БЕРИАТЕ 250 IU/2.5 ML Порошок и раствор для инъекционного/инфузионного раствора

Содержание инструкции

1. Beriate 250 IU, 500 IU, 1000 IU
   1. What Beriate is and what it is used for
   2. What you need to know before using Beriate
   3. How to use BERIATE
   4. Possible side effects
   5. How to store Beriate
   6. Contents of the pack and other information
2. Beriate is presented as a white powder and the package also includes water for

Beriate 250 IU, 500 IU, 1000 IU

Beriate 2000 IU
Powder and solvent for solution for injection or infusion
Human coagulation Factor VIII

Read this leaflet carefully before using this medicinebecause it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any doubts, ask your doctor or pharmacist.
• This medicine has been prescribed for you personally. Never give it to other people, even if their symptoms of illness are the same as yours, because it could be dangerous.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.
• 1. What Beriate is and what it is used for
• 2. What you need to know before you use Beriate
• 3. How to use Beriate
• 4. Possible side effects
• 5. How to store Beriate
• 6. Contents of the pack and other information

1. What Beriate is and what it is used for

Beriate is presented as a powder and solvent. The resulting solution must be
administered by injection or intravenous infusion.
Beriate is obtained from human plasma (which is the liquid component of blood) and contains human coagulation Factor VIII. It is used to prevent or stop
bleeding caused by a lack of Factor VIII in the blood (hemophilia A). It can also
be used in the treatment of acquired Factor VIII deficiency.
Factor VIII is involved in blood coagulation. A lack of Factor VIII
means that the blood coagulates less quickly than it should, resulting in
an increased tendency to bleed. Replacing Factor VIII with Beriate
temporarily normalizes the coagulation mechanism.

2. What you need to know before using Beriate

The following paragraphs contain information that you and your doctor need to consider before using Beriate.

Do not use Beriate:

• If you are allergic (hypersensitive) to human coagulation Factor VIII or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions:
Traceability
It is strongly recommended that, whenever Beriate is administered, the date of administration, the product batch number and the volume of product infused are recorded in your treatment diary.
Consult your doctor or pharmacist before taking Beriate.

• Allergic-type hypersensitivity reactions are possible. The doctor must inform you of what the first signs of a hypersensitivity reactionare. These include hives, widespread skin rash, a feeling of tightness in the chest, difficulty breathing, low blood pressure and anaphylaxis (a severe allergic reaction that causes severe difficulty breathing or dizziness). If these symptoms occur, you must immediately stop administering the product and contact your doctor.
• The formation of inhibitors (antibodies) is a known complication that can occur during treatment with all factor VIII-based medicines. Inhibitors, especially at high levels, prevent the treatment from working properly and you or your child will be carefully monitored to check for the development of these inhibitors. If Beriate does not control bleeding in you or your child, inform your doctor immediately.
• If you are aware of having heart problems or being at risk of heart problems, tell your doctor or pharmacist.
• If a central venous access device (CVAD) needs to be used to administer Beriate, your doctor must consider the risk of complications related to the CVAD, including local infections, the presence of bacteria in the blood (bacteremia) and the formation of a blood clot in the blood vessel (thrombosis) into which the catheter was inserted.

Your doctor will carefully assess the benefit-risk ratio of treatment with Beriate and the risk of these complications.

Viral safety
When medicines are prepared from human blood or plasma, specific measures are taken to prevent the transmission of infections to patients. These measures include careful selection of blood and plasma donors to ensure that potentially infected donors are excluded, and testing of each donation and plasma pool for the possible presence of infections/viruses. Manufacturers of these medicines also introduce certain steps into the production process that are capable of inactivating or removing viruses. Despite these measures, the possibility of transmission of infectious agents cannot be completely excluded when medicinal products prepared from human blood or plasma are administered. This also applies to unknown or emerging viruses, or other types of infectious agents.
The measures taken are considered effective against enveloped viruses such as the human immunodeficiency virus (HIV, the AIDS virus), the hepatitis B virus and the hepatitis C virus (liver inflammation) and against non-enveloped viruses such as the hepatitis A virus and parvovirus B19.
Your doctor may recommend that you get vaccinated against hepatitis A and hepatitis B if you regularly/repeatedly use medicines derived from human plasma (e.g. Factor VIII).

