Prospecto: information for the user

Berinert500 UI

Powder and solvent for injectable solution and for infusion.

Human C1 esterase inhibitor

1. What isBerinertand for what it is used

2. What you need to know before starting to use Berinert

3. How to use Berinert

4. Possible adverse effects

5. Conservation ofBerinert

6. Contents of the package and additional information

What is Berinert?

Berinert is presented as powder and solvent.The prepared solution must be administered via injection or infusion into a vein.

Berinert is prepared from human plasma (the liquid part of blood), the active ingredient 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 system disease. HAE is not an allergic disease.HAEis caused by insufficient, absent, or defective synthesis of C1 esterase inhibitor, an important protein.The disease is characterized by the following symptoms:

- sudden swelling of hands and feet,

- sudden facial swelling with a feeling of tightness,

- swelling of eyelids, lips, possible laryngeal swelling (voice organ) with respiratory difficulties,

- swelling of the tongue,

- colicky pain in the abdominal region.

Generally, all parts of the body can be affected.

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 protein or to any of the other components of this medication (including those listed in section6).

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

Warnings and precautions

• If you havehad allergic reactionsto Berinert in the past.You should take antihistamines and corticosteroids as prophylaxis, if advised by your doctor.
• Whenallergic reactions or anaphylactic reactions(severe allergic reaction that causes severe respiratory difficulties or dizziness).The administration of Berinert should be stopped immediately (for example, by interrupting the infusion).
• If you sufferswelling in the larynx(laryngeal edema). Youshould be closely monitored and have emergency treatment ready to be used.
• Duringuse for the treatment of indicationsand dosagesfor which the medicationhas not been approved(for example, Capillary Leak Syndrome, CLS).Seethe section4. "Possible adverse effects".

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

Viral safety

When administering blood-derived or plasma-derived medications, certain measures should be taken to prevent the transmission of infections to patients. Such measures include:

• Careful selection of blood and plasma donors to exclude those at risk of being carriers of infectious diseases, and
• Analysis of specific virus and infection markers in individual donations and plasma mixtures,

The manufacturers of these products also include stages in the processing of blood or plasma to eliminate or inactivate viruses. Despite this, when administering blood-derived or plasma-derived medications, the possibility of transmission of infectious agents cannot be entirely ruled out. This also applies to emerging or unknown viruses or other types of infections.

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

Your doctor may recommend vaccination against hepatitis A and B if you are treated periodically/repeatedly with plasma-derived medications.

It is strongly recommended that each time Berinert is administered, your doctor records the date of administration, the batch number, and the volume injected.

Use of Berinert with other medications

• Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication, including over-the-counter medications.
• Berinert should not be mixed with other medications and diluents in the same syringe or infusion equipment.

Pregnancy and breastfeeding

• 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, Berinert should only be used if clearly indicated.

Driving and operating machinery

The influence of Berinert on the ability to drive and operate machinery is negligible or insignificant.

Berinert contains sodium

Berinert contains up to 49 mg of sodium (main component of table salt/for cooking) in each vial. This corresponds to 2.5% of the maximum daily sodium intake recommended for an adult.

The treatment must be initiated and supervised by a doctor with experience in the treatment of C1 esterase inhibitor deficiency.

Dosage

Adults

Treatment of acute angioedema attacks:

20 UI per kilogram of body weight (20 UI/kg of b.w.).

Preoperative prevention of acute angioedema attacks:

1000 UI before 6 hours of a medical, dental, or surgical intervention.

Pediatric population

Treatment of acute angioedema attacks:

20 UI per kilogram of body weight (20 UI/kg of b.w.).

Preoperative prevention of acute angioedema attacks:

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

If you use more Berinert than you should

No cases of overdose have been described.

Reconstitution and administration form

Berinert is injected intravenously (intravenous administration), usually by your doctor or nurse. You or your caregiver can also inject Berinert, but only after receiving proper training. If your doctor decides that you can treat yourself at home, he will give you detailed instructions. You will be given a diary where you will record each injection administered at home, which you will bring with you each time you visit your doctor. You will be regularly reviewed or your caregiver on how to administer the injections to ensure that you do it correctly over time.

General instructions

• The powder must be dissolved and extracted from the vial under aseptic conditions. Use the syringe provided with the product.
• The prepared solution must be transparent and clear.After filtering or transferring the solution (see below), visually check that the solution does not contain particles or present discoloration before administering it.
• Do not use the solution if it is visibly turbid or contains particles or residues.
• Any unused amount of the medication or any residual material must be disposed of in accordance with local regulations and following the instructions of your doctor.

