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FIBROGAMMIN 250 IU POWDER AND SOLVENT FOR SOLUTION FOR INJECTION OR INFUSION

Active substance: FACTOR XIII

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pbE8601_Fibrogammin_250_IU_28_600x270 03.12.2013 06:18 Seite 1
mit Perforation

®

FIBROGAMMIN 250 IU
Powder and solvent for injection or infusion
Read all of this leaflet carefully before you start using this medicine.
Keep this leaflet. You may need to read it again. If you have further questions, please ask
your doctor or your haemophilia nurse. This medicine has been prescribed for you
personally and you should not pass it on to others. It may harm them, even if their
symptoms are the same as yours.
IN THIS LEAFLET:
1. What Fibrogammin is and what it is used for
2. Before you use Fibrogammin
3. How to use Fibrogammin
4. Possible side effects
5. Storing Fibrogammin
6. Further information
1.

WHAT FIBROGAMMIN IS AND WHAT IT IS USED FOR

Fibrogammin (Factor XIII) is a product made from human plasma (this is the liquid part of
the blood). It is used to prevent or stop the bleeding that you might get because of a lack
of factor XIII in your blood, a condition that you have had from birth. Factor XIII is needed
for the formation of blood clots which help bleeding to stop and helps slow healing
wounds to heal more quickly.
2.

BEFORE YOU USE FIBROGAMMIN

Do not use Fibrogammin
• If you are allergic to any of the ingredients (see section 6). If you are unsure about this,
ask your doctor.
Take special care with Fibrogammin
• If you experience any signs of an allergic reaction to Fibrogammin (for example a rash,
tight chest, wheezing or feeling dizzy), stop injecting the product immediately and
contact your doctor.
• You should visit your doctor or haemophilia treatment centre regularly to ensure that
your dose is correct. The doctor may wish to carry out some tests to make sure that
you are getting the right amount.
• If your bleeding is not being controlled with Fibrogammin, tell your doctor
immediately. You may have developed an inhibitor (an antibody which can cancel
out the effects of factor XIII) and your doctor may wish to carry out more tests to confirm
this. Note: After repeated treatment, patients should be carefully monitored for the
development of inhibitors to Factor XIII by appropriate clinical observation and
laboratory tests.
• If you have ever had a blood clot (thrombosis), you should ask your doctor for advice.
See section 4 for signs of a thrombosis.
Taking or using other medicines
There are no medicines that are known to react with Fibrogammin. However, if you are
taking another medicine and are concerned, please ask your doctor or haemophilia nurse.
Fibrogammin must not be mixed with other medicinal products except those mentioned
in section 3 and should be administered by a separate infusion line.

3.

Important information about some of the ingredients of Fibrogammin
Fibrogammin contains up to 189 mmol/L sodium (17 mg per vial). Please take this into
account if you are on a sodium (salt) controlled diet as you may need to cut down on the
salt in your diet.
Fibrogammin contains 24 mg glucose per vial. Please take this into account if you have
diabetes.
Important safety information related to infections
When medicines are made from human blood, steps are taken to prevent virus infections
being passed on to the patient. These steps include:
E8601 G28 A

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SUMMARY OF PRODUCT CHARACTERISTICS

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6. Gently swirl the product vial with the transparent adapter
attached until the substance is fully dissolved. Do not shake.

7. Draw air into an empty, sterile syringe. While the product vial
is upright, connect the syringe to the Mix2Vial's Luer Lock
fitting. Inject air into the product vial.

8. While keeping the syringe plunger pressed, turn the system
upside down and draw the solution into the syringe by pulling
the plunger back slowly.

8

9. Now that the solution has been transferred into the syringe,
firmly hold on to the barrel of the syringe (keeping the syringe
plunger facing down) and disconnect the transparent
Mix2Vial adapter from the syringe.

9

3

4. Place the product vial on an even and firm surface. Invert
the solvent vial with the Mix2Vial set attached and push the
spike of the transparent adapter end straight down
through the product vial stopper. The solvent will automatically
flow into the product vial.

4

CLINICAL PARTICULARS

4.1 Therapeutic indications
Congenital deficiency of Factor XIII and resultant haemorrhagic diathesis, haemorrhages
and disturbances in wound healing.
4.2 Posology and method of administration
Posology
1 ml is equivalent to 62.5 IU, and 100 IU are equivalent to 1.6 ml, respectively.
Important: The amount to be administered and the frequency of administration should
always be orientated towards clinical efficacy in the individual case.
The following table can be used to guide dosing in bleeding episodes and surgery for
adults and children:
Type of
treatment

1

3. Carefully remove the blister package from the Mix2Vial set
by holding at the rim and pulling vertically upwards. Make
sure that you only pull away the blister package and not the
Mix2Vial set.

