Package Insert: Information for the User

Berinert1500 UI

Powder and solvent for injectable solution

Human C1 esterase inhibitor

Read this package insert carefully before starting to use this medication, as it contains important information for you.

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

1. What is Berinert and how is it used

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

3. How to use Berinert

4. Possible adverse effects

5. Storage of Berinert

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 into a vein.

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

- sudden swelling of hands and feet,

- sudden swelling of the face with a sensation of tightness,

- swelling of the eyelids, lips, possible swelling of the larynx (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 (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 breathing difficulties or dizziness).The administration of Berinert should be stopped immediately (for example, by interrupting the injection).
• 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 medication has not been approved(for example, Capillary Leak Syndrome, CLS).Seethe section4. "Possible side effects".

Your doctor will carefully weigh the benefits of treatment with Berinert against the risk of 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 non-enveloped viruses such as hepatitis A virus (liver inflammation) and parvovirus B19.

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

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

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.

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

No studies have been conducted 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”.

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

Dosage

Adults

Acute angioedema attack treatment:

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

Acute angioedema attack treatment:

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 (i.v.), 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 to 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 to ensure that you are performing the injections 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 to slightly opalescent.After filtering or transferring the solution (see below), visually check that the solution does not contain particles or discoloration before administering it.
• Do not use the solution if it is visibly turbid or contains particles or residues.
• Any unused medication or residual material must be disposed of in accordance with local regulations and following your doctor's instructions.

Reconstitution

Before opening any vial, warm 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 above 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 by slow intravenous injection (i.v.).

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 leaflet.

Adverse effects with Berinert are rare.

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

• There isa higher risk of blood clot formationin prophylactic or therapeutic treatment of Hereditary Angioedema (HAE), for example, during or after cardiac surgery with cardiopulmonary bypass.See section2.“Warnings and Precautions”.

• Increased body temperature, as well asburning and itching at the site where the injection was administered.
• Allergic or hypersensitivity reactions(such as irregular heart rate, rapid heartbeat, low blood pressure, skin redness, rash, respiratory difficulties, headache, dizziness, nausea).

In very rare cases (may affect up to 1 in 10,000 people), allergic reactions can lead to anaphylactic 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 listed in this leaflet. You can also report them directly to the Spanish 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 that appears on the label and the carton packaging.
• Do not store at a temperature above 30 °C.
• Do not freeze.
• Store the vial in the outer 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 and should only be stored in the vial.

Berinert Composition

The active ingredient is:

Human C1 esterase inhibitor (1500 UI/vial; after reconstitution with 3 ml of water for injectable preparations 500 UI/ml)

For more information see 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 injectable preparations.

Product appearance and packaging contents

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

The prepared solution must be transparent and cleara slightly opalescent.

Presentation

Box containing 1500UI contains:

1 vial with powder (1500UI)

1 vial with 3 ml of water for injectable preparations

1 transfer set with filter 20/20

Administration equipment (inner box):

1 5 ml single-use syringe

1 venipuncture set

2 alcohol wipes

1 dressing

Marketing authorization holder andmanufacturer

CSL Behring GmbH

Emil-von-Behring-Strasse 76

35041 Marburg (Germany)

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

CSL Behring S.A

c/ Tarragona 157, floor 18

08014 Barcelona

Spain

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

Berinert 1500 IE Powder and

Solvent for the preparation of an

InjectionAustria

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

Berinert 1500, 500 IU Powder and solvent

for solution for injectionBulgaria

Berinert 1500 IUCzech Republic, Slovakia

BerinertDenmark, Italy

Berinert 1500 IU, infuusiokuiva-aine

and liuotin, liuosta vartenFinland

Berinert 1500 UI, powder and solvent for

solution injectableFrance

Berinert 1500 NE por és oldószer

oldatos injekcióhozHungary

Berinert 1500 IU powder and væske til

injeksjons, oppløsningNorway

Berinert 1500, pulbere si solvent

pentru solutie injectabilaRomania

Berinert 1500 i.e. prašekin vehikel za

Raztopino za injiciranjeSlovenia

Berinert 1500 UI Powder and

disolvente para solución

inyectableSpain

Berinert 1500 IE, powder and vätska till

injektionsvätska, lösning_______Sweden

Berinert 1500 UI powder and solvent

for solution for injectionUnited Kingdom

Last review date of this leaflet:October 2021

The detailed and updated information about this medicine 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.