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Off-Label Use of Medication

  • Rita-Marié Jansen

Abstract

The term “off-label” means that a medicine is used for an indication, age group, in a dose, or route other than those specified in the conditions of registration/marketing authorization of the medicine and as reflected in its official labeling. The off-label use of medicine is an important part of mainstream, legitimate medical practice worldwide and accounts for an estimated 21 % of drug use overall. Medicine is generally used off-label because effective, approved drugs are scarce or are not available. It can vary between state-of-the-art treatment, standard practice, innovative use, and a “last resort.” Off-label prescription raises important questions about efficacy and safety; therefore, the benefits should be carefully balanced against the risks. This chapter gives an overview of the current regulatory framework regarding medicines and its impact on the off-label use of medication; considers the therapeutic areas where off-label use frequently occurs; outlines the legal position of prescribers; reviews the different perspectives regarding the dissemination of information on off-label use; and provides general guidance to prescribers considering off-label use.

Keywords

European Union European Medicine Evaluation Agency Current Regulatory Framework Official Label Medical Journal Article 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Raine JM. Off-label use of medicines: legal aspects. In: Thomsen HS, Webb JAW, editors. Contrast media: safety issues and ESUR guidelines. 2nd ed. Berlin: Springer; 2009.Google Scholar
  2. 2.
    Jansen R-M. Dissemination of information on the off-label (unapproved) use of medication: a comparative analysis. Med Law. 2011;30:115–32.PubMedGoogle Scholar
  3. 3.
    Levêque D. Off-label use of anticancer drugs. Lancet Oncol. 2008;9:1102–7.PubMedCrossRefGoogle Scholar
  4. 4.
    Strauss SA. “Off-label” use of medicine: some legal and ethical implications. SA Pract Manag. 1998;19(1):12–9.Google Scholar
  5. 5.
    O’Reilly J, Dalal A. Off-label or out of bounds? Prescriber and marketer liability for unapproved uses of FDA-approved drugs. Ann Health Law. 2003;12:295–324.PubMedGoogle Scholar
  6. 6.
    Blondon K, Desmeules J, Vogt-Ferrier N, et al. Off-label prescribing. Rev Med Suisse. 2008;4(165):1661–5.PubMedGoogle Scholar
  7. 7.
    Dresser R, Frader J. Off-label prescribing: a call for heightened professional and government oversight. J Law Med Ethics. 2009;37(3):476–86.PubMedCrossRefGoogle Scholar
  8. 8.
    Gillick MR. Controlling off-label medication use. Ann Intern Med. 2009;150(5):344–7.PubMedCrossRefGoogle Scholar
  9. 9.
    Pharmaceutical Product Development 2008. Safety trends in drug regulation and their implications. P4. www.ppdi.com. Accessed 18 June 2010.
  10. 10.
    Niederauer HH. Off-label prescription of drugs in the statutory health insurance. Gesundheitswesen. 2010;72(2):116–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Gazarian M, et al. Off-label use of medicines: consensus recommendations for evaluating appropriateness. Med J Aust. 2006;185(10):544–8.PubMedGoogle Scholar
  12. 12.
    Kalb PE, Greenberg PE. Legal and economic perspectives concerning US government investigations of off-label promotion by drug manufacturers. Pharmacoeconomics. 2009;27(8):623–5.PubMedCrossRefGoogle Scholar
  13. 13.
    Casali PG. The off-label use of drugs in oncology: a position paper by the European Society for Medical Oncology (ESMO). Ann Oncol. 2007;18:1923–5.PubMedCrossRefGoogle Scholar
  14. 14.
    Ladewski LA, Belknap SM, Nebeker JR, et al. Dissemination of information on potentially fatal adverse drug reactions for cancer drugs from 2000 to 2002: first results from the research on adverse drug events and report projects. J Clin Oncol. 2003;21:3859–66.PubMedCrossRefGoogle Scholar
  15. 15.
    Lindell-Osuagwu L, Korhonen MJ, Saano S, et al. Off-label and unlicensed drug prescribing in three paediatric wards in Finland and review of the international literature. Clin Pharm Ther. 2009;34(3):277–87.Google Scholar
  16. 16.
    Choonara I, Conroy S. Unlicensed and off-label drug use in children: implications for safety. Drug Saf. 2002;25(1):1–5.PubMedCrossRefGoogle Scholar
  17. 17.
    Bradford GE, Elben CC. The drug package insert and the PDR as establishing the standard of care in prescription drug liability cases. J Mo Bar. 2001;57(5):233–42.Google Scholar
  18. 18.
    Jansen R-M, Gouws C. Clinical, legal and ethical implications of the intra-ocular (off-label) use of bevacizumab (Avastin) – a South African perspective. SAMJ. 2009;99(6):446–9.PubMedGoogle Scholar
  19. 19.
    Royal College of Ophthalmologists. The intravitreal use of bevacizumab (Avastin) in age-related macular degeneration. 2009. www.rcophth.ac.uk/core/core/_picker/download.asp?id+175. Accessed 3 Aug 2011.
  20. 20.
