Berinert 1500

Poland
Brand name Berinert 1500
Form solution for injection, powder and solvent for preparation of
Active substance / Dosage
Human C1 esterase inhibitor · 450-625 IU/ml
Prescription type Prescription only
ATC code
B02AB03
Registration number 100338807
Manufacturer CSL Behring GmbH
Berinert 1500 solution for injection, powder and solvent for preparation of

Table of Contents

Berinert 1500
1500 IU
powder and solvent for solution for injection
Human C1 esterase inhibitor
Read the entire leaflet before using this medicine.

  • Keep this leaflet for future reference.
  • If you have any questions, ask your doctor or pharmacist.
  • This medicine has been prescribed for a specific individual. Do not give it to others. This medicine may harm other people, even if their symptoms are the same.
  • If the patient experiences any adverse reactions, including any possible side effects not listed in this leaflet, inform a doctor or pharmacist immediately.

Package leaflet contents:

  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. After reconstitution, it is administered as an intravenous injection.
Berinert is manufactured from human plasma (the liquid component of blood). Its active ingredient is a protein called human C1 esterase inhibitor.

What Berinert is used for
Berinert is used for the treatment and prevention of attacks of hereditary angioedema type I and II (HAE, edema = swelling). Angioedema is an inherited disorder of blood vessels. It is not an allergic disease. It is caused by a deficiency, absence, or malfunction in the synthesis of an important protein called C1 esterase inhibitor.

The disease is characterized by the following symptoms:

  • sudden swelling of hands and feet,
  • sudden facial swelling with a feeling of tightness,
  • swelling of the eyelids, lips, or larynx, accompanied by breathing difficulties,
  • swelling of the tongue,
  • colicky abdominal pain.
    Essentially, swelling may affect any part of the body.

2. IMPORTANT INFORMATION BEFORE USING BERINERT

This section of the leaflet contains information that should be considered before starting treatment
with the medicine Berinert.
When not to use Berinert:

  • if the patient is allergic to C1-esterase inhibitor or to any of the other components of this medicine (listed in section 6). Inform your doctor or pharmacist if you have hypersensitivity to any medicine or food.

Warnings and precautions:

  • if allergic reactions occurred after previous administration of Berinert. Antihistamines and corticosteroids should be administered prophylactically.
  • if allergic symptoms or an anaphylactic reaction occur (severe allergic symptoms may cause significant breathing difficulties or dizziness). Administration of Berinert must be immediately stopped (i.e. stop the injection).
  • if laryngeal edema has occurred. The patient should be closely monitored in a setting where immediate medical intervention is possible (hospital).
  • if the medicine is used off-label or at incorrect doses (e.g. Capillary Leak Syndrome - CLS). See section 4. "Possible undesirable effects".

The benefit-risk ratio should always be carefully considered before administering Berinert.
Viral safety
When medicines are produced from human blood or plasma, various measures are taken to prevent
transmission of infectious agents. These include:

  • careful selection of blood and plasma donors to minimize the risk of transmission of infectious agents
  • testing of each donation and plasma pools for markers of infection.

Manufacturers of such medicines apply virus inactivation or removal methods during production.
Despite these measures, it cannot be completely excluded that medicines derived from human blood
or plasma may transmit infectious agents, including unknown or newly emerging viruses and other
pathogens.
The safety measures taken are effective against enveloped viruses such as human immunodeficiency
virus (HIV, causing AIDS), hepatitis B virus (HBV, causing hepatitis B), hepatitis C virus (HCV,
causing hepatitis C), as well as against non-enveloped viruses such as hepatitis A virus (HAV,
causing hepatitis A) and parvovirus B19.
For patients receiving repeated treatments with products derived from human plasma, vaccination
against hepatitis A and B should be considered.
Each time Berinert is administered, the date of administration, batch number, and volume infused
should be recorded in the patient's medical documentation.
Berinert and other medicines

  • Inform your doctor or pharmacist if you are taking any other medicines, including those available without a prescription.
  • Berinert must not be mixed in the same syringe with other medicinal products or with other solvents.

Pregnancy and breastfeeding

  • If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to become pregnant, she should consult her doctor or pharmacist before using this medicine.
  • During pregnancy and breastfeeding, Berinert should be used only when clearly indicated.

Driving and operating machinery
No studies have been conducted on the effects on the ability to drive vehicles or operate machinery.
Important information about some components of Berinert
The medicine Berinert 1500 contains less than 1 mmol (23 mg) of sodium per vial, i.e. the medicine is considered "sodium-free".

