Haemoctin 500

Package leaflet: Information for the user

Haemoctin 250
Haemoctin 500
Haemoctin 1000
Powder and solvent for solution for injection
Human coagulation factor VIII
Please read all of this leaflet carefully before using this medicine, because it contains
important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Contents of the leaflet:

1. What Haemoctin is and what it is used for
2. What you need to know before using Haemoctin
3. How to use Haemoctin
4. Possible side effects
5. How to store Haemoctin
6. Contents of the package and other information

1. What Haemoctin is and what it is used for

Haemoctin is a medicine derived from human plasma. It contains coagulation factor VIII, which is necessary for normal blood clotting. After dissolving the powder in water for injections, the solution is ready for intravenous administration.
Haemoctin is used in the treatment and prevention of bleeding episodes in patients with haemophilia A (congenital factor VIII deficiency).
Haemoctin does not contain von Willebrand factor in pharmacologically effective amounts and therefore is not intended for the treatment of von Willebrand disease.

2. Important information before using Haemoctin

When not to use Haemoctin

• if the patient is allergic to the active substance or to any of the other ingredients of this medicine (listed in section 6). An allergic reaction may include rash, itching, difficulty breathing, or swelling of the face, lips, throat, or tongue.

Warnings and precautions
The development of inhibitors (antibodies) is a known complication that may occur during
treatment with any Factor VIII-containing medicinal products. These inhibitors, especially at high
levels, may interfere with proper treatment, and the patient will be closely monitored for the
development of such inhibitors.
If bleeding is not properly controlled with Haemoctin, inform the doctor immediately.
If the patient has existing cardiovascular risk factors, treatment with Haemoctin may increase
cardiovascular risk. In case of doubt, discuss this with the doctor.
Complications related to vascular catheter insertion: If a central venous access device (CVAD) is
required, the risk of complications associated with CVAD should be considered, including local
infections, bacteremia, and thrombosis at the catheter insertion site.

Viral safety
When medicinal products are manufactured from human blood or plasma, specific measures are
taken to prevent transmission of infections to patients. These include:

• careful selection of blood and plasma donors to ensure exclusion of donors who may be carriers of infections,
• testing of all collected samples and plasma pools for the presence of viruses/infections,
• implementation of steps in the manufacturing process designed to inactivate or remove viruses. Despite these measures, the possibility of transmitting infection with products made from human blood or plasma cannot be completely excluded. This also applies to unknown or newly emerging viruses or other types of infections.

The measures taken are considered effective against enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus, and hepatitis C virus, as well as non-enveloped viruses such as hepatitis A virus. However, the measures may have limited effectiveness against non-enveloped viruses such as parvovirus B19. Parvovirus B19 infection may be dangerous for pregnant women (fetal infection) and for individuals with weakened immune systems or certain types of anemia (e.g. sickle cell or hemolytic anemia).
The treating physician may recommend that the patient consider vaccination against hepatitis A and B if receiving repeated or regular treatment with Factor VIII products derived from human plasma.
It is strongly recommended that the name and batch number of each dose of Haemoctin administered be recorded to allow traceability of the batches used in the future.

Children and adolescents
Warnings and precautions for use described for adults also apply to children and adolescents.

Haemoctin and other medicines
Inform the doctor about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.
No interactions between Haemoctin and other medicinal products have been reported.

Pregnancy, breastfeeding, and fertility
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.
Due to the rarity of hemophilia A in women, there is limited experience with the use of Factor VIII during pregnancy or breastfeeding. Animal studies during pregnancy and lactation have not been conducted.

Driving and operating machinery
Haemoctin has no effect or has a negligible effect on the ability to drive and operate machinery.

Haemoctin contains sodium
Haemoctin 250 contains up to 16.1 mg (0.70 mmol) of sodium (a main component of table salt) per vial. This corresponds to 0.81% of the maximum recommended daily dietary sodium intake for adults.
Haemoctin 500/1000 contains up to 32.2 mg (1.40 mmol) of sodium (a main component of table salt) per vial. This corresponds to 1.61% of the maximum recommended daily dietary sodium intake for adults.

