BERINERT 1500 IU POWDER AND SOLVENT FOR INJECTABLE SOLUTION

Introduction

Package Leaflet: Information for the User

Berinert 1500 IU

Powder and solvent for solution for injection

Human C1 esterase inhibitor

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

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the package leaflet

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

1. What is Berinert and what is it used for

What is Berinert?

Berinert is presented as a powder and solvent. The prepared solution should be administered by injection into a vein.

Berinert is prepared from human plasma (the liquid part of the blood). The active substance is human C1 esterase inhibitor protein, obtained from plasma.

What is Berinert used for?

Berinert is used for the treatment and preoperative prevention of hereditary angioedema type I and II (HAE, edema = swelling). Hereditary angioedema is a congenital vascular disease. It is not an allergic disease. HAE is caused by insufficient, absent, or defective synthesis of C1 esterase inhibitor, which is an important protein. The disease is characterized by the following symptoms:

• sudden swelling of hands and feet,
• sudden swelling of the face with a feeling of tightness,
• swelling of the eyelids, lips, possible swelling of the larynx (voice organ) with breathing difficulties,
• swelling of the tongue,
• colic-like pain in the abdominal region.

Generally, all parts of the body can be affected.

2. What you need to know before you use Berinert

The following sections contain information that your doctor should consider before administering Berinert to you.

Do not use Berinert:

• If you are allergic to C1 esterase inhibitor or any of the other components of this medicine (listed in section 6).

Tell your doctor or pharmacist if you are allergic to any medicine or food.

Warnings and precautions

• If you have suffered allergic reactions to Berinert in the past. You should take antihistamines and corticosteroids as prophylaxis, if advised by your doctor.
• When allergic or anaphylactic reactions (severe allergic reaction causing severe breathing difficulties or dizziness) occur. Berinert administration should be discontinued immediately (e.g., by interrupting the injection).
• If you suffer from laryngeal swelling (laryngeal edema). You should be closely monitored and have emergency treatment ready for use.
• During use for the treatment of indications and dosages for which the medicine has not been approved (e.g., Capillary Leak Syndrome,CLS). See section 4 "Possible side effects".

Your doctor will carefully weigh the benefit of treatment with Berinert against the risk of these complications.

Viral safety

When administering medicines derived from human blood or plasma, certain measures must be taken to prevent infections from being transmitted to patients. These measures include:

• careful selection of blood and plasma donors to exclude those who are at risk of being carriers of infectious diseases, and
• testing for specific virus and infection markers in individual donations and plasma pools.

Manufacturers of these products also include stages in the processing of blood or plasma to eliminate or inactivate viruses. Despite this, when administering medicines derived from human blood or plasma, the possibility of transmitting infectious agents cannot be entirely excluded. This also applies to emerging or unknown viruses or other types of infections.

The measures taken are considered effective for enveloped viruses such as human immunodeficiency virus (HIV, the AIDS virus), hepatitis B virus, hepatitis C virus (liver inflammation), and for non-enveloped viruses such as hepatitis A virus (liver inflammation) and parvovirus B19.

It is possible that your doctor may recommend vaccination against hepatitis A and B if you are treated periodically/repeatedly with human plasma-derived medicines.

It is strongly recommended that each time Berinert is administered, the administration date, batch number, and injected volume be recorded.

Using Berinert with other medicines

• Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines, including those without a prescription.
• Berinert should not be mixed with other medicines and diluents in the same syringe.

Pregnancy and breastfeeding

• 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.
• During pregnancy and breastfeeding, Berinert should only be used if clearly indicated.

Driving and using machines

No studies have been performed on the effects on the ability to drive and use machines.

Berinert contains sodium

Berinert contains less than 23 mg of sodium (1 mmol) per vial; this is essentially "sodium-free".

3. How to use Berinert

Treatment should be initiated and supervised by a doctor experienced in the treatment of C1 esterase inhibitor deficiency.

Dosage

Adults

Treatment of acute angioedema attacks:

20 IU per kilogram of body weight (20 IU/kg body weight).

Preoperative prevention of angioedema attacks:

1000 IU before 6 hours of a medical, dental, or surgical procedure.

Pediatric population

Treatment of acute angioedema attacks:

20 IU per kilogram of body weight (20 IU/kg body weight).

Preoperative prevention of angioedema attacks:

15 to 30 IU per kilogram of body weight (15-30 IU/kg body weight) before 6 hours of a medical, dental, or surgical procedure. The dose should be chosen taking into account the clinical circumstances (e.g., the type of procedure and the severity of the disease).

If you use more Berinert than you should

No cases of overdose have been reported.

Reconstitution and method of administration

Berinert is injected into a vein (intravenous administration), usually by your doctor or nurse. You or your caregiver may also inject Berinert, but only after receiving adequate training. If your doctor decides that you can treat yourself at home, they will give you detailed instructions. You will be given a diary to record each injection administered at home, which you should bring with you every time you visit your doctor. You or your caregiver will be regularly reviewed on how to perform the injections to ensure they are done correctly over time.