Note for patients on a low sodium diet
Fibrogammin contains 116.6 to 183.2 mg (5.07 to 7.97 mmol) sodium per dose
(bodyweight 75 kg), if the maximal daily dose (2625 IU = 42 ml) is applied. To be taken
into consideration in patients on a controlled sodium diet.

Withdrawal and application
4.

Prophylaxis of
haemorrhages

The solution should be clear or slightly opalescent. After filtering/withdrawal the
reconstituted product should be inspected visually for particulate matter and discoloration
prior to administration. Do not use solutions which are cloudy or contain residues
(deposits/particles).
Once you have made up the solution, it should be used immediately. If this is not possible
it should be used up within 8 hours. The solution should be put back in the fridge during
this time.
Care should be taken that no blood enters the syringe filled with product, as there is a
risk that the blood could coagulate in the syringe and fibrin clots could therefore be
administered to the patient.
In case more than one vial of Fibrogammin is required, it is possible to pool several vials
of Fibrogammin for a single infusion via a commercially available infusion device.
The Fibrogammin solution must not be diluted.
The reconstituted solution should be administered by a separate injection/infusion line by
slow intravenous injection, at a rate not exceeding 4 ml per minute.
Any unused solution should be left in the vial or syringe. Dispose of all vials, needles,
syringes and antiseptic swabs as you have been told. Do not throw them away with your
household rubbish.
If you use more Fibrogammin than you should
No cases of overdose have been reported.
If you forget to use Fibrogammin
Inject your normal dose as soon as you remember and then continue as instructed by your
doctor or haemophilia nurse.
4.

POSSIBLE SIDE EFFECTS

4.4 Special warnings and precautions for use
If anaphylactic reactions occur (see section 4.8) the administration of Fibrogammin should
be discontinued immediately and appropriate treatment initiated. The current medical
standards for shock treatment should be observed.
In the case of patients with known allergies to the product, with symptoms such as
generalised urticaria, rash, a fall in blood pressure, dyspnoea, antihistamines and
corticosteroids may be administered prophylactically.
In cases of fresh thromboses caution should be exercised on account of the fibrin-stabilising
effect of Factor XIII.
After repeated Fibrogammin treatment, patients should be carefully monitored for the
development of inhibitors to FXIII by appropriate clinical observation and laboratory tests.
Note for diabetic patients
Fibrogammin contains glucose (24 mg per 250 IU). When administering a dose of
10 IU/kg body weight to a patient with 75 kg body weight, a maximum of 72 mg glucose
will be supplied. In cases of the maximum daily dose of 35 IU/kg body weight (assuming
the same body weight), a maximum of 252 mg glucose would be supplied.

68 – 135 mg
250 IU
24 – 64 mg

3. PHARMACEUTICAL FORM
Powder (white) and solvent for solution for injection or infusion.

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1. Open the Mix2Vial package by peeling off the lid. Do not
remove the Mix2Vial from the blister package!

2

Powder
Human plasma fraction with a factor XIII activity of
Total protein

Excipients with known effect:
Sodium (as chloride and hydroxide): 2.78 to 4.36 mg/ml (120 to 189 mmol/L)
For the full list of excipients, see section 6.1.

Directions for preparing and administering Fibrogammin
Wash your hands thoroughly using soap and warm water.
Warm the Fibrogammin powder and liquid (Water for Injections) vials to room temperature
without opening either container. You can do this by leaving them to stand at room
temperature for about an hour after taking them out of the fridge or if you need them
quickly, hold them in your hands for a few minutes.
DO NOT expose the containers to direct heat or stand them on a radiator. They must not
be heated above body temperature (37º C).
Ensure that product and solvent vial flip caps are removed and the stoppers are treated
with an aseptic solution and allowed to dry, prior to opening the Mix2Vial package.

2. Place the solvent vial on an even, clean surface and hold
the vial tight. Take the Mix2Vial together with the blister
package and push the spike of the blue adapter end
straight down through the solvent vial stopper.

1. NAME OF THE MEDICINAL PRODUCT
Fibrogammin®
Powder and solvent for solution for injection or infusion
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Active ingredient: Fibrogammin is a purified concentrate of blood coagulation factor XIII.
It is derived from human plasma, and is presented as a white powder.