3. How to use Haemoctin

This medicine should always be used as directed by the physician. If in doubt, consult your
doctor, pharmacist, or nurse.
Haemoctin is administered as an intravenous injection (intravenous administration). Treatment
should be supervised by a physician experienced in the management of haemophilia A.
Dosage and frequency of administration
The dose and duration of treatment depend on the severity of factor VIII deficiency, the site and extent
of bleeding, and the patient's clinical condition. The physician will determine the appropriate dose for the patient.
Instructions for use
If the patient has been given Haemoctin for home use, the doctor or nurse must ensure that the patient
knows how to administer it correctly.
Only the provided infusion set should be used, as adsorption of factor VIII onto the internal surfaces of certain
infusion sets may lead to therapeutic failure.
Sterile conditions must be maintained during preparation and administration of Haemoctin.

Fig. 1 Fig. 2 Fig. 3

Fig. 4 Fig. 5 Fig. 6 Fig. 7

Reconstitution of the concentrate:

• Allow the diluent (water for injections) and the product to reach room temperature in their unopened vials. If using a water bath for warming, take care not to wet the vial stoppers or caps, as this may lead to contamination of the medicinal product.
• Remove the caps from the diluent vial and the product vial to expose the central portions of the rubber stoppers (Fig. 1). Disinfect the rubber stoppers of both vials with a suitable antiseptic.
• Fully pull off the top of the transfer system packaging (Fig. 2). Do not touch the spike.
• Place the diluent vial on a flat surface. Insert the blue part of the transfer system straight down into the blister, positioning it vertically onto the upright diluent vial (Fig. 3) until it clicks into place. Do not twist the transfer system!
• Peel off the remaining part of the blister from the transfer system. This exposes the white part of the transfer system (Fig. 4).
• Place the product vial on a flat surface.
• Turn the connected transfer system and diluent vial upside down. Insert the spike of the white adapter part vertically downward through the stopper of the product vial (Fig. 5) until it clicks into place. The vacuum in the product vial will draw the diluent into the product vial.
• Gently swirl the product vial to aid dissolution of the powder. Do not shake vigorously; avoid foaming! The solution should be clear or slightly opalescent.

The reconstituted solution should be used immediately after reconstitution. Do not use solutions that are cloudy or contain particulate matter.
Administration:

• After dissolving the powder as described above, attach the provided syringe to the Luer-lock connector of the product vial via the white part of the transfer system (Fig. 7). This allows easy withdrawal of the dissolved medicine (Haemoctin 250: total volume 2.5 ml, Haemoctin 500/1000: total volume 5 ml) into the syringe. A separate filter is not required, as the transfer system includes an integrated filter.
• Carefully disconnect the vial with the white part of the transfer system from the syringe. Slowly administer the solution intravenously using the provided butterfly needle. The recommended infusion rate should not exceed 2–3 ml per minute.
• After use, the butterfly needle can be protected with its safety cap.

Use of a higher than recommended dose of Haemoctin
If the patient believes they have received too high a dose of Haemoctin, they should contact their doctor,
who will decide on further management.
Missed dose of Haemoctin
In such a case, the treating physician will decide whether further treatment is necessary.
Discontinuation of Haemoctin
Do not stop using Haemoctin without consulting your doctor.
If there are any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
If you notice any of the following symptoms, inform your doctor immediately:

• skin redness,
• burning and stinging sensation at the injection site,
• chills,
• sudden flushing of the face,
• headache,
• urticaria (hives),
• hypotension,
• drowsiness,
• nausea,
• restlessness,
• tachycardia,
• chest tightness,
• tingling,
• vomiting,
• wheezing. These may be signs of an allergic reaction, severe allergic reaction (anaphylactic shock), or hypersensitivity reaction.

The following adverse reactions have been observed during treatment with Haemoctin:
Unknown frequency: cannot be estimated from the available data

• shock (anaphylactic), allergic reaction
• skin redness, itching, urticaria

In previously untreated children receiving medicines containing factor VIII, inhibitory 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 (more than 150 days of treatment), the risk is uncommon (less than 1 in 100 patients). If this occurs, the patient's medication may no longer work properly and persistent bleeding may occur. If this happens, contact your doctor immediately.

Adverse reactions in children and adolescents
Except for the development of inhibitors (antibodies), adverse reactions in children are expected to be the same as in adults.

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store Haemoctin

Keep the medicine out of the sight and reach of children.
Store the vials in the outer packaging to protect from light.
After first opening, the product must be used immediately.
Do not store above 25°C. Do not freeze.
Do not use this medicine after the expiry date stated on the vial label and
outer packaging following: Expiry date.
Any unused product or waste material should be disposed of in accordance with local
regulations. Medicines should not be disposed of via wastewater or household waste.
Ask your pharmacist how to dispose of medicines no longer required. This will help
protect the environment.

