HAEMOCTIN 1000 POWDER AND SOLVENT FOR INJECTABLE SOLUTION

2. What you need to know before you use Haemoctin

Do not use Haemoctin

• If you are allergic to coagulation factor VIII or any of the other components 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 formation of inhibitors (antibodies) is a known complication that can occur during treatment with all medicines composed of factor VIII. These inhibitors, especially in large quantities, prevent the treatment from working properly, so you and your child will be carefully monitored for the development of such inhibitors. If your bleeding or your child's bleeding is not being controlled with Haemoctin, consult your doctor immediately.

If you have cardiovascular risk factors, treatment with Haemoctin may increase the risk of cardiovascular events. If you are unsure, you should discuss this with your doctor.

Complications related to the use of a catheter: If a central venous access device (CVAD) is required, the risk of complications associated with it should be considered, including local infections, bacteremia, and thrombosis at the catheter insertion site.

Viral safety

When human plasma or blood-derived medicines are administered, certain measures must be taken to prevent infections from being passed on to patients. Such measures include:

• careful selection of donors to exclude those at risk of being carriers of infectious diseases,
• testing for specific virus/infection markers in individual donations and plasma pools,
• inclusion of stages in the manufacturing process to eliminate/inactivate viruses.

Despite this, when human blood or plasma-derived medicines are administered, the possibility of transmitting infectious agents cannot be entirely excluded. This also applies to emerging or unknown viruses or other types of infections.

These measures are considered effective for enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus, and hepatitis C virus, and for the non-enveloped hepatitis A virus. The measures taken may have limited value against other non-enveloped viruses such as parvovirus B19. Parvovirus B19 infection can be severe for a pregnant woman (fetal infection) and for subjects whose immune system is depressed or who have a type of anemia (e.g., sickle cell disease or hemolytic anemia).

Your doctor may recommend that you consider vaccination against hepatitis A and B if you regularly/repeatedly receive human plasma-derived factor VIII products.

It is highly recommended that each time you receive a dose of Haemoctin, you keep a record of the name of the medicine and batch number administered to maintain a record of the batches used.

Children and adolescents

The warnings and precautions for use mentioned for adults should also be considered for children and adolescents.

Other medicines and Haemoctin

Tell your doctor if you are using, have recently used, or might use any other medicines.

No interactions between Haemoctin and other medicines have been reported.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine.

Due to the low incidence of haemophilia A in women, there is no experience with the use of factor VIII during pregnancy or breastfeeding. No studies have been conducted in animals during pregnancy or breastfeeding.

Driving and using machines

Haemoctin has no or negligible influence on the ability to drive and use machines.

Haemoctin contains sodium

Haemoctin 500/1000: contains up to 32.2 mg (1.40 mmol) of sodium (main component of cooking/table salt) per vial. This is equivalent to 1.61% of the maximum recommended daily sodium intake for an adult.

3. How to use Haemoctin

Haemoctin is prepared for intravenous administration (injection into a vein). Treatment should be administered under the supervision of a doctor experienced in the treatment of haemophilia A. Follow your doctor's instructions for administration of Haemoctin exactly. Consult your doctor if you have any doubts.

The dose and durationof treatment depend on the severity of the factor VIII deficiency, the location and extent of the bleeding, and your clinical condition. Your doctor will determine the appropriate dose for you.

Make sure to work under sterile conditions at all stages of the process.

Reconstitution of the concentrate:

• Allow the closed vials of solvent (water for injections) and the product to reach room temperature. If a water bath is used to warm up, make sure that no water comes into contact with the stopper or cap of the vials. Otherwise, the medicine could become contaminated.
• Very importantfor proper use of the transfer system: before opening, make sure that the white lower part of the transfer system is placed directly on the bottom of the blister (Fig. 1a: correct / Fig. 1b: incorrect). If not correct: push the transfer system down in the blister until the white lower part of the transfer system is placed directly on the bottom of the blister (Fig. 1c).
• Remove the caps from the solvent vial and the product vial to expose the central parts of the rubber stoppers (Fig. 2). Clean the rubber stoppers of the product and solvent with a disinfectant.
• Remove the rest of the packaging from the transfer system (Fig. 3).
• Place the solvent vial on a flat surface. Connect the blue part of the transfer system from the inside of the blister to the solvent vial in a vertical position (Fig. 4). Do not twist the transfer system!
• Remove the rest of the blister from the transfer system. Do not squeeze the blister! Now the white part of the transfer system is visible (Fig. 5).
• Place the vial with the product on a flat surface.
• Place the transfer system assembly with the solvent vial upside down. Insert the tip of the white adapter into the product vial through the stopper (Fig. 6). The vacuum present in the product vial causes the solvent to be transferred to the product vial.
• Gently swirl the vial with the product to help dissolve the powder. Do not shake vigorously to avoid foaming! The solution should be clear or slightly opalescent.
• Then unscrew the blue part of the transfer system along with the solvent vial by turning it counterclockwise (Fig. 7). Discard the solvent vial along with the blue part of the transfer system. The Luer-Lock connector is now visible.

The solution ready for use should be administered immediately after reconstitution. Do not use cloudy solutions or those containing visible particles.

Injection:

• Once the powder has been dissolved as indicated, screw the provided syringe onto the Luer-Lock connector of the product vial with the white part of the transfer system (Fig. 8). This will allow easy transfer of the dissolved medicine to the syringe. No separate filter is needed because the transfer system already has its own incorporated filter.
• Carefully disconnect the vial with the white part of the transfer system from the syringe. Using the included butterfly needle, administer immediately by slow intravenous injection. The injection rate should not exceed 2-3 ml/minute.
• After using the butterfly needle, you can put the protective cap on as a safety measure.

