Berinert: detailed information

PACKAGE LEAFLET: INFORMATION FOR THE PATIENT

Berinert

500 IU
Powder and solvent for solution for injection / infusion.
Human C1-esterase inhibitor
Please read this leaflet carefully before using this medicine because it contains
important information for you.

Keep this leaflet. 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. Never give it to others, even if their symptoms are the same as yours, because it may be harmful.
If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

What this leaflet contains:

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 (lyophilisate) together with its corresponding solvent. Once reconstituted, the solution must be administered by intravenous injection or infusion.
Berinert is derived from human plasma (i.e. the liquid portion of blood) and contains, as its active substance, human C1-esterase inhibitor.

What is Berinert used for?
Berinert is used for the treatment and preoperative prophylaxis of hereditary angioedema type I and II (HAE, edema = swelling). HAE is not an allergic disease but an inherited disorder of the vascular system. HAE is caused by deficiency, absence, or impaired synthesis of an important protein called C1-esterase inhibitor. The characteristic symptoms of the disease are:

sudden swelling of the hands and feet,
sudden facial swelling with a sensation of tightness,
swelling of the eyelids, lips, possible laryngeal swelling (mouth) causing breathing difficulties,
swelling of the tongue,
abdominal colic. In general, any part of the body may be affected.

2. WHAT YOU SHOULD KNOW BEFORE TAKING BERINERT

The following sections contain information that your treating physician should consider before prescribing Berinert to you.
Do not take Berinert:

If you are allergic to C1-esterase inhibitor protein or to any of the other ingredients of this medicinal product listed in section 6. Please inform your doctor or pharmacist if you are allergic to any medicinal products or food substances.

Warnings and precautions:

If you have previously experienced allergic reactions to Berinert. If advised by your physician, you should take antihistamines or corticosteroids prophylactically.
If allergic or anaphylactic reactions occur (a severe allergic reaction causing severe breathing difficulties or dizziness), in such case administration of Berinert must be immediately stopped (e.g. by interrupting the infusion).
If you have laryngeal swelling (laryngeal edema), you must be closely monitored with emergency treatment immediately available.
If used for unapproved indications or with unapproved dosages (e.g. Capillary Leak Syndrome, CLS). See section 4, "Possible side effects".

Your doctor will carefully evaluate the benefit-risk ratio of treatment with Berinert versus the risks associated with these complications.
Viral safety
In the manufacturing of medicinal products derived from human blood or plasma, certain precautions are adopted to prevent transmission of infections to patients. These measures include:

careful selection of blood and plasma donors to exclude those who may be carriers of infections, and
testing of each individual donation and plasma pools to detect the possible presence of viruses/infections.

Manufacturers of these medicinal products also implement production steps specifically designed to inactivate or eliminate viruses during processing of blood or plasma. Despite these measures, when administering products prepared from human blood or plasma, the possibility of transmitting infections cannot be completely ruled out. This also applies to emerging or previously unknown viruses, or other types of infections.
The measures adopted are considered effective against both enveloped viruses such as human immunodeficiency virus (HIV, the AIDS virus), hepatitis B virus, hepatitis C virus (liver inflammation), and non-enveloped viruses such as hepatitis A virus (liver inflammation) and parvovirus B19.
If you regularly or repeatedly use products derived from human plasma, your doctor may recommend considering vaccination against hepatitis A and B.
It is strongly recommended that, with every administration of Berinert, the date of administration, the product batch number, and the infused quantity be recorded.
Other medicines and Berinert

Consult your doctor or pharmacist if you are currently taking, or have recently taken, any other medicines, including those obtained without a prescription.
Berinert must not be mixed with other medicinal products or diluents in the syringe/infusion set.

Pregnancy and breastfeeding

If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding, please consult your doctor or pharmacist before taking this medicine.
During pregnancy or breastfeeding, Berinert should be administered only if clearly indicated.

Driving and use of machines
No studies have been conducted to assess the effects on the ability to drive vehicles or operate machinery.
Berinert contains sodium
Berinert contains up to 49 mg of sodium (a main component of table salt) in each vial. This corresponds to 2.5% of the maximum recommended daily dietary intake of sodium for an adult.

3. HOW TO TAKE BERINERT

Treatment must be initiated and supervised by a physician experienced in the management of
C1-esterase inhibitor deficiency.
Dosage
Adults
Treatment of acute angioedema attacks:
20 IU per kilogramm of body weight (20 IU/kg b.w.).
Preoperative prophylaxis of angioedema attacks:
1000 IU less than 6 hours before a medical, dental, or surgical procedure.
Use in children and adolescents
Treatment of acute angioed mucosal attacks:
20 IU per kilogramm of body weight (20 IU/kg b.w.).
Preoperative prophylaxis of angioedema attacks:
15 to 30 IU per kilogramm of body weight (15–30 IU/kg b.w.) less than 6 hours before a medical, dental, or surgical procedure. The dose should be selected based on clinical condition (e.g., type of procedure and severity of disease).
If you take more Berinert than you should
Cases of overdose have not been reported.
Reconstitution and method of administration
Berinert is normally administered intravenously (IV) by your doctor or healthcare professional.
Only after adequate training may you or a family member administer Berinert by injection. If your
doctor considers you capable of self-treatment at home, he or she will provide detailed instructions
on self-infusion. You will be asked to keep a diary to document every treatment performed at home.
This diary must be presented to your doctor during each outpatient visit. Furthermore, regular
checks of the injection technique used by you or your family member will be required to ensure
continued proper use.
General instructions

The powder must be dissolved and withdrawn from the vial under aseptic conditions. Use the syringe provided with the product.
The resulting solution must be clear and colourless. After filtration/withdrawal (see below), the reconstituted product should be inspected visually for particulate matter or discoloration prior to administration.
Do not use the solution if it is visually cloudy or contains flakes or particles.
Any waste material generated or unused must be disposed of in accordance with local regulations and as recommended by your doctor.

