Adverse Events Associated with Use of Digoxin Immune Fab Reported to the US Food and Drug Administration Adverse Event Reporting System, 1986–2019
Tóm tắt
Digoxin immune fab products, DigiBind and DigiFab, are antidotes for the treatment of patients with life-threatening or potentially life-threatening digoxin toxicity or overdose. Although approved by the US Food and Drug Administration (FDA) in 1986 (DigiBind) and 2001 (DigiFab), there remains a paucity of literature describing the safety of these products in the postmarketing setting. We sought to assess US adverse event (AE) reports submitted to the FDA Adverse Event Reporting System (FAERS) for DigiBind and DigiFab in the postmarketing period. We searched reports for DigiBind and DigiFab submitted from the time of each product approval through December 31, 2019. Descriptive statistics were used to assess AE reports for DigiBind and DigiFab. Empirical Bayes geometric means (EBGMs) and their 90% confidence intervals were computed to identify disproportionate (i.e., at least twice the expected) reporting of DigiBind and DigiFab. Reports describing selected AEs and death outcomes were individually reviewed. A total of 78 DigiBind and 43 DigiFab reports were identified, of which 68 DigiBind (87.2%) and 27 DigiFab (62.8%) reports were serious. Among the most frequently reported AEs for both products [DigiBind, DigiFab, respectively] were cardiac (bradycardia [3.8%, 3.9%], cardiac arrest [3.3%, 3.9%], and hypotension [2.4%, 2.6%]) and non-cardiac (nausea [1.9%, 2.6%] and hyperkalemia [1.4%, 1.9%]) events. These AEs were labeled events or confounded by indication for use (digoxin toxicity). Nineteen (24.4%) DigiBind and 13 (30.2%) DigiFab reports described an outcome of death, of which seven (53.8%) DigiFab reports were attributed to poisoning with non-digoxin cardiac glycosides. No deaths could be attributed to DigiBind or DigiFab administration. Our analysis did not identify new safety concerns for DigiBind or DigiFab. Most AEs reported were labeled events or confounded by indication for use.
Tài liệu tham khảo
U.S. Food and Drug Administration. DigiFab (Digoxin Immune Fab [Ovine]).
https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/digifab
. Accessed 20 July 2020.
citation_journal_title=Proc Natl Acad Sci USA; citation_title=Digoxin-specific antibodies; citation_author=VP Butler, JP Chen; citation_volume=57; citation_issue=1; citation_publication_date=1967; citation_pages=71-78; citation_doi=10.1073/pnas.57.1.71; citation_id=CR2
citation_journal_title=N Engl J Med.; citation_title=Reversal of advanced digoxin intoxication with Fab fragments of digoxin-specific antibodies; citation_author=TW Smith, E Haber, L Yeatman, VP Butler; citation_volume=294; citation_issue=15; citation_publication_date=1976; citation_pages=797-800; citation_doi=10.1056/NEJM197604082941501; citation_id=CR3
citation_journal_title=J Am Osteopath Assoc.; citation_title=Treatment of chronically digoxin-poisoned patients with a newer digoxin immune fab—a retrospective study; citation_author=TH Schaeffer, SL Mlynarchek, CF Stanford, J Delgado, CP Holstege, D Olsen; citation_volume=110; citation_issue=10; citation_publication_date=2010; citation_pages=587-592; citation_id=CR4
citation_journal_title=Ther Drug Monit.; citation_title=Comparison of the pharmacokinetics and in vivo bioaffinity of DigiTAb versus Digibind; citation_author=SB Ward, L Sjostrom, MR Ujhelyi; citation_volume=22; citation_issue=5; citation_publication_date=2000; citation_pages=599-607; citation_doi=10.1097/00007691-200010000-00016; citation_id=CR5
citation_journal_title=N Engl J Med.; citation_title=Emergency hospitalizations for adverse drug events in older Americans; citation_author=DS Budnitz, MC Lovegrove, N Shehab, CL Richards; citation_volume=365; citation_issue=21; citation_publication_date=2011; citation_pages=2002-2012; citation_doi=10.1056/NEJMsa1103053; citation_id=CR6
citation_journal_title=Clin Toxicol (Phila).; citation_title=Digoxin-specific antibody fragments in the treatment of digoxin toxicity; citation_author=BS Chan, NA Buckley; citation_volume=52; citation_issue=8; citation_publication_date=2014; citation_pages=824-836; citation_doi=10.3109/15563650.2014.943907; citation_id=CR7
US Food and Drug Administration. Questions and answers on FDA’s adverse event reporting system.
https://www.fda.gov/drugs/surveillance/fda-adverse-event-reporting-system-faers
. Accessed 26 May 2020.
