Pharmacokinetics and safety of fibrinogen concentrate

Abstract

Summary. Background: Although fibrinogen concentrate has been available for the treatment of congenital fibrinogen deficiency for years, knowledge of its pharmacokinetics comes from only two small studies. Objectives: To assess the pharmacokinetic (PK) profile, clot integrity and safety of fibrinogen concentrate (human) (FCH) in patients with afibrinogenemia. Patients and methods: A multinational, prospective, open-label, uncontrolled study of patients with afibrinogenemia ‡ 6 years of age was conducted in the USA and Italy. Plasma was collected before and after infusion for PK analyses and evaluation by rotational thromboelastometry of maximum clot firmness (MCF) to assess clot integrity. Safety was assessed on the basis of adverse events and laboratory parameters. Results: After a single dose of 70 mg kg )1 body weight (b.w.)FCH in 14 patients, median incremental in vivo recovery was a 1.7 mg dL )1 increase per mg kg )1 b.w., and median levels were 1.3 g L )1 for fibrinogen activity and antigen 1 h after infusion.Median half-life (t 1/2 ) was 77.1 h for fibrinogen activity and 88.0 h for antigen. Plasma recovery in children < 16 years old was similar to that in adults aged 16 to < 65 years, but the t 1/2 and area under the curve were decreased, with an increased steady-state volume and clearance. MCF increased by a mean of 8.9 mm from baseline to 1 h after infusion of FCH (P < 0.0001). All four adverse events reported were mild, and none was serious or related to study drug. Conclusions: These PK findings confirm a rapid increase in plasma fibrinogen levels after infusion with FCH. Together with the clot integrity and safety data and published data on efficacy, the results support the idea that FCH substitution can restore hemostasis with a good safety profile.

Effects of Fibrinogen Concentrate as First-line Therapy during Major Aortic Replacement Surgery

“…Nevertheless, the lack of conclusive between-group differences in safety is consistent with the previously reported safety of fibrinogen concentrate, including a very low risk of thromboembolic complications 26 and an excellent margin of virus safety. 27 Four patients in the fibrinogen concentrate group underwent reoperation compared with one in the placebo group. Surgical bleeding was identified in all five of these cases.…”

Introduction of an algorithm for ROTEM-guided fibrinogen concentrate administration in major obstetric haemorrhage

“…Fibrinogen concentrate (Haemocomplettan â P; CSL Behring GmBH, Marburg, Germany) has been extensively and exclusively used in place of cryoprecipitate in major obstetric haemorrhage protocols in various countries across Europe for many years, because of its improved safety profile [11][12][13]. It is a pasteurised, freeze-dried product that is readily and quickly available for treatment, without the need for thawing or crossmatch.…”

Observational study of fibrinogen concentrate in massive hemorrhage

“…There are primarily two reasons for this. First, being a procoagulatory drug, a major concern is that its administration could cause thromboembolic complications and there are limited data published addressing this topic [25,26]. Second, it is unclear how much fibrinogen concentrate has to be administered in an acute setting to effectively raise plasma levels due to a striking paucity of evidence given in various guidelines [5,6].…”