3. HOW TO USE BERINERT

Treatment should be initiated and supervised by a physician experienced
in the use of C1 esterase inhibitor in patients with deficiency of this protein.
Dosage
Adults
Treatment of acute attacks of hereditary angioedema:
20 IU per kilogram of body weight (20 IU/kg b.w.)
Procedural prophylaxis of hereditary angioedema attacks:
1000 IU less than 6 hours before a medical, dental, or surgical procedure.
Children and adolescents
Treatment of acute attacks of hereditary angioedema:
20 IU per kilogram of body weight (20 IU/kg b.w.)
Procedural prophylaxis of hereditary angioedema attacks:
15 to 30 IU per kilogram of body weight (15–30 IU/kg b.w.) less than 6 hours before a medical, dental, or surgical procedure. The dose should be adjusted according to clinical circumstances (e.g., type of procedure and severity of the condition).
Overdose
No cases of overdose have been reported.
Reconstitution and method of administration
Berinert P is usually administered intravenously by a nurse or physician. A patient or caregiver may also administer the injection, but only after appropriate training. If the physician decides that home treatment is appropriate, detailed instructions will be provided. The patient will be required to keep a treatment diary to document every injection administered at home. This diary must be brought by the patient to every medical visit. Regular assessment of the injection technique performed by the patient or caregiver will be conducted to ensure continued proper administration.
General instructions

  • The powder should be reconstituted and withdrawn from the vial under 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 particulate matter or discoloration.
  • If the solution is cloudy or contains flakes or other particles, do not administer the reconstituted medicine.
  • Any unused medicinal product or unused parts of the kit must be destroyed in accordance with applicable regulations. Disposal instructions should be provided by the treating physician.

Instructions for preparing the solution
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 the hands for several minutes.
DO NOT apply direct heat to the vials. The vials must not be heated above body temperature (37°C).
Carefully remove the caps from the vials containing the powder and solvent.
Disinfect the rubber stopper with an alcohol swab (use a separate swab for each vial) and allow it to dry.
The solvent can be mixed with the powder using the transfer device provided in the kit (Mix2Vial).
Follow the instructions provided below.

1
Schematic drawing of a black line illustrating a cylindrical container with a circular opening at the top and internal partitions
  1. 1. Open the packaging containing the Mix2Vial by removing the cap. Do not remove the Mix2Vial from the blister.
2
Schematic illustration showing a vertical cylinder with a black downward-pointing arrow, superimposed on a glass vial with a cap
  1. 2. Place the vial of solvent on a flat, clean surface and hold it firmly. Without removing the Mix2Vial from its blister, place the blue-ended piercing end of the Mix2Vial device onto the stopper of the solvent vial and press vertically downward to pierce the stopper.
3
Technical schematic drawing showing disassembled components of a mechanism with a vertical upward-pointing arrow indicating lifting motion
  1. 3. While holding the edge of the Mix2Vial device, carefully remove the blister by pulling it vertically upward. Take care to remove only the blister, not the entire Mix2Vial device.
4
Schematic illustration showing the screwing of the upper part of the device onto the neck of a glass vial containing medication, indicated by a black downward-pointing arrow
  1. 4. Place the vial containing the powder on a flat, hard surface. Invert the solvent vial with the attached Mix2Vial device and insert the transparent piercing end of the connector vertically downward into the stopper of the powder vial. The solvent will automatically transfer into the vial containing the powder.
5
Diagram showing the process of unscrewing the upper part of the cylinder from the lower base using a curved arrow indicating a downward rotational movement
  1. 5. With one hand, hold the part of the Mix2Vial device attached to the vial now containing the solution, and with the other hand, hold the connector part attached to the solvent vial. Carefully unscrew and separate the two connector parts. Remove the empty solvent vial with the attached blue end of the Mix2Vial device.
6
Schematic drawing of a white package with a cap and two black arrows indicating rotational movement around the base of the object
  1. 6. Gently swirl the vial with the attached transparent end of the Mix2Vial device containing the solution until the medicinal product is completely dissolved. Do not shake.
7
Schematic illustration showing a syringe with a plunger moving downward toward a vial containing medication, indicating direction of movement
  1. 7. Draw air into the empty, sterile syringe. Use the syringe provided with the product. Holding the vial of medicinal product upright with the stopper facing upward, attach the syringe to the Luer Lock connector of the Mix2Vial device. Inject air into the vial.

