Haemoctin

Package leaflet: Information for the user

Haemoctin 250 IU, 500 IU, 1000 IU

Powder and solvent for injectable solution
Coagulation Factor VIII derived from 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, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to other people, even if their symptoms are the same as yours, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of this 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 pack and other information

1. What Haemoctin is and what it is used for

Haemoctin is a medicinal product derived from human plasma, containing coagulation factor VIII
required for the normal blood clotting process. After reconstitution of the powder with
water for injection, the solution is ready for intravenous injection.
Haemoctin is used for the treatment and prophylaxis of bleeding episodes in patients with haemophilia A
(congenital factor VIII deficiency).
Haemoctin does not contain von Willebrand factor in pharmacologically active amounts and
therefore is not suitable for the treatment of von Willebrand disease.

2. What you should know before using Haemoctin

Do not use Haemoctin

• if you are allergic to coagulation factor VIII 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 all factor VIII-containing 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 Haemoctin does not control bleeding in you or your child, inform your doctor immediately.
If you have pre-existing cardiovascular risk factors, treatment with Haemoctin may increase cardiovascular risk. If in doubt, discuss this with your doctor.
Catheter-related complications: if a central venous access device (CVAD) is required, the risk of CVAD-related complications, including local infections, bacteraemia, and catheter-site thrombosis, must be taken into consideration.
Viral safety
When medicinal products are prepared from human blood or plasma, measures are taken to prevent transmission of infections to patients. These measures include:

• careful selection of blood and plasma donors to ensure exclusion of potential carriers of infections.
• testing of each donation and pooled plasma for viruses/infections.
• inclusion of viral removal and/or inactivation procedures in the manufacturing process of blood- or plasma-derived products. Despite these measures, the possibility of transmitting infections cannot be completely ruled out when products derived from human blood or plasma are administered. This also applies to unknown or emerging viruses or other types of infections.

These procedures are considered effective against enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus, and hepatitis C virus, as well as the non-enveloped hepatitis A virus.
The procedures adopted may have limited effectiveness against other non-enveloped viruses such as parvovirus B19. Parvovirus B19 infection may be serious for pregnant women (fetal infection) and for individuals with compromised immune systems or certain types of anaemia (such as sickle cell anaemia or haemolytic anaemia).
If you regularly or repeatedly receive plasma-derived factor VIII products, your doctor may recommend vaccination against hepatitis A and hepatitis B.
It is strongly recommended to record the name and batch number of the product each time a dose of Haemoctin is received, in order to allow traceability of the batches used.
Children and adolescents
The warnings and precautions described for adults should also be considered for children and adolescents.
Other medicines and Haemoctin
Inform your doctor if you are taking, have recently taken, or might take any other medicines.
No interactions of Haemoctin with other medicines have been reported.
Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor before taking this medicine.
Since haemophilia A is extremely rare in women, data regarding the use of factor VIII during pregnancy or breastfeeding are not available. Animal studies during pregnancy or the postpartum period have not been conducted.
Driving and using machines
Haemoctin has no or negligible effect on the ability to drive vehicles or operate machinery.
Haemoctin contains sodium
Haemoctin 250 IU contains up to 16.1 mg (0.70 mmol) of sodium (the main component of table salt) per vial. This corresponds to 0.81% of the maximum daily recommended dietary intake for an adult.
Haemoctin 500/1000 IU contains up to 32.2 mg (1.40 mmol) of sodium (the main component of table salt) per vial. This corresponds to 1.61% of the maximum daily recommended dietary intake for an adult.

