Berinert 500

PATIENT INFORMATION LEAFLET

Berinert 500

500 IU
powder and solvent for solution for injection/infusion
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 those 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. After dissolution, it is administered either by intravenous injection or infusion.
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 treat and prevent hereditary angioedema type I and II (HAE, edema = swelling). 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, 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 treatment with Berinert.

When not to use Berinert:

• if you are allergic 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 sensitive to any medicine or food.

Warnings and precautions:

• if you have had allergic reactions to Berinert in the past. As a precaution, antihistamines and corticosteroids should be used.
• if allergic symptoms or anaphylactic reaction (severe allergic symptoms can cause significant breathing difficulties or dizziness) occur. Administration of

Berinert must be stopped immediately (i.e., discontinuation of injection or infusion).

• if you have had laryngeal edema. The patient should be closely monitored in a place where immediate medical intervention is possible (hospital).
• if the medicine is used contrary to indications and dosage (e.g., capillary leak syndrome - CLS). See section 4. "Possible side effects".

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 methods include:

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

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 B 19.
In patients who receive products derived from human plasma repeatedly, vaccination against viral hepatitis A and B should be considered.
Each time Berinert is administered, the administration date, batch number, and administered volume should be recorded in the patient's medical records.

Berinert and other medicines

• Tell your doctor or pharmacist about any other medicines you are taking, including those available without a prescription.
• Berinert must not be mixed in a syringe/infusion set 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, consult your doctor or pharmacist before using this medicine.
• During pregnancy and breastfeeding, Berinert should only be used if clearly necessary.

Driving and using machines

No studies have been conducted on the effects on the ability to drive and use machines.

Important information about some ingredients of Berinert

Berinert 500 contains 49 mg of sodium (the main component of common salt) in each vial.
This corresponds to 2.5% of the maximum recommended daily intake of sodium in the diet for adults.

3. HOW TO USE BERINERT

Treatment should be started and supervised by a doctor who has experience in using C1-esterase inhibitor in patients with deficiencies of this protein.

Dosage

Adults

Treatment of acute angioedema attack:
20 IU/kg body weight (20 IU/kg body weight)
Preoperative prophylaxis of angioedema:
1000 IU less than 6 hours before medical, dental, or surgical procedures.

Children and adolescents

Treatment of acute angioedema attack:
20 IU/kg body weight (20 IU/kg body weight)
Preoperative prophylaxis of angioedema:
15 to 30 IU/kg body weight (15-30 IU/kg body weight) less than 6 hours before medical, dental, or surgical procedures. The dose should be chosen based on clinical circumstances (e.g., type of procedure and severity of the disease).

Reconstitution and administration

Berinert is usually administered intravenously by a nurse or doctor. The patient or their caregiver can also administer the injection, but only after proper training. If the doctor decides that the patient can undergo home therapy, they will provide detailed instructions. The patient will be required to keep a treatment diary to document each injection performed at home. This diary should be brought by the patient 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 instructions

• 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 colorless and clear. 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.
• Medicine that has not been used, as well as any unused component of the kit, should be disposed of in accordance with applicable regulations. Disposal instructions should be provided by the treating physician.

Method of reconstitution
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 (each vial with a separate swab) and let it dry.
The solvent can be combined with the powder using the provided administration set (Mix2Vial). Follow the instructions below.

1	1. Open the packaging containing the Mix2Vial by removing the cap. Do not remove the Mix2Vial from the blister pack.
2	2. Place the vial with the solvent on a flat, clean surface and hold it firmly. Without removing the Mix2Vial set from the blister pack, place the blue end of the set with the needle onto the vial stopper and push down vertically to puncture the stopper.
3	3. Holding the edge of the Mix2Vial set, carefully remove the blister pack by pulling it upwards. Make sure to remove only the blister pack and not the entire Mix2Vial set.
4	4. Place the vial with the powder on a flat, hard surface. Invert the vial with the solvent and the attached Mix2Vial set and insert the transparent end of the connector into the vial stopper with a downward motion. The solvent will automatically be transferred to the vial with the powder.
5	5. With one hand, grasp the part of the Mix2Vial set in the vial containing the solution, and with the other hand, hold the connector on the side of the vial with the solvent. Carefully unscrew the two parts of the connector from each other. Remove the vial with the solvent from the Mix2Vial set.

