HAEMOCTIN 500 U.I. Powder and solvent for injectable solution

Зміст інструкції

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. Package Contents and Other Information

Haemoctin 250 U.I.
Haemoctin 500 U.I.
Haemoctin 1000 U.I.
Powder and solvent for injectable solution
Factor VIII of coagulation derived from human plasma

Read this leaflet carefully before you use this medicine as 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 others, even if they have the same symptoms as you, as it may be harmful.
• If you get any side effects, even 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 you use 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 medicine derived from human plasma, which contains coagulation factor VIII
necessary for the normal blood clotting process. After reconstitution of the powder with
water for injectable preparations, the solution is ready for intravenous injection.
Haemoctin is used for the treatment and prophylaxis of bleeding in patients with hemophilia A
(congenital factor VIII deficiency).
Haemoctin does not contain von Willebrand factor in pharmacologically active quantities and is
therefore not suitable for the treatment of von Willebrand's disease.

2. What you need to know before using Haemoctin

Do not use Haemoctin

• if you are allergic to coagulation factor VIII or any of the other ingredients of this medicine (listed in section 6). An allergic reaction may include skin rash, itching, difficulty breathing or swelling of the face, lips, throat or tongue.

Warnings and precautions
The formation of inhibitors (antibodies) is a known complication that can occur during treatment
with all factor VIII-based medicines. Inhibitors, especially at high levels, prevent the
treatment from working correctly and you or your child will be closely monitored to
check for the development of these inhibitors. If Haemoctin does not keep bleeding under control in you or
your child, inform your doctor immediately.
If you have pre-existing cardiovascular risk factors, therapy with Haemoctin may increase the risk
cardiovascular. If you have concerns, discuss them with your doctor.
Catheter-related complications: if a central venous access device (CVAD) is necessary
the risk of CVAD-related complications, including
local infections, bacteremia and thrombosis at the catheter site, must be considered.

Viral safety
When medicinal products are made from human blood or plasma, measures are taken
to prevent infections from being passed on to patients. The measures include:

• careful selection of blood and plasma donors to ensure the exclusion of possible carriers of infections.
• testing of each donation and plasma pools for viruses/infections.
• inclusion of procedures for removing and/or inactivating viruses in the manufacturing process of blood or plasma-derived products. Despite these measures, when products derived from human blood or plasma are administered, the transmission of infections cannot be completely excluded. This also applies to unknown or emerging viruses or other types of infections.

These procedures are considered effective against enveloped viruses, such as the human immunodeficiency virus (HIV), hepatitis B virus and hepatitis C virus, and the non-
enveloped hepatitis A virus.
The procedures used may be of limited effectiveness against other non-enveloped viruses
such as parvovirus B19. Parvovirus B19 infection can be severe for pregnant women
(fetal infection) and for those with a compromised immune system or certain forms of
anemia (such as sickle cell anemia or hemolytic anemia).
If you take factor VIII-derived plasma human products regularly/repeatedly
your doctor may recommend vaccination against hepatitis A and hepatitis B.
It is strongly recommended that you record the name and batch number of the product each time you receive
a dose of Haemoctin, in order to be able to always trace the batches used.

Children and adolescents
The warnings and precautions for use reported for adults must also be taken into consideration
for children and adolescents.

Other medicines and Haemoctin
Tell 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 are pregnant or are planning to become pregnant, or if you are breastfeeding with
breast milk, ask your doctor for advice before taking this medicine.
Since hemophilia A is very rare in women, there are no data on the use of
factor VIII during pregnancy or breastfeeding. Studies in pregnant animals or during the
post-partum period have not been conducted.

Driving and operating machinery
Haemoctin does not impair or negligibly impairs the ability to drive vehicles or operate machinery.

Haemoctin contains sodium
Haemoctin 250 I.U. 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 recommended maximum daily intake with
the diet of an adult.
Haemoctin 500/1000 I.U. 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 recommended maximum daily
intake with the diet of 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 hemophilia A. Always use
Haemoctin exactly as your doctor has instructed. If you have any doubts, consult your doctor.

The dose and durationof treatment depend on the severity of the factor VIII deficiency, the site,
the extent of the bleeding, and the patient's clinical condition. The dose for each specific case
must be determined by the physician.
Ensure perfect sterility in all stages 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 closed vials of solvent (water for injections) and the product to room temperature. If you use a water bath for heating, it is essential to ensure that water does not come into contact with the crimp caps or the vial stoppers, otherwise contamination of the medicinal product may occur.
• Very importantfor the correct use of the transfer system: before opening, make sure that the white lower 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 inside the blister until the white lower part of the transfer system is in direct contact with the bottom of the blister (Fig. 1c).
• Remove the crimp caps from the solvent vial and the product vial to expose the central part of the rubber stoppers (Fig. 2). Ensure that the rubber stoppers of the vials containing the product and the solvent have been treated with a disinfectant.
• 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, which is located inside the blister, over the vial containing the solvent held in an upright position (Fig. 4). Do not twist the transfer system!
• Remove the remaining part of the blister from the transfer system. Do not crush 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 downwards to pierce the stopper of the vial containing the product (Fig. 6). The absence of air in the product vial allows the solvent to enter the product vial.
• Gently move the vial with the product to dissolve the powder. Do not shake vigorously, to avoid foaming! The solution is clear or slightly opalescent.
• Subsequently, unscrew the blue part of the transfer system together with the solvent vial by rotating 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 ready-to-use solution must be used immediately after being dissolved. Do not
use turbid solutions or those containing visible particles.

