PATIENT INFORMATION LEAFLET

Haemate P 1200UI FVW/500 UIFVIII

Powder and solvent for injectable solution and for infusion

Human von Willebrand factor (FVW)

Human coagulation factor VIII (FVIII)

1. What isHaemate Pand what it is used for

2. What you need to knowbeforestarting touse Haemate P

3. Howto use Haemate P

4. Possible side effects

5. Storage ofHaemate P

6. Contents of the pack andadditional information

¿What is Haemate P?

Haemate P is presented as a powder accompanied by a solvent. The resulting solution is administered by intravenous injection or infusion. Haemate P belongs to a type of medication called antihemorrhagics.

Haemate P is manufactured from human plasma (the liquid part of the blood) and contains human von Willebrand factor (FVW) and human coagulation factor VIII (FVIII).

What is Haemate P used for?

Since Haemate P contains both FVIII and FVW, it is essential to know which factor is needed more. If you have hemophilia A, your doctor will prescribe Haemate P with the specified units of FVIII. If you have von Willebrand disease, your doctor will prescribe Haemate P with the specified units of FVW.

Von Willebrand disease

Prophylaxis and treatment of bleeding or surgical bleeding in von Willebrand disease, when treatment with desmopressin alone is ineffective or contraindicated.

Hemophilia A (congenital deficiency of factor VIII)

Treatment and prophylaxis of bleeding in patients with hemophilia A.

This product may be useful in the management of acquired factor VIII deficiency.

The following sections contain information that your doctor should consider before prescribing Haemate P.

Do not use Haemate P:

• If you are allergic (hypersensitive) to human von Willebrand factor, human coagulation factor VIII, or to any of the other components of this medication (listed in section 6).

Inform your doctor if you are allergic to any medication or food.

Warnings and precautions:

Traceability

Your doctor should keep a record of the date of administration, the batch number of the medication each time Haemate P is administered.

Consult with your doctor or pharmacist before starting to use Haemate P:

• In case of allergic or anaphylactic reactions(severe allergic reactions that cause severe breathing difficulties or dizziness). Severe allergic reactions may occur. Your doctor should inform you of the first symptoms of hypersensitivity reactions. These include hives, widespread itching, chest pressure, breathing difficulties, low blood pressure, and anaphylaxis (severe allergic reactions that cause severe breathing difficulties or dizziness).If these symptoms occur, stop using the product immediately and contact your doctor.
• The formation of inhibitors (antibodies),is a known complication that may occur during treatment with all factor VIII medications. These inhibitors, especially in large quantities, prevent the treatment from working properly, so you and your child will be closely monitored for the development of these inhibitors. If your bleeding or your child's bleeding is not being controlled with Haemate P, consult your doctor immediately.
• If you have a heart condition or are at risk of developing one, inform your doctor or pharmacist.
• If a central venous access device (CVD) is needed to administer Haemate P, your doctor should consider the risk of complications related to the catheter, including local infections, bloodstream infections (bacteremia), and blood clot formation (thrombosis) at the catheter insertion site.

Von Willebrand disease

• In the case of a risk of blood clot formation (thrombotic effects, including blood clots in the lungs),particularly in the case of clinical or laboratory risk factors (for example, in perioperative periods without anticoagulant prophylaxis, delayed mobilization, obesity, overdose, cancer),you should be monitored for the first symptoms of thrombosis. Preventive measures for venous thrombosis should be established in accordance with current recommendations.Patients with von Willebrand disease, especially those with type 3 of this disease, may develop neutralizing antibodies (inhibitors) against von Willebrand factor. Your doctor will perform the necessary tests to detect their presence and consider whether to continue or discontinue this therapy.

Your doctor will have to carefully consider the benefits of treatment with Haemate P compared to the risks of these complications.

Viral safety

When administering human plasma or blood-derived medications, the transmission of infectious agents cannot be completely ruled out. This also applies to the possible transmission of unknown or emerging pathogens or other types of infections. However, the risk of transmission of infectious agents is reduced by:

• The careful selection of blood and plasma donors to ensure that potential carriers of infections are excluded;
• Analysis of each donation and plasma mixture to detect signs of viruses/infections;
• Inclusion of stages in the manufacturing process of blood or plasma to inactivate or eliminate viruses.