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The amount of factor XIII you need will depend on several factors, such as your weight,
the severity of your condition, the site and severity of bleeding or the need to prevent
bleeding during an operation or investigation.
Fibrogammin is given by injection or infusion into a vein.
If you have been prescribed Fibrogammin to use at home, your doctor or haemophilia
centre nurse will make sure that you are shown how to inject it and how much to use.
If you are in any doubt about injecting Fibrogammin, go back to your doctor
or haemophilia centre for more advice and training before attempting to treat
yourself.
Follow the directions given to you by your doctor or haemophilia nurse. You can also use
the directions given below as a guide.

4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

5. With one hand grasp the product-side of the Mix2Vial set and
with the other hand, grasp the solvent-side and unscrew the
set carefully into two pieces.
Discard the solvent vial with the blue Mix2Vial adapter attached.

HOW TO USE FIBROGAMMIN

Pregnancy and breast-feeding
If you are pregnant or planning a family soon, or if you are breast-feeding, ask your doctor
for advice before using this product.
Driving and using machines
No studies on the effects on the ability to drive and use machines have been performed.

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PATIENT INFORMATION LEAFLET

• Careful selection of the blood donors to ensure that those at risk of carrying infections
are excluded,
• Testing of each donation for signs of infection,
• Steps in the manufacture to inactivate or remove viruses.
The measures taken are considered effective for enveloped viruses such as HIV,
hepatitis B and C and for the non-enveloped viruses hepatitis A and parvovirus B19.
However, there is still a small chance of an infection being passed on to the patient.
This may include a new virus or other type of infection.
Your doctor may recommend that you consider vaccination against hepatitis A and B if
you regularly/repeatedly receive human plasma-derived factor XIII products.
Every time you receive a dose of Fibrogammin, it is important to note the
name and batch number of the medicine (shown on the carton) in order to
maintain a record of the batches used.

Dosage
International Units
[IU] per kg body
weight [b.w.]

Frequency of doses /
Duration of Treatment

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Approx. once a month. The interval
is to be shortened if spontaneous
haemorrhages develop.

Virus safety
Standard measures to prevent infections resulting from the use of medicinal products
prepared from human blood or plasma include selection of donors, screening of individual
donations and plasma pools for specific markers of infection and the inclusion of effective
manufacturing steps for the inactivation/removal of viruses. Despite this, when medicinal
products prepared from human blood or plasma are administered, the possibility of
transmitting infective agents cannot be totally excluded. This also applies to unknown or
emerging viruses and other pathogens.
The measures taken are considered effective for enveloped viruses such as human
immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) and for
the non-enveloped viruses hepatitis A and parvovirus B19.
Appropriate vaccination (hepatitis A and B) should be considered for patients in
regular/repeated receipt of human plasma-derived factor XIII products.
It is strongly recommended that whenever Fibrogammin is administered to a patient,
the product name and batch number are recorded in order to maintain a link between
the patient and the batch of the product.
4.5 Interactions with other medicinal products and other forms of interaction
No interaction studies have been performed.

Before surgical
operations

Up to 35

Immediately before surgery, then
the required efficacy should be
maintained by repeated injections
until the wound has healed
completely.

Therapy

10 – 20

Daily, for severe haemorrhages
and extensive haematomas until
bleeding has stopped.

4.6 Fertility, pregnancy and lactation
Pregnancy
The safety of Fibrogammin for use in human pregnancy has not been established in
controlled clinical trials.
Experimental animal studies are insufficient to assess the safety with respect to development
of the embryo or foetus, the course of gestation and peri- and postnatal development.
The clinical use of Fibrogammin in pregnancy did not show any negative effects on the course
of gestation and the peri- or postnatal development. The efficacy of Fibrogammin in pregnant
women with congenital factor-XIII-deficiency has been described.
Therefore, Fibrogammin may be used during pregnancy after careful consideration.

In acute bleeding episodes, especially intracranial bleedings, factor XIII must be raised to
normal levels, which can be achieved by doses up to 50 IU/kg.
Due to the different pathogenesis of factor-XIII-deficiencies the data available on half-lives
differ considerably. Thus, monitoring the increase in factor-XIII-activity with a factor-XIIIassay is recommended. In the case of major surgery and severe haemorrhages the aim is
to obtain normal values.
Paediatric population
No data are available.
Method of administration
For instructions on reconstitution of the medicinal product before administration, see
section 6.6. The preparation should be warmed to room or body temperature before
administration. Slowly inject or infuse intravenously at a rate which the patient finds
comfortable. The injection or infusion rate should not exceed approx. 4 ml per minute.
Observe the patient for any immediate reaction. If any reaction takes place during the
administration of Fibrogammin, the rate of infusion should be decreased or the infusion
stopped, as required by the clinical condition of the patient (see also section 4.4).