Injection:

• After dissolving the powder as described above, screw the included 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 drug (Haemoctin 250 I.U.: total volume 2.5 ml, Haemoctin 500 I.U./1000 I.U.: total volume 5 ml) into the syringe. It is not necessary to use a separate filter, as a filter is already present in the transfer system.
• Carefully disconnect the vial with the white part of the transfer system from the syringe. Use the butterfly needle included in the package and administer immediately by slow intravenous injection. The injection rate should not exceed 2-3 ml/minute.
• After using the butterfly needle, be sure to cover it with the protective closing cap for safety.

If you use more Haemoctin than you should
If you believe you have received an excessive amount of Haemoctin, inform your doctor, who will decide how
to proceed with treatment.

If you forget to use Haemoctin
In this case, the doctor will decide whether further treatment is necessary.

If you stop using Haemoctin
Do not stop using Haemoctin without consulting your doctor.
If you have any doubts about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Inform your doctor immediately if you notice any of the following effects:

• redness of the epidermis,
• burning and tingling at the infusion site,
• chills,
• flushing,
• headache,
• urticaria,
• hypotension,
• drowsiness,
• nausea,
• state of restlessness,
• tachycardia,
• feeling of tightness in the chest,
• 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 based on available data

• Shock (anaphylactic), allergic reaction
• Redness of the skin, itching, urticaria

For children not previously treated with factor VIII-based medicines, the development of
inhibitor antibodies (see section 2) may be very common (more than 1 in 10 patients); however, in
patients who have received previous treatment with factor VIII (more than 150 days of
treatment) the risk is uncommon (less than 1 in 100 patients). If this happens, the medicine may stop
working properly for you or your child and you or your child may experience prolonged bleeding.
If this happens, you should contact your doctor immediately.

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

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. You can also report side effects
directly to adverse-reactions. 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 at a temperature above 25°C. Do not freeze.
Do not use Haemoctin after the expiry date which is stated on the vial label and on the
carton.
Unused medicine and waste derived from this medicine must be disposed of in accordance with
current local regulations.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. 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 in the form of a lyophilized powder (freeze-dried). Water for injections serves as the solvent. The dissolved product 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 a built-in filter
• A cannula with a butterfly needle

Marketing Authorisation 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 determination of factor VIII levels is recommended to define the dose to be administered and the frequency with which infusions should be repeated. The response to factor VIII may vary from patient to patient, with different half-lives and different recovery levels. In underweight or overweight patients, dose adjustment based on body weight may be necessary. In particular, in the case of major surgery, precise monitoring of replacement therapy by means of coagulation testing (plasma factor VIII activity) is essential.
When using a one-stage coagulation test in vitrobased on activated partial thromboplastin time (aPTT) to determine factor VIII activity in patient blood samples, the results for plasma factor VIII activity may be significantly altered by both the type of aPTT reagent and the reference standard used in the test. In addition, there may be significant discrepancies between the results obtained with a one-stage coagulation test based on aPTT and those obtained with the chromogenic test conforming to the European Pharmacopoeia. This aspect is of particular importance when the laboratory and/or the reagents used in the test change.

Dosage
The dose and duration of replacement therapy depend on the severity of the factor VIII deficiency, the site and extent of the bleeding, and the patient's clinical condition.
The number of units of factor VIII administered is expressed in International Units (IU), in relation to the current WHO standard for factor VIII-based products. The activity of factor VIII in plasma is expressed either as a percentage (relative to normal human plasma) or preferably in International Units (in reference to an International Standard for Factor VIII in plasma).
The activity of 1 International Unit (IU) of factor VIII is equivalent to the amount of factor VIII found in 1 ml of normal human plasma.

On-demand treatment
The calculation of the necessary dose of factor VIII is based on the empirical data that 1 International Unit (IU) of factor VIII per kg of body weight increases the activity of factor VIII in plasma by 1 - 2% of normal activity. The necessary dose is determined by applying the following formula:
Units required = body weight (kg) × desired increase in factor VIII (%) × 0.5
The amount to be administered and the frequency of administration must always take into account clinical efficacy in individual specific cases.
In the case of bleeding episodes reported in the table below, the activity of factor VIII must not be lower than the activity level indicated (in % of normal) in the corresponding period.
The following table can be used as a reference for dosage in the treatment of bleeding episodes and in surgical practice:

Grade of bleeding /
Type of surgical procedure
Required level of
Factor VIII (%)
Frequency of doses (hours) /
duration of therapy (days)
Bleeding
Beginning of hemarthrosis,
muscle bleeding
or oral

• 20 - 40 Repeat every 12 / 24 hours, at least for one day, until the bleeding stops, as indicated by the disappearance of pain, or until healing. More extensive hemarthrosis, muscle bleeding or hematoma
• 30 - 60 Repeat every 12 / 24 hours for
• 3 – 4 days or more, until the pain disappears and the acute condition of the disease resolves. Life-threatening bleeding
• 60 - 100 Repeat every 8 / 24 hours until the patient is out of danger. Surgery Minor surgeryIncluding tooth extraction
• 30 - 60 Every 24 hours, at least for 1 day, until healing. Major surgery80 - 100 (pre- and post-operative) Repeat every 8 / 24 hours until adequate wound healing, then continue therapy for at least another 7 days to maintain factor VIII activity at 30 - 60%.

Prophylaxis
In long-term prophylaxis of bleeding in patients with severe hemophilia A, the usual dosage is 20 - 40 IU of factor VIII per kilogram of body weight at intervals of 2 – 3 days. In some cases, especially in younger patients, more frequent dosing intervals or higher doses may be necessary.

Route of administration
For intravenous use. It is recommended not to administer more than 2-3 ml per minute.
Use only the supplied infusion set, as otherwise therapy may be ineffective due to adsorption of factor VIII on the internal surfaces of some infusion devices.
Haemoctin must not be mixed with other medicinal products.