These procedures are considered effectivefor enveloped viruses such as human immunodeficiency virus (HIV, the virus that causes AIDS), hepatitis B virus, and hepatitis C virus (which cause liver inflammation) and for non-enveloped viruses such as hepatitis A virus (liver inflammation).

The inactivation/elimination procedures may have limited value for non-enveloped viruses such as parvovirus B19.

Parvovirus B19 infection can be severe for a pregnant woman (fetal infection) and for individuals with immunodeficiency or increased hematopoiesis (for example, with hemolytic anemia).

Your doctor may recommend that you be vaccinated against hepatitis A and B if you regularly or repeatedly receive concentrates of human von Willebrand factor and human coagulation factor VIII.

Use of Haemate P with other medications

• Inform your doctor or pharmacist if you are using or have used recently or may need to use any other medication.
• This medication should not be mixed with other medications, solvents, and diluents.

Pregnancy, breastfeeding, and fertility

• If you are pregnant or breastfeeding, or if you think you may be pregnant, consult your doctor or pharmacist before using this medication.
• Due to the rarity of hemophilia A in women, there is no experience with the use of factor VIII during pregnancy and breastfeeding.
• In the case of von Willebrand disease, women are even more affected than men. Based on the accumulated experience after marketing, it may be recommended to substitute FVW in the prevention and treatment of acute bleeding. There are no available clinical studies on the substitutive therapy with FVW in women during pregnancy and breastfeeding.
• During pregnancy and breastfeeding, Haemate P should only be administered if clearly indicated.

Driving and operating machinery

Haemate P does not affect the ability to drive vehicles and operate machinery.

Haemate P contains sodium

Haemate P 1200 UI VWF/500 UI FVIII contains 26 mg of sodium (main component of table salt/for cooking) in each vial. This is equivalent to 1.3% of the maximum recommended daily intake for an adult.

The treatment should be initiated and supervised by a doctor with experience in the treatment of blood coagulation disorders.

Dosage

The amount of von Willebrand factor and factor VIII needed and the duration of treatment depend on several factors, such as your weight, the severity of the disease, the location and intensity of the bleeding or the need to prevent it during surgery or investigation (see the section "This information is intended solely for healthcare professionals).

If you have been prescribed Haemate P to use at home, the doctor should ensure that you know how to inject it and the amount you should use.

Follow exactly the administration instructions for Haemate P indicated by your doctor or healthcare staff at the hemophilia center.

If you use more Haemate P than you should

No adverse effects of overdose with FVW and FVIII have been reported. However, the risk of developing blood clots (thrombosis) cannot be excluded in the case of an extremely high dose, especially with products containing FVW with a high content of FVIII.

Reconstitution and administration

Ensure that you work in sterile conditions at all stages of the process.

General instructions

• The lyophilized powder must be mixed (reconstituted) with the solvent (liquid) and extracted from the vial in aseptic conditions.
• The solution must be transparent or slightly opalescent. After filtration/transfusion (see below and before administering it to the patient), the solution obtained must be visually examined to check that it does not contain particles or discoloration. Although the reconstitution recommendations are followed precisely, it is not uncommon for some residues or particles to remain. The filter included in the Mix2Vial device eliminates these particles completely. Filtration does not affect dosage calculations.
• Do not use turbid solutions or solutions that still contain particles or residues after filtration.
• After administration, the amount of unused medication and residual material must be disposed of in accordance with local regulations and following the doctor's instructions.

Reconstitution:

Before opening any of the vials, warm the Haemate P powder and the accompanying solvent to room temperature. To do this, you can leave the vials at room temperature for about an hour or place them in your closed hands for a few minutes. Do not expose the vials to direct heat. The vials should not be heated to a temperature higher than the body temperature (37°C).

Carefully remove the protective capsules from the solvent vial and the Haemate P vial. Clean the exterior of the rubber stoppers of both vials with an alcohol-soaked swab and let them dry. You can now transfer the solvent to the powder vial with the administration system included (Mix2Vial). Please follow the instructions below:

Administration

Once the product has been transferred to the syringe, it must be used immediately.

For the injection of Haemate P, it is recommended to use disposable plastic syringes, as the glass surface of the completely glass syringes tends to stick with this type of solution.

The reconstituted solution must be administered slowly by intravenous route at a rate not exceeding 4 ml per minute. Be careful not to let blood enter the syringe filled with the product.

