The Value of the Black Box Warning in Dermatology

July 2015 | Volume 14 | Issue 7 | Editorials | 660 | Copyright © July 2015


Laura Winterfield MD MPH,a Ruth Ann Vleugels MD MPH,b and Kelly K. Park MD MSLa

aDivision of Dermatology, Loyola University Stritch School of Medicine, Maywood, IL
bDepartment of Dermatology, Brigham and Women's Hospital, Boston, MA

  1. Buckley NA, Rossi S. Bringing greater transparency to "black box" warnings. Clin Toxicol (Phila). 2011;49:448-51.
  2. O'Connor NR. FDA boxed warnings: how to prescribe drugs safely. Am Family Physician. 2010;81:298-303.
  3. Lasser KE, Allen PD, Woolhandler SJ, Himmelstein DU, Wolfe SM, Bor DH. Timing of new black box warnings and withdrawals for prescription medications. JAMA. 2002;287:2215-20.
  4. Ring J, Mohrenschlager M, Henkel V. The US FDA 'black box' warning for topical calcineurin inhibitors: an ongoing controversy. Drug Saf. 2008;31:185-98.
  5. Botox® (botulinum toxin A) [package insert]. Irvine, CA: Allergan. 2015, April.
  6. Drug Lookup. Epocrates, Inc. 2015. (Accessed April 22, 2015, at https://online.epocrates.com/noFrame/).
  7. Matlock A, Allan N, Wills B, Kang C, Leikin JB. A continuing black hole? The FDA boxed warning: an appeal to improve its clinical utility. Clin Toxicol (Phila). 2011;49:443-7.
  8. Guidance for Industry. October 2011. (Accessed April 22, 2015, at http://www.fda.gov/downloads/drugs/GuidanceComplianceRegulatoryInformation/Guidances/ ucm075096.pdf.)
  9. Ormerod AD. Topical tacrolimus and pimecrolimus and the risk of cancer: how much cause for concern? Br J Dermatol. 2005;153:701-5.
  10. Liang BA. FDA use of the black box warning: time for reevaluation as a safety tool. J Clin Anesth. 2002;14:561-3.
  11. Cook DM, Gurugubelli RK, Bero LA. Risk management policy and black-box warnings: a qualitative analysis of US FDA proceedings. Drug Saf. 2009;32:1057-66.
  12. Panagiotou OA, Contopoulos-Ioannidis DG, Papanikolaou PN, Ntzani EE, Ioannidis JP. Different black box warning labeling for same-class drugs. J Gen Intern Med. 2011;26:603-10.
  13. Murphy MD, Ogle CA, Bertz SH. Opening the 'black box': oscillations in organocuprate conjugate addition reactions. Chem Commun (Camb). 2005:854-6.
  14. Willy ME, Li Z. What is prescription labeling communicating to doctors about hepatotoxic drugs? A study of FDA approved product labeling. Pharmacoepidemiol Drug Saf. 2004;13:201-6.
  15. Lal R, Kremzner M. Introduction to the new prescription drug labeling by the Food and Drug Administration. Am J Health Syst Pharm. 2007;64:2488-94.
  16. Wang LM, Wong M, Lightwood JM, Cheng CM. Black box warning contraindicated comedications: concordance among three major drug interaction screening programs. Ann Pharmacother. 2010;44:28-34.
  17. Guidance for Industry Development and Use of Risk Minimization Action Plans. 2005. (Accessed April 22, 2015, at http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM126830.pdf.)
  18. Weatherby LB, Nordstrom BL, Fife D, Walker AM. The impact of wording in "Dear doctor" letters and in black box labels. Clin Pharmacol Ther. 2002;72:735-42.
  19. Food and Drug Administration Amendments Act of 2007. (Accessed April 22, 2015, at http://www.gpo.gov/fdsys/pkg/PLAW-110publ85/html/PLAW-110publ85.htm.)
  20. Sec. 505-1. [21 USC §355-1] Risk evaluation and mitigation strategies. (Accessed April 22, 2015, at https://www.law.cornell.edu/uscode/text/21/355-1.)
  21. Mullady RG. Everything you needed and wanted to know about black boxed warnings. Defense Counsel J, 2001; 68:50-64.
  22. Fuller JM. Drug stung by rivals, new label; competitors moved in as warning was added to Seldane. Kan City Star. 1996 May 30: B1.
  23. Appendix G. Risk Intervention Examples. (Accessed April 22, 2015, at http://www.fda.gov/Safety/SafetyofSpecificProducts/ucm180605.htm.)
  24. Siegfried EC, Jaworski JC, Hebert AA. Topical calcineurin inhibitors and lymphoma risk: evidence update with implications for daily practice. Am J Clin Derm. 2013;14:163-78.
  25. Johnson & Johnson Organization v. Karl. (Accessed April 22, 2015 at http://www.courtswv.gov/supreme-court/docs/spring2007/33211.pdf.)
  26. Ceilley R, Eisenthal A. The unintended effects of a boxed warning. J Clin Aesthet Dermatol. 2009;2:33-9.
  27. Berger TG, Duvic M, Van Voorhees AS, VanBeek MJ, Frieden IJ. The use of topical calcineurin inhibitors in dermatology: safety concerns. Report of the American Academy of Dermatology Association Task Force. J Am Acad Dermatol. 2006;54:818-23.
  28. Parakkal D, Sifuentes H, Semer R, Ehrenpreis ED. Hepatosplenic T-cell lymphoma in patients receiving TNF-alpha inhibitor therapy: expanding the groups at risk. Eur J Gastroenterol Hepatol. 2011;23:1150-6.
  29. Lopez-Olivo MA, Tayar JH, Martinez-Lopez JA, et al. Risk of malignancies in patients with rheumatoid arthritis treated with biologic therapy: a meta-analysis. JAMA. 2013;308:898-908.
  30. Postmarket Drug Safety Information for Patients and Providers. (Accessed April 22, 2015 at http://www.fda.gov/drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders/ default.htm.)
  31. Yu DT, Seger DL, Lasser KE, et al. Impact of implementing alerts about medication black-box warnings in electronic health records. Pharmacoepidemiol Drug Saf. 2011;20:192-202.
  32. Lasser KE, Seger DL, Yu DT, et al. Adherence to black box warnings for prescription medications in outpatients. Arch Intern Med. 2006;166:338-44.

AUTHOR CORRESPONDENCE