Emoclot

Package Leaflet: Information for the User

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 carefully the entire leaflet before using this medicine, as it contains important information for you.

Important information for patients.

• You should keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, please inform your doctor. See section 4.

Contents of the pack:

• 1. What is EMOCLOT and what is it 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 is EMOCLOT and what is it used for

EMOCLOT is a highly purified concentrate of factor VIII obtained from human plasma. Factor VIII is a protein with anti-haemorrhagic activity.
EMOCLOT is used:

• for the treatment and prevention of bleeding in patients with congenital factor VIII deficiency (haemophilia A);
• for the treatment of bleeding in patients with acquired factor VIII deficiency;
• for the treatment of patients with haemophilia and factor VIII inhibitors.

This medicinal product does not contain a pharmacologically effective amount of von Willebrand factor, and is therefore not indicated for the treatment of von Willebrand's disease.

2. Important information before using EMOCLOT

When not to use EMOCLOT

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

Warnings and precautions

Before starting treatment with EMOCLOT, you should discuss it with your doctor.
Hypersensitivity
It is possible that allergic reactions of the hypersensitivity type associated with EMOCLOT may occur.
EMOCLOT contains trace amounts of human proteins other than factor VIII. Patients should be informed of the early signs of hypersensitivity reactions. Administration of the medicinal product should be discontinued immediately if the patient experiences any of the following symptoms that may indicate an allergic reaction: rash, generalised urticaria, chest tightness, wheezing, low blood pressure, and acute allergic reaction.
In case of shock, administration should be discontinued immediately and shock treatment should be initiated according to the guidelines.
Antibodies
The formation of inhibitors (antibodies) is a known complication that may occur during treatment with all factor VIII products. These inhibitors, especially at high titres, disrupt the normal treatment and the patient will be closely monitored for the development of these inhibitors. If bleeding in the patient is not properly controlled after using EMOCLOT, you should inform your doctor immediately.
Cardiovascular events
In patients with existing risk factors for cardiovascular disease, substitution therapy with factor VIII may increase the risk of cardiovascular disorders.
Complications related to catheter administration
In case of need to use a device for central venous administration, the risk of complications associated with its use should be considered, including local infection, bacteraemia, and thrombosis at the catheter insertion site.
Viral safety
For medicinal products manufactured from human blood or plasma, appropriate measures are taken to prevent the transmission of infectious agents to patients. These include:

• careful selection of blood and plasma donors to ensure that individuals at risk of transmitting infectious agents are excluded;
• testing of each donation and plasma pool (a collection of donations) for viruses and infections.
• incorporation into the manufacturing process of procedures that inactivate or remove viruses. Despite these measures, it cannot be completely excluded that the transmission of infectious agents cannot be completely ruled out. This also applies to unknown or newly discovered viruses and other pathogens. It is considered that the measures taken are effective against enveloped viruses, such as HIV, HBV, and HCV, and non-enveloped viruses, such as HAV. These measures may have limited effectiveness against non-enveloped viruses, such as parvovirus B19. Infection with parvovirus B19 can be harmful to pregnant women (fetal infection) and to patients with immune deficiencies or certain types of anaemia (e.g. sickle cell anaemia or haemolytic anaemia).

It is strongly recommended that every time EMOCLOT is administered to a patient, the name and batch number of the product should be recorded in order to maintain a record of the batches used.
For patients receiving regular or repeated factor VIII treatment, consideration should be given to appropriate vaccinations (against hepatitis A and B).
Children and adolescents
The above warnings and precautions apply to both adults and children.
More information can be found at the end of the leaflet in the section intended for healthcare professionals.

EMOCLOT and other medicines

Tell your doctor or pharmacist about all the medicines you are taking or have recently taken, as well as any medicines you plan to take.
No interactions between factor VIII and other medicines have been reported.
There are no special data on the use in children.