If you need to administer higher doses, it can also be done by infusion. For this purpose, transfer the reconstituted product to an approved infusion system. The infusion must be carried out following the doctor's instructions.

Observe if you present any immediate reaction. If any reaction occurs that may be related to the administration of Haemate P, stop the injection or infusion immediately (see also section 2).

If you use more Haemate P than you should

No adverse effects of overdose with FVW and FVIII have been reported. However, the risk of developing blood clots (thrombosis) cannot be excluded in the case of an extremely high dose, especially with products containing FVW with a high content of FVIII.

If you have any other questions about the use of the product, ask your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

The following side effects have been observed very rarely (in less than 1 in 10,000 patients):

• Animmediate allergic reaction(such as angioedema, burning or itching at the infusion site, chills, flushing, generalized urticaria, headache, hives, hypotension, lethargy, nausea, restlessness, tachycardia, chest pressure, tingling sensation, vomiting, or difficult breathing) and in some cases may progress to severe anaphylaxis (including shock).
• Increased body temperature (fever).

Von Willebrand disease

• Very rarely, there isan increased risk of thrombotic or thromboembolic eventsincluding blood clots in the lung (risk of formation and migration of blood clots in the vascular system, formed by arteries and veins, with potential impact on organs).
• In patients receiving products with FVW, sustained elevated plasma levels of FVIII:C may increase the risk of blood clot formation(see also section 2).
• Patients with von Willebrand disease may very rarely develop inhibitors (neutralizing antibodies) against FVW. If such inhibitors appear, a lack of clinical response leading to continuous bleeding occurs. This occurs especially in patients with a specific type of von Willebrand disease, called type 3. These antibodies precipitate and may appear at the same time as anaphylactic reactions. Therefore, the presence of an inhibitor should be evaluated in patients experiencing anaphylactic reactions. In such cases, contact with a specialized hemophilia center is recommended.

Hemophilia A

• In children who have not received prior treatment with factor VIII-containing medications, inhibitors (see section 2) may occur very frequently (more than 1 in 10 patients); however, in patients who have received prior treatment with factor VIII (more than 150 days of treatment), the risk is infrequent (less than 1 in 100 patients). If this happens, the medications you or your child take may not work properly and you or your child may experience persistent bleeding. In that case, contact your doctor immediately.

Other adverse effects in children and adolescents

The frequency, type, and severity of adverse effects in children are expected to be the same as in adults.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that does not appear in this prospectus. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicinal Products for Human Use:www.notificaRAM.es.

For information on viral safety, see “Warnings and precautions” (section 2).

• Keep this medication out of the sight and reach of children
• Do not use this medication after the expiration date that appears on the label and on the box after EXP. The expiration date is the last day of the month indicated.
• Store below 25°C.
• Do not freeze.
• Keep the vial in the outer packaging to protect it from light.
• Haemate P does not contain preservatives, so the prepared solution must be used immediately.
• If the prepared solution is not administered immediately, it must be used within a period of 3 hours.
• Once the product has been transferred to the syringe, it must be used immediately.

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and unused medications. By doing so, you will help protect the environment.

Composition of Haemate P

The active principles are: Human von Willebrand factor and human coagulation factor VIII.

The other components are: Human albumin, glycine, sodium chloride, sodium citrate, sodium hydroxide or hydrochloric acid (in small quantities to adjust the pH).

Dissolvent:Water for injection preparations.

Appearance of the product and contents of the package

Haemate P is presented as a white or pale yellow powder or friable solid and is supplied with water for injection preparations as a solvent. The prepared solution must be transparent or slightly opalescent, i.e., it may shine when placed under light, but it must not contain any detectable particles.

Presentation

Box containing:

1 vial with powder

1 vial with 10 ml of water for injection preparations

1 transfer filter with 20/20

Administration equipment (inner box):

1 10 ml single-use syringe

1 venous puncture set

2 alcohol wipes

1 non-sterile adhesive dressing

Holder of the marketing authorization and responsible for manufacturing

CSL Behring, S.A.

c/ Tarragona 157, floor 18

08014 Barcelona (Spain)

Responsible for manufacturing

CSL Behring, GmbH

Emil-von-Behring-Str. 76

35041 Marburg (Germany)

Last review date of this leaflet: July 2023

The detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) (http://www.aemps.gob.es/)

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This information is intended solely for healthcare professionals:

Dosage

Von Willebrand disease

It is essential to calculate the dose using the specified FVW:RCo UI number.

