Berinert 2000

PATIENT INFORMATION LEAFLET

Berinert 2000

2000 IU
powder and solvent for solution for injection
Human C1-esterase inhibitor

Read the package leaflet carefully before using the medicine.

• 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. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, please inform your doctor or pharmacist.

Table of contents of the leaflet:

• 1. What is Berinert and what is it used for
• 2. Important information before using Berinert
• 3. How to use Berinert
• 4. Possible side effects
• 5. How to store Berinert
• 6. Contents of the pack and other information

1. WHAT IS BERINERT AND WHAT IS IT USED FOR

What is Berinert
Berinert is a medicine that comes in the form of a powder and a solvent. The prepared solution should be administered by subcutaneous injection.
Berinert is produced from human plasma (the liquid part of the blood). Its active ingredient is a protein - human C1-esterase inhibitor.
What is Berinert used for
Berinert is used to prevent recurrent attacks of hereditary angioedema (HAE, edema = swelling) in adolescents and adults. Hereditary angioedema is a congenital blood vessel disease. It is not an allergic disease. It is caused by a deficiency, lack, or disorder of the synthesis of an important protein called C1-esterase inhibitor.
The disease is characterized by the following symptoms:

• sudden swelling of the hands and feet,
• sudden swelling of the face with a feeling of tension,
• swelling of the eyelids, lips, swelling of the larynx with difficulty breathing,
• swelling of the tongue,
• colic abdominal pain. In principle, swelling can affect any part of the body.

2. IMPORTANT INFORMATION BEFORE USING BERINERT

This section of the leaflet contains information that you should consider before starting to use Berinert.

When not to use Berinert:

• if the patient has experienced life-threatening, immediate allergic reactions, including anaphylaxis to C1-esterase inhibitor or any of the other ingredients of this medicine (listed in section 6).

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

Warnings and precautions:

Before using Berinert, discuss it with your doctor or pharmacist.

• if severe allergic symptoms or anaphylactic reaction occur (severe allergic symptoms can cause significant difficulty breathing or dizziness).

Berinert administration must be stopped immediately (i.e., the injection must be interrupted).

• if the patient has a history of blood clotting problems. Blood clots have occurred in patients receiving Berinert intravenously. Very high doses of Berinert for the treatment of diseases other than HAE may have increased the risk of blood clots. However, in the case of subcutaneous administration of Berinert, no association with blood clot formation has been shown at the recommended doses. Tell your doctor if you have a history of heart or blood vessel disease, stroke, blood clots, or thickened blood, have had a permanent catheter/venous access inserted into one of your veins, or have been immobilized for a period of time. These factors may increase the risk of blood clots after using Berinert. Tell your doctor about the medicines you are taking, as some medicines, such as birth control pills or certain androgens, may increase the risk of blood clots.

Always consider the benefit-risk ratio of using Berinert.
Viral safety
When medicines are produced from human blood or plasma, various measures are taken to protect the patient from the transmission of infectious agents. These measures include:

• proper selection of blood and plasma donors to exclude the risk of transmitting infectious agents
• testing each donation and plasma pool for markers of infection.

Manufacturers of such medicines use methods of inactivation or removal of viruses during production.
Despite the use of the above methods, it is not possible to completely exclude the possibility of transmitting infectious agents after administering a medicinal product derived from human blood or plasma.
This risk also applies to unknown or newly discovered viruses and other infectious agents.
The measures taken are effective against enveloped viruses such as human immunodeficiency virus (HIV, the virus that causes AIDS), hepatitis B virus (HBV, which causes hepatitis B), and hepatitis C virus (HCV, which causes hepatitis C), as well as non-enveloped viruses such as hepatitis A virus (HAV, which causes hepatitis A) and parvovirus B19.
For patients who receive products derived from human plasma repeatedly, consideration should be given to vaccination against viral hepatitis A and B.
Each time Berinert is administered, the administration date, batch number, and volume administered should be recorded in the patient's medical record.

Berinert and other medicines

• Tell your doctor or pharmacist about all the medicines you are taking, or have recently taken, and about the medicines you plan to take, including those available without a prescription.
• Berinert must not be mixed in a syringe with other medicinal products or with other solvents.

Pregnancy and breastfeeding

• If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, ask your doctor or pharmacist for advice before using this medicine.

Driving and using machines

Berinert does not affect the ability to drive and use machines.

Berinert contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per vial, which is considered to be essentially sodium-free.