If you use more Haemoctin than you should

If you think you have been given too much Haemoctin, inform your doctor. He will decide on the treatment.

If you forget to use Haemoctin

In this case, your doctor will decide whether to continue treatment.

If you stop treatment with Haemoctin

Do not stop treatment with Haemoctin without consulting your doctor.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

4. Possible side effects

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

If you notice any of the following side effects, tell your doctor immediately:

• skin redness,

• burning sensation and itching at the infusion site,
• chills,
• flushing,
• headache,
• hives,
• hypotension,
• lethargy,
• nausea,
• restlessness,
• tachycardia,
• chest tightness,
• tingling,
• vomiting,
• wheezing.

This may be a severe allergic reaction (anaphylactic shock) or a hypersensitivity reaction.

The following adverse reactions have also been reported with Haemoctin

Frequency not known: cannot be estimated from the available data

• Shock (anaphylactic), allergic reaction
• Skin redness, itching, hives

In children who have not received previous treatment with factor VIII medicines, inhibitor antibodies (see section 2) may occur very frequently (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 infrequent (less than 1 in 100 patients). If this happens, the medicines you or your child are taking may stop working properly, and you or your child may experience persistent bleeding. In this case, contact your doctor immediately.

Side effects in children and adolescents

Except for the production of inhibitors (antibodies), it is expected that the adverse reactions in children will be the same as in adults.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Haemoctin

Keep this medicine out of the sight and reach of children.

Store the vials in the outer packaging to protect them 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 carton.

Disposal of unused medicine and all materials that have come into contact with it will be carried out 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. Container Content and Additional Information

Composition ofHaemoctin

• The active ingredient is human coagulation factor VIII.
• The other components are glycine, sodium chloride, sodium citrate, and calcium chloride.
• The solvent vial contains water for injectable preparations.

Appearance of theproductand container content

Haemoctin is supplied as a lyophilized powder. Water for injectable preparations is used as a solvent. The dissolved product is transparent or slightly opalescent.

Haemoctin 500: contains 1 vial with 500 IU and 1 vial with 5 ml of water for injectable preparations (100 IU/ml)

Haemoctin 1000: contains 1 vial with 1000 IU and 1 vial with 5 ml of water for injectable preparations (200 IU/ml)

Each container contains:

• A disposable syringe
• A transfer system with an integrated filter
• A butterfly needle

Marketing authorization holder and manufacturer

Biotest Pharma GmbH

Landsteinerstrasse 5

63303 Dreieich

Germany

Phone: +49 6103 801-0

Fax: +49 6103 801-150

Email: [email protected]

Grifols Movaco, S.A.

Can Guasc, s/n – Parets del Vallès

08150 Barcelona

Spain

Date of the last revision of this leaflet: 04/2023

This information is intended only for healthcare professionals:

Monitoring of treatment

During treatment, it is recommended to properly monitor factor VIII levels to determine the dose to be administered and the frequency of repeated infusions. Each patient's response to factor VIII may vary and achieve different half-lives and recoveries. The dose based on body weight may need to be adjusted in patients with below-normal weight or overweight. In the particular case of major surgery, it is essential to monitor the substitution therapy accurately through coagulation tests (plasma activity of factor VIII).

When using a one-stage coagulation test based on thromboplastin time (TTPa) invitroto determine the activity of factor VIII in patient blood samples, the results of plasma activity of factor VIII may be significantly affected by both the type of TTPa reagent and the reference pattern used in these tests. There may also be significant discrepancies between the results of analyses obtained through one-stage coagulation tests based on TTPa and those of the chromogenic assay according to the European Pharmacopoeia. This is especially important when changing laboratories and/or reagents used in analyses.

Posology

The dose and duration of substitution therapy depend on the severity of the factor VIII deficiency, the location and extent of the hemorrhage, and the patient's clinical condition.

The number of units of factor VIII administered is expressed in International Units (IU), which correspond to the current standard of factor VIII concentrate of the WHO for products containing factor VIII. The plasma activity of factor VIII can be expressed as a percentage (referenced to normal human plasma) or preferably in International Units (referenced to an International Standard for plasma factor VIII).

One International Unit (IU) of factor VIII activity is equivalent to the amount of factor VIII in one ml of normal human plasma.

On-demand treatment

The calculation of the required dose of factor VIII is based on the empirical finding that 1 International Unit (IU) of factor VIII per kg of body weight increases the plasma activity of factor VIII by 1% to 2% of normal activity.

The required dose is determined using 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 should always be guided by clinical efficacy in each particular case.

In the following hemorrhagic episodes, the activity of factor VIII should not be lower than the indicated plasma activity level (as a percentage of the normal level) during the corresponding period. The following table can be used as a dosage guide in hemorrhagic episodes and surgery:

Prophylaxis

For long-term prophylaxis of hemorrhages in patients with severe hemophilia A, the usual doses are 20 to 40 IU of factor VIII per kg of body weight, at intervals of 2 or 3 days. In certain cases, especially in young patients, it may be necessary to shorten the intervals between administrations or use higher doses.

Method of administration:

Intravenous route. It is recommended not to administer more than 2-3 ml per minute.

Only the infusion equipment supplied should be used because treatment failure may occur due to the adsorption of human coagulation factor VIII to the inner surface of some infusion equipment.

Haemoctin should not be mixed with other medications.