Berinert 2000

Berinert 2000
2000 IU
powder and solvent for solution for injection
Human C1-esterase inhibitor
Please read the entire leaflet before using this medicine.

• Keep this leaflet for future reference.
• If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not share it with others. This medicine may harm others, even if their symptoms are identical.
• If the patient experiences any adverse reactions, including any possible adverse reactions not listed in this leaflet, inform your doctor or pharmacist immediately.

Table of 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. The prepared solution is intended for subcutaneous injection.
Berinert is manufactured from human plasma (the liquid component of blood). Its active ingredient is a protein – human C1-esterase inhibitor.

What Berinert is used for
Berinert is used for the treatment of acute attacks of hereditary angioedema (HAE, angioedema = swelling) in adolescents and adults. Angioedema is a hereditary blood vessel disorder. It is not an allergic disease. It is caused by a deficiency, absence, or dysfunction of a key protein called C1-esterase inhibitor. The disease is characterized by the following symptoms:

• sudden swelling of hands and feet,
• sudden facial swelling with a sensation 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 has experienced life-threatening, immediate allergic reactions, including anaphylactic shock, to C1-esterase inhibitor or to any of the other components of this medicine (listed in section 6). You should inform your doctor or pharmacist if you have hypersensitivity to any medicine or food.

Warnings and precautions:
Before using Berinert, discuss this with your doctor or pharmacist.

• if severe 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. discontinuation of the infusion).
• if the patient has a history of blood clotting disorders. Blood clots have occurred in patients receiving Berinert intravenously. Very high doses of Berinert used in the treatment of diseases other than HAE may increase the risk of blood clots. However, with subcutaneous administration of Berinert, no association with blood clot formation has been observed at doses recommended by the physician. Inform your doctor if the patient has previously had heart or vascular diseases, stroke, blood clots, thickened blood, a permanently implanted catheter/venous access device placed in one of the patient's veins, or if the patient has been immobilized for a period of time. These factors may increase the risk of blood clots after administration of Berinert. Inform your doctor about all medications the patient is taking, as certain drugs, such as oral contraceptives or certain androgens, may increase the risk of blood clots.

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

• careful selection of blood and plasma donors to exclude 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 administration of a medicinal product derived from human blood or plasma may transmit infectious agents. This risk also applies to unknown or newly emerging viruses and other infectious agents.
The protective 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 non-enveloped viruses such as hepatitis A virus (HAV, causing hepatitis A) and parvovirus B19.
Patients who repeatedly receive products derived from human plasma should be considered for vaccination against hepatitis A and B.
Each time Berinert is administered, the date of administration, batch number, and volume infused should be recorded in the patient's medical records.
Berinert and other medicines

• Inform your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, including medicines the patient plans to take and 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 is planning to become pregnant, she should consult her doctor or pharmacist before using this medicine.

Driving and operating machinery
Berinert has no influence on the ability to drive vehicles or operate machinery.
Berinert contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per vial, which means it is considered "sodium-free".

3. HOW TO USE BERINERT

Berinert is intended for self-administration as a subcutaneous injection.
The patient or caregiver should be trained in the proper method of administering Berinert.
Dosage
The recommended dose of Berinert is 60 IU/kg body weight.
Use in children
The recommended dose is the same as for adults.
Overdose
No cases of overdose have been reported.
Reconstitution and method of administration
If the physician decides that home therapy is appropriate, detailed instructions will be provided.
The patient must 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 carried out to ensure continued proper administration.
General instructions

• The powder must be reconstituted and withdrawn from the vial under aseptic conditions. Use only the syringe supplied with the product.
• The prepared solution should be colorless and clear to slightly opalescent. After filtration or withdrawal from the vial (see below) and prior to administration, the solution should be carefully inspected for particulate matter, cloudiness, 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 components 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 warmed above body temperature (37°C).
Carefully remove the caps from the vials containing the powder and solvent.
Clean the rubber stopper of each vial with a separate alcohol swab and allow to dry.
The solvent may be combined with the powder using the device supplied in the kit (Mix2Vial).
Follow the instructions provided below.

1	1. Open the package containing the Mix2Vial by removing the cap. Do not remove the Mix2Vial from the blister.
2	2. Place the vial containing the diluent on a flat, clean surface and hold it firmly. Without removing it from the blister, place the blue-bladed end of the Mix2Vial device onto the diluent vial stopper and press vertically downward to pierce the diluent vial stopper.
3	3. 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	4. Place the vial containing the powder on a flat, hard surface. Invert the diluent vial with the attached Mix2Vial device and, moving vertically downward, insert the transparent end of the connector into the stopper of the vial containing the powder. The diluent will automatically transfer into the vial with the powder.
5	5. With one hand, hold the part of the Mix2Vial device in the vial now containing the solution, and with the other hand, hold the connector part attached to the diluent vial, then carefully unscrew the two connector parts in a counterclockwise direction. Remove the empty diluent vial with the attached blue end of the Mix2Vial device.
6	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	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 upward, attach the syringe to the Luer Lock connector of the Mix2Vial device by turning it clockwise. Inject air into the vial with the medicinal product.

