Berinert 3000 IU powder and solvent for subcutaneous injection solution: detailed information

Brand name Berinert 3000 IU powder and solvent for subcutaneous injection solution

Form powder and solvent for solution for injection

Active substance / Dosage

C1 ESTERASE INHIBITOR · 3000 UI

Prescription type Hospital Use Only

ATC code

B06A B06AC B06AC01

Registration number 82885

Manufacturer Csl Behring Gmbh

Berinert 3000 IU powder and solvent for subcutaneous injection solution powder and solvent for solution for injection

Table of Contents

Package leaflet: Information for the user
Introduction
1. What Berinert is and what it is used for
2. What you need to know before using Berinert
3. How to use Berinert
4. Possible adverse effects
5. Storage of Berinert
6. Contents of the pack and other information

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Berinert 3000 IU

Powder and solvent for subcutaneous injectable solution

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, 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.

Contents of this leaflet:

What Berinert is and what it is used for
What you need to know before using Berinert
How to use Berinert
Possible side effects
How to store Berinert
Contents of the pack and other information

1. What Berinert is and what it is used for

What is Berinert?

Berinert is supplied as a powder and solvent. The prepared solution must be administered by subcutaneous injection.

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

What is Berinert used for?

Berinert is used for the prevention of recurrent attacks of hereditary angioedema (HAE) in adolescent and adult patients. Hereditary angioedema is a congenital disorder of the vascular system. 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 and lips, possible swelling of the larynx (voice organ) with breathing difficulties,
swelling of the tongue,
colicky abdominal pain.

Generally, any part of the body may be affected.

2. What you need to know before using Berinert

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

Do not use Berinert:

If you have experienced life-threatening immediate hypersensitivity reactions, including anaphylaxis, to C1 esterase inhibitor protein or to any of the other components of this medicine (listed in section 6).

Inform your doctor or pharmacist if you are allergic to any medicines or foods.

Warnings and precautions

Talk to your doctor or pharmacist before starting Berinert,

if allergic or anaphylactic reactions occur (severe allergic reactions causing serious breathing difficulties or dizziness). Administration of Berinert must be stopped immediately (e.g., by stopping the injection).
If you have a history of blood clotting disorders. Blood clots have occurred in patients treated with intravenous Berinert. The use of high-dose Berinert for conditions other than HAE may increase the risk of blood clots. However, with subcutaneous Berinert, there is no established association with blood clots at the dose recommended by your doctor. Consult your doctor if you have a history of heart or blood vessel disease, heart attack, blood clots, thick blood, a permanent catheter/device in one of your veins, or if you have been immobilized for a period of time. These conditions may increase your risk of developing a blood clot after using Berinert. Also inform your doctor about any medications you are taking, as some medicines—such as contraceptives or certain androgens—may increase the risk of developing a blood clot.

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

Viral safety

When medicines derived from human blood or plasma are administered, certain measures are taken to prevent infections from being passed to patients. These measures include:

Careful selection of blood and plasma donors to exclude those at risk of carrying infectious diseases, and
Testing individual donations and pooled plasma for specific markers of viruses and infections.

Manufacturers of these products also include steps in the processing of blood or plasma to inactivate or remove viruses. Despite these measures, however, the possibility of transmitting infectious agents cannot be completely ruled out when administering medicines derived from human blood or plasma. This also applies to emerging or unknown viruses and other types of infections.

The measures applied are considered effective against enveloped viruses such as human immunodeficiency virus (HIV, the AIDS virus), hepatitis B virus, hepatitis C virus (liver inflammation), and against 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 regularly or repeatedly with medicines derived from human plasma.

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 medicines

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines, including over-the-counter medicines.
Berinert must not be mixed with other medicines or diluents in the same syringe.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medicine.

Driving and using machines

Berinert does not affect your ability to drive or operate machinery.

Berinert contains sodium

This medicine contains 29 mg of sodium (the main component of table/cooking salt) per vial. This corresponds to 1.5% of the maximum daily recommended sodium intake for an adult.

3. How to use Berinert

Berinert is indicated for self-administration by subcutaneous injection. You or your caregiver must be trained, as thoroughly as necessary, in the method of administering Berinert.

Dosage

The recommended dose of Berinert is 60 IU/kg body weight.

Paediatric population

The recommended dose is the same as in adults.

If you use more Berinert than you should

Cases of overdose have not been reported.

