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Clinical Drug Investigation

, Volume 38, Issue 9, pp 867–872 | Cite as

Botulinum Toxin Type A Overdoses: Analysis of the FDA Adverse Event Reporting System Database

  • Rashid Kazerooni
  • Edward P. Armstrong
Short Communication

Abstract

Introduction

Published literature on overdoses related to botulinum toxin A (BtxA) agents is scarce.

Objective

The aim of this study was to assess the BtxA drug class’ respective agents for associations with overdose.

Methods

United States Food and Drug Administration (FDA) adverse event reporting system (FAERS) database was utilized to search for overdoses. The analysis was conducted on data between second quarter 2014 and third quarter 2017. BtxA cases were included when they were considered the “Primary Suspect” drug. Overdose was defined as presence of ‘overdose’ being reported as an adverse event. Primary outcome was incidence of ‘overdose’ compared within the respective agents. Additionally, a disproportionality analysis was conducted utilizing reporting odds ratio (ROR) versus onabotulinumtoxinA as a referent while controlling for confounding variables.

Results

A total of 3,837,406 unique adverse events were reported during the study period for all drugs in the FAERS database. Of which, 13,078 were BtxA cases. The rate of adverse events involving overdose for abobotulinumtoxinA (20.2%; 215/1065) was significantly higher than both onabotulinumtoxinA (0.4%; 48/11,323; p < 0.0001) and incobotulinumtoxinA (0.1%; 1/690; p < 0.0001). In the regression analysis, abobotulinumtoxinA (ROR 73.26; 95% CI 51.17–104.90) had a significant association with overdose, whereas incobotulinumtoxinA (ROR 0.73; 95% CI 0.10–5.36) did not, versus the referent onabotulinumtoxinA.

Conclusion

The present analysis showed adverse events of abobotulinumtoxinA were significantly associated with overdose versus the other two BtxA agents. Overdose can be difficult to research, particularly for in-clinic administered drugs. Future studies should venture to confirm these results in new and novel ways.

Notes

Compliance with ethical standards

Conflict of interest

Dr. Rashid Kazerooni conducted this analysis as part of an independent graduate research project with the University of Wyoming. Dr Kazerooni was also an employee of Merz North America, Inc. at the time this analysis was conducted. Dr. Kazerooni’s graduate program was partially funded by Merz North America, Inc. via a tuition reimbursement employee benefit program. The comments in the manuscript do not necessarily reflect the views of Merz North America, Inc. Dr. Edward P. Armstrong has nothing to disclose.

Funding

The present study was not funded by extramural sources.