Pregnancy and breastfeeding

• If you are pregnant or breastfeeding, think you may be pregnant or plan to have a child, ask your doctor for advice before taking this medicine.
• No studies on the effects of factor VIII on reproductive function in animals have been conducted. Due to the rare occurrence of haemophilia A in women, there is a lack of experience with the use of factor VIII in pregnant and breastfeeding women. Therefore, factor VIII may only be used during pregnancy and lactation if strictly necessary.

Driving and using machines

EMOCLOT has no influence on the ability to drive and use machines.

EMOCLOT contains sodium

The medicinal product contains up to 41 mg of sodium (the main component of common salt) per 10 ml vial. This corresponds to 2.05% of the maximum recommended daily intake of sodium in the diet for adults.

3. How to use EMOCLOT

This medicinal product should always be used as directed by your doctor. Treatment should be initiated under the supervision of a doctor experienced in the treatment of haemophilia.

Recommended dose

Dosage and duration of substitution therapy depend on the degree of factor VIII deficiency, the location and extent of bleeding, and the patient's clinical condition.
On-demand treatment
When determining the required dose and frequency of administration, the clinical efficacy in the individual case should be taken into account.
Prophylaxis
In long-term prophylaxis of bleeding in patients with severe haemophilia A, doses of 20 to 40 IU of factor VIII per kg body weight are usually administered at intervals of 2 to 3 days.
In some cases, especially in younger patients, it may be necessary to administer the medicinal product at shorter intervals or in higher doses.
Patients treated with factor VIII should be closely monitored for the development of antibodies.
During treatment, the appropriate factor VIII level should be evaluated in order to adjust the dosage and frequency of infusions. In particular, in the case of major surgical procedures, precise monitoring of substitution therapy using coagulation tests (factor VIII activity in plasma) is necessary to determine the exact dosage and frequency of infusions.
Children and adolescents
EMOCLOT is not recommended for use in children under 12 years of age due to insufficient data on safety and efficacy.
More information on dosing and duration of treatment can be found at the end of this leaflet in the section intended for doctors and healthcare professionals.

Method of administration

The medicinal product is administered intravenously by injection or slow infusion.
In the case of intravenous injection, it is recommended to maintain the administration time from 3 to 5 minutes, checking the patient's heart rate and discontinuing administration or reducing the infusion rate if the heart rate increases.
The infusion rate should be determined individually for each patient.
Only the enclosed injection or infusion sets should be used, as adsorption of human factor VIII onto the inner surfaces of some injection or infusion sets may be the cause of therapeutic failure.
Incompatibilities: due to the lack of compatibility studies of this medicinal product, it must not be mixed with other medicinal products.

Reconstitution of the 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 the protective caps from the vial of powder and the vial of solvent;
• 4. clean the stopper surface of both vials with alcohol;
• 5. open the packaging of the medical device for reconstitution by removing the cover carefully, without touching the device inside the packaging (fig. A);
• 6. do not remove the device from the packaging;
• 7. turn the packaging with the device upside down and insert the plastic spike through the stopper into the vial of solvent to connect the blue part of the device to the solvent vial (fig. B);
• 8. holding the edge of the packaging, pull it off the device without touching it (fig. C);
• 9. ensure that the vial of powder is placed on a safe surface, turn the connected device and solvent vial upside down so that the vial is on top; press the transparent adapter onto the stopper of the powder vial so that the plastic spike of the device passes through 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 remove it (fig. E);
• 11. gently swirl until the powder is completely dissolved (fig. F);
• 12. do not shake vigorously, avoid foaming the solution.

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 particles or flakes.
The reconstituted solution should be inspected visually for particulate matter or discolouration before administration.
The solution should be clear or slightly opalescent. Do not use cloudy or precipitated solutions.

• 1. Fill the syringe with air by pulling back the plunger, connect the syringe to the device and, by pushing the plunger, introduce air into the vial with the reconstituted solution (fig. G);
• 2. holding the plunger in place, turn the vial and syringe upside down so that the vial containing the reconstituted solution is on top, slowly pull back the plunger to draw the solution into the syringe (fig. H);
• 3. disconnect the syringe by turning it in the opposite direction to the arrow;
• 4. check the solution in the syringe, which should be clear or slightly opalescent, without particles;
• 5. connect the butterfly needle to the syringe and administer by infusion or slow intravenous injection.

