclot

Package leaflet: Information for the user

EMOCLOT 500 IU/10 ml Powder and solvent for solution for infusion, 1000 IU/10 ml Powder and solvent for solution for infusion

Coagulation factor VIII, human plasma
Please read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as yours, because it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What EMOCLOT is and what it is used for
2. What you need to know 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 solution of coagulation factor VIII derived from human plasma.
Factor VIII is a protein that has antihemorrhagic activity.
EMOCLOT is used in the following therapies:
in the treatment and prevention of bleeding in patients affected by hereditary deficiency of
factor VIII activity (haemophilia A);
in the treatment of bleeding in patients with acquired deficiency of factor VIII activity due to other diseases;
in the treatment of haemophilic patients who have developed antibodies against factor VIII (inhibitors).

2. What you should know before using EMOCLOT

Do not use EMOCLOT

• if you are allergic to human factor VIII or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Talk to your doctor before using EMOCLOT.
Allergic reaction
Allergic-type hypersensitivity reactions may occur with EMOCLOT.
EMOCLOT contains traces of human proteins other than factor VIII. If during administration you notice any of the symptoms listed below, stop administration immediately and contact your doctor, as these symptoms could be the first signs of an allergic reaction. Symptoms may include: hives, generalized urticaria, tightness in the chest, wheezing, drop in blood pressure, and even severe allergic reaction.
In case of shock, standard shock management guidelines must be followed.
Inhibitors
The development of inhibitors (antibodies) is a known complication that may occur during treatment with all factor VIII medicines. Inhibitors, especially at high levels, may prevent the treatment from working properly, and you or your child will be closely monitored for the development of such inhibitors. If EMOCLOT does not control bleeding in you or your child, inform your doctor immediately.
Cardiovascular events
In patients with cardiovascular risk factors, replacement therapy with FVIII may increase cardiovascular risk.
Complications related to catheter use
If a central venous access device is required, the risk of device-related complications should be considered, including local infections, bacteremia, and thrombosis at the catheter site.
Viral safety
When medicines are prepared from human blood or plasma, specific measures are taken to prevent transmission of infections to patients. These measures include:

• careful selection of blood and plasma donors to ensure potentially infected donors are excluded;
• testing of each donation and plasma pool (a mixture of several donations) to detect the presence of infections/viruses;
• inclusion in the manufacturing process of steps capable of inactivating or removing viruses.

Despite these measures, when administering medicines prepared from human blood or plasma, the possibility of transmitting infectious agents cannot be completely ruled out. This also applies to emerging or unknown viruses or other types of infectious agents. The measures taken are considered effective against lipid-enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis A virus (HAV), which lacks a lipid envelope. The measures taken may have limited effect against non-enveloped viruses such as parvovirus B19. Parvovirus B19 infection may be severe during pregnancy (fetal infection) and in individuals with depressed immune systems or certain types of anemia (e.g., sickle cell anemia or hemolytic anemia).

It is strongly recommended that each time you receive a dose of EMOCLOT, both the name and batch number of the product are recorded, to ensure traceability of the batch used.
Your doctor may advise you to consider vaccination against hepatitis A and B if you regularly/repeatedly receive coagulation factor VIII derived from human plasma.
Children
Specific data in the pediatric population are not available.
More information is provided at the end of the package leaflet in the section intended for
doctors or healthcare professionals.
Other medicines and EMOCLOT
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
No interactions have been reported between human coagulation factor VIII products and other medicinal products.
Specific data in the pediatric population are not available.
Pregnancy, breastfeeding and fertility

• If you are pregnant, suspect you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
• Animal reproduction studies with factor VIII have not been conducted. Due to the rarity of hemophilia A in women, data on the use of factor VIII during pregnancy and breastfeeding are not available. Therefore, factor VIII should be used during pregnancy and breastfeeding only if clearly indicated.

Driving and use of machinery
EMOCLOT has no effect on the ability to drive or operate machinery.
EMOCLOT contains sodium
This medicine contains up to a maximum of 41 mg of sodium (a main component of table salt) per 10 ml vial.
This corresponds to 2.05% of the maximum daily recommended dietary intake for an adult.

3. How to use EMOCLOT

Use this medicine exactly as instructed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
Dosage
The dose and duration of replacement therapy depend on the severity of factor VIII deficiency,
the location and extent of bleeding, and your clinical condition.
On-demand treatment
The amount of medicine and frequency of administrations you should receive must be
determined based on your clinical response.
Prophylaxis
For long-term prevention of bleeding episodes in patients with severe haemophilia A, the usual
doses are 20 to 40 IU (International Units) of factor VIII per kg of body weight, administered every 2–3
days. In some cases, especially in younger patients, shorter treatment intervals or higher doses may be required.
You should be carefully monitored for the possible development of factor VIII inhibitors through appropriate clinical observations and laboratory tests.
During treatment, appropriate measurement of factor VIII levels is required to adjust the dose and frequency of repeated infusions. In particular, in the case of major surgical procedures, it is essential that your replacement therapy be precisely monitored by coagulation analyses (plasma factor VIII activity).
Use in children and adolescents
The safety and efficacy of EMOCLOT in children under 12 years of age have not yet been established. For adolescents (12–18 years), the dose for each indication will be adjusted according to body weight.
Further information regarding dosage and duration of therapy is provided at the end
of this leaflet in the section intended for doctors or healthcare professionals.
Instructions for correct use
This product must be administered intravenously, either by injection or slow infusion.
For intravenous injection, a administration time of 3 to 5 minutes is recommended. Monitor the pulse and interrupt or reduce the injection rate if pulse rate increases.
The infusion rate should be individually adjusted for each patient.
Only the injection/infusion devices supplied in the package must be used, as treatment failure may occur because part of the factor VIII may be retained on the surfaces of certain devices.
Incompatibilities: In the absence of compatibility studies, EMOCLOT must not be mixed with other
medicinal products.
Reconstitution of the powder with solvent:

1. Bring the vial of powder and the solvent vial to room temperature;
2. Maintain this temperature throughout the entire reconstitution process (within a maximum of 10 minutes);
3. Remove the protective caps from the powder and solvent vials;
4. Clean the stoppers of both vials with alcohol;
5. Open the device package by removing the top; take care not to touch the inside (Fig. A);
6. Do not remove the device from its packaging;
7. Invert the device package and insert the plastic spike through the stopper of the solvent vial so that the blue part of the device is attached to the solvent vial (Fig. B);
8. Grasp the edge of the device package and pull it off to release the device without touching it (Fig. C);
9. Ensure the vial containing the powder is placed on a stable surface; invert the system so that the solvent vial is positioned above the device; press the transparent/white adapter onto the stopper of the vial containing the powder so that the plastic spike pierces the stopper of the powder vial; the solvent will be automatically drawn into the powder vial (Fig. D);
10. After solvent transfer, unscrew the blue part of the transfer system with the attached solvent vial and remove it (Fig. E);
11. Gently rotate the vial until the powder is completely dissolved. Do not shake vigorously to avoid foam formation (Fig. F). Ensure the powder is completely dissolved, otherwise product activity may be reduced.

Administration of the solution
After reconstitution, the solution may contain a few small filaments or particles.
The reconstituted medicine should be visually inspected before administration for the presence of particulate matter or discoloration. The solution should be clear or slightly opalescent. Do not use cloudy solutions or those containing deposits.

1. Draw air into the syringe by pulling back the plunger, attach the syringe to the device, and inject the air into the vial containing the reconstituted solution (Fig. G);
2. While keeping the plunger steady, invert the system so that the vial with the reconstituted solution is positioned above the device, and slowly draw the concentrate into the syringe by pulling back the plunger (Fig. H);
3. Disconnect the syringe by rotating it counterclockwise;
4. Visually inspect the solution in the syringe, which should appear clear or slightly opalescent and free of particles;
5. Attach the butterfly needle to the syringe and administer the solution slowly by intravenous infusion or injection.

If you use more EMOCLOT than you should
The consequences of overdose are unknown.
In case of accidental ingestion/overdose of EMOCLOT, inform your doctor immediately or go to the nearest hospital.
If you have any doubts about the use of EMOCLOT, consult your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
If you experience any of the following side effects, contact your doctor immediately or go to the
nearest hospital:

• Severe allergic reactions (hypersensitivity): rapid swelling of the skin and mucous membranes around the mouth and face (angioedema). This side effect has been observed rarely and in some cases may lead to severe acute allergic reactions (anaphylaxis), including shock.
• Patients with haemophilia A may develop neutralizing antibodies against factor VIII (inhibitors). The presence of these inhibitors may manifest as a poor clinical response. In such cases, it is advisable to contact a specialized haemophilia treatment centre.

Other side effects:

• Other allergic reactions (hypersensitivity) may include: burning sensation and stinging pain at the infusion site; chills, flushing, generalized skin rash (generalized urticaria), wheals; headache; drop in blood pressure (hypotension), restlessness, increased heart rate (tachycardia), feeling of tightness in the chest, wheezing; drowsiness (lethargy); nausea, vomiting; tingling (paresthesia). These side effects have been observed rarely and in some cases may lead to severe acute allergic reactions (anaphylaxis), including shock.
• Fever has been observed.

In previously untreated children receiving factor VIII-containing medicines, the development of
inhibitor antibodies (see section 2) may be very common (more than 1 in 10 patients); however, in
patients who have previously received factor VIII treatment (more than 150 days of treatment), the risk is uncommon (less than 1 in 100). If this occurs, the medicine may no longer work properly and you or your child may experience persistent bleeding. If this happens, you must contact your doctor immediately.
Additional side effects in children
Although specific data in the paediatric population are limited, the few published data from efficacy and safety studies have not shown significant differences between adults and children affected by the same condition.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-
avverse .
By reporting side effects, you can help provide more information on the safety of this medicine.
For safety information regarding transmissible agents, see section 2 “What you need to know before using EMOCLOT”.