References

  1. 1.
    Ubbink DT, Santema TB, Lapid O. Shared decision-making in cosmetic medicine and aesthetic surgery. Aesthet Surg J. 2016;36(1):NP14-9.CrossRefGoogle Scholar
  2. 2.
    Walker TJ, Dayan SH. Comparison and overview of currently available neurotoxins. J Clin Aesthet Dermatol. 2014;7(2):31–9.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Allergan, Inc. Botox® (onabotulinumtoxinA) prescribing information. 2018. https://www.allergan.com/assets/pdf/botox_pi.pdf. Accessed 10 Mar 2018.
  4. 4.
    Allergan, Inc. Botox Cosmetic® (onabotulinumtoxinA) prescribing information. 2018. https://www.allergan.com/assets/pdf/botox_cosmetic_pi.pdf. Accessed 10 Mar 2018.
  5. 5.
    Ipsen Biopharm Ltd. Dysport® (abobotulinumtoxinA) prescribing information. 2018. https://www.dysport.com/docs/pdfs/Dysport_Full_Prescribing_Information.pdf. Accessed 10 Mar 2018.
  6. 6.
    Merz North America, Inc. Xeomin® (incobotulinumtoxinA) prescribing information. 2018. http://www.xeomin.com/wp-content/uploads/xeomin-full-prescribing-information.pdf. Accessed 10 Mar 2018.
  7. 7.
    Rodriguez EM, Staffa JA, Graham DJ. The role of databases in drug postmarketing surveillance. Pharmacoepidemiol Drug Saf. 2001;10:407–10.CrossRefGoogle Scholar
  8. 8.
  9. 9.
    Fadini GP, Sarangdhar M, Avogaro A. Glucagon-like peptide-1 receptor agonists are not associated with retinal adverse events in the FDA adverse event reporting system. BMJ Open Diabetes Res Care. 2018;6(1):e000475.CrossRefGoogle Scholar
  10. 10.
    US FDA. FDA adverse event reporting system (FAERS): Latest quarterly data files. https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/AdverseDrugEffects/ucm082193.htm. Accessed 10 Mar 2018.
  11. 11.
    MedDRA. https://www.meddra.org/. Accessed 10 Mar 2018.
  12. 12.
    Sakaeda T, Tamon A, Kadoyama K, Okuno Y. Data mining of the public version of the FDA adverse event reporting system. Int J Med Sci. 2013;10(7):796–803.CrossRefGoogle Scholar
  13. 13.
    Bate A, Evans SJ. Quantitative signal detection using spontaneous ADR reporting. Pharmacoepidemiol Drug Saf. 2009;18:427–36.CrossRefGoogle Scholar
  14. 14.
    Hauben M, Reich L. Drug-induced pancreatitis: lessons in data mining. Br J Clin Pharmacol. 2004;58:560–2 [PMC free article].CrossRefGoogle Scholar
  15. 15.
    Almenoff J, Tonning JM, Gould AL, et al. Perspectives on the use of data mining in pharmaco-vigilance. Drug Saf. 2005;28:981–1007.CrossRefGoogle Scholar
  16. 16.
    Almenoff JS, Pattishall EN, Gibbs TG, et al. Novel statistical tools for monitoring the safety of marketed drugs. Clin Pharmacol Ther. 2007;82:157–66.CrossRefGoogle Scholar
  17. 17.
    Hauben M, Bate A. Decision support methods for the detection of adverse events in post-marketing data. Drug Discov Today. 2009;14:343–57.CrossRefGoogle Scholar
  18. 18.
    Humphrey S. Neurotoxins: evidence for prevention. J Drugs Dermatol. 2017;16(6):s87–90.PubMedGoogle Scholar
  19. 19.
    Concato J, Feinstein AR, Holford TR. The risk of determining risk with multivariable models. Ann Intern Med. 1993;118:201–10.CrossRefGoogle Scholar
  20. 20.
    Benecke R, Jost WH, Kanovsky P, Ruzicka E, Comes G, Grafe S. A new botulinum toxin type A free of complexing proteins for treatment of cervical dystonia. Neurology. 2005;64(11):1949–51.CrossRefGoogle Scholar
  21. 21.
    Roggenkämper P, Jost WH, Bihari K, Comes G, Grafe S, NT 201 Blepharospasm Study Team. Efficacy and safety of a new botulinum toxin type A free of complexing proteins in the treatment of blepharospasm. J Neural Transm (Vienna). 2006;113(3):303–12.CrossRefGoogle Scholar
  22. 22.
    Kane MA, Gold MH, Coleman WP 3rd, Jones DH, Tanghetti EA, Alster TS, Rohrer TE, Burgess CM, Shamban AT, Finn E. A Randomized, double-blind trial to investigate the equivalence of incobotulinumtoxinA and onabotulinumtoxinA for glabellar frown lines. Dermatol Surg. 2015;41(11):1310–9.CrossRefGoogle Scholar
  23. 23.
    Sattler G, Callander MJ, Grablowitz D, Walker T, Bee EK, Rzany B, Flynn TC, Carruthers A. Noninferiority of incobotulinumtoxinA, free from complexing proteins, compared with another botulinum toxin type A in the treatment of glabellar frown lines. Dermatol Surg. 2010;36(Suppl 4):2146–54.CrossRefGoogle Scholar
  24. 24.
    Nüssgens Z, Roggenkämper P. Comparison of two botulinum-toxin preparations in the treatment of essential blepharospasm. Graefes Arch Clin Exp Ophthalmol. 1997;235:197–9.CrossRefGoogle Scholar
  25. 25.
    Bentivoglio AR, Fasano A, Ialongo T, Soleti F, Lo Fermo S, Albanese A. Outcome predictors, efficacy and safety of Botox and Dysport in the long-term treatment of hemifacial spasm. Eur J Neurol. 2009;16(3):392–8.CrossRefGoogle Scholar
  26. 26.
    Kerscher M, Roll S, Becker A, Wigger-Alberti W. Comparison of the spread of three botulinum toxin type A preparations. Arch Dermatol Res. 2012;304(2):155–61.CrossRefGoogle Scholar
  27. 27.
    Weber J. Epidemiology of adverse reactions to nonsteroidal anti-inflammatory drugs. Adv Inflamm Res. 1984;6:1–7.Google Scholar
  28. 28.
    Hoffman KB, Dimbil M, Erdman CB, Tatonetti NP, Overstreet BM. The Weber effect and the United States Food and Drug Administration’s Adverse Event Reporting System (FAERS): analysis of sixty-two drugs approved from 2006 to 2010. Drug Saf. 2014;37:283–94.CrossRefGoogle Scholar
  29. 29.
    Rothman KJ, Lanes S, Sacks ST. The reporting odds ratio and its advantages over the proportional reporting ratio. Pharmacoepidemiol Drug Saf. 2004;13:519–23.CrossRefGoogle Scholar
  30. 30.
  31. 31.
    US FDA. FDA adverse event reporting system (FAERS) public dashboard. https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/AdverseDrugEffects/ucm070093.htm. Accessed 10 Mar 2018.

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Medical Affairs, Merz North America, Inc.RaleighUSA
  2. 2.University of Wyoming School of Pharmacy, Health Services Administration Graduate ProgramLaramieUSA

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