Fig. G
Fig. H

Use of a higher than recommended dose of EMOCLOT

There are no known symptoms of overdose of human factor VIII.
In case of accidental ingestion or overdose of EMOCLOT, you should immediately contact the nearest hospital.
In case of any further doubts about the use of this medicinal product, you should consult your doctor.

4. Possible side effects

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

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

Other possible side effects:

• Other allergic reactions (hypersensitivity) may include:
• burning and pain at the injection site;
• chills, sudden flushing of the face, generalised urticaria (occurring on the skin all over the body), rash;
• headache
• low blood pressure (hypotension), anxiety, rapid heartbeat (tachycardia), chest tightness, wheezing;
• drowsiness (lethargy);
• nausea, vomiting;
• tingling sensation. The above side effects have been observed in rare cases after administration of factor VIII products, but in some cases may worsen to acute allergic reactions, including anaphylactic shock.

The frequency of side effects after the marketing authorisation of EMOCLOT is unknown, which means that it cannot be estimated from the available data.
Fever has also been observed.
In children not previously treated with factor VIII products, inhibitory antibodies (see section 2) may develop very frequently (more than 1 in 10 patients). However, in patients who have previously been treated with factor VIII (more than 150 days of treatment), the risk is not very common (less than 1 in 100 patients). If this happens, the medicines may stop working properly in the patient and persistent bleeding may occur. If this happens, you should contact your doctor immediately.
Additional side effects in children
Although there are no special data on the paediatric population, several published data on efficacy and safety studies did not show significant differences between adults and children with the same condition.

Reporting of side effects

If you experience any side effects, including any not listed in this leaflet, you should inform your doctor or nurse. Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Jerozolimskie Avenue 181C,
02-222 Warsaw,
tel: 22 4921301,
fax: 22 4921309,
Website: https://smz.ezdrowie.gov.pl
By reporting side effects, you can help provide more information on the safety of this medicinal product.
Side effects can also be reported to the marketing authorisation holder.
Information on safety related to the transmission of infectious agents, see section 2.

5. How to store EMOCLOT

Keep this medicinal product out of the sight and reach of children. Do not use this medicinal product after the expiry date which is stated on the carton after EXP. The expiry date refers to the last day of the month stated.
Store in a refrigerator (2°C - 8°C). Do not freeze. Store in the outer carton in order to protect from light.
Before use and during the shelf-life of the medicinal product, the powder vial may be stored at room temperature (not above 25°C) for a maximum of 6 consecutive months. After this time, the medicinal product should be discarded. In no case can the medicinal product be returned to the refrigerator if it has been stored at room temperature.
The initial date of storage at room temperature should be recorded on the outer carton (box).
After opening, the contents of the vial should be used immediately. The contents of one vial are intended for one administration only.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What EMOCLOT contains

The active substance is human coagulation factor VIII.

The potency of the product (IU) has been determined using a chromogenic method in accordance with the European Pharmacopoeia.
The specific activity of the medicinal product is approximately 80 IU/mg protein.
The medicinal product is produced from human plasma 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 size and not less than 20 IU/ml for the 1000 IU/10 ml size.
Other ingredients 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 particles or flakes.
The reconstituted solution should be inspected visually for particulate matter or discolouration.
The solution should be clear or slightly opalescent. Do not use cloudy or precipitated solutions.
The EMOCLOT pack contains one vial of powder, one vial of solvent for preparation of the solution for administration, and a sterile device for reconstitution and administration consisting of a reconstitution device, a syringe for single use, and a butterfly needle with a PVC tube.
Emoclot, 500 IU/10 ml
1 vial of powder + 1 vial of solvent + device for reconstitution and administration.
Emoclot, 1000 IU/10 ml,
1 vial of powder + 1 vial of solvent + device 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
In order to obtain more detailed information, you should contact the representative of the marketing authorisation holder
MB&S, Chełmska 30/34, Warsaw
Tel/fax: 22 8515210