Reconstitution and method of administration

If your doctor decides that you can treat yourself at home, they will provide you with detailed instructions. You will be given a diary in which to record each injection administered at home, which you must bring with you every time you visit your doctor. You or your caregiver will be reviewed regularly on how to administer the injections to ensure correct technique 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 transparent and clear to slightly opalescent. After filtering or transferring the solution (see below), the solution must be inspected visually for particulate matter and discoloration prior to administration.
Do not use the solution if it is visibly cloudy or contains particles or residues.
Any unused portion of the medicine or residual materials must be disposed of in accordance with local regulations and your doctor's instructions.

Reconstitution

Before opening any vial, allow the Berinert powder and the solvent to reach room temperature. To achieve this, leave the vials at room temperature for approximately one hour, or hold them in closed hands for several minutes. DO NOT expose the vials to direct heat. The vials must 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-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:

1	Open the Mix2Vial blister by peeling off the seal. Do not remove the Mix2Vial from the blister.
2	Place the solvent vial on a clean, flat surface and hold it firmly. Hold the Mix2Vial with the blister and push the blue end downward, inserting it into the stopper of the solvent vial.
3	Carefully remove the blister from the Mix2Vial by holding the edge and pulling vertically upward. Make sure you remove only the blister and not the Mix2Vial.
4	Place the vial containing the lyophilized powder on a flat, stable surface. Invert the solvent vial with the attached Mix2Vial and push the transparent adapter end downward into the stopper of the vial containing the powder. The solvent will automatically transfer into the vial with the lyophilized powder.
5	With one hand, hold the vial containing the product with the Mix2Vial attached; with the other hand, hold the solvent vial. Carefully unscrew the system counterclockwise, separating it into two parts. Discard the solvent vial with the blue adapter of the Mix2Vial attached.
6	Gently rotate the vial containing the reconstituted solution with the transparent adapter attached until the substance is completely dissolved. Do not shake.
7	Draw air into a sterile, empty syringe. Use the syringe provided with the product. With the solution vial held in an upright position, attach the syringe to the Luer Lock adapter of the attached Mix2Vial by screwing it clockwise. Inject the air into the solution vial.

Transfer and administration

8	While keeping the syringe plunger depressed, invert the system and draw the solution into the syringe by slowly pulling back the syringe plunger.
9	Once the solution has been transferred into the syringe, firmly hold the barrel of the syringe (keeping the plunger pointing downward) and disconnect the transparent Mix2Vial adapter from the syringe by unscrewing it counterclockwise.

Administration

Self-administration (subcutaneous administration)

Your doctor will teach you how to safely administer Berinert. Once you know how to self-administer the medication, follow the instructions provided below.

Table 2. Instructions for self-administration of Berinert

Step 1: Attach the accessories

Take the Berinert syringe, the following disposable accessories, and other items (needles or other packaging, treatment diary or patient logbook):

Hypodermic needle or subcutaneous infusion set
Sterile needle (use a silicone-free needle)
Alcohol wipes
Gloves (if recommended by your healthcare professional)

Step 2: Clean the surface

Thoroughly clean a table or flat surface using alcohol wipes.

Step 3: Wash your hands

Wash and dry your hands thoroughly.
If you have been advised to wear gloves during preparation of the infusion, put on the gloves.

Step 4: Prepare the injection site

Unless your doctor has instructed you to use another area, select an area of your abdomen (stomach) for the injection (Figure 1).
Use a different site from your last injection; you should rotate injection sites.
New injection sites should be at least 2 inches (5 centimeters) away from the site of the previous injection.
Never inject into an area where the skin is itchy, swollen, painful, wounded, or red.
Avoid injecting into areas with scars or stretch marks.
Clean the skin at the injection site with an alcohol wipe and allow the skin to dry (Figure 2).

Schematic drawing of the human torso with small squares indicating the areas of the

Figure 1

Schematic drawing of a hand pressing and rotating a medical device on the skin with a curved arrow indicating rotational movement

Figure 2

Step 5: Abdominal injection

As instructed by your healthcare professional:

Attach a hypodermic needle or subcutaneous infusion set (butterfly) to the syringe according to your healthcare professional's instructions. Prepare the needle or tubing as necessary and as you have been taught.

Injection with hypodermic needle:

Insert the needle into the skin fold (Figure 3).

Injection with subcutaneous infusion set:

Insert the needle into the skin fold (Figure 4).