Other medicines and Beriate:

• Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
• Beriate must not be mixed with other medicines, nor with diluents and solvents other than those recommended by the manufacturer (see section 6). Pregnancy, breastfeeding and fertility
• If you are pregnant, suspect you are pregnant, are planning to become pregnant or are breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.
• During pregnancy and breastfeeding, Beriate should only be used if clearly indicated.
• No data on fertility are available.

Driving and operating machinery
Beriate does not affect your ability to drive vehicles and operate machinery.

Beriate contains Sodium
Beriate 250 IU and 500 IU contain less than 1 mmol of sodium (23 mg) per vial, i.e. essentially “sodium-free”.
Beriate 1000 IU and 2000 IU contain 27.55 mg of sodium (the main component of table salt) per vial. This is equivalent to 1.4% of the maximum recommended daily intake of sodium with the diet of an adult.

3. How to use BERIATE

Use this medicine following exactly the instructions of your doctor. If you have any
doubts, contact your doctor or pharmacist.
The treatment of Hemophilia A must be initiated and continued under the supervision of a
doctor experienced in this type of pathology.
The dose of Factor VIII you need and the duration of therapy depend on numerous
factors, such as your body weight, the severity of the disease, the location and extent of the
bleeding, or the need to prevent bleeding during surgical
procedures or diagnostic investigations.
In case of home administration of Beriate, the doctor will ensure that you have been
shown how to perform the infusion and how much product to use.

Follow carefully the instructions given by the doctor or the paramedical staff of the
hemophilia care center.
Use in children and adolescents
The dose is based on body weight and, generally, the same guidelines as for
adults apply.

If you take more Beriate than you should
No symptoms of overdose with Factor VIII are known to date.

If you forget to use Beriate
Proceed immediately with the next dose and continue at regular intervals as recommended by
your doctor. Do not take a double dose to make up for the missed dose.

Reconstitution and administration
General instructions:

• The lyophilized (powder) must be mixed (reconstituted) with the solvent (liquid) and drawn from the vial under aseptic conditions.
• The reconstituted solution should be clear or slightly opalescent, meaning that, held against the light, it may present some shimmer. Occasionally, a small amount of flocculi or particles may appear in the vial. The filter included in the Mix2Vial device removes these particles. This filtration does not affect the dosage calculation. After filtration and withdrawal of the product into the syringe (see below) and before administration, the solution in the syringe must be visually inspected for the presence of corpuscles or color changes. Do not use solutions that appear cloudy or contain deposits or particles in the syringe.
• Once the product has been transferred to the syringe, it must be used immediately. Do not store the product in the syringe.
• Unused product and waste resulting from this medicine must be disposed of in accordance with local regulations and according to the instructions given by the doctor.

Reconstitution:
Without opening either of the two vials, bring to room temperature or warm to
body temperature both the Beriate lyophilized (powder) and the solvent (liquid). This
can be done by leaving the two vials at room temperature for about an hour or
holding them in your hands for a few minutes.
DO NOT EXPOSE the vials directly to heat. The vials must not be brought to
a temperature higher than body temperature (37 ºC).
Carefully remove the protective caps from the vials containing the powder
and the solvent and clean the surface of the rubber stoppers with an alcohol-soaked swab.
Wait for the stoppers to dry before opening the Mix2Vial package, then
follow the instructions below.

a 1	i 1. Open the Mix2Vial package, removing the l closure. Do not remove the Mix2Vial from the blister pack!
t I a i 2	2. Place the solvent vial on a flat and clean surface, holding the vial firmly. Take the Mix2Vial together with the blister pack and push the end of the blue adapter down directly into the cap of the solvent vial.
z n e g 3	3. Carefully remove the blister pack from the Mix2Vial set by holding it by the edge and pulling vertically upwards. Make sure to pull only the blister pack and not the Mix2Vial set.

4	4. Place the product vial on a flat and stable surface. Invert the solvent vial with the Mix2Vial set inserted and push the end of the transparent adapter down directly into the cap of the vial containing the product. Automatically the solvent will flow into the vial containing the product.
5	m 5. Holding the Mix2Vial set side by one hand and the solvent side of the Mix2Vial set with the other hand, gently separate the 2 parts of the set by unscrewing in a counterclockwise direction. Discard the solvent vial with the blue Mix2Vial adapter attached.
6	6. Gently rotate the product vial with the transparent adapter attached until complete dissolution of its contents. Do not shake.
7	d 7. Draw air into a sterile empty syringe. Keeping the product vial in a vertical position, connect the syringe to the Luer Lock connector of the Mix2Vial by screwing clockwise. Inject the air into the vial containing the product.