Reconstitution

Before opening any vial, temper the Berinert powder and the solvent until they are at room temperature.To achieve this, you can leave the vials at room temperature for about an hour or you can 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 higher than the body temperature (37 °C).

Remove the protective capsules from the solvent vial and the powder vial with care.Clean the exposed rubber stoppers of both vials with an alcohol-soaked swab and let them dry.Now you can transfer the solvent to the powder vial with the administration system included (Mix2Vial).Please follow the instructions below:

Transferring the reconstituted solution to the syringe and administration

Administration

The solution must be administered intravenously (i.v.) slowly, either by injection or by infusion (4 ml/minute).

Like all medications, this medication may produce adverse effects, although not all people will experience them.

Immediately contact your doctor

• if any adverse effect occurs or
• if you notice any adverse effect not mentioned in this prospectus.

Adverse effects with Berinert are rare.

The following adverse effects have been observed rarely (between 1 and 10 out of every 10,000 people/patients):

?There is agreater risk of thrombosis(formation of blood clots) in prophylactic or therapeutic treatment of Capillary Leak Syndrome (escape of fluid from small blood vessels into tissues), for example, during and after cardiac surgery with extracorporeal circulation.See section2.“Warnings and Precautions”.

• Increased body temperature, as well asburning and itching at the site where the injection was administered.
• Reactions of hypersensitivity or allergy(such as, for example, irregular heart rate, heart beats faster, drop in blood pressure, skin redness, rash, respiratory difficulties, headache, dizziness, feeling sick).

In very rare cases (less than 1 out of every 10,000 patients/people or isolated cases) allergic reactions can lead to shock.

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not appearing in this prospectus. You can also report them directly through theSpanish System for Pharmacovigilance of Medicinal Products for Human Use:www.notificaRAM.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medication.

• Keep this medication out of the sight and reach of children.
• Do not use Berinert after the expiration date, which appears on the label and on the carton packaging.
• Do not store at a temperature above 30°C.
• Do not freeze.
• Store the container in the packaging to protect it from light.
• Berinert does not contain preservatives, so it is preferable to use the prepared solution immediately.
• If the prepared solution is not administered immediately, it should be used within 8 hours. The reconstituted product should only be stored in the vial.

Composition of Berinert

The active ingredient is:

Inhibitor of human C1 esterase (500 UI/vial; after reconstitution: 50 UI/ml)

For more information, see the section“This information is intended solely for healthcare professionals”.

The other components are:

Glycine, sodium chloride, sodium citrate.

See the last paragraph of section2. "Berinert contains sodium”.

Vehicle:Water for injection.

Appearance of the product and contents of the package

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

The prepared solution must be transparent and clear.

Presentation

Box containing 500UI contains:

1 vial with powder (500UI)

1 vial with 10ml of water for injection

1 transfer set with filter 20/20

Administration equipment (inner box):

1 10ml single-use syringe

1 venipuncture set

2 alcohol wipes

1 dressing

Holder of the marketing authorization and responsible for manufacturing

CSL Behring GmbH

Emil von Behring Strasse, 76

35041 Marburg, Germany

For further information about this medicinal product, please contact the local representative of the marketing authorization holder:

CSL Behring S.A.

c/ Tarragona 157, floor 18

08014 Barcelona

Spain

This medicinal product is authorized in the member states of the European Economic Areaand in the United Kingdom (Northern Ireland)with the following names:

Berinert 500 IE Powder and

Solvent for the preparation of an

Injection or Infusion SolutionAustria

Berinert 500Belgium, Cyprus, Germany, Greece, Luxembourg, Poland, Portugal

Berinert 500, 500 IU Powder and solvent

for solution for injection/infusionBulgaria

Berinert 500 IUCzech Republic, Slovakia

BerinertDenmark, Italy

Berinert 500 IU, injektio/infuusiokuiva-aine

ja liuotin, liuosta vartenFinland

Berinert 500 UI, powder and solvent for

solution injectable/perfusionFrance

Berinert 500 NE por és oldószer

oldatos injekcióhoz vagy infúzióhozHungary

Berinert 500 IU powder and liquid for

injection/infusion, solutionNorway

Berinert 500 UI, powder and solvent

for solution for injection/infusionRomania

Berinert 500 i.e. prašekin vehicle za

raztopino za injiciranje ali infundiranjeSlovenia

Berinert 500 UI Powder and solvent for solution

for injection and for perfusionSpain

Berinert 500 IE, powder and liquid for

injection/infusion, solutionSweden

Berinert 500 UI powder and solvent

for solution for injection/infusionUnited Kingdom

Date of the last review of this leaflet:October 2021

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

This information is intended solely for healthcare professionals

QUALITATIVE AND QUANTITATIVE COMPOSITION

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