PROSPECTO:INFORMATION FOR THE USER

Beriate 1000 UIpowder and solvent for injectable solution and for infusion

Human coagulation Factor VIII

Read this prospectus carefully before starting to use this medication because it contains important information for you.

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

1. What isBeriateand for what it is used

2. What you need to knowbefore starting to useBeriate

3. How to useBeriate

4. Possible adverse effects

5. Conservation ofBeriate

6. Contents of the package and additional information

What is Beriate

Beriate is presented as a powder, accompanied by a solvent. The resulting solution must be administered through a vein, either by injection or by infusion.

Beriate is obtained from human plasma (the liquid part of blood) and contains human coagulation factor VIII. It is used to prevent or stop bleeding caused by a lack of factor VIII (hemophilia A) in the blood. It can also be used in the treatment of acquired factor VIII deficiency.

What is Beriate used for

Factor VIII is involved in blood coagulation. A lack of factor VIII means that blood does not clot as quickly as it should, resulting in an increased tendency to bleed. Beriate provides factor VIII, normalizing, temporarily, the mechanisms of coagulation.

The following paragraphs contain information that you and your doctor should consider before using Beriate.

Do not use Beriate:

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

Warnings and precautions

Traceability

It is strongly recommended that each time Beriate is administered, you record the date of administration, the batch number, and the volume injected in your treatment diary.

Consult your doctor or pharmacist before starting to use Beriate.

• Allergic reactions may occur. Your doctor will inform you about the early signs of allergic reactions, including hives, generalized urticaria, chest pressure, difficulty breathing, low blood pressure, and anaphylaxis (a severe allergic reaction that causes severe breathing problems or dizziness).If these symptoms occur, you should stop using the medication immediately and contact your doctor..
• The formation of inhibitors (antibodies) is a known complication that can occur during treatment with all factor VIII products. 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 Beriate, 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 (DAVC) is needed for the administration of Beriate, your doctor will consider the risk of complications related to the catheter, including local infections, bacterial infections (bacteremia), and the formation of blood clots (thrombosis) at the catheter insertion site.

Your doctor will carefully evaluatethe benefit of treatment with Beriate against the risk of these complications.

Viral safety

When administering blood-derived or plasma-derived medications,certain measures are taken to prevent the transmission of infections to patients. This includes the careful selection of blood and plasma donors to exclude those who may pose a risk of transmission of infections, and the analysis of each donor and plasma bank for signs of viruses/infections. Manufacturers of these products also include stages in the production process that can inactivate or eliminate viruses or other pathogens. Despite this, when administering blood-derived or plasma-derived medications, the possibility of transmission of infectious agents cannot be completely ruled out. This also applies to emerging or unknown viruses and other pathogens.

These procedures are considered effective against enveloped viruses such as human immunodeficiency virus (HIV, AIDS virus), hepatitis B virus, and hepatitis C virus (liver inflammation), as well as non-enveloped viruses such as hepatitis A virus andparvovirus B19.

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

Use of Beriate with other medications:

• Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication.
• Beriate should not be mixed with other medications, diluents, and solvents, except those recommended by the manufacturer (see section 6).

Pregnancy, breastfeeding, and fertility

• If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor or pharmacist before using this medication.
• During pregnancy and breastfeeding, Beriate should only be used if clearly indicated.
• No information is available on fertility

Driving and operating machinery

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

Beriatecontains sodium

Beriate 1000 UI contains 27.55 mg of sodium (main component of table salt/for cooking) in each vial. This is equivalent to 1.4% of the maximum daily sodium intake recommended for an adult.

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, consult again with your doctor or pharmacist.

The treatment of hemophilia A should be initiated under the supervision of a doctor with experience in treating this type of alteration.

Dosage

The dose of factor VIII that you need and the duration of treatment depend on various factors, such as your body weight, the severity of your disease, the location and importance of the hemorrhage, or the need to prevent bleeding during surgery or medical review.

If you have been instructed to use Beriate at home, your doctor will ensure that you receive the necessary instructions on how to inject the product and how much product to use.

Follow the instructions given by your doctor or the indications of the nurses at your hemophilia center.

Use in children and adolescents

The dose is calculated based on body weight and determined in the same way as for adults.

If you use more Beriate than you should

No adverse effects of overdosing with factor VIII have been reported.

If you forgot to use Beriate

Apply the next dose immediately and continue at regular intervals following your doctor's instructions.Do not take a double dose to compensate for the missed doses.

