Safety of a pasteurized plasma‐derived Factor VIII and von Willebrand factor concentrate: analysis of 33 years of pharmacovigilance data

Abstract

BACKGROUND Haemate‐P/Humate‐P (Humate‐P) is a pasteurized human plasma‐derived concentrate containing both Factor VIII and von Willebrand factor for treatment of hemophilia A and von Willebrand disease (VWD). STUDY DESIGN AND METHODS We analyzed the safety of Humate‐P based on more than 33 years of postmarketing pharmacovigilance data, representing an estimated exposure of approximately 25,000 patient‐years. The analysis comprises reports of potential adverse drug reactions (ADRs) from all sources, reported as part of routine pharmacovigilance at CSL Behring. ADRs considered clinically relevant or potential risks of Humate‐P were identified based on defined and standardized Medical Dictionary for Regulatory Activities queries. Recognizing the limitations of spontaneous reporting, we also reviewed the literature, including clinical trials with mandatory reporting. RESULTS From 1982 to 2015, a total of 670 postmarketing cases had been reported via pharmacovigilance, for an overall reporting rate of approximately one ADR per 3900 administered standard doses. Of these cases, 343 involved ADRs considered clinically relevant risks (33 thromboembolic complications, 97 inhibitor formation, 110 hypersensitivity or allergic reactions) or potential risks (103 suspected virus transmissions) for Humate‐P. Most thromboembolic complications occurred in patients undergoing surgery or with other known risk factors. Inhibitor formation occurred mostly in patients with hemophilia A (24 cases were high titer). Most patients with hypersensitivity or allergic reactions had VWD. None of the reported suspected virus transmission cases were confirmed to be associated with Humate‐P. Reported results of company‐sponsored studies showed a low incidence of adverse events possibly or probably related to Humate‐P. CONCLUSIONS More than 33 years of pharmacovigilance data continue to support the safety of Humate‐P.

A Systematic Review of Efficacy and Safety of Plasma-Derived von Willebrand Factor/Factor VIII Concentrate (Voncento) in von Willebrand Disease

“…25 Safety data were heterogeneously reported across studies but the rate of SAEs was low with no cases of severe hypersensitivity reactions, in agreement with previous studies with similar products. 24,26 The only TEE reported from 307 clinical trial patients within this review was a DVT, and was classified as unrelated to treatment. 13 Pharmacovigilance data summarized key risks associated with pdVWF/FVIII treatment including development of Anti-FVIII inhibitors (n) 1 0…”

Perioperative hemostasis management in patients with von Willebrand disease: an institutional experience

“…Lethagen et al reported one occurrence of pulmonary embolism; this was in a patient with multiple risk factors and the event resolved without sequelae [20]. A pharmacovigilance study covering 25 000 patient-years of exposure to Haemate P reported low numbers of clinically relevant thromboembolic complications ( n = 33) [32]. Several other concentrates are also available, such as concentrates with a lower concentration of FVIII or lacking this factor altogether, as well as a recombinant concentrate, but these were not used during this study.…”

Managing Pregnant Women with Hemophilia and von Willebrand Disease: How Do We Provide Optimum Care and Prevent Complications?

“…24 The largest experience has been with the VWF containing plasma derived FVIII concentrate, Humate P, while the recombinant VWF product Vonvendi may theoretically be more effective with added 3-6 hours to the half-life, requiring less doses and theoretically less risk of post-partum thrombosis as it does not contain FVIII. 25 Ongoing studies are comparing a conservative management with a more aggressive one aiming to higher target levels and taking into consideration the expansion in blood volume that occurs during pregnancy. 26 Figure 4 depicts management when PPH continues, despite adequate factor replacement usually when there is super-imposed uterine atony or placental abnormalities or uterine, cervical, or vaginal trauma.…”