Berinert 3000

PATIENT INFORMATION LEAFLET

Berinert 3000

3000 IU
powder and solvent for solution for injection
Human C1-esterase inhibitor

Read the contents of the leaflet 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.

Contents of the pack:

• 1. What Berinert is and what it is 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 BERINERT IS AND WHAT IT IS USED FOR

What Berinert is
Berinert is a medicine available as a powder and 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 Berinert is used for
Berinert is used to prevent recurrent attacks of hereditary angioedema (HAE, edema = swelling) in adolescents and adults. Hereditary angioedema is a rare genetic disorder. It is not an allergic disease. It is caused by a deficiency, lack, or dysfunction 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, which appears suddenly,
• 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 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:

Before using Berinert, discuss with your doctor or pharmacist,

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

Berinert must be discontinued immediately (i.e., injection stopped).

• 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. 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 benefits and risks of using Berinert.
Virus 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 virus inactivation or removal methods during production.
Despite the use of the above methods, it cannot be completely excluded that the transmission of infectious agents may occur after the administration of a medicinal product derived from human blood or plasma.
This risk also applies to unknown or newly discovered viruses and other infectious agents.
The safety 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 receiving multiple doses of products derived from human plasma, 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, have recently taken, or 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 baby, 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 means it is 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 taken to each doctor's visit. Regular verification of the injection technique by the patient or their caregiver will be performed to ensure continued proper administration.
General guidelines

• The powder should be reconstituted and withdrawn from the vial in aseptic conditions. Use the syringe provided with the product.
• The prepared solution should be colorless and clear 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 contains particles, do not administer the reconstituted medicine.
• Any unused medicine and all components of the administration set should be disposed of in accordance with local requirements. Disposal instructions should be provided by your doctor.

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 tip of the Mix2Vial onto the vial stopper and push down vertically to puncture the stopper.
3	3. Holding the edge of the Mix2Vial, carefully remove the blister by pulling it straight up. Make sure to only remove the blister, not the entire Mix2Vial.
4	4. Place the vial with the powder on a flat, hard surface. Invert the vial with the solvent and the attached Mix2Vial, and insert the spike of the transparent connector into the powder vial stopper with a downward motion. The solvent will automatically transfer to the powder vial.
5	5. Hold the Mix2Vial in the powder vial with one hand and the connector part on the solvent side with the other hand. Carefully twist the two parts in opposite directions (counter-clockwise) to separate them. Remove the vial with the solvent from the Mix2Vial.
6	6. Gently swirl the vial with the powder and the attached transparent end of the Mix2Vial in a circular motion to completely dissolve the medicine. 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 connector of the Mix2Vial in a clockwise direction. Inject air into the vial.

Withdrawal and administration

8	8. Holding the syringe plunger, invert the vial with the syringe and slowly pull back the plunger to draw 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 counter-clockwise to detach 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, follow the instructions below.

Table 2. Instructions for self-administration of Berinert

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 area for injection on the abdomen, unless your doctor has informed you to prepare a different site (Fig.1). Choose a different site than 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 using an alcohol swab and let it dry (Fig.2).	Figure 1 Figure 2
Step 5: Inject into the abdominal area Follow 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 required and according to the instructions. Injection using a subcutaneous injection needle: Insert the needle into a skin fold (Fig.3). Injection using a subcutaneous infusion set: Insert the needle into a skin fold (Fig.4).	Figure 3
	Figure 4
Step 6: Clean up After injecting the entire dose of Berinert, remove the needle. Dispose of any unused solution and all administration set components 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, this medicine can cause side effects, although not everybody gets them.

Seek immediate medical attention if:

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

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

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

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

• hypersensitivity or allergic symptoms, 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 in order to protect from light.
• Berinert does not contain preservatives; therefore, 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 be stored in the vial.
• The batch number is printed on the label and carton after (Lot).

6. OTHER INFORMATION

What Berinert contains Active substance:

Human C1-esterase inhibitor (3000 IU/vial; after reconstitution in 5.6 ml water for injections: 500 IU/ml).
See section "Information intended for healthcare professionals only" for more detailed information.
Excipients:
Glycine, sodium chloride, sodium citrate.
Solvent:Water for injections

What Berinert looks like and contents of the pack

Berinert is available as a white powder and solvent, which is water for injections.
The prepared solution should be colorless and clear to slightly opalescent.
Pack sizes
The pack contains:
1 vial with powder
1 vial with 5.6 ml water for injections
1 Mix2Vial transfer system with filter
Administration set (inner packaging):
1 single-use 10 ml syringe,
1 subcutaneous injection needle
1 subcutaneous infusion set
2 alcohol swabs,
1 plaster
Pack containing 5 x 3000 IU, including 5 administration set accessories
Pack containing 20 x 3000 IU, including 4 packs of 5 administration set accessories
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 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
Беринерт 3000, Прах и разтворител за инжекционен разтвор
C1-естеразен инхибитор, човешки __________ 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 şi solvent pentru soluţie injectabilă ______________ 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 revision of the leaflet:12/2021

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.