3. How to use Haemoctin

Haemoctin is intended for intravenous administration (injection into a vein). Treatment must be carried out under the direct supervision of a physician experienced in the treatment of haemophilia A. Always use Haemoctin exactly as prescribed by your doctor. If you have any doubts, consult your doctor.
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 dose for each individual case must be determined by the physician.
Ensure complete sterility throughout all steps of the procedure.
Fig. 1a Fig. 1b Fig. 1c Fig. 2 Fig. 3

Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8

Reconstitution of the powder:

• Bring the unopened vials of solvent (water for injections) and product to room temperature. If a water bath is used for warming, ensure carefully that water does not come into contact with the closure caps or stoppers of the vials, as contamination of the medicinal product may occur.
• Extremely important for correct use of the transfer system: before opening, ensure that the lower white part of the transfer system is in direct contact with the bottom of the blister (Fig. 1a: correct / Fig. 1b: incorrect). If incorrectly positioned: push the transfer system downwards within the blister until the lower white part of the transfer system is in direct contact with the bottom of the blister (Fig. 1c).
• Remove the closure caps from the solvent vial and from the product vial to expose the central portion of the rubber stoppers (Fig. 2). Ensure that the rubber stoppers of the vials containing the product and solvent have been disinfected.
• Remove the upper part of the transfer system packaging (Fig. 3).
• Place the solvent vial on a flat surface. Position the blue part of the transfer system, located inside the blister, over the upright solvent vial (Fig. 4). Do not twist the transfer system!
• Remove the remaining part of the blister from the transfer system. Do not squeeze the blister! The white part of the transfer system is now visible (Fig. 5).
• Place the vial containing the product on a flat surface.
• Invert the solvent vial together with the transfer system. Push the tip of the white part of the transfer system downward to pierce the stopper of the vial containing the product (Fig. 6). The absence of air in the product vial allows the solvent to flow into the product vial.
• Gently swirl the vial with the product to dissolve the powder. Do not shake vigorously, to avoid foam formation! The solution should be clear or slightly opalescent.
• Then unscrew the blue part of the transfer system together with the solvent vial by turning counterclockwise (Fig. 7). Remove the solvent vial with the blue part of the transfer system still attached. The Luer-Lock connector is now visible.

The reconstituted solution must be used immediately after dissolution. Do not use solutions that are cloudy or contain visible particles.
Injection:

• After dissolving the powder as described above, screw the provided syringe onto the Luer-Lock connector of the vial containing the product with the white part of the transfer device (Fig. 8). This allows easy aspiration of the reconstituted medication (Haemoctin 250 IU: total volume 2.5 ml, Haemoctin 500 IU/1000 IU: total volume 5 ml) into the syringe. A separate filter is not required, as the transfer system already contains a filter.
• Carefully disconnect the vial with the white part of the transfer system from the syringe. Use the butterfly needle supplied in the package and administer immediately via slow intravenous injection. The injection rate must not exceed 2–3 ml per minute.
• After using the butterfly needle, ensure that it is covered with the protective safety cap.

If you use more Haemoctin than you should
If you think you have received an excessive amount of Haemoctin, inform your doctor, who will decide on further management.
If you forget to use Haemoctin
In this case, your doctor will decide whether additional treatment is needed.
If you stop using Haemoctin
Do not stop using Haemoctin without consulting your doctor.
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
Immediately inform your doctor if you notice any of the following symptoms:

• redness of the epidermis,
• burning and itching at the infusion site,
• chills,
• flushing,
• headache,
• urticaria,
• hypotension,
• drowsiness,
• nausea,
• restlessness,
• tachycardia,
• feeling of chest tightness,
• tingling sensation,
• vomiting,
• wheezing.

These may be signs of an allergic reaction, a severe allergic reaction (anaphylactic shock), or a hypersensitivity reaction.

The following side effects have been reported with Haemoctin
Not known: frequency cannot be estimated from the available data

• Shock (anaphylactic), allergic reaction
• Skin redness, pruritus, urticaria

In previously untreated children receiving factor VIII-containing medicinal products, the development of inhibitory antibodies (see section 2) may be very common (more than 1 in 10 patients). However, in patients who have previously received treatment with factor VIII (more than 150 days of treatment), the risk is uncommon (less than 1 in 100 patients). 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.