MedDRA. Introductory Guide: MedDRA version 20.1.
https://www.meddra.org/sites/default/files/guidance/file/intguide_20_1_english_0.pdf
. Published September 2017. Accessed 21 May 2020.
citation_journal_title=Drug Saf.; citation_title=vigiGrade: a tool to identify well-documented individual case reports and highlight systematic data quality issues; citation_author=T Bergvall, GN Noren, M Lindquist; citation_volume=37; citation_issue=1; citation_publication_date=2014; citation_pages=65-77; citation_doi=10.1007/s40264-013-0131-x; citation_id=CR10
US Government Publishing Office. Postmarketing reporting of adverse experiences. 21 CFR section 600.80.
https://www.govinfo.gov/app/details/CFR-2018-title21-vol7/CFR-2018-title21-vol7-sec600-80
. Published April 1, 2018. Accessed 18 July 2020.
citation_journal_title=Pharmacotherapy; citation_title=Atypical antipsychotics and pituitary tumors: a pharmacovigilance study; citation_author=A Szarfman, JM Tonning, JG Levine, PM Doraiswamy; citation_volume=26; citation_issue=6; citation_publication_date=2006; citation_pages=748-758; citation_doi=10.1592/phco.26.6.748; citation_id=CR12
citation_journal_title=Am Stat; citation_title=Bayesian data mining in large frequency tables, with an application to the FDA spontaneous reporting system; citation_author=W DuMouchel; citation_volume=53; citation_publication_date=1999; citation_pages=177-190; citation_id=CR13
citation_journal_title=Drug Saf.; citation_title=Use of screening algorithms and computer systems to efficiently signal higher-than-expected combinations of drugs and events in the US FDA's spontaneous reports database; citation_author=A Szarfman, SG Machado, RT O'Neill; citation_volume=25; citation_issue=6; citation_publication_date=2002; citation_pages=381-392; citation_doi=10.2165/00002018-200225060-00001; citation_id=CR14
Office of the Federal Register and the Government Publishing Office. Electronic Code of Federal Regulations.
https://www.ecfr.gov/cgi-bin/retrieveECFR?gp=&SID=83cd09e1c0f5c6937cd9d7513160fc3f&pitd=20180719&n=pt45.1.46&r=PART&ty=HTML#se45.1.46_1104
. Accessed 25 May 2020.
citation_journal_title=JACC Heart Fail.; citation_title=Temporal trends of digoxin use in patients hospitalized with heart failure: analysis from the American Heart Association Get With The Guidelines-Heart Failure Registry; citation_author=N Patel, C Ju, C Macon, U Thadani, PJ Schulte, AF Hernandez; citation_volume=4; citation_issue=5; citation_publication_date=2016; citation_pages=348-356; citation_doi=10.1016/j.jchf.2015.12.003; citation_id=CR16
citation_journal_title=JACC Heart Fail.; citation_title=Digoxin toxicity and use of digoxin immune fab: insights from a national hospital database; citation_author=PJ Hauptman, SW Blume, EF Lewis, S Ward; citation_volume=4; citation_issue=5; citation_publication_date=2016; citation_pages=357-364; citation_doi=10.1016/j.jchf.2016.01.011; citation_id=CR17
citation_journal_title=Circulation; citation_title=Treatment of 150 cases of life-threatening digitalis intoxication with digoxin-specific Fab antibody fragments. Final report of a multicenter study; citation_author=EM Antman, TL Wenger, VP Butler, E Haber, TW Smith; citation_volume=81; citation_issue=6; citation_publication_date=1990; citation_pages=1744-1752; citation_doi=10.1161/01.cir.81.6.1744; citation_id=CR18
citation_journal_title=J Am Coll Cardiol.; citation_title=Digoxin Immune Fab therapy in the management of digitalis intoxication: safety and efficacy results of an observational surveillance study; citation_author=AR Hickey, TL Wenger, VP Carpenter, HH Tilson, MA Hlatky, CD Furberg; citation_volume=17; citation_issue=3; citation_publication_date=1991; citation_pages=590-598; citation_doi=10.1016/s0735-1097(10)80170-6; citation_id=CR19
citation_journal_title=J Toxicol Clin Toxicol.; citation_title=Digoxin specific antibody (Fab) fragments in 34 cases of severe digitalis intoxication; citation_author=A Smolarz, E Roesch, E Lenz, H Neubert, P Abshagen; citation_volume=23; citation_issue=4–6; citation_publication_date=1985; citation_pages=327-340; citation_doi=10.3109/15563658508990641; citation_id=CR20