Withdrawal and administration:

t I a i z 8	8. Keeping the syringe plunger pressed down, invert the system and draw the solution into the syringe by slowly pulling back the plunger.
n e g 9	9. After all the solution has been transferred into the syringe, firmly grasp the syringe cylinder (keeping the syringe plunger pointing downwards) and disconnect the transparent Mix2Vial adapter from the syringe by unscrewing in a counterclockwise direction.

It is recommended to use the infusion set provided with the medicine; insert the needle into a
vein. Allow blood to flow back into the distal end of the cannula. Attach the syringe
to the threaded connection, screwing the injection set into the vein tightly.

Inject the reconstituted solution slowly into the veinfollowing the doctor's instructions.
The rate of injection or infusion should not exceed 2 ml per minute. Be careful not to
allow blood to flow back into the syringe containing the product.
When a large volume is required, an alternative may be
infusion. In this case, the reconstituted product must be transferred to a suitable
infusion system. The infusion should then be carried out following the instructions given by
the doctor.
Pay attention to any side effects that may occur during
administration. If you experience any side effect that may be related to the administration of Beriate, the injection or infusion must be stopped
(see section 2).
If you have any further questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although
not everyone experiences them.

If you experience any of the following side effects, contact your doctor immediately
or go to the Emergency Room or the Hemophilia Center of the nearest Hospital to
you:

• Symptoms of angioedema such as:
• swelling of the face, tongue or pharynx;
• difficulty swallowing;
• urticaria and difficulty breathing. These side effects have been observed very rarely (may affect up to 1 in 10,000 people), and in some cases they may progress to severe allergic reactions (anaphylaxis) including shock. Loss of efficacy (continued bleeding)
• In children not previously treated with factor VIII-based medicines, the formation of inhibitor antibodies (see section 2) may be very common (more than 1 in 10 patients); however, in patients who have received previous treatment with factor VIII (more than 150 days of treatment) the risk is uncommon (less than 1 in 100 patients). If this happens, the medicine for you or your child may stop working properly and you or your child may experience persistent bleeding. Other side effects:
• Allergic reactions (hypersensitivity) which may include:
• a burning sensation and stinging pain in the area where the injection or infusion was given;
• shivers, flushing, rash all over the body, hives;
• headache;
• low blood pressure, agitation, rapid heartbeat, chest tightness, wheezing;
• fatigue (lethargy);
• nausea, vomiting;
• tingling. These side effects have been observed very rarely and in some cases may progress to the development of severe allergic reactions (anaphylaxis) including shock.
• In very rare cases, fever has been observed.

Side effects in children and adolescents
It is expected that the frequency, type and severity of adverse reactions in children will be the same
as in adults.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, please
tell your doctor, nurse or pharmacist.
You can also report side effects directly through the national reporting system at www.aifa.gov.it/content/segnalazioni-reazioni-avverse .
By reporting side effects you can help provide more information on the
safety of this medicine.

5. How to store Beriate

Do not use this medicine after the expiry date indicated on the label and on the
pack. The expiry date refers to the last day of that month.

• Store in a refrigerator between 2°C and 8°C.
• During the validity period, Beriate may be stored at a temperature of up to 25°C for a total period not exceeding 1 month. Individual storage periods at room temperature must be recorded in your treatment diary to ensure that the overall limit of 1 month is respected.
• Beriate does not contain preservatives, therefore the reconstituted product should preferably be used immediately.
• If the reconstituted product is not used immediately, it may be stored in the vial at room temperature for no more than 8 hours. Once transferred into the syringe, the product must be used immediately.
• Do not freeze. Keep the container in the outer packaging to protect it from light. Keep this medicine out of the sight and reach of children.