3. HOW TO USE BERINERT

Berinert is intended for self-administration by subcutaneous injection.
The patient or their caregiver should be trained in how to administer Berinert.

Dosage

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

Use in children

The recommended dose is the same as for adults. Overdose

No cases of overdose have been reported.

Reconstitution and administration

If your doctor decides that you can be treated at home, they will provide detailed instructions. You will need to keep a treatment diary to document each injection performed at home. This diary should be brought to each doctor's visit. Regular verification of the injection technique by the patient or their caregiver will be performed to ensure continuity of proper administration.
General guidelines

• The powder should be reconstituted and withdrawn from the vial in aseptic conditions. The syringe provided with the product should be used.
• The prepared solution should be clear and colorless to slightly opalescent. After filtration or withdrawal from the vial (see below) and before administration, the solution should be carefully inspected for any impurities or sediment and for any change in color.
• If the solution is cloudy or visible particles are present, do not administer the reconstituted medicine.
• Any unused solution and all components of the administration set should be disposed of in accordance with local requirements. Disposal instructions should be provided by the treating physician.

Reconstitution procedure
Without opening the vials, warm the Berinert powder and solvent to room temperature.
This can be achieved by leaving the vials at room temperature for 1 hour or by holding them in your hands for a few minutes.
DO NOTheat the vials directly. The vials should not be heated above body temperature (37°C).
Carefully remove the caps from the vials containing the powder and solvent.
Wipe the injection site on the stopper with an alcohol swab (use a separate swab for each vial) and let it dry.
The solvent can be connected to the powder using the provided Mix2Vial adapter. Follow the instructions below.

1	1. Open the Mix2Vial package by removing the cap. Do not remove the Mix2Vial from the blister.
2	2. Place the vial with the solvent on a flat, clean surface and hold it firmly. Without removing the Mix2Vial from the blister, place the blue end of the Mix2Vial adapter onto the vial stopper and push down vertically to puncture the stopper.
3	3. Holding the edge of the Mix2Vial adapter, carefully remove the blister by pulling it straight up. Make sure to only remove the blister and not the entire Mix2Vial adapter.
4	4. Place the vial with the powder on a flat, hard surface. Invert the vial with the solvent and the attached Mix2Vial adapter and insert the spike of the transparent end of the adapter into the powder vial stopper with a downward motion. The solvent will automatically transfer to the powder vial.
5	5. Holding one hand on the Mix2Vial adapter in the powder vial, and the other hand on the transparent end of the adapter, carefully twist the two parts of the adapter in opposite directions to separate them. Remove the vial with the solvent from the Mix2Vial adapter.
6	6. Gently swirl the vial with the reconstituted solution and the attached Mix2Vial adapter to ensure complete dissolution of the powder. Do not shake.

7	7. Draw air into an empty, sterile syringe. Use the syringe provided with the product. Holding the vial with the medicine upright, attach the syringe to the Luer Lock connection of the Mix2Vial adapter by turning it clockwise. Inject air into the vial.

Withdrawal and administration

8	8. Holding the syringe plunger, invert the vial with the syringe and slowly withdraw the solution into the syringe.
9	9. After filling the syringe with the solution, firmly hold the syringe cylinder (with the syringe plunger facing down) and twist the transparent end of the Mix2Vial adapter counterclockwise to remove it from the syringe.

Administration

For self-administration by the patient (subcutaneous injection)

Your doctor will teach you how to safely administer Berinert. After learning how to self-administer the medicine, follow the instructions below.

Table 2. Instructions for self-administration of Berinert

to clean the surface
Step 3: Wash your hands Wash your hands thoroughly and dry them. If you have been informed that you need to prepare the infusion wearing gloves, put on the gloves.
Step 4: Prepare the injection site Choose an injection site in the abdominal area, unless your doctor tells you to prepare a different site (Fig.1). Choose a different site than the one used for the last injection; you should rotate the injection sites. The new injection site should be at least 5 cm away from the previous injection site. Never inject into an area where the skin is itchy, swollen, painful, bruised, or red. Avoid injecting into areas with scars or stretch marks. Clean the skin at the injection site with an alcohol swab and let it dry (Fig.2).	Figure 1 Figure 2
Step 5: Inject into the abdominal area According to the instructions of medical personnel: Attach the subcutaneous injection needle or subcutaneous infusion set to the syringe according to the instructions of medical personnel. Fill the needle or tubing as needed and according to the instructions. Subcutaneous injection:	Figure 3
	Figure 4
Step 6: Clean up After injecting the entire dose of Berinert, remove the needle. Discard any unused solution and all components of the administration set in accordance with local requirements.
Step 7: Record treatment Record the batch number from the Berinert vial label and the date and time of administration in your treatment diary or logbook each time Berinert is administered.