Side effects in children and adolescents
With the exception of inhibitor (antibody) formation, side effects in children are expected to be identical to those observed in adults.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system: reactions-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Haemoctin

Keep this medicine out of the sight and reach of children.
Keep the vials in the outer packaging to protect the medicine from light.
Do not store above 25°C. Do not freeze.
Do not use Haemoctin after the expiry date stated on the vial label and on the carton.
Unused medicine and waste material from this medicine must be disposed of in accordance with local regulations.
Do not dispose of any medicine 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 Haemoctin contains:

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

Description of the appearance of Haemoctin and contents of the pack
Haemoctin is supplied as a lyophilized powder (lyophilisate). Water for injections serves as the solvent. The reconstituted solution is clear or slightly opalescent.
Haemoctin 250 IU contains 1 vial with 250 IU and 1 vial with 2.5 ml of water for injections (100 IU/ml).
Haemoctin 500 IU contains 1 vial with 500 IU and 1 vial with 5 ml of water for injections (100 IU/ml).
Haemoctin 1000 IU 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
• A transfer system with integrated filter
• A butterfly needle cannula

Marketing Authorization Holder and Manufacturer
Biotest Pharma GmbH
Landsteinerstrasse 5
63303 Dreieich
Germany
Telephone: +49 6103 801-0
Fax: +49 6103 801-150
E-mail: [email protected]

The following information is intended exclusively for healthcare professionals:

Treatment Monitoring
During treatment, appropriate monitoring of factor VIII levels is recommended to determine the dose to be administered and the frequency of infusions. Response to factor VIII may vary among patients, with different half-lives and recovery levels. Dose adjustments based on body weight may be necessary in underweight or overweight patients. Particularly during major surgical procedures, careful monitoring of replacement therapy using coagulation tests (plasma factor VIII activity) is essential.

When using a one-stage in vitro coagulation assay based on activated partial thromboplastin time (aPTT) to determine factor VIII activity in patient blood samples, results for plasma factor VIII activity may be significantly influenced by both the type of aPTT reagent and the reference standard used in the assay. Furthermore, significant discrepancies may exist between results obtained with a one-stage aPTT-based coagulation assay and those obtained with a chromogenic assay compliant with the European Pharmacopoeia. This is particularly important when changing laboratories and/or reagents used in testing.

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

One International Unit (IU) of factor VIII activity corresponds to the amount present in 1 ml of normal human plasma.

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

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

The amount and frequency of administration should always take into account the clinical efficacy observed in individual cases.

For the bleeding episodes listed in the table below, factor VIII activity should not fall below the indicated plasma activity level (expressed as % of normal) during the corresponding period.

The following table may be used as a guide for dosing in the treatment of bleeding episodes and surgical procedures:

| Bleeding / Surgical Procedure | Required Factor VIII Level (%) | Dosing Frequency (hours) / Duration of Therapy (days) | |-----------------------------------|------------------------------------|----------------------------------------------------------| | Early haemarthrosis, muscle bleeding, or oral bleeding | 20 - 40 | Repeat every 12 / 24 hours, for at least one day until bleeding stops, as indicated by resolution of pain, or until healing. | | More extensive haemarthrosis, muscle bleeding, or haematoma | 30 - 60 | Repeat every 12 / 24 hours for 3–4 days or longer, until pain subsides and the acute phase resolves. | | Life-threatening bleeding | 60 - 100 | Repeat every 8 / 24 hours until the patient is out of danger. | | Surgery | | | | Minor surgery
including tooth extraction | 30 - 60 | Every 24 hours, for at least 1 day until healing. | | Major surgery
(pre- and post-operative) | 80 - 100 | Repeat every 8 / 24 hours until adequate wound healing is achieved; continue therapy for at least another 7 days to maintain factor VIII activity at 30 - 60%. |

Prophylaxis
For long-term prophylaxis against bleeding in patients with severe haemophilia A, the usual dose is 20–40 IU of factor VIII per kg of body weight, administered every 2–3 days. In some cases, particularly in younger patients, more frequent dosing or higher doses may be required.

Method of Administration
For intravenous use only. Administration should not exceed 2–3 ml per minute.

Use only the infusion set provided, as factor VIII may be adsorbed onto the internal surfaces of certain infusion devices, potentially rendering therapy ineffective if other sets are used.

Haemoctin must not be mixed with other medicinal products.