6. Contents of the pack and other information

What Beriate contains
The active substance is:
Beriate is presented as a powder (with a nominal content of 250 IU, 500 IU, 1000
IU or 2000 IU of human coagulation Factor VIII per vial) plus a liquid
(solvent). The reconstituted solution is intended for administration by injection or
infusion.
Beriate 250 IU/vial, 500 IU/vial and 1000 IU/vial, after reconstitution,
with 2.5 ml, 5 ml or 10 ml of water for injections respectively, contains approximately
100 IU/ml of human coagulation Factor VIII. Beriate 2000 IU/vial
should be reconstituted with 10 ml of water for injections and contains approximately 200 IU/ml of
human coagulation factor VIII.
The other ingredients are:
Glycine, calcium chloride, sodium hydroxide (in small quantities) for pH adjustment,
sucrose, sodium chloride. Solvent:Water for injections 2.5 ml, 5 ml and 10 ml
respectively.

Description of the appearance of Beriate and contents of the pack

Beriate is presented as a white powder and the package also includes water for

injectable preparations.
The reconstituted solution must be clear or slightly opalescent, in the sense that –
held against the light – it may present some shimmer, but must never contain evident
particles.

Presentations
Box of 250 U.I. containing:
1 vial with powder
1 vial with 2.5 ml of water for injectable preparations
1 transfer device 20/20 with integrated filter
Administration set (inner box):
1 single-use 5 ml syringe
1 set for intravenous injection
2 alcohol-soaked swabs
1 non-sterile plaster
Box of 500 U.I. containing:
1 vial with powder
1 vial with 5 ml of water for injectable preparations
1 transfer device 20/20 with integrated filter
Administration set (inner box):
1 single-use 5 ml syringe
1 set for intravenous injection
2 alcohol-soaked swabs
1 non-sterile plaster
Box of 1000 U.I. containing:
1 vial with powder
1 vial with 10 ml of water for injectable preparations
1 transfer device 20/20 with integrated filter
Administration set (inner box):
1 single-use 10 ml syringe
1 set for intravenous injection
2 alcohol-soaked swabs
1 non-sterile plaster
Box of 2000 U.I. containing:
1 vial with powder
1 vial with 10 ml of water for injectable preparations
1 transfer device 20/20 with integrated filter
Administration set (inner box):
1 single-use 10 ml syringe
1 set for intravenous injection
2 alcohol-soaked swabs
1 non-sterile plaster
It is possible that not all pack sizes are marketed.

MARKETING AUTHORISATION HOLDERANDMANUFACTURER
CSL Behring GmbH
Emil von Behring- Str. 76
35041 Marburg
Germany

Representative for Italy
CSL Behring S.p.A. – 20151 Milan.

This medicinal product is authorised in the following Member States of the European
Community with the name:
Austria:
Beriate 100 I.E./ml Pulver und Lösungsmittel zur Herstellung einer Injektions- oder
Infusionslösung (250 I.E., 500 I.E., 1000 I.E.)
Beriate 200 I.E./ml Pulver und Lösungsmittel zur Herstellung einer Injektions- oder
Infusionslösung (2000 I.E.)
Bulgaria:
Beriate 250 IU Powder and solvent for solution for injection or infusion
Beriate 500 IU Powder and solvent for solution for injection or infusion
Beriate 1000 IU Powder and solvent for solution for injection or infusion
Beriate 2000 IU Powder and solvent for solution for injection or infusion
Croatia:
Beriate 250 IU prašak i otapalo za otopinu za injekciju ili infuziju
Beriate 500 IU prašak i otapalo za otopinu za injekciju ili infuziju
Beriate 1000 IU prašak i otapalo za otopinu za injekciju ili infuziju
Beriate 2000 IU prašak i otapalo za otopinu za injekciju ili infuziju
Estonia:
Beriate
Germany:
Beriate 250, Beriate 500, Beriate 1000, Beriate 2000
Latvia:
Beriate 250 SV pulveris un šķīdinātājs injekciju vai infūziju šķīduma pagatavošanai
Beriate 500 SV pulveris un šķīdinātājs injekciju vai infūziju šķīduma pagatavošanai
Beriate 1000 SV pulveris un šķīdinātājs injekciju vai infūziju šķīduma pagatavošanai
Beriate 2000 SV pulveris un šķīdinātājs injekciju vai infūziju šķīduma pagatavošanai
Lithuania:
Beriate® 250 TV milteliai ir tirpiklis injekciniam ar infuziniam tirpalui
Beriate® 500 TV milteliai ir tirpiklis injekciniam ar infuziniam tirpalui
Beriate® 1000 TV milteliai ir tirpiklis injekciniam ar infuziniam tirpalui
Beriate® 2000 TV milteliai ir tirpiklis injekciniam ar infuziniam tirpalui
Poland:
Beriate 250
Beriate 500
Beriate 1000
Beriate 2000
Portugal:
Beriate
Czech Republic:
Beriate 250 IU, Beriate 500 IU, Beriate 1000 IU, Beriate 2000 IU
Romania:
Beriate 250 pulbere şi solvent pentru soluţie injectabilă/perfuzabilă
Beriate 500 pulbere şi solvent pentru soluţie injectabilă/perfuzabilă
Beriate 1000 pulbere şi solvent pentru soluţie injectabilă/perfuzabilă
Beriate 2000 pulbere şi solvent pentru soluţie injectabilă/perfuzabilă
Slovakia:
Beriate 250 IU
Beriate 500 IU
Beriate 1000 IU
Beriate 2000 IU
Slovenia:
Beriate 250 i.e. prašek in vehikel za raztopino za injiciranje/infundiranje
Beriate 500 i.e. prašek in vehikel za raztopino za injiciranje/infundiranje
Beriate 1000 i.e. prašek in vehikel za raztopino za injiciranje/infundiranje
Beriate 2000 i.e. prašek in vehikel za raztopino za injiciranje/infundiranje
Spain:
Beriate 250 UI polvo y disolvente para solución inyectable o perfusión
Beriate 500 UI polvo y disolvente para solución inyectable o perfusión
Beriate 1000 UI polvo y disolvente para solución inyectable o perfusión
Beriate 2000 UI polvo y disolvente para solución inyectable o perfusión
Hungary:
Presentations of Beriate 250, 500 and 1000:
BERIATE 100 NE/ml por és oldószer oldatos injekcióhoz vagy infúzióhoz
Presentation 2000:
BERIATE 200 NE/ml por és oldószer oldatos injekcióhoz vagy infúzióhoz

