FIBROGAMMIN P 250IU

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PATIENT INFORMATION LEAFLET

Important information about some of the ingredients of Fibrogammin P Fibrogammin P 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 P 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 stop infections (e.g. HIV and Hepatitis) being passed on to the patient. This includes: Careful selection of the blood donors Testing of each donation for signs of infection Steps in the manufacture which can kill or remove viruses However, there is still a small chance of an infection being passed on to the patient. This may include a new virus or infection. Therefore, every time Fibrogammin P is used, it is important to note the name and batch number of the medicine (found on the carton). 3. HOW TO USE FIBROGAMMIN P 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 P is given by injection or infusion into a vein. If you have been prescribed Fibrogammin P 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 P, 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.

SUMMARY OF PRODUCT CHARACTERISTICS 1. NAME OF THE MEDICINAL PRODUCT Fibrogammin P Powder and solvent for solution for injection or infusion 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Active ingredient: Fibrogammin P is a purified concentrate of blood coagu lation 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

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 P, 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). 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 P 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, anti histamines 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 P 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 P 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 P 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 HIV, HBV and HCV and for the non enveloped virus HAV. The measures taken may be of limited value against other non enveloped viruses such as parvovirus B19. Parvovirus B19 infection may be serious for pregnant women (foetal infection) and for individuals with immunodeficiency or increased erythropoiesis (e.g. haemolytic anaemia). Vaccination against hepatitis A and hepatitis B should be considered for patients in regular receipt of medicinal products derived from human blood or plasma. It is strongly recommended that whenever Fibrogammin P 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 P 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.

FIBROGAMMIN P 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 P is and what it is used for 2. Before you use Fibrogammin P 3. How to use Fibrogammin P 4. Possible side effects 5. Storing Fibrogammin P 6. Further information 1. WHAT FIBROGAMMIN P IS AND WHAT IT IS USED FOR Fibrogammin P (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 P Do not use Fibrogammin P 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 P If you experience any signs of an allergic reaction to Fibrogammin P (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 P, 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 P. 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.

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.] 10 Frequency of doses/ Duration of Treatment

Directions for preparing and administering Fibrogammin P Wash your hands thoroughly using soap and warm water. Warm the Fibrogammin P 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 C). 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 P than you should No cases of overdose have been reported. If you forget to use Fibrogammin P 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 P can cause side effects, although not everybody gets them. 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 2

Prophylaxis of haemorrhages Before surgical operations

Approx. once a month. The interval is to be shortened if spontaneous haemorrhages develop. Immediately before surgery, then the required efficacy should be maintained by repeated injections until the wound has healed completely. Daily, for severe haemorrhages and extensive haematomas until bleeding has stopped.

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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 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.
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The clinical use of Fibrogammin P in pregnancy did not show any negative effects on the course of gestation and the peri or postnatal development. The efficacy of Fibrogammin P in pregnant women with congenital factor XIII deficiency has been described. Therefore, Fibrogammin P 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. 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: 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 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 P was determined to be 9.2 days (median). Fibrogammin P 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 P has not been reported to be associated with embryo foetal toxicity, oncogenic or mutagenic potential. 7

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 P 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 P 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. 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. 7. MARKETING AUTHORISATION HOLDER CSL Behring GmbH, Emil von Behring Strasse 76, 35041 Marburg, Germany 8. MARKETING AUTHORISATION NUMBER(S) PL 15036/0006 9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 22 June 1998 / 30 October 2003 10. DATE OF REVISION OF THE TEXT 8

Fibrogammin P 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 P is less effective than usual, contact your doctor or haemophilia centre immediately. 5. STORING FIBROGAMMIN P Store in a fridge at 2 C to 8 C in the original packaging. Do not freeze. Keep out of the sight and reach of children. Do not use Fibrogammin P after the expiry date on the carton. 6. FURTHER INFORMATION What Fibrogammin P 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 October 2012. For further information contact CSL Behring UK Limited, Hayworth House, Market Place, Haywards Heath, West Sussex RH16 1DB, UK Telephone number: 01444 447 405

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