Safety of Factor XIII Concentrate: Analysis of More than 20 Years of Pharmacovigilance Data

Abstract

Background: Plasma-derived factor XIII (FXIII) concentrate is an effective treatment for FXIII deficiency. We describe adverse drug reactions (ADRs) reported during pharmacovigilance monitoring of Fibrogammin®/Corifact® and review published safety data. Methods: Postmarketing safety reports recorded by CSL Behring from June 1993 to September 2013 were analyzed. Clinical studies published during the same period were also reviewed. Results: Commercial data indicated that 1,653,450,333 IU FXIII concentrate were distributed over the review period, equivalent to 1,181,036 doses for a 70 kg patient. 75 cases were reported (one/15,700 standard doses or 22,046,000 IU). Reports of special interest included 12 cases of possible hypersensitivity reactions (one/98,400 doses or 137,787,500 IU), 7 with possible thromboembolic events (one/168,700 doses or 236,207,200 IU), 5 of possible inhibitor development (one/236,200 doses or 330,690,100 IU), and 20 of possible pathogen transmission (one/59,100 doses or 82,672,500 IU). 19 pathogen transmission cases involved viral infection; 4 could not be analyzed due to insufficient data, but for all others a causal relationship to the product was assessed as unlikely. A review of published literature revealed a similar safety profile. Conclusion: Assessment of ADRs demonstrated that FXIII concentrate carries a low risk of ADRs across various clinical situations, suggesting a favorable safety profile.

Tailored prophylaxis with rFXIII (NovoThirteen®) in a young girl with severe FXIII deficiency and previous cephalohaematoma

“…Date (dd/mm/yyyy) TA B L E 1 Number of assays performed from the start of prophylaxis with NovoThirteen 80 IU/dL every 8 wk, actual days between two consecutive FXIII infusions, trough level and peak reached at each check patients, 10 which was also confirmed by pharmacovigilance analyses on the use of plasma-derived FXIII. 8 In our case, the peak reached between NovoThirteen ® infusions remained within the safe range throughout. This is the first report on the use of high-dose rFXIII for prophylaxis to prevent bleeding and extend infusion time.…”

“…Although very high post-infusion peaks might predispose to thrombosis, a definitive correlation between high levels of FXIII and venous thromboembolism has not been established yet and the role of different FXIII-A and FXIII-B polymorphisms is still under investigation. 9 Nonetheless, four cases of deep vein thrombosis or pulmonary embolism were reported after administration of plasma-derived FXIII, 8 whereas no thromboembolic events have been described so far during rFXIII treatment. Moreover, elevated FXIII levels also seem to correlate with an increased risk of myocardial infarction and peripheral artery disease, especially in the female F I G U R E 1 Pharmacokinetic profile after administration of rFXIII 50 IU/kg using the Phoenix® WinNonlin® V6.4 (Certara USA Inc, Princeton, NJ, USA) (see also text).…”

Recombinant FXIII (rFXIII-A2) Prophylaxis Prevents Bleeding and Allows for Surgery in Patients with Congenital FXIII A-Subunit Deficiency

“…This has been reported in several patients treated with pdFXIII-containing products. 26 In the current mentor™2 trial as well as in the entire mentor™ trial programme, no patients have developed inhibitors and in the entire mentor™ trial programme only five individuals, all younger than 18 years, have developed transient, non-neutralizing antibodies to rFXIII-A 2 [reviewed in Carcao et al 21 ]. These antibodies have been shown to have no inhibitory activity and the individuals did not experience any AEs or bleeding as a result of or in association with these antibodies.…”

Use of factor concentrates for the management of perioperative bleeding: guidance from the SSC of the ISTH

“…No studies have assessed the efficacy of FXIII supplementation in postpartum hemorrhage. Lastly, FXIII supplementation may increase the risk of thrombotic events, but this potential has not been adequately assessed . To summarize, the benefit of FXIII supplementation on bleeding and transfusion requirement remains unproven in the context of acquired FXIII deficiency.…”