Date of last revision of the leaflet:

Information intended for healthcare professionals only:

Monitoring of treatment
During treatment, the appropriate factor VIII level should be evaluated in order to adjust the dosage and frequency of infusions. The response to factor VIII may vary from patient to patient in terms of half-life and recovery levels. Dosing based on body weight may need to be adjusted in patients who are underweight or overweight.
Particularly in the case of major surgical procedures, precise monitoring of substitution therapy through coagulation tests (factor VIII activity in plasma) is necessary to determine the exact dosage and frequency of infusions.
The above warnings and precautions apply to both adults and children.
More information can be found below.

Dosage

Dosage and duration of substitution therapy depend on the degree of factor VIII deficiency, the location and extent of bleeding, and the patient's clinical condition.
The number of units of factor VIII administered 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 factor VIII standards 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
The calculation of the required dose of factor VIII is based on empirical data demonstrating that 1 IU of factor VIII per kg body weight increases the factor VIII activity in plasma by 1.5% to 2%.
The required dose is determined according to the following formula:
Required number of units = body weight [kg] x desired increase in factor VIII activity [%] x 0.4
When determining the required dose and frequency of administration, the clinical efficacy in the individual case should always be taken into account.
In the following cases of bleeding, factor VIII activity in plasma should not fall below the specified value (% of normal or IU/ml).

Severity of bleeding / Type of surgical procedure

Frequency of dosing (hours) /

Duration of treatment (days)

Bleeding:
Early bleeding into a joint,
bleeding into muscles or from
the mouth

Required factor VIII level (%) (IU/ml)

• 20 - 40 Repeat infusions every 12 to 24 hours for at least 1 day, until bleeding has stopped as assessed by the disappearance of pain or healing of the wound. More extensive bleeding into a joint, bleeding into muscles or haematoma
• 30 - 60 Repeat every 12-24 hours for 3-4 days or longer until pain and acute disability have resolved. Life-threatening bleeding
• 60 - 100 Repeat every 8 to 24 hours until the risk has been resolved Surgical procedures: Minor surgical procedures, including tooth extraction
• 30 – 60 Repeat infusions every 24 hours for at least 1 day, until healing. Major surgical procedures
• 80 – 100 (before and after surgery) Repeat every 8 to 24 hours until wound healing, then for at least 7 days to maintain factor VIII activity at a level of 30% to 60% (30 IU/ml - 60 IU/ml).

Prophylaxis
In long-term prophylaxis of bleeding in patients with severe haemophilia A, doses of 20 to 40 IU of factor VIII per kg body weight are usually administered at intervals of 2 to 3 days.
In some cases, especially in younger patients, it may be necessary to administer the medicinal product at shorter intervals or in higher doses.
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.
In the case of intravenous injection, it is recommended to maintain the administration time from 3 to 5 minutes, checking the patient's heart rate and discontinuing administration or reducing the infusion rate if the heart rate increases.
The infusion rate should be determined individually for each patient.
Instructions for reconstitution of the medicinal product before administration, see section 3. How to use EMOCLOT.
Inhibitors
The clinical significance of an inhibitor will depend on the inhibitor titre, with low-titre inhibitors posing a lower risk of inadequate clinical response than high-titre inhibitors.
Generally, all patients treated with factor VIII products must be closely monitored for the development of inhibitors through clinical observation and laboratory tests. If, despite the administration of the recommended dose, it is not possible to achieve the expected factor VIII level in plasma or to control bleeding, a test to detect the presence of factor VIII inhibitors should be performed. In patients with significant inhibitor activity, treatment with factor VIII may be ineffective and alternative treatment options should be considered. The treatment of such patients should be managed under the guidance of physicians experienced in the treatment of haemophilia and factor VIII inhibitors.