Reconstitution
Before opening the Berinert vials containing the powder and the solvent, bring them to room
temperature. This can be achieved either by leaving the vials at room temperature for about one
hour or by warming them in your hands for several minutes. DO NOT expose the vials to direct
heat sources. The vials must not be heated above body temperature (37°C).
Carefully remove the pull-off protective caps from the vials containing the product and the solvent, respectively. Disinfect the rubber stoppers of both vials with an alcohol swab and wait until they have dried. Then, using the provided transfer set (Mix2Vial), transfer the solvent into the vial containing the powder. Follow carefully the instructions described below.

1	1. Open the Mix2Vial package by breaking the seal. Do not remove the Mix2Vial from the package!
2	2. Place the vial of solvent on a flat, clean surface, holding it firmly. Take the Mix2Vial with its package and push the terminal end of the blue adapter into the stopper of the solvent vial.
3	3. Carefully remove the package from the Mix2Vial set by holding it at the end and lifting it vertically. Make sure to pull only the package upwards, not the Mix2Vial set.
4	4. Securely place the product vial on a flat surface, invert the solvent vial connected to the Mix2Vial, and push the tip of the transparent adapter into the stopper of the vial containing the product. The solvent will be automatically transferred into the product vial.
5	5. Hold the Mix2Vial set with one hand on the side of the product vial, grasp the other side at the solvent vial with the other hand, and carefully unscrew the set into its two components. Dispose of the solvent vial with the attached blue Mix2Vial adapter.
6	6. Gently rotate the product vial with the attached transparent adapter until the substance is completely dissolved. Do not shake the vial.
7	7. Draw air into a sterile, empty syringe. Use the syringe provided with the product. Holding the product vial upright, attach the syringe to the Luer Lock connector of the Mix2Vial set and inject the air into the product vial.

Withdrawal and administration

8	8. While pressing the plunger of the syringe, invert the system and slowly pull back the plunger to draw the solution into the syringe.
9	9. After the solution has been transferred into the syringe, firmly hold the syringe barrel (with the syringe plunger pointing downward) and disconnect the transparent Mix2Vial adapter from the syringe.

Administration
The solution must be injected or infused slowly by intravenous (i.v.) route (4 ml/minute).
If you have any further questions about the use of this medicinal product, consult your doctor or pharmacist.

4. POSSIBLE ADVERSE REACTIONS

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.
If you experience any of the following adverse reactions, contact your doctor immediately.
If you notice any adverse reactions not described in this leaflet, contact your doctor immediately.

Adverse reactions with the use of Berinert are rare.
The following adverse reactions have been observed rarely (1 or more of 1 in 10,000 and less than 1 in 1,000 patients):

Increased risk of developing blood clots in attempts to treat prophylaxis or therapy of Capillary Leak Syndrome (CLS - i.e.: leakage of fluids from small blood vessels into tissues), e.g. during or after cardio-surgery with extracorporeal circulation. See section 2 “Warnings and precautions”.
Increased body temperature or sensation of burning and stabbing pain at the injection site.
Hypersensitivity or allergic-type reactions (such as: irregular heartbeat, increased heart rate, decreased blood pressure, skin flushing, skin rash, breathing difficulties, migraine, dizziness, nausea).

In very rare cases (less than 1 in 10,000 patients, including individual cases), hypersensitivity reactions have progressed to shock.

Reporting of adverse reactions
If you experience any side effects, consult your doctor or pharmacist. This includes any adverse reactions not listed in this leaflet.
You can also report adverse reactions directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse .
By reporting side effects, you can help provide further information on the safety of this medicine.

5. HOW TO STORE BERINERT

Keep this medicine out of the sight and reach of children.
Berinert must not be used after the expiry date stated on the label and packaging.
Do not store above +30 °C.
Do not freeze.
Keep the vial in its outer packaging to protect it from light.
Berinert does not contain preservatives; therefore, the solution should preferably be administered immediately after reconstitution.
If the solution is not administered immediately after reconstitution, it must be used within 8 hours and stored in the vial.

6. PACK CONTENTS AND OTHER INFORMATION

What Berinert contains
Active substance:
Human C1-esterase inhibitor (500 IU/vial; equivalent to 50 UI/mL after reconstitution)
For further information, see the section “The following information is intended exclusively for
medical or paramedical personnel”.

Other excipients:
Glycine, sodium chloride, sodium citrate. See the last paragraph of section 2, “Important
information on some of the excipients in Berinert”.
Solvent: Water for injections.

What Berinert looks like and contents of the pack
Berinert is a white powder supplied with a vial of water for injections as solvent.
The resulting solution should be clear and transparent.

Packaging
Box of 500 IU containing:

1 vial with powder (500 IU)
1 vial with 10 mL of water for injections
1 transfer device with 20/20 filter
Administration kit (inner box):
1 single-use 10 mL syringe
1 infusion set
2 alcohol swabs
1 plaster

Marketing Authorisation Holder and Manufacturer
CSL Behring GmbH
Emil-von-Behring-Str. 76
35041 Marburg, Germany

This product is authorised in the following European Community Member States 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, 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 NE por és oldószer
oldatos injekcióhoz vagy infúzióhoz: Hungary
Berinert 500 IU pulver og væske til
injeksjons-/infusjonsvæske, oppløsning: Norway
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 UI
Polvo para solución
Inyectable y para infusión: Spain
Berinert 500 IE, pulver och vätska till
injektions-/infusionsvätska, lösning: Sweden
Berinert 500 IU powder and solvent
for solution for injection/infusion: United Kingdom

The following information is intended exclusively for medical or paramedical personnel
QUALITATIVE AND QUANTITATIVE COMPOSITION
The activity of human C1-esterase inhibitor is expressed in International Units (IU), which are
referenced to the current WHO standard for C1-esterase inhibitor products.