citation_journal_title=Ann Intern Med.; citation_title=Influence of digoxin immune Fab therapy and renal dysfunction on the disposition of total and free digoxin; citation_author=MR Ujhelyi, S Robert, DM Cummings, RD Colucci, PJ Green, J Sailstad; citation_volume=119; citation_issue=4; citation_publication_date=1993; citation_pages=273-277; citation_doi=10.7326/0003-4819-119-4-199308150-00004; citation_id=CR21
citation_journal_title=Trop Med Int Health.; citation_title=Epidemic of self-poisoning with seeds of the yellow oleander tree (Thevetia peruviana) in northern Sri Lanka; citation_author=M Eddleston, CA Ariaratnam, WP Meyer, G Perera, AM Kularatne, S Attapattu; citation_volume=4; citation_issue=4; citation_publication_date=1999; citation_pages=266-273; citation_doi=10.1046/j.1365-3156.1999.00397.x; citation_id=CR22
citation_journal_title=J Emerg Med.; citation_title=Cardiac toxicity from intentional ingestion of pong-pong seeds (Cerbera odollam); citation_author=ME Wermuth, R Vohra, N Bowman, RB Furbee, DE Rusyniak; citation_volume=55; citation_issue=4; citation_publication_date=2018; citation_pages=507-511; citation_doi=10.1016/j.jemermed.2018.05.021; citation_id=CR23
citation_journal_title=Ann Emerg Med.; citation_title=Oleander poisoning: treatment with digoxin-specific Fab antibody fragments; citation_author=GM Shumaik, AW Wu, AC Ping; citation_volume=17; citation_issue=7; citation_publication_date=1988; citation_pages=732-735; citation_doi=10.1016/s0196-0644(88)80625-5; citation_id=CR24
citation_journal_title=Chest; citation_title=Treatment of toad venom poisoning with digoxin-specific Fab fragments; citation_author=JR Brubacher, PR Ravikumar, T Bania, MB Heller, RS Hoffman; citation_volume=110; citation_issue=5; citation_publication_date=1996; citation_pages=1282-1288; citation_doi=10.1378/chest.110.5.1282; citation_id=CR25
citation_journal_title=Clin Chim Acta.; citation_title=The Fab fragment of anti-digoxin antibody (digibind) binds digitoxin-like immunoreactive components of Chinese medicine Chan Su: monitoring the effect by measuring free digitoxin; citation_author=A Dasgupta, AE Lopez, A Wells, M Olsen, J Actor; citation_volume=309; citation_issue=1; citation_publication_date=2001; citation_pages=91-95; citation_doi=10.1016/s0009-8981(01)00499-5; citation_id=CR26
citation_journal_title=Am J Clin Pathol.; citation_title=Neutralization of free digoxin-like immunoreactive components of oriental medicines Dan Shen and Lu-Shen-Wan by the Fab fragment of antidigoxin antibody (Digibind); citation_author=A Dasgupta, KA Szelei-Stevens; citation_volume=121; citation_issue=2; citation_publication_date=2004; citation_pages=276-281; citation_doi=10.1309/93UF-4YEL-EMG9-V548; citation_id=CR27
citation_journal_title=Ann Emerg Med.; citation_title=Near-fatal yew berry intoxication treated with external cardiac pacing and digoxin-specific FAB antibody fragments; citation_author=RO Cummins, J Haulman, L Quan, JR Graves, D Peterson, S Horan; citation_volume=19; citation_issue=1; citation_publication_date=1990; citation_pages=38-43; citation_doi=10.1016/s0196-0644(05)82138-9; citation_id=CR28
citation_journal_title=Ann Pharmacother.; citation_title=Clinical toxicology of yew poisoning; citation_author=AW Labossiere, DF Thompson; citation_volume=52; citation_issue=6; citation_publication_date=2018; citation_pages=591-599; citation_doi=10.1177/1060028017754225; citation_id=CR29
citation_journal_title=Expert Opin Drug Saf.; citation_title=Empirical estimation of under-reporting in the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS); citation_author=YM Alatawi, RA Hansen; citation_volume=16; citation_issue=7; citation_publication_date=2017; citation_pages=761-767; citation_doi=10.1080/14740338.2017.1323867; citation_id=CR30