Lactation
The safety of Fibrogammin for use during breastfeeding has not been established in
controlled clinical trials. Fibrogammin may be used during lactation after careful
consideration.

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Fertility
Experimental animal studies are insufficient to assess the safety with respect to
reproduction.
4.7 Effects on ability to drive and use machines
No studies on the effects on the ability to drive and use machines have been performed.
4.8 Undesirable effects
The following adverse reactions are based on post-marketing experience.
The following standard categories of frequency are used:

3

Immune system disorders
In rare cases allergic-anaphylactic reactions, e.g. generalised urticaria, rash, hypotension,
dyspnoea are observed. The treatment required depends on the nature and severity of the
side effects (see section 4.4).
In very rare cases the development of inhibitors to Factor XIII may occur.
General disorders and administration site conditions
In rare cases a rise in temperature can be observed.
For safety with respect to transmissible agents, see section 4.4.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is
important. It allows continued monitoring of the benefit/risk balance of the medicinal
product. Healthcare professionals are asked to report any suspected adverse reactions via
the Yellow Card Scheme.
Website: www.mhra.gov.uk/yellowcard
4.9 Overdose
No cases of overdose have been reported.
5.

PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Antihaemorrhagics
ATC code: B02B D07
Biochemically, factor XIII acts as transglutaminase.
Factor XIII connects the amino group of lysine with glutamine via its enzymatic function
(transamidase activity), thereby leading to the cross-linking of fibrin molecules. This is the
final stage of blood coagulation. Fibrin cross-linking and stabilisation promote the
penetration of fibroblasts and support wound healing.
5.2 Pharmacokinetic properties
Distribution
The product is administered intravenously, and is thus immediately bioavailable resulting
in a plasma concentration corresponding to the applied dose.
Elimination
In congenital factor-XIII-deficiency the biological half-life of Fibrogammin was determined
to be 9.2 days (median). Fibrogammin is metabolised in the same way as is the endogenous
coagulation factor XIII.
5.3 Preclinical safety data
Concentrate of human factor XIII as a normal constituent of the human plasma acts like
the physiological factor XIII. Single dose toxicity testing revealed no adverse findings in
different species even at dose levels several times higher than the recommended human
dose.
Repeated dose toxicity testing is impracticable due to the development of antibodies in
animal models.
To date, Fibrogammin has not been reported to be associated with embryo-foetal toxicity,
oncogenic or mutagenic potential.
6.

PHARMACEUTICAL PARTICULARS

6.1 List of excipients
Human albumin
Glucose
Sodium chloride*
Hydrochloric acid or sodium hydroxide (for pH adjustment)
*see also section 4.4
Supplied solvent: Water for Injections 4 ml
6.2 Incompatibilities
Fibrogammin must not be mixed with other medicinal products except those mentioned
in section 6.6 and should be administered by a separate infusion line.
6.3 Shelf life
3 years
Do not use after the expiry date given on the pack and container.
From a microbiological point of view, and as Fibrogammin contains no preservative, the
reconstituted product should be used immediately.
If it is not administered immediately, storage shall not exceed 8 hours at +2 to +8 °C.

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

2

Very common: ≥ 1/10
Common: ≥ 1/100 and < 1/10
Uncommon: ≥ 1/1,000 and < 1/100
Rare: ≥ 1/10,000 and < 1/1,000
Very rare: < 1/10,000

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pbE8601_Fibrogammin_250_IU_28_600x270 03.12.2013 06:18 Seite 7

6.5 Nature and contents of container
Vials:
Powder: 6 ml injection vial of colourless glass, sealed with a rubber stopper, an aluminium
cap and a plastic disc.
Solvent (Water for Injections): 6 ml vial of colourless glass
Presentation:
1 vial with powder
1 vial with 4 ml Water for Injections
1 filter transfer device 20/20
6.6 Special precautions for disposal and other handling
General instructions
• The solution should be clear or slightly opalescent. After filtering/withdrawal (see below)
the reconstituted product should be inspected visually for particulate matter and
discoloration prior to administration.
• Reconstitution and withdrawal must be carried out under aseptic conditions.
• Do not use solutions which are cloudy or contain residues (deposits/particles).
Reconstitution:
Bring the solvent to room temperature. Ensure product and solvent vial flip caps are
removed and the stoppers are treated with an aseptic solution and allowed to dry prior
to opening the Mix2Vial package.
1. Open the Mix2Vial package by peeling off the lid. Do not
remove the Mix2Vial from the blister package!