PACKAGE LEAFLET: INFORMATION FOR THE USER

Berinert

1500 IU
Powder and solvent for injectable solution
Human C1-esterase inhibitor
Read this leaflet carefully before taking this medicine.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or pharmacist.
This medicine has been prescribed for you personally. Never give it to others, even if their symptoms are the same as yours, as it may be harmful.
If you notice any adverse reactions, including those not listed in this leaflet, inform your doctor or pharmacist. 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 (lyophilisate) and solvent. Once reconstituted, the solution must be administered by intravenous injection.
Berinert is derived from human plasma (i.e. the liquid portion of blood). It contains, as the active substance, human C1-esterase inhibitor.

What is Berinert used for?
Berinert is used for the treatment and preoperative prophylaxis of hereditary angioedema type I and II (HAE, edema = swelling). HAE is not an allergic disease but a congenital disorder of the vascular system. HAE is caused by a deficiency, absence, or defective synthesis of an important protein called C1-esterase inhibitor. The characteristic symptoms of the disease are the following:

sudden swelling of hands and feet,
sudden facial swelling with a sensation of tightness,
swelling of the eyelids, swelling of the lips, possible laryngeal swelling (mouth) with breathing difficulties,
swelling of the tongue,
abdominal colic. In general, any part of the body may be affected.

2. WHAT YOU SHOULD KNOW BEFORE USING BERINERT

The following sections contain information that your treating physician should consider before prescribing Berinert to you.
Do not take Berinert:

If you are allergic to C1-esterase inhibitor protein or to any of the excipients of this medicinal product listed in section 6. Please inform your doctor or pharmacist if you are allergic to any medicinal product or to any food substance.

Warnings and precautions:

If you have previously experienced allergic reactions to Berinert. If advised by your doctor, you should take antihistamines or corticosteroids prophylactically.
If allergic or anaphylactic reactions occur (a severe allergic reaction causing severe breathing difficulties or dizziness). In such cases, administration of Berinert must be stopped immediately (e.g. by interrupting the injection).
If you have laryngeal swelling (laryngeal edema). Close monitoring must be ensured, with emergency treatment immediately available.
If used for unapproved indications or with unapproved dosages (e.g. Capillary Leak Syndrome, CLS). See section 4, “Possible undesirable effects”.

Your doctor will carefully evaluate the benefit-risk ratio of treatment with Berinert versus the risks associated with these complications.
Viral safety
In the production of medicinal products derived from human blood or plasma, certain precautions are adopted to prevent transmission of infections to patients. These measures include:

careful selection of blood and plasma donors to exclude individuals who may be carriers of infections, and
testing of each individual donation and plasma pools to detect the possible presence of viruses/infections.

Manufacturers of these medicinal products also implement production steps specifically designed to inactivate or eliminate viruses during the processing of blood or plasma. Despite these measures, when administering products derived from human blood or plasma, transmission of infections cannot be completely ruled out. This also applies to emerging or hitherto unknown viruses, or other types of infections.
The measures adopted are considered effective against enveloped viruses such as human immunodeficiency virus (HIV, the AIDS virus), hepatitis B virus, hepatitis C virus (liver inflammation), as well as against non-enveloped viruses such as hepatitis A virus (liver inflammation) and parvovirus B19.
If you regularly or repeatedly use products derived from human plasma, your doctor may recommend that you consider vaccination against hepatitis A and B.
It is strongly recommended that, with each administration of Berinert, the date of administration, the product batch number, and the injected volume be recorded.

Other medicines and Berinert Consult your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those obtained without a prescription.
Berinert must not be mixed with other medicinal products or diluents in the syringe.

Pregnancy and breastfeeding

If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
During pregnancy or breastfeeding, Berinert should only be administered if clearly indicated.

Driving and use of machines
No studies have been conducted to assess the effects on the ability to drive vehicles or operate machinery.
Berinert contains sodium
Berinert contains less than 1 mmol of sodium (23 mg) per vial, i.e. essentially "sodium-free".

3. HOW TO USE BERINERT

Treatment must be initiated and supervised by a physician experienced in the management of
C1-esterase inhibitor deficiency.
Dosage
Adults
Treatment of acute attacks of angioedema:
20 IU per kilogram of body weight (20 IU/kg b.w.).
Preoperative prophylaxis of angioedema attacks:
1000 IU less than 6 hours before a medical, dental, or surgical procedure.
Use in children and adolescents
Treatment of acute attacks of angioedema:
20 IU per kilogram of body weight (20 IU/kg b.w.).
Preoperative prophylaxis of 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 selected based on clinical
conditions (e.g., type of procedure and severity of disease).
If you take more Berinert than you should
Cases of overdose have not been reported.
Reconstitution and method of administration
Berinert is normally administered intravenously (i.v.) by your doctor or nurse. Only after
adequate training may you or a family member administer Berinert. If your doctor considers you
capable of performing home treatment, your doctor will provide you with detailed instructions.
You will be asked to keep a diary to document each treatment administered at home. This diary
must be presented to your doctor at every outpatient visit. Regular review of the injection
technique used by you or your family member will also be required to ensure continued proper
use.
General instructions

The powder must be dissolved and withdrawn from the vial under aseptic conditions. Use the syringe supplied with the product.
The resulting solution should be clear and colourless to slightly opalescent. After filtration/withdrawal (see below), the reconstituted product should be inspected visually for particulate matter or discoloration prior to administration.
Do not use solutions that are visibly cloudy or contain particles or deposits.
Unused product and waste material derived from this medicinal product must be disposed of in accordance with local regulations and as recommended by your doctor.

Reconstitution
Before opening the vials, bring the Berinert powder and solvent to room temperature.
This can be achieved by leaving the vials at room temperature for about one hour or by warming
them in the hands for several minutes. DO NOT expose the vials directly to a heat source. The
vials must not be warmed above body temperature (37°C).
Carefully remove the pull-off protective caps from the vials containing the product and the solvent, respectively. Disinfect the rubber stoppers of both vials with an alcohol swab and allow them to dry. Using the provided solution set (Mix2Vial), the solvent can now be transferred into the vial containing the powder. Follow carefully the instructions provided below.