Download and method of administration

8	8. Holding the syringe plunger, invert the vial together with the syringe and draw the solution into the syringe by slowly pulling back the plunger.
9	9. Once the syringe is filled with the solution, firmly grasp the syringe barrel (keeping the syringe with the plunger facing downward) and unscrew the transparent end of the Mix2Vial transfer set in a counterclockwise direction to disconnect it from the syringe.

Method of administration
For self-administration by the patient (subcutaneous administration)
The physician will teach the patient how to safely administer Berinert. After becoming familiar with the proper method of self-administration, follow the instructions below.
Table 2. Instructions for self-administration of Berinert

Step 1: Gathering Supplies Assemble the syringe with Berinert medication and single-use accessories, as well as other items (needles, additional containers, treatment diary or record book): Subcutaneous injection needle or subcutaneous infusion set. Sterile syringe (use a silicone-free syringe) Alcohol swabs Gloves (if recommended by healthcare professionals)
Step 2: Cleaning the Surface Thoroughly clean the table or another smooth surface using
alcohol swabs.
Step 3: Hand Washing Wash and dry hands thoroughly If the patient has been instructed to prepare the infusion while wearing gloves, put on gloves.
Step 4: Preparing the Injection Site Select an abdominal area for injection unless otherwise instructed by a physician (Fig. 1). Choose a different site than the previous injection; the patient should rotate injection sites. The new injection site should be at least 5 cm away from the previous injection site. Never inject into areas where the skin is itchy, swollen, painful, bruised, or red. Avoid injecting into areas with scars or stretch marks. Clean the skin at the injection site using an alcohol swab and allow it to dry (Fig. 2).	Figure 1 Figure 2
Step 5: Abdominal Injection Following instructions from healthcare professionals: Attach the subcutaneous injection needle or subcutaneous infusion set (butterfly set) to the syringe according to healthcare professional instructions. Prime the needle or tubing as required and per instructions. Injection using a subcutaneous injection needle: Insert the needle into a skin fold (Fig. 3). Injection using a subcutaneous infusion set: Insert the needle into a skin fold (Fig. 4).	Figure 3
	Figure 4
Step 6: Cleaning Up After injecting the full dose of Berinert, remove the needle. Dispose of any unused solution and all administration set components according to local regulations.
Step 7: Recording Treatment Record in the treatment diary or record book the batch number from the Berinert vial label, as well as the date and time of infusion, each time Berinert is administered.

4. POSSIBLE ADVERSE REACTIONS

Like all medicines, this medicine can cause adverse reactions, although not everybody will experience 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 very commonly (may affect more than 1 in 10
patients):

• Reactions at the injection site (bruising, cold sensation, leakage, redness, haematoma, bleeding, induration, swelling, pain, itching, rash, scar, puffiness, urticaria, warmth).
• Nasopharyngitis (runny or thick nasal discharge, nasal congestion, watery eyes).

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

• Hypersensitivity or allergic symptoms such as: hypersensitivity, redness, itching, and urticaria.
• Dizziness.

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
Adverse reactions can also be reported to the Marketing Authorisation Holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. HOW TO STORE BERINERT

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the label and outer packaging following the abbreviation EXP.
• Do not store above 30°C.
• Do not freeze.
• Store the vial in the outer carton 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 no later than within 8 hours after preparation and must be stored exclusively in the vial.
• The batch number is indicated on the label and box following the abbreviation (Lot).

6. OTHER INFORMATION

What Berinert contains
Active substance:
Human C1-esterase inhibitor (2000 IU/vial; after reconstitution with 4 ml of water for injections: 500 IU/ml).
See section "Information intended solely for healthcare professionals" for more detailed information.
Excipients:
Glycine, sodium chloride, sodium citrate.
Solvent: Water for injections

What Berinert looks like and contents of the pack
Berinert is presented as a white powder and solvent, which is water for injections.
The reconstituted solution should be colourless and clear to slightly opalescent.

Pack sizes
The pack contains:
1 vial of powder
1 vial containing 4 ml of water for injections
1 transfer system 20/20 with filter
Administration set (inner packaging):
1 single-use 5 ml syringe,
1 subcutaneous administration needle
1 subcutaneous infusion set
2 alcohol-impregnated swabs
1 plaster
Pack containing 5 x 2000 IU, including 5 administration accessories
Pack containing 20 x 2000 IU, including 4 packs of 5 administration accessories

Not all pack sizes may be marketed.

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

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

Information intended solely for 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.