Document Detail


Safety update on the use of recombinant factor VIIa and the treatment of congenital and acquired deficiency of factor VIII or IX with inhibitors.
MedLine Citation:
PMID:  18684126     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Recombinant factor VIIa (rFVIIa, NovoSeven) has been licensed for treatment of haemophilia with inhibitors in Europe since 1996 and in North America since 1999. Overall, approximately 1.5 million doses have since been administered. Safety data from licensure to April 2003 revealed 25 thromboembolic (TE) adverse events (AE) from over 700 000 doses given, a remarkably low incidence of TE events. Recent reports have cited a higher prevalence of TE events with rFVIIa use, especially when used off-label. This report reviews the TE and fatal events with use of rFVIIa for congenital and acquired haemophilia A or B from May 2003 to December 2006. Approximately 800 000 standard doses of rFVIIa have been administered during this time frame. All clinical trials, spontaneous and solicited reports, as well as a detailed literature review, were included in the data analysis. There were a total of 30 TE events and 6 TE-associated fatal events. Spontaneous reports captured 14/71 (20%) TE/AE and 2/34 TE-associated/total fatal events. From solicited reports, 5/40 (12.5%) were associated with a TE and 1/32 TE-associated fatal events. Literature review revealed 11/19 (58%) TE events and 3/6 TE-associated fatal events. Despite the use of high-dose rFVIIa (270 mug kg(-1)) in some clinical trials and registries, rFVIIa appears safe, when used for congenital and acquired haemophilia. The prevalence of TE associated with rFVIIa use is less than 4/100 000 and a TE-associated fatal event is also extremely rare. However, use of rFVIIa for off-label indications should continue to be monitored closely via clinical trials and carefully designed registries.
Authors:
T Abshire; G Kenet
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Publication Detail:
Type:  Journal Article; Review     Date:  2008-08-04
Journal Detail:
Title:  Haemophilia : the official journal of the World Federation of Hemophilia     Volume:  14     ISSN:  1365-2516     ISO Abbreviation:  Haemophilia     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-10-21     Completed Date:  2008-12-10     Revised Date:  2009-10-21    
Medline Journal Info:
Nlm Unique ID:  9442916     Medline TA:  Haemophilia     Country:  England    
Other Details:
Languages:  eng     Pagination:  898-902     Citation Subset:  IM    
Affiliation:
Aflac Cancer Center and Blood Disorders Service, Emory University, Atlanta, GA, USA. thomas.abshire@emory.edu
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Child
Factor IX / immunology
Factor VIII / immunology
Factor VIIa / adverse effects*,  therapeutic use
Hemophilia A / drug therapy*,  immunology
Hemophilia B / drug therapy*,  immunology
Humans
Isoantibodies / blood
Male
Middle Aged
Recombinant Proteins / adverse effects,  therapeutic use
Thromboembolism / chemically induced
Young Adult
Chemical
Reg. No./Substance:
0/Isoantibodies; 0/Recombinant Proteins; 0/recombinant FVIIa; 9001-27-8/Factor VIII; 9001-28-9/Factor IX; EC 3.4.21.21/Factor VIIa

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