6	6. The vial with the attached transparent end of the Mix2Vial set, containing the solution, should be gently swirled in a circular motion until the powder is completely dissolved. Do not shake.
7	7. Draw air into an empty, sterile syringe. Use the syringe provided with the product. Holding the vial with the medicinal product upright with the stopper facing upwards, attach the syringe to the Luer Lock connection of the Mix2Vial set. 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 (holding the syringe with the plunger facing downwards) and detach the transparent end of the Mix2Vial set from the syringe.

Administration method
The prepared solution should be administered slowly intravenously by injection or infusion (4 ml/min).

4. POSSIBLE SIDE EFFECTS

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

Seek immediate medical attention if:

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

In most patients, side effects after administration of Berinert are rare.
Rarely, the following side effects have been observed (frequency of occurrence 1 or more than 1 in 10,000 and less than 1 in 1,000 patients):

• During prophylaxis or treatment of patients with capillary leak syndrome (fluid leakage from small vessels into tissue), there is a risk of increased formation of blood clots, e.g., during or after cardiac surgery performed with extracorporeal circulation. See section 2. "Warnings and precautions".
• Increased body temperature, as well as a burning sensation and tingling at the injection site.
• Hypersensitivity or allergic symptoms, such as: irregular heartbeat, rapid heartbeat, decreased blood pressure, skin redness, feeling of heat and facial redness, breathing difficulties, pain, and dizziness, nausea.

Very rarely (less than 1 in 10,000 patients or single cases), hypersensitivity reactions can lead to shock.

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, please inform your doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring of the 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 the medicine out of the sight and reach of children.
• Do not use Berinert after the expiry date stated on the label and outer packaging after the abbreviation EXP.
• Do not store above 30°C.
• Do not freeze.
• Store the vial in the closed outer packaging to protect it from light.
• Berinert does not contain preservatives, so after reconstitution, it should be used immediately.
• If the solution is not used immediately after preparation, it should be administered no later than 8 hours after preparation and should only be stored in the syringe.

The batch number of the product on the packaging with the administration set, outer packaging, and immediate packaging is written after the abbreviation: Lot.

6. OTHER INFORMATION

What Berinert contains Active substance:

Human C1-esterase inhibitor (500 IU/vial; after reconstitution 50 IU/ml).
See the section "Information intended for healthcare professionals only" for more detailed information.
Excipients:
Glycine, sodium chloride, sodium citrate.
See the last paragraph of section 2. "Important information about some ingredients of Berinert".
Solvent:Water for injections

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 injections.
The reconstituted solution should be colorless and clear.
Pack sizes
The pack with 500 IU contains:
1 vial with powder (500 IU)
1 vial with 10 ml water for injections
1 transfer system with a 20/20 filter
Administration set (inner packaging)
1 single-use syringe with a capacity of 10 ml,
1 injection set,
2 alcohol swabs,
1 non-sterile plaster

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 500 IE Pulver und Lösungsmittel zur Herstellung einer Injektions- oder Infusionslösung ____________ Austria
Berinert 500 ____________________________ Belgium, Cyprus, Germany, Greece, Luxembourg, Poland,
Berinert 500, 500 IU Powder and solvent for solution for injection/infusion ___________ Bulgaria
Berinert 500 IU _________________________ Czech Republic, Slovakia
Berinert _______________________________ Denmark, Italy, Portugal
Berinert 500 IU, injektio/infuusiokuiva-aine ja liuotin, liuosta varten ___________________ Finland
Berinert 500 UI, poudre et solvant pour solution injectable/perfusion _______________ France
Berinert 500 UI Polvo para solución inyectable y para perfusión ________________ Spain
Berinert 500 IU pulver og væske til injeksjons-/infusjonsvæske, oppløsning ______ Norway
Berinert 500 NE por és oldószer oldatos injekcióhoz vagy infúzióhoz _________ Hungary
Berinert 500 UI, pulbere şi solvent pentru soluţie injectabilă/perfuzabilă ________ Romania
Berinert 500 i.e. prašek in vehikel za raztopino za injiciranje/infundiranje _________ Slovenia
Berinert 500 IE, pulver och vätska till injektions-/infusionsvätska, lösning_______Sweden
Berinert 500 IU powder and solvent for solution for injection/infusion ___________ United Kingdom

Date of approval of the leaflet: October 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.