Haemate P 2400/1000 IU powder and solvent for solution for injection or infusion

Package leaflet: Information for the user

Introduction

PACKAGE LEAFLET: INFORMATION FOR THE USER

Haemate P 2400UI FVW/1000 UI FVIII

Powder and solvent for solution for injection and for infusion

Human von Willebrand factor (FVW)

Human coagulation factor VIII (FVIII)

Read all of this leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are adverse effects not listed in this leaflet. See section 4.

Leaflet contents

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

1. What Haemate P is and what it is used for

What is Haemate P?

Haemate P is presented as a powder together with its solvent. The solution obtained is administered by intravenous injection or infusion. Haemate P belongs to a class of medicines known as antihemorrhagics.

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

What is Haemate P used for?

Since Haemate P contains both FVIII and VWF, it is important to know which factor is primarily required. If you have haemophilia A, your doctor will prescribe Haemate P specifying the number of units of FVIII. If you have von Willebrand disease, your doctor will prescribe Haemate P specifying the number of units of VWF.

Von Willebrand disease

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

Haemophilia A (congenital factor VIII deficiency)

Treatment and prophylaxis of bleeding episodes in patients with haemophilia A.

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

2. What you need to know before using Haemate P

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 medicine (listed in section 6).

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

Warnings and precautions:

Traceability

It is strongly recommended that each time Haemate P is administered, your doctor records the date of administration and the batch number of the medicine to maintain a record of the batches used.

Talk to your doctor or pharmacist before starting to use Haemate P:

• If allergic or anaphylactic reactions occur (severe allergic reactions causing serious breathing difficulties or dizziness). Hypersensitivity-type allergic reactions may occur. Your doctor should inform you about the early symptoms of hypersensitivity reactions. These include hives, generalized rash, chest tightness, difficulty breathing, drop in blood pressure, and anaphylaxis (severe allergic reactions causing serious breathing difficulties or dizziness). If these symptoms occur, stop using the product immediately and contact your doctor.
• The development of inhibitors (antibodies) is a known complication that may occur during treatment with all factor VIII-containing medicines. These inhibitors, especially when present in large amounts, may prevent the treatment from working properly, so you and your child will be closely monitored for the development of such inhibitors. If your bleeding or your child's bleeding is not being controlled with Haemate P, contact your doctor immediately.
• If you have heart disease or are at risk of developing it, inform your doctor or pharmacist.
• If a central venous access device (CVAD) is required for the administration of Haemate P, your doctor must consider the risk of catheter-related complications, including local infections, bacteria in the blood (bacteremia), and blood clot formation (thrombosis) at the catheter insertion site.

von Willebrand disease

• If there is a risk of blood clot formation (thrombotic events, including blood clots in the lung), particularly if you have clinical or laboratory risk factors (e.g., during perioperative periods without thrombosis prophylaxis, delayed mobilization, obesity, overdose, cancer), you should be monitored for early signs of thrombosis. Prophylaxis for venous thrombosis should be established according to current recommendations. Patients with von Willebrand disease, especially those with type 3, may develop neutralizing antibodies (inhibitors) against von Willebrand factor. Your doctor will perform the necessary tests to detect their presence and will consider whether to continue this therapy.

Your doctor must carefully weigh the benefits of treatment with Haemate P against the risks of these complications.

Viral safety

When medicines derived from human plasma or blood are administered, the risk of transmitting infectious agents causing diseases cannot be completely excluded. This also applies to the potential transmission of pathogens of unknown or emerging nature or other types of infections. However, the risk of transmission of infectious agents is reduced by:

• careful selection of blood and plasma donors to ensure that potential carriers of infections are excluded;
• testing of each donation and plasma pool for signs of viruses/infections;
• inclusion of steps in the manufacturing process to inactivate or remove viruses.

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

Virus inactivation/removal procedures may have limited effectiveness against non-enveloped viruses such as parvovirus B19.

Parvovirus B19 infection may be serious for pregnant women (fetal infection) and for individuals with immunodeficiency or increased red blood cell production (e.g., hemolytic anemia).

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

Use of Haemate P with other medicines

• Inform your doctor or pharmacist if you are using, have recently used, or might need to use any other medicines.
• This medicine must not be mixed with other medicines, solvents, or diluents.

Pregnancy, breastfeeding, and fertility

• If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.
• Because haemophilia A is rare in women, there is no experience regarding the use of factor VIII during pregnancy and breastfeeding.
• In von Willebrand disease, women are even more frequently affected than men. Based on post-marketing experience, FVW replacement may be recommended for the prevention and treatment of acute bleeding. There are no clinical studies available on FVW replacement therapy in women during pregnancy and breastfeeding.
• During pregnancy and breastfeeding, Haemate P should only be administered if clearly indicated.

Driving and use of machines

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

Haemate P contains sodium

Haemate P 2400 IU VWF/1000 IU FVIII contains 52.5 mg of sodium (main component of table/cooking salt) per vial. This corresponds to 2.6% of the maximum daily recommended intake for an adult.