1	1. Open the Mix2Vial package by removing the seal. Do not remove the Mix2Vial from the package!
2	2. Place the solvent vial on a flat and clean surface, holding it firmly. Take the Mix2Vial together with its package and push the terminal end of the blue adapter into the stopper of the diluent vial.
3	3. Carefully remove the package from the Mix2Vial set by holding it at the end and lifting it vertically. Make sure to pull only the package upwards, not the Mix2Vial set.
4	4. Securely place the product vial on a flat surface. Invert the solvent vial connected to the Mix2Vial and push the tip of the transparent adapter into the stopper of the vial containing the product. The diluent will automatically transfer into the product vial.
5	5. Hold the Mix2Vial set with one hand on the side of the product vial, grasp the other side at the solvent vial, and carefully unscrew the set into its two components. Dispose of the solvent vial with the attached blue Mix2Vial adapter.
6	6. Gently rotate the product vial with the attached transparent adapter until the substance is completely dissolved. Do not shake the vial.
7	7. Draw air into a sterile, empty syringe. Use the syringe provided with the product. Holding the product vial upright, connect the syringe to the Luer Lock connector of the Mix2Vial set and inject the air into the product vial.

Withdrawal and administration

8	8. While pressing the plunger of the syringe, invert the system and slowly draw back the plunger to aspirate the solution into the syringe.
9	9. After all the solution has been transferred into the syringe, firmly hold the syringe barrel (with the syringe plunger pointing downward) and disconnect the transparent Mix2Vial adapter from the syringe.

Administration
The solution must be administered by slow intravenous (i.v.) injection.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. POSSIBLE ADVERSE REACTIONS

Like all medicines, Berinert may cause adverse reactions, although not everyone experiences them.
If you experience any of the following adverse reactions, contact your doctor immediately.
If you notice any adverse reactions not described in this leaflet, contact your doctor immediately.
Adverse reactions with the use of Berinert are rare.
The following adverse reactions have been observed rarely (may affect up to 1 in 1,000 patients):

Increased risk of developing blood clots during attempts to treat Capillary Leak Syndrome (CLS - i.e., leakage of fluids from small blood vessels into tissues), for example during or after cardiac surgery with extracorporeal circulation. See section 2, “Take special care with Berinert”.
Increased body temperature or sensation of burning and stabbing pain at the injection site.
Hypersensitivity or allergic-type reactions (such as: irregular heartbeat, rapid heartbeat, decreased blood pressure, skin redness, skin rash, breathing difficulties, headache, dizziness, nausea)

In very rare cases (may affect up to 1 in 10,000 patients), hypersensitivity reactions may progress to shock.

Reporting of adverse reactions
If adverse reactions occur, inform your doctor or pharmacist, even if the adverse reactions are not listed in this leaflet. You may also report adverse reactions directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting adverse reactions, you help provide further information on the safety of this medicine.

5. HOW TO STORE BERINERT

Keep out of the sight and reach of children.
Berinert must not be used after the expiry date stated on the label and packaging.
Do not store above 30 °C.
Do not freeze.
Keep the vial in its outer packaging to protect it from light.
Berinert does not contain preservatives; therefore, the reconstituted solution should preferably be administered immediately after preparation.
If the reconstituted solution is not administered immediately after preparation, it must be used within 8 hours and stored exclusively in the vial.

6. PACK CONTENTS AND OTHER INFORMATION

What Berinert contains
Active substance:
Human C1-esterase inhibitor (1500 IU/vial; equivalent to 500 IU/mL after reconstitution with
3 mL of water for injections)
For further information, see the section "The following information is intended for healthcare
professionals only"
Other excipients:
Glycine, sodium chloride, sodium citrate.
See the last paragraph of section 2, "Important information about certain excipients of
Berinert"
Solvent: Water for injections.

Presentation of Berinert and pack contents
Berinert is a white powder supplied with a vial of water for injections as solvent.
The resulting solution should be clear and colourless to slightly opalescent.
Packaging
Box containing 1500 IU comprising:

1 vial of powder (1500 IU)
1 vial containing 3 mL of water for injections
1 transfer device with 20/20 filter
Administration set (inner box):
- 1 single-use 5 mL syringe
- 1 infusion set
- 2 alcohol swabs
- 1 plaster.

Marketing Authorisation Holder and Manufacturer
CSL Behring GmbH
Emil-von-Behring-Str. 76
35041 Marburg
Germany
This product is authorised in the following European Community Member States 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, 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 IU pulver og væske til
injeksjonsvæske, oppløsning ____________ Norway
Berinert 1500 UI, pulbere şi solvent
pentru soluţie injectabilă _______________ Romania
Berinert 1500 i.e. prašek in vehikel za
raztopino za injiciranje ________________ Slovenia
Berinert 1500 UI Polvo para solución
inyectable ___________________________ Spain
Berinert 1500 IE, pulver och vätska till
injektionsvätska, lösning _______ Sweden
Berinert 1500 IU powder and solvent
for solution for injection _______________ United Kingdom

Date of the latest revision of this package leaflet:
The following information is intended for healthcare professionals only

QUALITATIVE AND QUANTITATIVE COMPOSITION
The activity of human C1-esterase inhibitor is expressed in International Units (IU), which are referenced to the current WHO standard for C1-esterase inhibitor products.

PATIENT INFORMATION LEAFLET

Berinert

2000 IU
Powder and solvent for injectable solution
Human C1-esterase inhibitor
Please read this leaflet carefully before using this medicine, as it contains
important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or pharmacist.
This medicine has been prescribed for you personally. Never give it to others, even if their symptoms are the same as yours, as it could be dangerous.
If you notice any adverse reactions, including those not listed in this leaflet, inform your doctor or pharmacist. 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 solution, once prepared, must be administered by subcutaneous injection.
Berinert is derived from human plasma (i.e. the liquid portion of blood). It contains, as the active substance, human C1-esterase inhibitor.