5. How to store EMOCLOT

Keep this medicine out of the sight and reach of children. Do not use EMOCLOT after the expiry date which is stated on the label and on the outer packaging following “Exp.”. The expiry date refers to the last day of that month.
Store in a refrigerator (2 °C - 8 °C). Do not freeze. Keep the vial in the outer packaging to protect the medicine from light.
Before use and within the expiry date, 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 vial containing the powder must be discarded. In any case, this vial must not be returned to the refrigerator if it has been stored at room temperature.
Record the date when storage at room temperature was started on the outer carton.
Once the infusion container has been opened, the contents must be used immediately. The contents of the vial must be used for a single administration only.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

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

The activity (IU) is determined using the chromogenic method of the European Pharmacopoeia.
The specific activity of EMOCLOT is approximately 80 IU/mg of protein.
Produced from plasma of human donors.
This preparation contains human von Willebrand factor.
The vial of powder contains human coagulation factor VIII (active substance),
sodium chloride, trisodium citrate, glycine, calcium chloride (excipients).
The solvent vial contains water for injections.

Description of the appearance of EMOCLOT and contents of the pack
Powder and solvent for solution for infusion.
After reconstitution, the solution may contain a few small filaments or particles.
The reconstituted (dissolved) medicinal product must be inspected visually before administration to detect suspended particles or abnormal discoloration. The solution should be clear or slightly opalescent. Do not use EMOCLOT if the solution appears cloudy or contains deposits.
The EMOCLOT pack contains one vial of powder, one vial of solvent used to prepare the solution for administration, and a sterile, pyrogen-free, single-use set consisting of a reconstitution device, an injection syringe, and a butterfly needle with PVC tubing.

Marketing Authorization Holder
Kedrion S.p.A. – Loc. Ai Conti, 55051 Castelvecchio Pascoli, Barga (Lucca), Italy

Manufacturer
Kedrion S.p.A. – 55027 Bolognana, Gallicano (Lucca), Italy.

The following information is intended exclusively for physicians or healthcare professionals:

Monitoring of treatment
During treatment, appropriate determination of factor VIII levels is required to adjust the dose and frequency of infusions. Response to factor VIII may vary among individual patients, showing different half-lives and recovery rates. Dosing calculated based on body weight may require adjustment in underweight or overweight patients.
In particular, during major surgical procedures, it is essential to closely monitor replacement therapy by means of coagulation assays (plasma factor VIII activity).
When using an in vitro “one-stage” coagulation assay based on activated partial thromboplastin time (aPTT) to determine factor VIII activity in patient blood samples, the results of plasma factor VIII activity may be significantly influenced by both the type of aPTT reagent and the reference standard used in the test. Furthermore, significant discrepancies may exist between results obtained with an aPTT-based “one-stage” coagulation assay and the chromogenic assay according to Ph. Eur. This is particularly important when changing laboratories and/or reagents used in testing.

Dosing
The dose 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 number of factor VIII units administered is expressed in International Units (IU), which are related to the current WHO standard 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 an international standard for plasma factor VIII).
The activity of one International Unit of factor VIII is equivalent to the amount of factor VIII contained in one milliliter of normal human plasma.

On-demand treatment
The calculation of the required factor VIII dose is based on the empirical observation that 1 International Unit (IU) of factor VIII per kg of body weight raises plasma factor VIII activity by 1.5% to 2% of normal activity. The required dose is determined using the following formula:
Units required = body weight (kg) × desired increase in factor VIII (%) (IU/dL) × 0.4
The amount to be administered and the frequency of administration should always be guided by the clinical efficacy observed in the individual case.

In the case of the following bleeding events, factor VIII activity during the corresponding period must not fall below the indicated plasma activity level (as % of normal). The following table may be used as a reference in bleeding episodes and surgical procedures:

Prophylaxis
For long-term prophylaxis of bleeding episodes in patients with severe haemophilia A, the usual doses are 20 to 40 IU of factor VIII per kg of body weight administered at intervals of 2 – 3 days. In some cases, particularly in younger patients, shorter treatment intervals or higher doses may be required.

Paediatric population
The safety and efficacy of EMOCLOT in children under 12 years of age have not yet been established. For adolescents (12–18 years), the dosage for each indication is based on body weight.

Method of administration
For intravenous use, by injection or slow infusion.
In the case of intravenous injection, a duration of administration between 3 and 5 minutes is recommended, monitoring the patient's pulse and interrupting or reducing the injection rate if pulse rate increases.
The infusion rate should be individually adjusted for each patient.
Reconstitute the powder as described in section “ 3. How to use EMOCLOT ” under the paragraph “ Instructions for correct use ”.

Inhibitors
In general, all patients treated with coagulation factor VIII products should be carefully monitored for the development of inhibitors through appropriate clinical observation and laboratory testing. If expected plasma factor VIII activity levels are not achieved, or if bleeding is not controlled with an appropriate dose, testing for the presence of factor VIII inhibitors should be performed. In patients with high inhibitor levels, therapy with factor VIII may be ineffective and alternative therapeutic options should be considered. The treatment of such patients should be managed by a physician experienced in the treatment of haemophilia and factor VIII inhibitors.