Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2018 Publisher: CSL Behring GmbH, Emil-von-Behring-Strasse 76, 35041, Marburg, Germany
Pharmacotherapeutic group: Antihaemorrhagics
ATC code: B02BD07
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.
In clinical studies that included subjects with congenital FXIII deficiency <18 years old, the prophylactic administration with Fibrogammin every 28 days was successful in maintaining trough FXIII activity levels of approximately 5% to 20%.
The product is administered intravenously, and is thus immediately bioavailable resulting in a plasma concentration corresponding to the applied dose.
In patients with congenital factor-XIII-deficiency the biological half-life of Fibrogammin was determined to be 6.6 ± 2.29 days (mean ± SD).
Fibrogammin is metabolised in the same way as is the endogenous coagulation factor XIII.
An overview of pharmacokinetic parameters (adult population/18 years and older) is given in the following table:
| Parameters | Median (min-max) |
|---|---|
| AUCss,0-∞ (units/hr/ml) | 182.9 (133.5-300.2) |
| Css,max (units/ml)* | 0.9 (0.6-1.2) |
| Css,min (units/ml)* | 0.07 (0.0-0.16) |
| Tmax (hr) | 1.2 (0.7-4.2) |
| T½ [days] | 7.8 (3.1-11.02) |
| CL [ml/hr/kg] | 0.22 (0.13-0.30) |
| Vss [ml/kg] | 49.4 (31.65-62.91) |
| MRT [days] | 11.7 (5.7-17.02) |
AUCss,(0-∞): Area under the plasma concentration curve from time 0 to infinity at steady state
* 100% activity corresponds to 1 unit/ml
Css,max: Peak concentration at steady state
Css,min: Trough concentration at steady state
Tmax: Time to peak concentration
T½: Half-life
CL: Clearance
Vss: Volume of distribution at steady state
MRT: Mean residence time
Of the 188 unique subjects in the Factor XIII concentrate (human) clinical studies, 117 were subjects <18 years of age at the time of enrolment (1 month to <2 years, n= 17; 2 to <12 years, n=62; 12 to <16 years, n=30; 17 to 18 years, n=8). In the pharmacokinetic study PK 2002, 5 of the 14 subjects ranged in age from 2 to <18 years (2-11 years, n=3; 12-16 years, n=2; 17-18 years, n=0). Subjects less than 16 years had a shorter half-life and faster clearance (half-life: 5.7±1.00 days; clearance: 0.291±0.12 ml/hr/kg) compared to adults (half-life: 7.1 ± 2.74 days, clearance: 0.22 ± 0.07 ml/hr/kg).
The product has a shorter half-life and faster clearance in children compared to adults. However, since across all age groups dosing is individually determined by subject weight and adjusted by trough FXIII activity, no specific age related dosing is needed.
The proteins contained in Fibrogammin are sourced from human plasma and act like human plasma proteins.
Single and repeated dose toxicity studies in animals did not reveal a toxic potential for Fibrogammin.
Studies on reproduction and embryo-foetal development have not been conducted.
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