What is Berinert used for?
Berinert is used for the prevention of acute episodes of recurrent hereditary angioedema (HAE) in adults and adolescents. HAE is a congenital disorder of the vascular system.
HAE is not an allergic disease. HAE is caused by a deficiency, absence, or defective synthesis of an important protein called C1-esterase inhibitor. The characteristic symptoms of the disease are as follows:

sudden swelling of the hands and feet,
sudden facial swelling with a sensation of tightness,
swelling of the eyelids, lips, possible laryngeal (throat) swelling with breathing difficulties,
swelling of the tongue,
abdominal colic. In general, any part of the body may be affected.

2. WHAT YOU SHOULD KNOW BEFORE USING BERINERT

The following sections contain information that your treating physician should consider before prescribing Berinert to you.
Do not take Berinert:

If you have previously experienced life-threatening immediate hypersensitivity reactions, including anaphylaxis, to C1-esterase inhibitor or to any other ingredient contained in this product, as listed in section 6. Please inform your doctor or pharmacist if you are allergic to any medicinal product or to any food substances.

Warnings and precautions:
Consult your doctor or pharmacist before starting treatment with Berinert:

if severe allergic or anaphylactic reactions (a serious allergic reaction causing severe breathing difficulties or dizziness) occur. In such a case, administration of Berinert must be stopped immediately (e.g. by interrupting the injection).
if you have previously suffered from coagulation disorders. Blood clots have been observed in patients who received Berinert intravenously. Very high doses of Berinert, used for conditions other than HAE, may increase the risk of clot formation. However, for subcutaneous administration of Berinert at the recommended doses, no association with clot formation has been established. Inform your doctor if you have previously had heart or vascular diseases, stroke, coagulation disorders or thrombophilia, if you have a permanent catheter/venous access, or if you have been immobilized for prolonged periods. These conditions may increase the risk of clot formation with the use of Berinert. Also inform your doctor about any medications you are taking, as certain drugs, such as oral contraceptives or specific androgens, may increase the risk of clot formation.

Your doctor will carefully evaluate the benefit-risk balance of treatment with Berinert versus the risks associated with these complications.
Viral safety
In the manufacturing of medicinal products derived from human blood or plasma, certain precautions are taken to prevent transmission of infections to patients. These measures include:

careful selection of blood and plasma donors to exclude individuals who may carry infections, and
testing of each individual donation and plasma pools to detect the possible presence of viruses/infections.

Manufacturers of these medicinal products also implement production steps during blood or plasma processing aimed at inactivating or eliminating viruses. Despite these measures, when administering products derived from human blood or plasma, transmission of infections cannot be completely ruled out. This also applies to emerging or previously unknown viruses, or other types of infections.
The measures taken are considered effective against enveloped viruses such as the 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.
If you regularly or repeatedly use products derived from human plasma, your doctor may recommend considering vaccination against hepatitis A and B.
It is strongly recommended that, with every administration of Berinert, the date of administration, the product batch number, and the injected volume be recorded.
Other medicines and Berinert

Consult your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those obtained without a prescription.
Berinert must not be mixed with other medicinal products or diluents in the syringe.

Pregnancy and breastfeeding

If you are pregnant, suspect you may be pregnant, planning a pregnancy, or are breastfeeding, please consult your doctor or pharmacist before taking this medicine.
During pregnancy or while breastfeeding, Berinert should be administered only if strictly necessary.

Driving and use of machines
Berinert does not impair the ability to drive vehicles or operate machinery.
Berinert contains sodium
This medicinal product contains less than 1 mmol (23 mg) of sodium per vial, i.e. essentially ‘sodium-free’.

3. HOW TO USE BERINERT

Berinert is intended for self-administration by subcutaneous injection. You or the person caring for you must receive adequate instructions on the correct method of administering Berinert.
Dosage
The recommended dose of Berinert is 60 IU/kg body weight.
Use in children and adolescents
The recommended dose is the same as that for adult patients.
If you take more Berinert than you should
Cases of overdose have not been reported.
Reconstitution and method of administration
If your doctor considers you capable of carrying out treatment at home, they will provide you with detailed instructions. You will be asked to keep a diary to document each treatment performed at home. This diary must be presented to your doctor at every outpatient visit. Furthermore, regular checks of the injection technique used by you or your family member will be necessary to ensure its appropriateness.
General instructions

The powder must be dissolved and withdrawn from the vial under aseptic conditions. Use the syringe supplied with the product.
The resulting solution must be clear and colorless to slightly opalescent. After filtration/withdrawal (see below), the reconstituted product must be visually inspected for the presence of particles or discoloration prior to administration.
Do not use the solution if it appears cloudy or contains particles or deposits.
Unused product and waste materials resulting from this medicine must be disposed of in accordance with local regulations and as recommended by your doctor.

Reconstitution
Before opening the vials, bring the Berinert powder and solvent to room temperature.
This can be achieved by allowing the vials to stand at room temperature for about one hour or by warming them in your hands for several minutes. DO NOT expose the vials directly to a direct heat source. The vials must not be heated above body temperature (37 °C).
Carefully remove the tear-off protective caps from the vials containing the product and the solvent, respectively. Disinfect the rubber stoppers of both vials with an alcohol swab and wait for them to dry. Then, using the provided reconstitution set (Mix2Vial), transfer the solvent into the vial containing the powder. Follow the instructions below carefully.

