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CC BY-NC-ND 4.0 · Thromb Haemost 2025; 125(01): 046-057
DOI: 10.1055/s-0044-1788305
Coagulation and Fibrinolysis

Long-Term Safety of a Four-Factor Prothrombin Complex Concentrate (Kcentra®/Beriplex® P/N): An Updated Pharmacovigilance Review

Truman J. Milling
1   Department of Clinical Sciences, Tilman J. Fertitta Family College of Medicine, University of Houston, Houston, Texas, United States
,
Anna Voronov
2   CSL Behring Australia Pty Ltd, Melbourne, Victoria, Australia
,
Dirk S. Schmidt
3   CSL Behring GmbH, Marburg, Germany
,
Edelgard Lindhoff-Last
4   Cardiology Angiology Center Bethanien, CCB Coagulation Research Center, Frankfurt, Germany
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Abstract

Introduction Four-factor prothrombin complex concentrate (4F-PCC) is recommended for vitamin K antagonist reversal in patients with major bleeding or in need of surgery. The most important risk associated with the use of 4F-PCC is the occurrence of thromboembolic events (TEEs). In this review, we aim to evaluate the safety profile of a 4F-PCC (Kcentra®/Beriplex® P/N; CSL Behring, Marburg, Germany) by reviewing pharmacovigilance data.

Methods A retrospective analysis of postmarketing pharmacovigilance data of Kcentra®/Beriplex® P/N from February 1996 to April 2022 was performed and complemented by a review of clinical studies published between January 2012 and April 2022.

Results A total of 2,321,443 standard infusions of Kcentra®/Beriplex® P/N were administered during the evaluation period. Adverse drug reactions (ADRs) were reported in 614 cases (∼1 per 3,781 standard infusions) and 233 of these cases (37.9%) experienced suspected TEEs related to 4F-PCC (∼1 per 9,963 standard infusions); most of these cases had pre-existing or concomitant conditions likely to be significant risk factors for thrombosis. TEE rates were similar when 4F-PCC was used on-label or off-label for direct oral anticoagulant-associated bleeding. Thirty-six cases (5.9%) reported hypersensitivity type reactions (∼1 per 64,485 standard infusions). No confirmed case of viral transmission related to 4F-PCC use was reported. The published literature also revealed a favorable safety profile of 4F-PCC.

Conclusion Analysis of postmarketing pharmacovigilance safety reports demonstrated that treatment with 4F-PCC was associated with few ADRs and a low rate of TEEs across multiple indications and settings, thus confirming a positive safety profile of 4F-PCC.

Keywords

four-factor prothrombin complex concentrate - safety - pharmacovigilance - oral anticoagulant reversal

Supplementary Material



Publication History

Received: 01 February 2024

Accepted: 28 May 2024

Article published online:
29 July 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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