Pill Identifier App

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

Active substance: FACTOR XIII

View full screen / Print PDF » Download PDF ⇩

Transcript
Perforation

N

Fibrogammin contains 24 mg glucose per vial. Please take this into account if you
have diabetes.

PATIENT INFORMATION LEAFLET

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.
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.
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.
E5854 G28 A

1

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:
• Careful selection of 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.
3. HOW TO USE FIBROGAMMIN
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.
Directions for preparing and administering Fibrogammin
• Wash your hands thoroughly using soap and warm water.
• Warm the Fibrogammin powder vial and the liquid (Water for Injections)
ampoule to room or body 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 by holding 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 (37 ºC).
• Hold the water ampoule upright and shake it to move any liquid from the
ampoule tip. Break off the ampoule tip with your thumb and index finger. Draw
the water up into a sterile syringe with a sterile needle attached.
• Remove the cap from the powder vial and clean the rubber stopper with
antiseptic solution. Allow to dry. Inject the water through the rubber stopper into
the powder vial and swirl gently to dissolve. The solution should be clear or
slightly cloudy, but should not contain 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.
• The solution should be injected at a maximum rate of 4 ml per minute.
• Any unused solution should be left in the vial or syringe. Dispose of all ampoules,
vials, needles, syringes and antiseptic swabs in a ‘Sharps box’ or 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
Like all medicines, Fibrogammin can cause side effects, although not everybody
gets them.
2

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).
SUMMARY OF PRODUCT CHARACTERISTICS

1. NAME OF THE MEDICINAL PRODUCT
Fibrogammin® 250 IU
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.
Powder
Human plasma fraction with a factor XIII activity of
Total protein

68 – 135 mg
250 IU
24 – 64 mg

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

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

Frequency of doses/
Duration of Treatment

Prophylaxis of
haemorrhages

10

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

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.

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-XIIIactivity with a factor-XIII-assay 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.
5

4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in
section 6.1.
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.
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.
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.
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-XIIIdeficiency has been described.
Therefore, Fibrogammin may be used during pregnancy after careful
consideration.
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.
6

Perforation

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:
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

N

Fertility
Experimental animal studies are insufficient to assess the safety with respect
to reproduction.

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.
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.

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
In rare cases a rise in temperature can be observed.
For safety with respect to transmissible agents, see section 4.4.
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 embryofoetal toxicity, oncogenic or mutagenic potential.

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): 4 ml ampoule of colourless glass
Presentation:
1 vial with powder
1 ampoule with 4 ml Water for Injections
6.6 Special precautions for disposal and other handling
General instructions
• Reconstitution and withdrawal must be carried out under aseptic
conditions.
• Do not use solutions which are cloudy or contain residues (deposits/
particles).
Reconstitution:
Warm both the solvent and powder in unopened vials to room or body
temperature (not above 37 °C).
Take the solvent ampoule upright in your hand and shake down the solvent
from the ampoule tip.
Break off the ampoule tip with thumb and forefinger. Withdraw the solvent
into a syringe.
Remove the cap from the substance vial. Treat the surface of the rubber
stopper with antiseptic solution and allow it to dry.
Insert the cannula of the syringe filled with the solvent into the rubber
stopper of the substance vial.
The vacuum will draw the solvent automatically into the vial with the powder.
Make sure that the powder is completely covered.
After complete transfer of the solvent to the substance vial gently swirl the vial
until the powder is reconstituted and the solution is ready for administration.
Avoid vigorous shaking causing formation of foam. A colourless, clear to
slightly opalescent solution of neutral pH is obtained.
The reconstituted product should be administered immediately (see section
6.3).
Any unused product or waste material should be disposed of in accordance
with local requirements.

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.
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.
6. FURTHER INFORMATION
What Fibrogammin contains
The active substance is:
• 250 International Units (IU) human plasma coagulation factor XIII
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.
Marketing Authorisation Holder and Manufacturer
CSL Behring GmbH
Emil-von-Behring-Strasse 76
35041 Marburg
Germany
This leaflet was last revised in August 2013.

7. MARKETING AUTHORISATION HOLDER
CSL Behring GmbH
Emil-von-Behring-Strasse 76
35041 Marburg
Germany
8. MARKETING AUTHORISATION NUMBER(S)
PL 15036/0006

6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Human albumin
Glucose
Sodium chloride*
Hydrochloric acid or sodium hydroxide (for pH adjustment)

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
22 June 1998 / 30 October 2003

*see also section 4.4

10. DATE OF REVISION OF THE TEXT

Supplied solvent: Water for Injections 4 ml

7

8

3

4

Expand view ⇕

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.

Hide
(web2)