1	1.Open the Mix2Vial package by removing the closure. Do not remove the Mix2Vial from the package!
2	2.Place the diluent vial on a flat and clean surface, holding it firmly. Take the Mix2Vial with its package and push the terminal end of the blue adapter into the stopper of the diluent vial.
3	3.Carefully remove the package from the Mix2Vial by holding its end and lifting it vertically upward. Make sure to pull only the package upward, not the Mix2Vial set.
4	4.Place the product vial on a flat and stable surface. Invert the diluent vial connected to the Mix2Vial and push the tip of the transparent adapter into the stopper of the vial containing the product. The diluent will automatically transfer into the product vial.
5	5.Hold the Mix2Vial set from the product vial side with one hand, grasp the end on the diluent vial side with the other hand, and carefully unscrew the set counterclockwise into its two components. Dispose of the diluent vial with the attached blue Mix2Vial adapter.
6	6.Gently rotate the product vial with the attached transparent adapter until the substance is completely dissolved. Do not shake the vial.
7	7.Draw air into a sterile, empty syringe. Use the syringe provided with the product. Holding the product vial upright, attach the syringe to the Luer Lock connector of the Mix2Vial by screwing it clockwise. Inject the air into the product vial.

Withdrawal and administration

8	8. While pressing the syringe plunger, turn the system upside down and slowly pull back the plunger to draw the solution into the syringe.
9	9. After the solution has been transferred into the syringe, firmly hold the syringe barrel (with the syringe plunger facing downwards) and disconnect the transparent Mix2Vial adapter from the syringe by unscrewing it counterclockwise.

Administration
Self-administration (subcutaneous administration)
Your doctor will provide you with appropriate instructions on how to safely administer
Berinert. Once you have learned how to perform self-administration,
follow the instructions below.
Berinert: instructions for self-administration

Step 1: Gather the materials Gather the syringe for Berinert administration, the following supplies (not provided in the package), and other necessary items (sharps container and treatment diary): • Hypodermic needle or subcutaneous infusion set • Sterile syringe (use a silicone-free syringe) • Alcohol wipes • Gloves (if recommended by your doctor).
Step 2: Clean the work surface • Clean the tabletop or another suitable flat surface thoroughly with alcohol wipes.
Step 3: Wash your hands • Wash and dry your hands thoroughly. • If you have been advised to wear gloves during infusion preparation, put them on.
Step 4: Prepare the injection site • Select an area in the abdominal region (stomach) for injection, unless your doctor has recommended another site (Figure 1). • Use a different site from the previous injection; rotating injection sites is recommended. • The new injection site should be at least 2 inches (5 cm) away from the previous injection site. • Never inject in areas where the skin is itchy, swollen, red, or feels warm or painful. • Avoid administering in areas with scars or stretch marks. • Clean the injection site thoroughly with an alcohol swab and allow the skin to dry (Figure 2).	Figure 1 Figure 2
Step 5: Injecting in the abdominal area As instructed by healthcare personnel: • Attach the hypodermic needle or subcutaneous infusion set (butterfly) as directed by healthcare personnel. Prime the needle or infusion set as instructed.
Injection with hypodermic needle: • Insert the needle into the skin fold (Figure 3). Subcutaneous infusion set injection: • Insert the needle into the skin fold (Figure 4).	Figure 3
	Figure 4
Step 6: Disposal of used materials • After the full dose of Berinert has been injected, the needle may be removed. • Dispose of any unused product and all administration materials properly according to local regulations.
Step 7: Keep a record of treatment • Each time you use Berinert, record in your treatment diary the batch number shown on the Berinert vial label, the date, and the time of administration.

4. POSSIBLE ADVERSE REACTIONS

Like all medicines, Berinert can cause adverse reactions, although not everyone experiences them.
Contact your doctor immediately

if any adverse reactions occur, or
if you notice any adverse reactions not described in this leaflet.

Adverse reactions due to the use of Berinert are rare.
The following adverse reactions have been observed very commonly (may affect more than 1 in 10 patients):

Reactions at the injection site (burning, cold sensation, leakage, erythema, hematoma, hemorrhage, induration, edema, pain, pruritus, rash, scarring, swelling, urticaria, warmth).
Rhinopharyngitis (runny nose or nasal congestion, sneezing, lacrimation).

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

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

Reporting of adverse reactions
If adverse reactions occur, inform your doctor or pharmacist, even if the reactions are not listed in this leaflet. You may also report adverse reactions directly through the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse .
By reporting adverse reactions, you help provide further information on the safety of this medicine.

5. HOW TO STORE BERINERT

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

6. CONTENTS OF THE PACKAGE AND OTHER INFORMATION

What Berinert contains
Active substance:
Human C1-esterase inhibitor (2000 IU/vial; equivalent to 500 IU/ml after reconstitution with 4
ml of water for injections).
For further information, see section "The following information is intended for healthcare
professionals only".
Other excipients:
Glycine, sodium chloride, sodium citrate.
Solvent: Water for injections.

What Berinert looks like and contents of the pack
Berinert is a white powder supplied with a vial of water for injections as solvent.
The resulting solution should be clear and colourless to slightly opalescent.
Packaging
Box containing:

1 vial of powder
1 vial with 4 ml of water for injections
1 transfer device with 20/20 filter
Administration kit (inner box):
- 1 single-use 5 ml syringe
- 1 hypodermic needle
- 1 subcutaneous injection set (butterfly needle)
- 2 alcohol swabs
- 1 adhesive plaster

Multipack of 5 x 2000 UI, containing one box with 5 administration kits.
Multipack of 20 x 2000 UI, containing 4 boxes with 5 administration kits each.
Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
CSL Behring GmbH
Emil-von-Behring-Strasse 76
35041 Marburg
Germany
Representative in Italy:
CSL Behring S.p.A. – Viale del Ghisallo, 20 – 20151 Milano

This product is authorized in the following European Union Member States under the following names:
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
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 latest revision of this summary of product characteristics:
The following information is intended for healthcare professionals only.
QUALITATIVE AND QUANTITATIVE COMPOSITION
The activity of human C1-esterase inhibitor is expressed in International Units (IU), which are referenced to the current WHO standard for C1-esterase inhibitor products.