6. Contents of the pack and other information

What the medicine contains Haemoctin

• The active substance is: human coagulation factor VIII.
• The other components are: glycine, sodium chloride, sodium citrate, and calcium chloride.
• The vial with solvent contains water for injections.

What Haemoctin looks like and contents of the pack
The medicine Haemoctin is supplied as a lyophilized powder (lyophilisate). Water for injections
is used as the solvent. The reconstituted product is clear or slightly opalescent.
Haemoctin 250 contains 1 vial with 250 IU and 1 vial with 2.5 ml of water for injections (100 IU/ml)
Haemoctin 500 contains 1 vial with 500 IU and 1 vial with 5 ml of water for injections (100 IU/ml)
Haemoctin 1000 contains 1 vial with 1000 IU and 1 vial with 5 ml of water for injections (200 IU/ml)
Each pack contains:

• one single-use syringe
• one transfer system with integrated filter
• one butterfly needle

Marketing Authorisation Holder and Manufacturer:
Biotest Pharma GmbH
Landsteinerstrasse 5
63303 Dreieich
Germany
Tel.: +49 6103 801-0
Fax: +49 6103 801-150
Email: [email protected]

Information intended exclusively for medical professionals:

Treatment Monitoring
Appropriate measurement of factor VIII levels is recommended during treatment to determine the dose to be administered and the frequency of repeated infusions. Individual patients may vary in their response to factor VIII, showing different half-life values and recovery levels. Doses based on body weight may require adjustment in patients who are underweight or overweight. Especially during major surgical procedures, precise monitoring of replacement therapy through coagulation testing (factor VIII activity in plasma) is essential.

When using a one-stage in vitro coagulation test 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 assay may significantly influence the results of factor VIII activity measurements. Considerable differences may also exist between results obtained with a one-stage aPTT-based coagulation test and those from a chromogenic assay according to the European Pharmacopoeia. This is particularly important when changing laboratories and/or reagents used in the test.

Dosage
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 amount of factor VIII administered is expressed in International Units (IU), referenced to the current WHO standard for factor VIII-containing products. Factor VIII activity in plasma is expressed either as a percentage (relative to normal human plasma) or preferably in International Units (relative to the International Standard for factor VIII in plasma).

One International Unit (IU) of factor VIII activity corresponds to the amount of factor VIII present in one millilitre of normal human plasma.

On-demand treatment
The required dose of factor VIII has been calculated based on empirical observations that 1 International Unit (IU) of factor VIII per kg of body weight raises plasma factor VIII activity by 1 to 2% of normal activity. The required dose can be calculated using the following formula:

Required number of units = body weight (kg) × desired increase in factor VIII (%) × 0.5

The required amount and frequency of administration should always be adjusted according to the individual clinical response.

In the following types of bleeding or surgical procedures, factor VIII activity should not fall below the indicated plasma activity level (% of normal). The table below may be used to determine dosing according to the type of bleeding or surgery:

| Bleeding / Surgical Procedure | Required Factor VIII Level (%) | Dosing Frequency (hours) / Duration of Therapy (days) | |-----------------------------------|------------------------------------|----------------------------------------------------------| | Bleeding | | | | Early joint, muscle, or oral cavity bleeding | 20 - 40 | Repeat every 12–24 hours. For at least 1 day, until resolution of pain caused by bleeding or wound healing. | | More severe joint, muscle bleeding, or hematoma | 30 - 60 | Repeat every 12–24 hours for 3–4 days or longer, until resolution of pain and acute functional impairment. | | Life-threatening bleeding | 60 - 100 | Repeat every 8–24 hours until the threat is resolved. | | Surgical Procedures | | | | Minor surgery
(e.g., tooth extraction) | 30 - 60 | Every 24 hours, for at least 1 day until healing is complete. | | Major surgery
(pre- and postoperative) | 80 - 100 | Repeat every 8–24 hours until adequate wound healing is achieved, followed by continued therapy for at least 7 additional days to maintain factor VIII activity at 30–60%. | | Prophylaxis | | | | Long-term prophylaxis of bleeding in patients with severe haemophilia A typically involves factor VIII doses of 20–40 IU/kg body weight administered every 2–3 days. In some cases, especially in younger patients, shorter intervals between doses or higher doses may be required. |

Method of administration:
Intravenous administration. It is recommended not to administer at a rate exceeding 2–3 ml/minute.

Haemoctin must not be mixed with other medicinal products.