The following information is intended exclusively for physicians or healthcare
professionals.
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Dosage

Monitoring of treatment
During the course of treatment, it is advisable to accurately determine the levels of factor
VIII in order to establish the dose to be administered and the frequency with which to repeat the infusions.
Individual patients may exhibit variability in their response to factor VIII, showing different
half-life values and recovery levels. Dosage based on body weight may require adjustments in
underweight or overweight patients. In the case of major surgery, in particular, precise
monitoring of replacement therapy through control of coagulation parameters (plasma activity
of factor VIII) is essential.
Patients should be monitored for the development of factor VIII inhibitors. See also section 2.
The number of units of Factor VIII administered is expressed in International Units (IU),
correlated with the current WHO concentrated standard for factor VIII-based products.
The activity of factor VIII in plasma is expressed as a percentage (relative to normal human
plasma) or preferably in IU (relative to an International Standard for Factor VIII in
plasma).
One IU of Factor VIII activity is equivalent to the amount of Factor VIII contained in 1 ml of
normal human plasma.

On-demand treatment
The calculation of the necessary dose of Factor VIII is based on the empirical data that 1 IU of Factor
VIII per kg of body weight increases the activity of Factor VIII in plasma by approximately 2% (2
IU/dl) of normal activity. The necessary dose is determined using the following
formula:
Units required = body weight (kg) x desired increase of FVIII (% or IU/dl) x 0.5
The dose to be administered and the frequency of administration must always be
oriented to clinical efficacy in the individual case.
In the case of the following bleeding events, the level of factor VIII during the corresponding
period must not fall below the indicated level of plasma activity (% of the normal value
or IU/dl). The following table can be used as a guide to establish the dosage in the case of
bleeding episodes and surgical interventions:

Prophylaxis
For long-term prophylaxis of bleeding in patients with severe hemophilia A, the usual
doses are between 20 and 40 IU of FVIII per kg of body weight, administered at
intervals of 2-3 days. In some cases, especially in younger patients, shorter administration
intervals or higher doses may be necessary.

Paediatric population
Dosage in children is based on body weight and therefore, in general, the same guidelines
indicated for adults apply. The frequency of administration must always be oriented to
achieving clinical efficacy in the individual case. Data are available on treatment in children
under 6 years of age.

Information on the pharmacological properties of vWf
In addition to having a function as a protective protein of factor VIII, von Willebrand factor
mediates the adhesion of platelets at sites of vascular damage and plays a role
in platelet aggregation.