3. How to use Haemate P

Treatment should be initiated and supervised by a physician experienced in the treatment of blood coagulation disorders.

Dosage

The amount of von Willebrand factor and factor VIII you require, and the duration of treatment, depend on several factors such as your body weight, the severity of the condition, and the site and intensity of bleeding or the need to prevent bleeding during surgery or invasive procedures (see the section "This information is intended for healthcare professionals only").

If your doctor has prescribed Haemate P for home use, your physician must ensure that you are properly trained in how to administer the injection and in the correct dosage to use.

Follow exactly the administration instructions for Haemate P provided by your doctor or hemophilia treatment center staff.

If you use more Haemate P than you should

Symptoms of overdose with von Willebrand factor (VWF) and factor VIII (FVIII) have not been reported. However, the risk of developing blood clots (thrombosis) cannot be excluded in cases of extremely high doses, particularly with VWF-containing products that have a high FVIII content.

Reconstitution and administration

Ensure that you work under sterile conditions at every step of the process.

General instructions

• The lyophilized powder must be mixed (reconstituted) with the solvent (liquid) and withdrawn from the vial under aseptic conditions.
• The solution should be clear or slightly opalescent. After filtration/transfer (see below and before administering to the patient), the resulting solution should be visually inspected for the presence of particles or discoloration. Even when reconstitution instructions are followed precisely, it is not uncommon for some residue or particles to remain. The filter included in the Mix2Vial device completely removes these particles. Filtration does not affect dosage calculations.
• Do not use solutions that are visibly cloudy or solutions that still contain particles or residue after filtration.
• After administration, any unused medication and residual materials must be discarded according to local regulations and your physician's instructions.

Reconstitution:

Before opening either vial, allow the Haemate P powder and the accompanying solvent vial to reach room temperature. This can be achieved by leaving the vials at room temperature for approximately one hour or by holding them in your closed hands for several minutes. Do not expose the vials to direct heat. Vials must not be heated to temperatures above body temperature (37 °C).

Carefully remove the protective caps from both the solvent vial and the Haemate P vial. Clean the outer surfaces of the rubber stoppers of both vials with an alcohol-impregnated wipe and allow them to dry. The solvent can now be transferred to the powder vial using the provided administration system (Mix2Vial). Please follow the instructions below:

Administration

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

For the injection of Haemate P, the use of disposable plastic syringes is recommended, as the ground glass surface of fully glass syringes tends to stick with solutions of this type.

The reconstituted solution must be administered slowly by intravenous route at a rate not exceeding 4 ml per minute. Take care to ensure that no blood enters the syringe filled with the product.

If higher doses need to be administered, infusion may also be used. For this purpose, transfer the reconstituted product to an approved infusion system. The infusion must be carried out according to the physician's instructions.

Observe for any immediate reactions. If any reaction possibly related to the administration of Haemate P occurs, the injection or infusion must be stopped immediately (see also section 2).

If you use more Haemate P than you should

Symptoms of overdose with VWF and FVIII have not been reported. However, the risk of developing blood clots (thrombosis) cannot be excluded in the case of extremely high doses, particularly with products containing VWF that have a high FVIII content.

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

4. Possible adverse effects

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

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

• A sudden allergic reaction (such as angioedema, burning or itching at the infusion site, chills, flushing, generalized urticaria, headache, hives, hypotension, lethargy, nausea, restlessness, tachycardia, chest tightness, tingling sensation, vomiting, or difficulty breathing); in some cases, this may progress to severe anaphylaxis (including shock).
• Increase in body temperature (fever).

Von Willebrand disease

• Very rarely, there is a risk of thrombotic or thromboembolic events, including blood clots in the lung (risk of formation and migration of blood clots in the vascular system, composed of arteries and veins, with potential impact on organs).
• In patients receiving von Willebrand factor (VWF) products, persistently excessive 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 VWF. If such inhibitors appear, a lack of clinical response occurs, leading to ongoing bleeding. This occurs particularly in patients with a specific form of von Willebrand disease called type 3. These antibodies may precipitate and may occur simultaneously with anaphylactic reactions. Therefore, the presence of an inhibitor should be evaluated in patients experiencing an anaphylactic reaction. In such cases, it is recommended to contact a specialized hemophilia center.

Hemophilia A

• In children who have not previously been treated with factor VIII-containing medicines, inhibitory antibodies (see section 2) may develop very frequently (more than 1 in 10 patients); however, in patients who have previously received factor VIII treatment (more than 150 days of treatment), the risk is uncommon (less than 1 in 100 patients). If this occurs, the medicines you or your child are taking may no longer work properly, and you or your child may experience persistent bleeding. In this 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 adverse effects, consult your doctor or pharmacist, even if they are possible adverse effects not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicinal Products: www.notificaRAM.es.