PATIENT INFORMATION LEAFLET: INFORMATION FOR THE PATIENT

Berinert

3000 UI
Powder and solvent for injectable solution
Human C1-esterase inhibitor
Please read this leaflet carefully before using this medicine, as it contains
important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or pharmacist.
This medicine has been prescribed for you personally. Never give it to others, even if their symptoms are the same as yours, as it could be dangerous.
If you notice any adverse reactions, including those not listed in this leaflet, inform your doctor or pharmacist. 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 IS BERINERT AND WHAT IS IT USED FOR?

sudden swelling of hands and feet,
sudden facial swelling with a sensation of tightness,
swelling of the eyelids, lips, possible laryngeal (throat) swelling with breathing difficulties,
swelling of the tongue,
abdominal colic. In general, any part of the body may be affected.

2. WHAT YOU SHOULD KNOW BEFORE USING BERINERT

The following sections contain information that your treating physician should consider before prescribing Berinert to you.
Do not take Berinert:

If you have previously experienced life-threatening immediate hypersensitivity reactions, including anaphylaxis, to C1-esterase inhibitor or to any other component of this product listed in section 6. Please inform your doctor or pharmacist if you are allergic to any medicinal product or to any food substances.

Warnings and precautions:
Consult your doctor or pharmacist before starting treatment with Berinert:

If severe allergic or anaphylactic reactions occur (a serious allergic reaction causing severe breathing difficulties or dizziness). In such cases, administration of Berinert must be stopped immediately (e.g. by interrupting the injection).
If you have previously suffered from coagulation disorders. Cases of blood clot formation have been reported in patients who received Berinert intravenously. Very high doses of Berinert, used for conditions other than HAE, may increase the risk of clot formation. However, for subcutaneous administration of Berinert at the recommended doses, no association with clot formation has been established. Inform your doctor if you have previously had heart or vascular diseases, stroke, coagulation disorders or thrombophilia, if you have a permanent catheter/venous access, or if you have been immobilized for prolonged periods. These conditions may increase the risk of clot formation during treatment with Berinert. Also inform your doctor about any medications you are taking, as certain drugs, such as oral contraceptives or specific androgens, may increase the risk of clot formation.

Your doctor will carefully evaluate the benefit-risk ratio of treatment with Berinert versus the potential risks of these complications.
Viral safety
In the manufacturing of medicinal products derived from human blood or plasma, certain precautions are taken to prevent transmission of infections to patients. These measures include:

careful selection of blood and plasma donors to exclude individuals who may carry infections, and
testing of each individual donation and plasma pools to detect the possible presence of viruses/infections.

Manufacturers of these medicinal products also implement production steps during blood or plasma processing aimed at inactivating or eliminating viruses. Despite these measures, when administering products derived from human blood or plasma, transmission of infections cannot be completely ruled out. This also applies to emerging or hitherto unknown viruses, or other types of infections.
The measures taken 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 (liver inflammation) and parvovirus B19.
If you regularly or repeatedly use products derived from human plasma, your doctor may recommend considering vaccination against hepatitis A and B.
It is strongly recommended that, with each administration of Berinert, the date of administration, the product batch number, and the injected volume be recorded.
Other medicines and Berinert

Consult your doctor or pharmacist if you are taking, have recently taken, or might take other medicines, including those available without a prescription.
Berinert must not be mixed with other medicinal products or diluents in the syringe.

Pregnancy and breastfeeding

If you are pregnant, suspect you may be pregnant, planning a pregnancy, or are breastfeeding, please seek advice from your doctor or pharmacist before taking this medicine.
During pregnancy or breastfeeding, Berinert should be administered only if strictly necessary.

Driving and use of machines
Berinert does not impair the ability to drive vehicles or operate machinery.
Berinert contains sodium
Berinert contains up to 486 mg of sodium (approximately 21 mmol) per 100 ml of solution. This should be taken into account if you are following a low-sodium diet.

3. HOW TO USE BERINERT

Berinert is intended for self-administration by subcutaneous injection. You or the person caring for you must receive adequate instruction on the correct method of administering Berinert.
Dosage
The recommended dose of Berinert is 60 IU/kg of body weight.
Use in children and adolescents
The recommended dose is the same as that for adult patients.
If you take more Berinert than you should
Cases of overdose have not been reported.
Reconstitution and method of administration
If your doctor considers you capable of performing treatment at home, they will provide you with detailed instructions. You will be asked to keep a diary to document each treatment administered at home. This diary must be presented to your doctor at every outpatient visit. Furthermore, regular checks of the injection technique used by you or your caregiver will be necessary to ensure its appropriateness.
General instructions

The powder must be dissolved and withdrawn from the vial under aseptic conditions. Use the syringe supplied with the product.
The resulting solution must be clear and colorless to slightly opalescent. After filtration/withdrawal (see below), the reconstituted product must be inspected visually before administration for the presence of particles or discoloration.
Do not use the solution if it is cloudy or contains particles or deposits.
Unused product and waste materials resulting from this medicinal product must be disposed of in accordance with local regulations and as recommended by your doctor.

Reconstitution
Before opening the vials, bring the Berinert powder and solvent to room temperature.
This can be achieved by leaving the vials at room temperature for about one hour or warming them in your hands for several minutes. DO NOT expose the vials directly to a direct heat source. The vials must not be heated above body temperature (37 °C).
Carefully remove the pull-off caps from the vials containing the product and the solvent, respectively. Disinfect the rubber stoppers of both vials with an alcohol swab and wait until they are dry. Then, using the infusion set provided (Mix2Vial), transfer the solvent into the vial containing the powder. Follow the instructions below carefully.