Reconstitution and administration

General instructions:

• The powder must be mixed (reconstituted) with the solvent (liquid) and removed from the vial under aseptic conditions.
• The reconstituted solution must be clear or slightly opalescent, i.e., it may shine when overlapped against a light.Occasionally, some flakes or particles may appear in the vial. The filter included in the Mix2Vial eliminates these particles. This filtration does not affect the dose calculations.After filtration and transfer of the reconstituted product to the syringe (see below), and before administration, the solution must be controlled by visual inspection to detect small particles and discolorations. Do not use solutions that present visible turbidity or that contain flakes or particles in the syringe.
• Once the product is transferred to the syringe, it must be used immediately.Do notstore the product in the syringe.
• The unused product and waste materials should be disposed of properly according to local requirements and according to your doctor's instructions.

Reconstitution:

Warm the Beriate vials (vial with powder and vial with liquid), without opening them, to room temperature. This can be done by leaving the vials at room temperature for 1 hour, or by holding them in your hands for a few minutes. DO NOT expose the vials to direct heat. The vials should not be heated above body temperature (37 °C).

Remove the protective capsules from the vials containing the powder and the solvent, and clean the exposed part of the stoppers with an alcohol-soaked swab. Allow the vials to dry before opening the Mix2Vial container, and follow the instructions below.

Application and removal:

Use the venous puncture equipment provided with the product. Insert the needle into the vein. Allow blood to enter the tube until the end. Attach the syringe to the rosette and closure of the venous puncture equipment.Inject the reconstituted solution slowly into the vein,following your doctor's instructions.The injection or perfusion speed should not exceed 2 ml per minute.Be careful not to allow blood to enter the syringe containing the product.

When a large volume needs to be administered, perfusion is an option to consider. The reconstituted product must be transferred to an authorized perfusion system. Perfusion should be performed according to your doctor's instructions.

Monitor yourself for any adverse effects that may occur immediately. If you have any adverse effects related to the administration of Beriate, the injection or perfusion should be interrupted (see also section 2).

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

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

If any of the following side effects occur, consult your doctor immediately or go to the Emergency Service or hemophilia center at your nearest hospital:

• Angioedema symptoms

• Swelling of the face, tongue, or pharynx,
• Difficulty swallowing,
• Hives and difficulty breathing.

These side effects have been observed very rarely (may affect up to 1 in 10,000 people), and in some cases may lead to severe allergic reactions (anaphylaxis), including shock

• Loss of effect (bleeding does not stop). In children who have not received previous treatment with factor VIII medications, inhibitors (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 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 side effects are:

• Allergic reactions (hypersensitivity), which may include:

• Burning sensation and itching at the site where the product was injected or infused.
• Chills, redness, skin rash all over the body, papules.
• Headache.
• Low blood pressure, restlessness, faster heart rate, chest tightness, difficult breathing.
• Drowsiness (lethargy).
• Nausea, vomiting.
• Tickling.

These side effects have been observed very rarely, but in some cases may evolve into severe allergic reactions (anaphylaxis), including shock.

• In very rare cases, fever has been observed.

Side effects in children and adolescents

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

Reporting of side effects

If you experience any type of side effect, consult your doctor, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use: www.notificaRAM.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Do not use this medication after the expiration date that appears on the label and on the packaging. The expiration date is the last day of the month indicated.

• Store in the refrigerator (between 2 °C and 8 °C).
• During its period of validity, Beriate can be stored up to 25 °C for a maximum period of 1 month. This storage period at room temperature must be recorded in your treatment diary in order to complete the 1-month period in its entirety.
• Beriate does not contain preservatives, so the reconstituted product should preferably be used immediately.
• If the reconstituted product is not administered immediately, storage in the vial at room temperature should not exceed an 8-hour period. Once transferred to the syringe, the product should be used immediately.
• Do not freeze.
• Store the vial in the original packaging to protect it from light.

Keep out of the sight and reach of children.

Composition of Beriate

The active principle is:

Beriate is presented as a powder (containing nominally 1000 UI of human coagulation factor VIII per vial) and a liquid (solvent). The reconstituted solution is administered, either by injection or by perfusion.

Beriate 1000 UI is reconstituted with 10 ml of water for injectable preparations and contains approximately 100 UI/ml of human coagulation factor VIII.

The other components are:

Glycine, calcium chloride, sodium hydroxide (in small quantities) to adjust the pH, sucrose and sodium chloride

Solvent: water for injectable preparations 10 ml.

Appearance of the product and contents of the package

Beriate is presented as a white powder, and is supplied with the corresponding water for injectable preparations.

The reconstituted solution must be clear or slightly opalescent, i.e., it may shine when overlapped against a light but must not contain particles.

Presentations:

Box with 1000 UI containing:

- 1 vial with powder

- 1 vial with 10 ml of Water for injectable preparations

- 1 transfer device with filter 20/20

Administration equipment (inner box):

- 1 10 ml single-use syringe

- 1 venipuncture device

- 2 alcohol-impregnated wipes

- 1 non-sterile dressing

Holder of the Marketing Authorization and responsible for manufacturing

CSL Behring GmbH

Emil-von-Behring-Straße 76

35041 Marburg, Germany

You can request more information about this medication by contacting the local representative of the Marketing Authorization Holder:

CSL Behring, S.A.

c/ Tarragona 157, 18th floor

08014 Barcelona

Spain

This medication is authorized in the member states of the European Economic Area with the following names:

Austria:

Beriate 100 I.E./ml Powder and solvent for solution for injection or infusion (250 I.E., 500 I.E., 1000 I.E.)