Download and method of administration

8
Technical schematic drawing of a disassembled medical device consisting of an upper cylinder with a cap and a lower plunger, with a black downward-pointing arrow
  1. 8. Holding the syringe plunger, turn the vial with the syringe upside down and draw the solution into the syringe by slowly pulling back the plunger.
9
Schematic illustration showing the process of screwing the upper part with a cap onto the lower element shaped like a long tube, using a curved arrow
  1. 9. After filling the syringe with the solution, firmly grasp the syringe barrel (keeping the syringe with the plunger facing downward) and disconnect the clear end of the Mix2Vial transfer set from it.

Administration method
The prepared solution should be administered slowly intravenously by injection.

4. POSSIBLE ADVERSE REACTIONS

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.
You should contact your doctor immediately if:

  • you experience any adverse reaction or
  • you experience any symptom not listed in this leaflet.

In most patients, adverse reactions after administration of Berinert are rare.
The following adverse reactions have been observed rarely (may affect no more than 1 in 1,000 patients):

  • During prophylaxis or treatment of patients with capillary leak syndrome (leakage of fluid from small blood vessels into tissues), there is a risk of increased frequency of blood clot formation, e.g. during or after cardiac surgery performed with extracorporeal circulation. See section 2. Warnings and precautions for use.
  • Increase in body temperature, as well as burning and stinging sensations at the site of intravenous injection.
  • Hypersensitivity or allergic symptoms such as: irregular heartbeat, rapid heartbeat, drop in blood pressure, skin redness, feeling of warmth and facial flushing, difficulty breathing, headache and dizziness, nausea.

Very rarely (may affect no more than 1 in 10,000 patients or isolated cases), hypersensitivity reactions may lead to shock.

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Reporting adverse reactions helps to provide more information on the safety of the medicine.
Adverse reactions may also be reported to the marketing authorization holder.

5. HOW TO STORE BERINERT

  • Keep this medicine out of the sight and reach of children.
  • Do not use Berinert after the expiry date stated on the label and outer packaging following the abbreviation EXP.
  • Do not store above 30°C.
  • Do not freeze.
  • Store the vial in its closed outer packaging to protect it from light.
  • Berinert does not contain preservatives; therefore, it should be used immediately after reconstitution.
  • If the solution is not used immediately after preparation, it should be administered within 8 hours of preparation and stored exclusively in a syringe.

The product batch number on the administration set package, outer packaging, and immediate packaging is indicated following the abbreviation: Lot.

6. OTHER INFORMATION

What Berinert contains
Active substance:
Human C1-esterase inhibitor (1500 IU/vial; after reconstitution in 3 ml of water for injections: 500 IU/ml).
See section "Information intended exclusively for medical personnel or healthcare professionals" for more detailed information.
Excipients:
Glycine, sodium chloride, sodium citrate.
See the last paragraph of section 2. "Important information about certain components of Berinert".
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 reconstituted solution should be colorless and clear to slightly opalescent.
Pack sizes
The 1500 IU pack contains:
1 vial of powder (1500 IU)
1 vial of 3 ml water for injections
1 20/20 transfer system with filter
Administration set (inner packaging):
1 single-use 5 ml syringe,
1 infusion set,
2 alcohol swabs,
1 non-sterile adhesive plaster

Marketing Authorisation Holder and Manufacturer
CSL Behring GmbH
Emil-von-Behring-Strasse 76
35041 Marburg
Germany

This medicinal product is authorised for sale in the European Economic Area countries under the following names:
Berinert 1500 IE Pulver und Lösungsmittel zur Herstellung einer Injektionslösung _____________________________ Austria
Berinert 1500 ___________________________ Belgium, Cyprus, Germany, Greece, Luxembourg, Poland
Berinert 1500, 500 IU Powder and solvent for solution for injection __________________ Bulgaria
Berinert 1500 IU ________________________ Czech Republic, Slovakia
Berinert _______________________________ Denmark, Italy, Portugal
Berinert 1500 IU, injektiokuiva-aine ja liuotin, liuosta varten ___________________ Finland
Berinert 1500 UI, poudre et solvant pour solution injectable ______________________ France
Berinert 1500 NE por és oldószer oldatos injekcióhoz ______________________ Hungary
Berinert 1500 UI, pulbere şi solvent pentru soluţie injectabilă __________________ Romania
Berinert 1500 i.e. prašek in vehikel za raztopino za injiciranje ___________________ Slovenia
Berinert 1 500 UI Polvo para solución Inyectable _____________________________ Spain
Berinert 1500 IU powder and solvent for solution for injection __________________ United Kingdom

Information intended exclusively for medical personnel or healthcare professionals.
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.