1	10. Open the Mix2Vial package by removing the seal. Do not remove the Mix2Vial from the packaging!
2	11. Place the solvent vial on a flat and clean surface, holding it firmly. Take the Mix2Vial together with its packaging and push the terminal end of the blue adapter into the stopper of the solvent vial.
3	12. Carefully remove the packaging from the Mix2Vial by holding its end and lifting it vertically. Make sure to pull only the packaging upwards, not the Mix2Vial set.
4	13. Place the product vial on a flat and stable surface. Invert the solvent vial connected to the Mix2Vial and push the tip of the transparent adapter down into the stopper of the vial containing the product. The solvent will automatically
	be transferred into the product vial.
5	14. Hold the Mix2Vial set with one hand on the side of the product vial, grasp the end on the solvent vial side with the other hand, and carefully unscrew the set counterclockwise into its two components. Dispose of the solvent vial with the attached blue Mix2Vial adapter.
6	15. Gently rotate the product vial with the attached transparent adapter until the substance is completely dissolved. Do not shake the vial.
7	16. Draw air into a sterile, empty syringe. Use the syringe provided with the product. Holding the product vial upright, connect the syringe to the Luer Lock connector of the Mix2Vial by screwing it on clockwise. Inject the air into the product vial.

Collection and administration

8	17. While pressing the plunger of the syringe, turn the system upside down and, slowly raising the plunger, draw the solution into the syringe.
9	18. After the solution has been transferred into the syringe, firmly hold the syringe barrel (with the syringe plunger facing downwards) and disconnect the transparent Mix2Vial adapter from the syringe by unscrewing it counterclockwise.

Step 1: Gather the materials Gather the syringe for Berinert administration and the following consumables (not provided in the package) and other supplies (sharps container for disposal of needles and other materials, treatment diary): • Hypodermic needle or subcutaneous infusion set • Sterile syringe (use a silicone-free syringe) • Alcohol swabs • Gloves (if recommended by your doctor).
Step 2: Clean the work surface • Clean the tabletop or other suitable flat surface thoroughly with alcohol wipes.
Step 3: Wash hands • Wash and dry hands thoroughly. • If wearing gloves during preparation of the infusion has been recommended, put them on.
Step 4: Prepare the injection site • Select an area in the abdominal region (stomach) for injection, unless your doctor has recommended another site (Figure 1). • Use a different area from the previous injection; rotating injection sites is recommended. • The new injection site should be at least 2 inches (5 cm) away from the previous injection site. • Never inject into areas where the skin is itchy, swollen, red, or where there is a sensation of burning or pain. • Avoid administering into areas with scars or stretch marks. • Clean the injection site area thoroughly with an alcohol swab and allow the skin to dry (Figure 2).	Figure 1 Figure 2
Step 5: Injecting in the abdominal area As instructed by healthcare professionals: • Attach the hypodermic needle or subcutaneous infusion set (butterfly) as instructed by healthcare personnel. Prime the needle or set as directed.
Injection with hypodermic needle: • Insert the needle into the skin fold (Figure 3). Subcutaneous infusion set injection: • Insert the needle into the skin fold (Figure 4).	Figure 3
	Figure 4
Step 6: Disposal of used materials • Once the entire dose of Berinert has been injected, the needle may be removed. • Dispose of any unused product and all administration materials properly according to local regulations.
Step 7: Keep track of treatment • Each time Berinert is used, record in the treatment diary the batch number shown on the Berinert vial label, the date, and time of administration.

4. POSSIBLE ADVERSE REACTIONS

Like all medicines, Berinert can cause adverse reactions, although not everyone experiences them.
Contact your doctor immediately

if any adverse reaction occurs, or
if you notice any adverse reactions not described in this leaflet.

Adverse reactions due to the use of Berinert are rare.
The following adverse reactions have been observed very commonly (may affect more than 1 in 10 patients):

Reactions at the injection site (burning, cold sensation, leakage, erythema, bruising, bleeding, induration, edema, pain, itching, rash, scarring, swelling, hives, warmth).
Rhinopharyngitis (runny nose or nasal congestion, sneezing, lacrimation).

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

Hypersensitivity or allergic-type reactions (such as hypersensitivity, itching, rash, or hives)
Dizziness

Reporting of adverse reactions
If you experience any adverse reactions, inform your doctor or pharmacist, even if they are not listed in this leaflet. You may also report adverse reactions directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting adverse reactions, you help provide further information on the safety of this medicine.

5. HOW TO STORE BERINERT

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

6. PACK CONTENTS AND OTHER INFORMATION

What Berinert contains
Active substance:
Human C1-esterase inhibitor (3000 IU/vial; equivalent to 500 IU/ml after reconstitution with
5.6 ml of water for injections).
For further information, see the section "The following information is intended for healthcare
professionals only".
Other excipients:
Glycine, sodium chloride, sodium citrate.
Solvent: Water for injections.

Packaging
Box containing:

1 vial of powder
1 vial with 5.6 ml of water for injections
1 transfer device with 20/20 filter
1 single-use 10 ml syringe
1 hypodermic needle
1 subcutaneous injection set (butterfly needle)
2 alcohol swabs
1 plaster

Multiple pack: 5 x 3000 IU, containing one box with 5 administration sets.
Multiple pack: 20 x 3000 IU, containing 4 boxes with 5 administration sets each.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
CSL Behring GmbH
Emil-von-Behring-Strasse 76
35041 Marburg
Germany
Local Representative in Italy:
CSL Behring S.p.A. – Viale del Ghisallo, 20 – 20151 Milano

This product is authorised in the following European Union Member States 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
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 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 NE por és oldószer
oldatos injekcióhoz ______________________Hungary
Berinert 3000 IU Powder and solvent
for solution for injection __________________United Kingdom, Malta, Ireland

Date of most recent approval of this leaflet:
The following information is intended for healthcare professionals only.
QUALITATIVE AND QUANTITATIVE COMPOSITION
The activity of human C1-esterase inhibitor is expressed in International Units (IU), which are referenced to the current WHO standard for C1-esterase inhibitor products.