1

2. Place the solvent vial on an even, clean surface and hold
the vial tight. Take the Mix2Vial together with the blister
package and push the spike of the blue adapter end
straight down through the solvent vial stopper.

2

3. Carefully remove the blister package from the Mix2Vial set
by holding at the rim, and pulling vertically upwards. Make
sure that you only pull away the blister package and not the
Mix2Vial set.

7. Draw air into an empty, sterile syringe. While the product vial
is upright, connect the syringe to the Mix2Vial's Luer Lock
fitting. Inject air into the product vial.

N

6.4 Special precautions for storage
Store in a refrigerator (+2 to +8 °C). Do not freeze. Keep the vial in the outer carton in
order to protect from light.

Rare side effects (affect less than 1 in 1,000 people):
• Rise in temperature
• Rash, itchy swellings on the skin (hives)
• Low blood pressure which could make you feel faint or dizzy
• Difficulty breathing

Fibrogammin could increase your risk of a thrombosis.
Symptoms of a thrombosis include:
• Unusual pain or swelling in your legs
• Sudden sharp pain in your chest
• Sudden difficulty breathing
• An unusual, severe or long-lasting headache
• Dizziness or fainting
If you have any of these symptoms, stop your injection immediately and contact your
doctor.
If you notice that your Fibrogammin is less effective than usual, contact your doctor or
haemophilia centre immediately.

7

Withdrawal and application
8. While keeping the syringe plunger pressed, turn the system
upside down and draw the solution into the syringe by pulling
the plunger back slowly.

Reporting of side effects
If you get any side effects, talk to your doctor, nurse or pharmacist. This includes any
possible side effects not listed in this leaflet. You can also report side effects directly, (see
details below). By reporting side effects, you can help provide more information on the
safety of this medicine.

8

9. Now that the solution has been transferred into the syringe,
firmly hold on to the barrel of the syringe (keeping the syringe
plunger facing down) and disconnect the transparent
Mix2Vial adapter from the syringe.

United Kingdom
Yellow Card Scheme
Website: www.mhra.gov.uk/yellowcard
9

5. STORING FIBROGAMMIN
Store in a fridge at 2 ºC to 8 ºC in the original packaging. Do not freeze.
Keep out of the sight and reach of children.
Do not use Fibrogammin after the expiry date on the carton.

Care should be taken that no blood enters the syringe filled with product, as there is a
risk that the blood could coagulate in the syringe and fibrin clots could therefore be
administered to the patient.
In case more than one vial of Fibrogammin is required, it is possible to pool several vials
of Fibrogammin for a single infusion via a commercially available infusion device.
The Fibrogammin solution must not be diluted.
The reconstituted solution should be administered by a separate injection/infusion line by
slow intravenous injection, at a rate not exceeding 4 ml per minute.
Any unused product or waste material should be disposed of in accordance with local
requirements.

6.

What Fibrogammin contains
The active substance is:
• 250 International Units (IU) human plasma coagulation factor XIII

7. MARKETING AUTHORISATION HOLDER
CSL Behring GmbH
Emil-von-Behring-Strasse 76
35041 Marburg
Germany

Other ingredients are:
• human albumin
• glucose
• sodium chloride
• traces of sodium hydroxide or hydrochloric acid may also be present, (used for pH
adjustment).
Bottles of product and liquid may appear partly empty but this is normal and does not
mean that there is the wrong amount of powder or solution.

8. MARKETING AUTHORISATION NUMBER(S)
PL 15036/0006
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
22 June 1998 / 30 October 2003

3

4. Place the product vial on an even and firm surface. Invert
the solvent vial with the Mix2Vial set attached and push the
spike of the transparent adapter end straight down
through the product vial stopper. The solvent will automatically
flow into the product vial.

FURTHER INFORMATION

Marketing Authorisation Holder and Manufacturer
CSL Behring GmbH
Emil-von-Behring-Strasse 76
35041 Marburg, Germany
This leaflet was last revised in 11/2013.

10. DATE OF REVISION OF THE TEXT

4

5. With one hand grasp the product-side of the Mix2Vial set and
with the other hand grasp the solvent-side and unscrew the
set carefully into two pieces.
Discard the solvent vial with the blue Mix2Vial adapter attached.

5

6. Gently swirl the product vial with the transparent adapter
attached until the substance is fully dissolved. Do not shake.

6

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4

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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