General instructions

• The powder must be dissolved and withdrawn from the vial under aseptic conditions. Use the syringe provided with the product.
• The prepared solution should be clear and colorless to slightly opalescent. After filtering or transferring the solution (see below), it should be visually checked for particles or discoloration before administration.
• Do not use the solution if it is visibly cloudy or contains particles or residues.
• Any unused medicine or material should be disposed of in accordance with local regulations and following the instructions of your doctor.

Reconstitution

Before opening any vial, allow the Berinert powder and solvent to reach room temperature. To do this, you can leave the vials at room temperature for about an hour or hold 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 above body temperature (37°C).

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

Transfer of the reconstituted solution to the syringe and administration

Administration

The solution should be administered by slow intravenous injection (i.v.).

4. Possible side effects

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

Contact your doctor immediately

Side effects with Berinert are rare.

The following side effects have been observed rarely (may affect up to 1 in 1,000 people):

• There is an increased risk of blood clot formation in attempts at prophylactic or therapeutic treatment of Capillary Leak Syndrome (fluid leakage from small blood vessels into tissues), for example, during or after cardiac surgery with extracorporeal circulation. See section 2 "Warnings and precautions".

• Increased body temperature, as well as burning and itching at the injection site.
• Hypersensitivity or allergic reactions (such as irregular heartbeat, rapid heartbeat, low blood pressure, skin redness, rash, breathing difficulties, headache, dizziness, feeling sick).

In very rare cases (may affect up to 1 in 10,000 people), allergic reactions can lead to shock.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Medicines and Healthcare Products Agency's website: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Berinert

• Keep this medicine out of the sight and reach of children.
• Do not use Berinert after the expiry date stated on the label and carton.
• Do not store above 30°C.
• Do not freeze.
• Store the vial in the outer packaging to protect it from light.
• Berinert does not contain preservatives, so the prepared solution should be used immediately.

If the prepared solution is not administered immediately, it should be used within 8 hours and only stored in the vial.

6. Contents of the pack and other information

Composition of Berinert

The active substance is:

Human C1 esterase inhibitor (1500 IU/vial; after reconstitution with 3 ml of water for injections 500 IU/ml)

For more information, see Section "This information is intended only for healthcare professionals".

The other ingredients are:

Glycine, sodium chloride, sodium citrate.

See the last paragraph of section 2 "Berinert contains sodium".

Solvent:water for injections.

Appearance and packaging

Berinert is presented as a white powder and is supplied with water for injections as a solvent.

The prepared solution should be clear and colorless to slightly opalescent.

Presentation

Box with 1500 IU contains:

1 vial with powder (1500 IU)

1 vial with 3 ml of water for injections

1 transfer device with 20/20 filter

Administration equipment (inner box):

1 single-use 5 ml syringe

1 venipuncture set

2 alcohol swabs

1 dressing

Marketing authorisation holder and manufacturer

CSL Behring GmbH

Emil-von-Behring-Strasse 76

35041 Marburg (Germany)

You can request more information about this medicine from the local representative of the marketing authorisation holder:

CSL Behring S.A.

c/ Tarragona 157, 18th floor

08014 Barcelona

Spain

This medicine is authorised in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

Berinert 1500 IU Powder and solvent for solution for injection Austria

Berinert 1500 Belgium, Cyprus, Germany, Greece, Luxembourg, Poland, Portugal

Berinert 1500, 500 IU Powder and solvent for solution for injection Bulgaria

Berinert 1500 IU Czech Republic, Slovakia

Berinert Denmark, Italy

Berinert 1500 IU, powder and solvent for solution for injection Finland

Berinert 1500 UI, powder and solvent for solution for injection France

Berinert 1500 NE por és oldószer oldatos injekcióhoz Hungary

Berinert 1500 IU pulver og væske til injeksjons, oppløsning Norway

Berinert 1500, pulbere si solvent pentru solutie injectabila Romania

Berinert 1500 i.e. prašek in vehikel za raztopino za injiciranje Slovenia

Berinert 1500 UI Polvo y disolvente para solución inyectable Spain

Berinert 1500 IE, pulver och vätska till injektionsvätska, lösning Sweden

Berinert 1500 UI powder and solvent for solution for injection United Kingdom

Date of last revision of this leaflet:October 2021

Detailed and up-to-date information on this medicine is available on the website of the Spanish Agency for Medicines and Healthcare Products (AEMPS) http://www.aemps.gob.es

This information is intended only for healthcare professionals

QUALITATIVE AND QUANTITATIVE COMPOSITION

The potency of human C1 esterase inhibitor is expressed in International Units (IU), which is related to the current WHO standard for C1 esterase inhibitor products.