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

5. Storage of Haemate P

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the label and the carton after EXP. The expiry date refers to 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; therefore, the reconstituted solution must be used immediately.
• If the reconstituted solution is not administered immediately, it must be used within 3 hours.
• Once the product has been transferred into the syringe, it must be used immediately.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging that you no longer need. This will help protect the environment.

6. Package contents and other information

Composition of Haemate P

The active substances 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 amounts to adjust pH).

Solvent: water for injections.

Appearance of the product and contents of the pack

Haemate P is presented as a white or pale yellow powder or friable solid and is supplied with water for injections as solvent. The reconstituted solution should be clear or slightly opalescent (i.e., it may shimmer when held up to the light), but must not contain any visible particles.

Pack presentation

Box contains:

1 vial of powder
1 vial of 15 ml water for injections
1 transfer device with 20/20 filter
Administration set (inner box):

• 1 single-use 20 ml syringe
• 1 venous puncture set
• 2 alcohol wipes
• 1 non-sterile adhesive dressing

Marketing Authorization Holder and Manufacturer

CSL Behring, S.A.
Tarragona 157, 18th floor
08014 Barcelona (Spain)

Manufacturer

CSL Behring, GmbH
Emil-von-Behring-Str. 76
35041 Marburg (Germany)

Date of the most recent review of this summary: July 2023

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS) (http://www.aemps.gob.es/)

This information is intended for healthcare professionals only:

Dosage

von Willebrand disease

It is important to calculate the dose using the specified number of IU of VWF:RCo.

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

Target levels should exceed 0.6 IU of VWF:RCo/ml (60%) and exceed 0.4 IU of FVIII:C/ml (40%).

Recommended doses to achieve hemostasis are 40–80 IU of VWF:RCo/kg body weight and 20–40 IU of FVIII:C/kg body weight.

In certain cases, an initial dose of 80 IU of von Willebrand factor may be required, especially in patients with type 3 von Willebrand disease, in whom maintenance therapy to sustain adequate levels may require higher doses than those needed for other types of von Willebrand disease.

Prevention of bleeding in surgery or severe trauma:

To prevent excessive bleeding during or after surgery, administration of the product should begin 1 to 2 hours before the surgical procedure.

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

When administering products containing both factor VIII and von Willebrand factor, the treating physician should be aware that continued treatment may lead to excessive increases in FVIII:C. After 24–48 hours of treatment, and to avoid undesirable increases in FVIII:C, consideration should be given to reducing the dose and/or increasing the intervals between administrations, or using von Willebrand factor products containing low levels of factor VIII.

Paediatric population

Dosage in paediatrics is based on body weight and therefore generally follows the same guidelines as for adults. The frequency of administration should always be guided by the need to achieve clinical efficacy in each individual case.

Haemophilia A

Monitoring of treatment

During treatment, it is recommended to appropriately monitor factor VIII levels to determine the required dose and the frequency of repeated infusions. Individual patient response to factor VIII therapy may vary, with different in vivo recovery levels and differing half-lives. Dose based on body weight may require adjustment in patients with low body weight or overweight. In the case of major surgical procedures, precise monitoring of replacement therapy using coagulation tests (plasma factor VIII activity) is essential.

Patients should be monitored for the development of factor VIII inhibitors. See also 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 important to calculate the dose using the specified number of IU of FVIII:C.

The number of factor VIII units administered is expressed in International Units (IU), relative to the current World Health Organization (WHO) standard for factor VIII concentrates. Factor VIII plasma activity is expressed as a percentage (relative to normal human plasma) or preferably in International Units (relative 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 required factor VIII dose is calculated based on the empirical observation that 1 IU of factor VIII per kg body weight increases plasma factor VIII activity by approximately 2% (2 IU/dl). The required dose is determined using the following formula:

Required units = body weight (kg) × desired increase in factor VIII (% or IU/dl) × 0.5

The dose and frequency of administration should always be determined based on the observed clinical efficacy in each individual case.

In cases of bleeding episodes as described below, factor VIII activity should not fall below the established plasma activity level (in % of normal plasma or IU/dl) during the corresponding period. The following table may be used as a dosing guide for bleeding episodes and surgery:

Prophylaxis

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

Pediatric population

There is no clinical experience in the treatment of children with Haemate P.

Warnings and special precautions for use

When using a product containing von Willebrand factor, the physician in charge of treatment should be aware that continuous treatment may lead to excessive increases in FVIII:C. In patients receiving FVW-containing products that also contain FVIII, plasma levels of FVIII:C should be monitored to avoid sustained excessive plasma levels, which could increase the risk of thrombotic events, and antithrombotic measures should be considered.

Adverse reactions

When very large or frequently repeated doses are required, when inhibitors are present, or when pre- or post-surgical care is involved, all patients should be monitored for symptoms of hypervolemia. In addition, in patients with blood groups A, B, and AB, monitoring should be performed for symptoms of intravascular hemolysis and/or decreases in hematocrit values.