    South African Vitreoretinal Society (SAVRS). Motivation for the off label use of bevacizumab (Avastin) and triamcinolene acetate (Kenalog) as intravitreal injections. http://www.ossa.co.za. Accessed 23 Oct 2008.
  21. 21.
    Steinbrook R. The price of sight – ranibizumab, bevacizumab, and the treatment of macular degeneration. N Engl J Med. 2006;355(14):1409–12.PubMedCrossRefGoogle Scholar
  22. 22.
    Rosenfeld PJ. Intravitreal Avastin: the low cost alternative to Lucentis? Am J Ophthalmol. 2006;142(1):141–3.PubMedCrossRefGoogle Scholar
  23. 23.
    Tolentino M. Systemic and ocular safety of intravitreal anti-VEGF therapies for ocular neovascular disease. Surv Opthalmol J Ophthalmol. 2011;56(2):95–113.CrossRefGoogle Scholar
  24. 24.
    Mehlman MJ. Off-label prescribing. http://www.thedoctorwillseeyounow.com/articles/bioethics/offlabel_11/. Accessed 9 Sept 2010.
  25. 25.
    Van Wyk v Lewis 1924 AD 438, 444.Google Scholar
  26. 26.
    Richardson v. Miller 44 S.W.3d 1 13, n.11 (Tenn. Ct. App. 2000).Google Scholar
  27. 27.
    Radley DC, Finkelstein SN, Stafford RS. Off-label prescribing among office-based physicians. Arch Intern Med. 2006;166:1020–6.CrossRefGoogle Scholar
  28. 28.
    Chen DT, Wynia MK, Moloney RM, Alexander C. U.S. physician knowledge of FDA-approved indications and evidence base for commonly prescribed drugs: Results of a national survey. Pharmacoepidemiol Drug Saf. 2009;18:1094–1100.PubMedCrossRefGoogle Scholar
  29. 29.
    Rheingold PD, Rheingold DB. Offence or defence? Managing the off-label use claim. Trial. 2001. p. 52–57.Google Scholar
  30. 30.
    Durr v ABSA Bank Ltd 1997 3 SA 448 (SCA).Google Scholar
  31. 31.
    Alvaraz v. Smith 714 So.2d 652 (Fla.Ct. App 1998).Google Scholar
  32. 32.
    Young K. Will everyone get their best medicine? Implications for off-label use of pharmaceuticals in an American universal healthcare regime. St Louis Univ J Health Law Policy. 2009;2:233–63.Google Scholar
  33. 33.
    Food and Drug Administration. Guidance for industry: Good reprint practices for the distribution of medical journal articles and medical or scientific reference publications on unapproved new uses of approved drugs and approved or cleared medical devices. 2009. http://www.fda.gov/oc/op/goodreprint.html. (Accessed 18 June 2010).
  34. 34.
    Life Sciences Health Industry. Review of Final FDA Guidance on Off-label Use Publications. ReedSmith; 2009. http:www.lifescienceslegalupdate.com/2009/01/articles/regulatory-developments/review-of-final-fda-guidance-on-offlabel-use-publications. Accessed 12 Feb 2013.
  35. 35.
    Stafford RS. Regulating off-label drug use – rethinking the role of the FDA. N Engl J Med. 2008;358:1427–9.PubMedCrossRefGoogle Scholar
  36. 36.
    Rifkees SA. Should off-label drug use be off-the-table? J Pediatr Endocrinol Metab. 2007;20(2):171–2.Google Scholar
  37. 37.
    Quinn E. The Obama administration’s aggressive push to regulate off-label drug promotion. http://www.quinnemanuel.com/news/article-february-2010-the-obama-administration. Accessed 29 May 2010.
  38. 38.
    Life Sciences Health Industry. Commentary: FDA’s new good reprint practice rule. ReedSmith, 2009. http:www.lifescienceslegalupdate.com/2009/01/articles/regulatory-developments/commentary-fds-new-good-reprint-practice-rule/. Accessed 12 Feb 2013.
  39. 39.
    Ray W, Stein CM. Reform of drug regulation – beyond an independent drug-safety board. N Engl J Med. 2006;354(2):194–201.PubMedCrossRefGoogle Scholar
  40. 40.
    Abbott FM, Dukes G. Global pharmaceutical policy. Cheltenham: Edward Elgar; 2009. p. 171–2.Google Scholar
  41. 41.
    Largent EA, Miller FG, Pearson SD. Going off-label without venturing off-course. Arch Intern Med. 2009;169(19):1745–7.PubMedCrossRefGoogle Scholar
  42. 42.
    Mühlbauer B, Janhsen K, Pichler J, Schoettler P. Off-label use of prescription drugs in childhood and adolescence – an analysis of prescription patterns in Germany. Dtsch Arztebl Int. 2009;106(12):210.Google Scholar
  43. 43.
    Bird JR. Package inserts for prescription drugs as evidence in medical malpractice suits. Univ Chic Law Rev. 1977;44:398–450.CrossRefGoogle Scholar
  44. 44.
  45. 45.
    NHS Survey. Recommendations to prescribers on the use of unlicensed medicines and licensed medicines for unlicensed indications. March 2010.Google Scholar
  46. 46.
    De Decker R, Gordan-Graham E, Seller N, Lawrenson J. Surprises of off-label drug use – where had all the Prostin gone? SAMJ. 2009;99(6):438–9.Google Scholar
  47. 47.
    Alexander GC. Clinical prescribing (and off-label use) in a second best world. Am Public Health Assoc: Med Care. 2010;48(4):285–7.Google Scholar
  48. 48.
    Bazzano AFT, Mangione-Smith R, Schonlau M, et al. Off-label prescribing to children in the United States outpatient setting. Acad Pediatr. 2009;9(2):81–8.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Department of Private LawUniversity of the Free StateBloemfonteinSouth Africa

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