4. POSSIBLE SIDE EFFECTS

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

Seek medical attention immediately if:

• any side effect occurs or
• any symptom not listed in this leaflet occurs.

Most patients who receive Berinert experience side effects rarely.
Very common side effects (may affect more than 1 in 10 patients) include:

• reactions at the injection site (bruising, feeling of cold, leakage, redness, hematoma, bleeding, hardening, swelling, pain, itching, rash, scarring, swelling, urticaria, warmth).
• nasopharyngitis (runny or stuffy nose, sneezing).

Common side effects (may affect up to 1 in 10 patients) include:

• hypersensitivity or allergic reactions, such as hypersensitivity, redness, itching, and urticaria.
• dizziness.

Reporting side effects

If you experience any side effects, including any not listed in this leaflet, please inform your doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring, Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl. Side effects can also be reported to the marketing authorization holder. By reporting side effects, you can help provide more information on the safety of this medicine.

5. HOW TO STORE 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 carton after EXP.
• Do not store above 30°C.
• Do not freeze.
• Store the vial in the outer carton to protect from light.
• Berinert does not contain preservatives, and after reconstitution, it should be used immediately.
• If the solution is not used immediately after preparation, it should be administered within 8 hours of preparation and should only be stored in the vial.
• The batch number is printed on the label and carton after the word Lot.

6. OTHER INFORMATION

What Berinert contains Active substance:

Human C1-esterase inhibitor (2000 IU/vial; after reconstitution in 4 ml of water for injection: 500 IU/ml).
See section "Information intended for healthcare professionals only" for more detailed information.
Excipients:
Glycine, sodium chloride, sodium citrate.
Solvent:Water for injection

What Berinert looks like and contents of the pack

Berinert comes in the form of a white powder and a solvent, which is water for injection.
The prepared solution should be clear and colorless to slightly opalescent.
Pack sizes
The pack contains:
1 vial with powder
1 vial with 4 ml of water for injection
1 transfer system with a 20/20 filter
Administration set (inner packaging):
1 single-use 5 ml syringe,
1 subcutaneous injection needle
1 subcutaneous infusion set
2 alcohol swabs,
1 plaster
Pack containing 5 x 2000 IU, including 5 administration sets
Pack containing 20 x 2000 IU, including 4 packs of 5 administration sets
Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

CSL Behring GmbH
Emil-von-Behring-Strasse 76
35041 Marburg
Germany

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

Berinert 2000 I.E. Pulver und Lösungsmittel zur Herstellung einer Injektionslösung __________________________ Austria
Berinert 2000 IE, poeder en oplosmiddel voor oplossing voor injectie _________________ Belgium
Berinert 2000 _____________________________ Cyprus, Germany, Greece, Poland, Portugal
Беринерт 2000, Прах и разтворител за инжекционен разтвор
C1-естеразен инхибитор, човешки __________ Bulgaria
Berinert 2000 IU __________________________ Czech Republic, Slovakia
Berinert _________________________________ Denmark, Italy
Berinert 2000 IU, injektiokuiva-aine ja liuotin, liuosta varten _____________________ Finland
Berinert 2000 UI, poudre et solvant pour solution injectable _________________________ France, Luxembourg
Berinert 2000 NE por és oldószer oldatos injekcióhoz ________________________ Hungary
Berinert 2000 IU pulver og væske til injeksjonsvæske, oppløsning _________________ Norway
Berinert 2000 2000 UI, pulbere şi solvent pentru soluţie injectabilă ______________ Romania
Berinert 2000 i.e. prašek in vehikel za raztopino za injiciranje _____________________ Slovenia
Berinert 2000 UI polvo y disolvente para solución inyectable subcutánea ___________ Spain
Berinert 2000 IE, pulver och vätska till injektionsvätska, lösning ____________________ Sweden
Berinert 2000 IU Powder and solvent for solution for injection ____________________ United Kingdom, Malta
Date of revision of the leaflet:10/2021

Information intended for healthcare professionals only.

QUALITATIVE AND QUANTITATIVE COMPOSITION

The activity of human C1-esterase inhibitor is expressed in international units (IU), which refer to the current WHO standards for C1-esterase inhibitor products.