FIBROGAMMIN

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. Dosage The dosing regimen should be individualised based on body weight, laboratory values, and the patient’s clinical condition.

Routine prophylaxis dosing schedule for treatment of congenital FXIII deficiency Initial dose • 40 International Units (IU) per kg body weight • The injection rate should not exceed 4 ml per minute. Subsequent dosing • Dosing should be guided by the most recent trough FXIII activity level, with dosing every 28 days (4 weeks) to maintain a trough FXIII activity level of approximately 5 to 20%.

• Recommended dosing adjustments of ± 5 IU per kg should be based on trough FXIII activity levels as shown in Table 1 and the patient’s clinical condition. • Dosing adjustments should be made on the basis of a specific, sensitive assay used to determine FXIII levels.

An example of dose adjustment using the standard Berichrom® FXIII activity assay is outlined in Table 1 below.

Table 1:

Dose adjustment using the Berichrom® FXIII activity assay Factor XIII Activity Trough Level (%) Dosage Change One trough level of <5% Increase by 5 units per kg Trough level of 5% to 20% No change Two trough levels of >20% Decrease by 5 units per kg One trough level of >25% Decrease by 5 units per kg The potency expressed in units is determined using the Berichrom® FXIII activity assay, referenced to the current International Standard for Blood Coagulation Factor XIII, Plasma.

Therefore, a unit is equivalent to an International Unit. Prophylaxis prior to surgery After the patient’s last routine prophylactic dose, if a surgery is scheduled: • Between 21 and 28 days later – administer the patient’s full prophylaxis dose immediately prior to surgery and the next prophylactic dose should be given 28 days later.

• Between 8 and 21 days later – an additional dose (full or partial) may be administered prior to surgery. The dose should be guided by the patient’s FXIII activity levels and clinical condition and should be adjusted according to the half- life of Fibrogammin.

• Within 7 days of last dose – additional dosing may not be needed. Adjustments to dosing may be different from these recommendations and should be individualised, based on FXIII activity levels and the patient’s clinical condition.

All patients should be monitored closely during and after surgery. It is recommended to monitor the increase in FXIII-activity with a FXIII assay. e. 4 IU/ml. Paediatric population The posology and method of administration in children and adolescents is based on body weight and is therefore generally based on the same guidelines as for adults.

The dose and/or frequency of administration for each individual should always be guided by the clinical effectiveness and FXIII activity levels. ) Elderly population The posology and method of administration in elderly people (> 65 years) has not been established in clinical studies.

6. After reconstitution the solution should be clear or slightly opalescent. 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 approximately 4ml per minute. Observe the patient for any immediate reaction. If any reaction takes place that might be related to the administration of Fibrogammin, the rate of infusion should be decreased or the infusion stopped, as required by the clinical condition of the patient.

The following adverse reactions are based on post-marketing experience. Tabulated list of adverse reactions The table presented below is according to the MedDRA system organ classification. Frequencies have been evaluated according to the following convention: 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.

MedDRA Standard System Organ Class Adverse Reaction Frequency Allergoid-anaphylactoid reactions (like generalised urticaria, rash, fall in blood pressure, dyspnoea) RareImmune System Disorders Development of inhibitors to FXIII Very rare General Disorders and Administration Site Conditions Rise in temperature Rare If allergoid-anaphylactoid reactions occur, the administration of Fibrogammin has to be discontinued immediately and an appropriate treatment initiated.

The current medical standards for shock treatment are to be observed. Paediatric population The safety profile for paediatric patients is no different from that of adults in clinical studies. 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 UK Yellow Card Scheme. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store

In 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. Allergic-type hypersensitivity reactions are possible with Fibrogammin.

If symptoms of hypersensitivity (such as hives, generalised urticaria, tightness of the chest, wheezing, hypotension, and anaphylaxis) occur, the Fibrogammin infusion should be discontinued immediately. In case of shock, the current medical standards for shock treatment should be implemented.

In cases of fresh thromboses caution should be exercised on account of the fibrin- stabilising effect of Factor XIII. Immunogenicity Development of inhibitory antibodies against FXIII has been detected in patients receiving Fibrogammin.

Therefore, patients should be monitored for possible development of inhibitory antibodies. The presence of inhibitory antibodies may manifest as an inadequate response to treatment. If expected plasma FXIII activity levels are not attained, or if breakthrough bleeding occurs during prophylaxis, FXIII inhibitory antibody concentrations should be measured.

Note for diabetic patients Fibrogammin contains glucose (24 mg per 250 IU). When administering a dose of 40 IU/kg body weight to a patient with 75 kg body weight, a maximum of 288 mg glucose will be supplied. 8 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. 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.

Appropriate vaccination (hepatitis A and B) should be considered for patients in regular/repeated receipt of human plasma-derived factor XIII products.

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