Technical drawing showing two hands holding a syringe to prepare the

Figure 3

Black line drawing showing two hands holding and opening a medical device applied to the

Figure 4

Step 6: Clean up

After injecting the full dose of Berinert, remove the needle.
Dispose of any unused solution and administration equipment according to local requirements.

Step 7: Record the treatment

Each time you use Berinert, record the lot number shown on the Berinert vial label in your treatment diary or patient logbook, along with the date and time of the infusion.

4. Possible adverse effects

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

Contact your doctor immediately

if any adverse effect occurs, or
if you notice any adverse effect not listed in this leaflet.

Adverse effects with Berinert are rare.

The following adverse effects have been observed very commonly (may affect more than 1 in 10 people):

Reactions at the injection site (bruising, cold sensation, oozing, erythema, hematoma, bleeding, hardening, edema, pain, pruritus, rash, scar, swelling, urticaria, warmth).
Nasopharyngitis (stuffy nose, sneezing, watery eyes).

The following adverse effects have been observed commonly (may affect up to 1 in 10 people):

Hypersensitivity or allergic reactions (such as hypersensitivity, pruritus, rash, and urticaria)
Dizziness

Reporting of 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 via the Spanish System for Pharmacovigilance of Human Medicines: www.notificaRAM.es. By reporting adverse 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 this medicine after the expiry date stated on the label and outer carton following EXP.
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; therefore, the prepared solution should preferably be used immediately.
If the prepared solution is not administered immediately, it must be used within 8 hours and should only be stored in the vial.

6. Contents of the pack and other information

Composition of Berinert

The active substance is:

Human C1 esterase inhibitor (3,000 IU/vial; after reconstitution with 5.6 ml of water for injections, 500 IU/ml).

For more information see the section "This information is intended for healthcare professionals only."

The other components are:

Glycine, sodium chloride, sodium citrate.

Solvent: water for injections.

Appearance of the product and contents of the container

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

The reconstituted solution should be transparent and clear to slightly opalescent.

Presentation

One pack contains:

1 vial with powder
1 vial with 5.6 ml of water for injections
1 transfer device with filter 20/20
Administration kit (inner box):

1 disposable 10 ml syringe
1 hypodermic needle
1 subcutaneous injection set (butterfly needle)
2 alcohol wipes
1 dressing

Multiple pack of 5 x 3,000 IU, including one box with 5 administration kits.
Multiple pack of 20 x 3,000 IU, including 4 boxes with 5 administration kits each.

Only certain pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

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.
Tarragona 157, 18th floor
08014 Barcelona
Spain

This medicinal product is authorized in the European Economic Area (EEA) Member States and in the United Kingdom (Northern Ireland) under the following names:

Berinert 3000 I.E. Pulver und
Lösungsmittel zur Herstellung einer
Injektionslösung Austria

Berinert 3000 IE, poeder en oplosmiddel
voor oplossing voor injectie Belgium, Netherlands

Berinert 3000 Cyprus, Germany, Greece, Poland, Portugal

???????? 3000, ???? ? ???????????
?? ??????????? ???????
C1- ????????? ?????????, ??????? Bulgaria

Berinert 3000 IU Czech Republic, Slovakia

Berinert 3000 IU prašak i otapalo za otopinu
za injekciju Croatia

Berinert Denmark, Italy

Berinert SC Estonia

Berinert 3000 IU, injektiokuiva-aine
ja liuotin, liuosta varten Finland

Berinert 3000 UI, poudre et solvant pour
solution injectable France, Luxembourg

Berinert 3000 NE por és oldószer
oldatos injekcióhoz Hungary

Berinert 3000 a.e. stungulyfsstofn
og leysir, lausn Iceland

Human C1-esterase inhibitor CSL Behring
3000 TV milteliai ir tirpiklis injekciniam
tirpalui Lithuania

Berinert 3000 IU pulver og væske til
injeksjonsvæske, oppløsning Norway

Berinert 3000 3000 UI, pulbere si
solvent pentru solutie injectabila Romania

Berinert 3000 i.e. prašek in vehikel za
raztopino za injiciranje Slovenia

Berinert 3000 UI polvo y disolvente
para solución inyectable subcutánea Spain

Berinert 3000 IE, pulver och vätska till
injektionsvätska, lösning Sweden

Berinert 3000 IU Powder and solvent
for solution for injection United Kingdom, Malta, Ireland

Date of the latest review of this leaflet: October 2021

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

This information is intended for healthcare professionals only

QUALITATIVE AND QUANTITATIVE COMPOSITION

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