Beriate 200 I.E./ml Powder and solvent for solution for injection or infusion (2000 I.E.)

Bulgaria:

Beriate 250 IU Powder and solvent for solution for injection or infusion

Beriate 500 IU Powder and solvent for solution for injection or infusion

Beriate 1000 IU Powder and solvent for solution for injection or infusion

Beriate 2000 IU Powder and solvent for solution for injection or infusion

Croatia:

Beriate 250 IU powder and solvent for solution for injection or infusion

Beriate 500 IU powder and solvent for solution for injection or infusion

Beriate 1000 IU powder and solvent for solution for injection or infusion

Beriate 2000 IU powder and solvent for solution for injection or infusion

Czech Republic:

Beriate 250 IU, Beriate 500 IU, Beriate 1000 IU, Beriate 2000 IU

Estonia:

Beriate

Germany:

Beriate 250, Beriate 500, Beriate 1000, Beriate 2000

Hungary:

Presentations of Beriate 250, 500 and 1000:

BERIATE 100 NE/ml por és oldószer oldatos injekcióhoz vagy infúzióhoz

Presentation 2000:

BERIATE 200 NE/ml por és oldószer oldatos injekcióhoz vagy infúzióhoz

Italy:

Beriate

Latvia:

Beriate 250 SV powder and solvent for solution for injection or infusion

Beriate 500 SV powder and solvent for solution for injection or infusion

Beriate 1000 SV powder and solvent for solution for injection or infusion

Beriate 2000 SV powder and solvent for solution for injection or infusion

Lithuania:

Beriate®250 TV vials and solvent for solution for injection or infusion

Beriate®500 TV vials and solvent for solution for injection or infusion

Beriate®1000 TV vials and solvent for solution for injection or infusion

Beriate®2000 TV vials and solvent for solution for injection or infusion

Poland:

Beriate 250

Beriate 500

Beriate 1000

Beriate 2000

Portugal:

Beriate

Romania:

Beriate 250 powder and solvent for solution for injection or infusion

Beriate 500 powder and solvent for solution for injection or infusion

Beriate 1000 powder and solvent for solution for injection or infusion

Beriate 2000 powder and solvent for solution for injection or infusion

Spain:

Beriate 500 UI powder and solvent for solution for injection or infusion

Beriate 1000 UI powder and solvent for solution for injection or infusion

Beriate 2000 UI powder and solvent for solution for injection or infusion

Slovakia:

Beriate 250 IU

Beriate 500 IU

Beriate 1000 IU

Beriate 2000 IU

Slovenia:

Beriate 250 i.e. powder and solvent for solution for injection or infusion

Beriate 500 i.e. powder and solvent for solution for injection or infusion

Beriate 1000 i.e. powder and solvent for solution for injection or infusion

Beriate 2000 i.e. powder and solvent for solution for injection or infusion

Last review date of this leaflet:April 2020

More detailed and updated information about this medication 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

Monitoring of treatment

During treatment, it is recommended to control the levels of factor VIII adequately to determine the dose to be administered and the frequency of repeated perfusions. The response of each patient to factor VIII can vary, demonstrating different half-lives and recoveries. The dose based on body weight may require adjustment in patients with low weight or obesity. In the case of major surgery, it is essential to monitor the substitution therapy with precision through coagulation tests (factor VIII plasma activity).

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

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

One UI 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 required 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 approximately by 2% (2 UI/dL) above normal activity. The required dose is determined by the following formula:

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

The amount administered and the frequency of administration will always be determined in relation to the observed efficacy in each case.

In subsequent bleeding episodes, the activity of factor VIII should not be less than the plasma activity level indicated (in % of normal level or UI/dL), during the corresponding period. The following table can be used as a guide to dosage in bleeding episodes and surgery.

Prophylaxis

For long-term prophylaxis of bleeding in patients with severe hemophilia A, the usual dose is 20-40 UI of factor VIII/kg of body weight at intervals of 2-3 days. In some cases, especially in young patients, it may be necessary to shorten the intervals of administration or administer higher doses.

Pediatric population

Dosage in pediatrics is based on body weight and is generally followed by the same guidelines as those used for adults. The frequency of administration should always be oriented towards achieving clinical efficacy in each particular case. There is some experience in the treatment of children under 6 years old.

Information on the pharmacological properties of Factor von Willebrand

In addition to the protective function of factor VIII, factor von Willebrand facilitates platelet adhesion at the site of a vascular injury and plays a role in platelet aggregation.