Generally, the administration of 1 UI of FVW:RCo/kg of body weight increases circulating VWF:RCo levels by 0.02 UI/ml, representing a 2% increase.

Levels above 0.6 UI of FVW:RCo/ml (60%) and levels above 0.4 UI of FVIII:C/ml (40%) should be achieved.

The recommended doses to achieve hemostasis are 40-80 UI of FVW:RCo/kg of body weight and 20-40 UI of FVIII:C/kg of body weight.

In certain cases, an initial dose of 80 UI of von Willebrand factor may be required, especially in patients with von Willebrand disease Type 3, in whom maintenance therapy to achieve adequate levels may require doses higher than those required by other types of von Willebrand disease.

Prevention of bleeding in cases of surgery or severe injuries:

To prevent profuse bleeding during or after surgery, the product administration should be initiated 1-2 hours before surgery begins.

A suitable dose should be repeated at intervals of 12-24 hours. The dose and duration of treatment depend on the patient's clinical condition, the type and severity of bleeding, and the levels of FVW:RCo and FVIII:C.

When administering products containing factor VIII and von Willebrand factor, the responsible physician should take into account that continuous treatment may cause excessive increases in FVIII:C. After 24-48 hours of treatment, and to avoid an undesirable increase in FVIII:C, consideration should be given to reducing doses and/or increasing intervals between administrations, or using von Willebrand factor products with low levels of factor VIII.

Pediatric population

The pediatric dosage is based on body weight and generally follows the same guidelines as those used for adults. The frequency of administration should always be oriented towards achieving clinical efficacy in each particular case.

Hemophilia A

Monitoring treatment

During the course of treatment, it is recommended to adequately control factor VIII levels to determine the dose to be administered and the frequency of repeated infusions. The individual response of patients to factor VIII therapy may vary, achieving different levels of in vivo recovery and demonstrating different half-lives. The dose based on body weight may require adjustment in patients with low or high body weight.

In the case of major surgical interventions, it is essential to monitor substitution therapy with precision through coagulation tests (plasma activity of factor VIII).

It is recommended to monitor patients for the development of factor VIII inhibitors. See section 2.

The dose and duration of treatment depend on the degree of factor VIII deficiency, the location and severity of bleeding, and the patient's clinical condition.

It is essential to calculate the dose using the specified FVIII:C UI number.

The number of factor VIII units administered is expressed in International Units (UI), in relation to the current World Health Organization (WHO) standard for factor VIII concentrates. Plasma activity of factor VIII is expressed as a percentage (in relation to normal human plasma) or preferably in International Units (in relation to an international standard for factor VIII in plasma).

The activity of one international unit of factor VIII is equivalent to the amount of factor VIII contained in 1 ml of normal human plasma.

On-demand treatment

The calculation of the necessary dose of factor VIII is based on the empirical observation that 1 UI of factor VIII per kg of body weight increases plasma activity of factor VIII by approximately 2% (2 UI/dl). The necessary dose is determined by the following formula:

Necessary units = body weight (kg) x desired increase in factor VIII (% or UI/dl) x 0.5

The dose and frequency of administration will always be established based on the observed clinical efficacy in each case.

In the case of hemorrhagic episodes such as those listed below, the activity of factor VIII should not be less than the established plasma activity level (in % of normal plasma or UI/dl) in the corresponding period. The following table may be used as a dosage guide for hemorrhagic episodes and surgery:

Prophylaxis

For long-term prophylaxis in patients with severe hemophilia A, the usual doses are 20-40 UI 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.

Pediatric population

No clinical experience is available for the treatment of children withHaemate P.

Special warnings and precautions for use

When using a product containing von Willebrand factor, the responsible physician should take into account that continuous treatment may cause excessive increases in FVIII:C. In patients receiving products withFVWcontaining FVIII, it is necessary to monitor plasma levels of FVIII:C to avoid sustained high plasma levels, which could increase the risk of thrombotic effects, and to evaluate antithrombotic measures.

Adverse reactions

When large or frequently repeated doses are needed, when inhibitors are present, or when pre- or postoperative care is involved, it is essential to monitor the appearance of symptoms of hypervolemia in all patients. Additionally, in patients with blood groups A, B, and AB, it is necessary to control for symptoms of intravascular hemolysis and/or decreased hematocrit values.