Skip to main content
SpringerLink
Log in

Fentanyl Formulations in the Management of Pain: An Update

  • Review Article
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Fentanyl is a synthetic, highly selective opioid with many desirable physicochemical properties, including a high lipophilicity and predictable pharmacokinetics. These properties have an established record in the management of pain in a variety of settings, particularly acute pain and breakthrough cancer pain. Fentanyl was initially developed for parenteral use; however, this is invasive and impractical in the outpatient setting. Unfortunately, the high first-pass metabolism of fentanyl makes oral formulations unfeasible. However, its high lipophilicity allows fentanyl to be absorbed via a number of other routes. Thus new formulations were designed to allow non-invasive methods of administration. Transmucosal and transdermal fentanyl formulations are well established, and have proven useful in the settings of breakthrough cancer pain, emergencies and in the paediatric population. The iontophoretic transdermal system was developed to provide a needle-free system of delivering bolus doses of fentanyl on demand, a novel way of delivering patient-controlled opioid analgesia. Transpulmonary administration of fentanyl remains experimental. The aim of this review is to provide an update on current non-parenteral fentanyl formulations, with attention to their particular pharmacokinetics and features relevant to clinical use in pain management.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Stanley TH, Egan TD, Van Aken H. A tribute to Dr. Paul A. J. Janssen: entrepreneur extraordinaire, innovative scientist, and significant contributor to anesthesiology. Anesth Analg. 2008;106(2):451–62. doi:10.1213/ane.0b013e3181605add.

    Article  PubMed  Google Scholar 

  2. Stanley TH. The fentanyl story. J Pain. 2014;15(12):1215–26. doi:10.1016/j.jpain.2014.08.010.

    Article  CAS  PubMed  Google Scholar 

  3. Maguire P, Tsai N, Kamal J, Cometta-Morini C, Upton C, Loew G. Pharmacological profiles of fentanyl analogs at mu, delta and kappa opiate receptors. Eur J Pharmacol. 1992;213(2):219–25.

    Article  CAS  PubMed  Google Scholar 

  4. Peng PW, Sandler AN. A review of the use of fentanyl analgesia in the management of acute pain in adults. Anesthesiology. 1999;90(2):576–99.

    Article  CAS  PubMed  Google Scholar 

  5. Chen C, Gupta A. Clinical and pharmacokinetic considerations of novel formulations of fentanyl for breakthrough cancer pain. Pain Manag. 2014;4(5):339–50. doi:10.2217/pmt.14.32.

    Article  PubMed  Google Scholar 

  6. Lötsch J, Walter C, Parnham MJ, Oertel BG, Geisslinger G. Pharmacokinetics of non-intravenous formulations of fentanyl. Clin Pharmacokinet. 2013;52(1):23–36. doi:10.1007/s40262-012-0016-7.

    Article  PubMed  CAS  Google Scholar 

  7. Henthorn TK, Liu Y, Mahapatro M, Ng KY. Active transport of fentanyl by the blood-brain barrier. J Pharmacol Exp Ther. 1999;289(2):1084–9.

    CAS  PubMed  Google Scholar 

  8. Mather LE. Clinical pharmacokinetics of fentanyl and its newer derivatives. Clin Pharmacokinet. 1983;8(5):422–46.

    Article  CAS  PubMed  Google Scholar 

  9. Mystakidou K, Katsouda E, Parpa E, Vlahos L, Tsiatas ML. Oral transmucosal fentanyl citrate: overview of pharmacological and clinical characteristics. Drug Deliv. 2006;13(4):269–76. doi:10.1080/10717540500394661.

    Article  CAS  PubMed  Google Scholar 

  10. Labroo RB, Paine MF, Thummel KE, Kharasch ED. Fentanyl metabolism by human hepatic and intestinal cytochrome P450 3A4: implications for interindividual variability in disposition, efficacy, and drug interactions. Drug Metab Dispos. 1997;25(9):1072–80.

    CAS  PubMed  Google Scholar 

  11. Poklis A, Backer R. Urine concentrations of fentanyl and norfentanyl during application of Duragesic transdermal patches. J Anal Toxicol. 2004;28(6):422–5.

    Article  CAS  PubMed  Google Scholar 

  12. Darwish M, Kirby M, Robertson P Jr, Tracewell W, Jiang JG. Absolute and relative bioavailability of fentanyl buccal tablet and oral transmucosal fentanyl citrate. J Clin Pharmacol. 2007;47(3):343–50.

    Article  CAS  PubMed  Google Scholar 

  13. Grape S, Schug SA, Lauer S, Schug BS. Formulations of fentanyl for the management of pain. Drugs. 2010;70(1):57–72. doi:10.2165/11531740-000000000-00000.

    Article  CAS  PubMed  Google Scholar 

  14. Dahan A, Yassen A, Bijl H, Romberg R, Sarton E, Teppema L, et al. Comparison of the respiratory effects of intravenous buprenorphine and fentanyl in humans and rats. Br J Anaesth. 2005;94(6):825–34. doi:10.1093/bja/aei145.

    Article  CAS  PubMed  Google Scholar 

  15. Streisand JB, Stanley TH, Hague B, van Vreeswijk H, Ho GH, Pace NL. Oral transmucosal fentanyl citrate premedication in children. Anesth Analg. 1989;69(1):28–34.

    Article  CAS  PubMed  Google Scholar 

  16. Fine PG, Narayana A, Passik SD. Treatment of breakthrough pain with fentanyl buccal tablet in opioid-tolerant patients with chronic pain: appropriate patient selection and management. Pain Med. 2010;11(7):1024–36. doi:10.1111/j.1526-4637.2010.00891.x.

    Article  PubMed  Google Scholar 

  17. Deandrea S, Corli O, Consonni D, Villani W, Greco MT, Apolone G. Prevalence of breakthrough cancer pain: a systematic review and a pooled analysis of published literature. J Pain Symptom Manage. 2014;47(1):57–76. doi:10.1016/j.jpainsymman.2013.02.015.

    Article  PubMed  Google Scholar 

  18. Elsner F, Zeppetella G, Porta-Sales J, Tagarro I. Newer generation fentanyl transmucosal products for breakthrough pain in opioid-tolerant cancer patients. Clin Drug Investig. 2011;31(9):605–18. doi:10.2165/11592910-000000000-00000.

    Article  CAS  PubMed  Google Scholar 

  19. Zeppetella G, Davies A, Eijgelshoven I, Jansen JP. A network meta-analysis of the efficacy of opioid analgesics for the management of breakthrough cancer pain episodes. J Pain Symptom Manage. 2014;47(4):772–85. doi:10.1016/j.jpainsymman.2013.05.020.

    Article  PubMed  Google Scholar 

  20. Smith H. A comprehensive review of rapid-onset opioids for breakthrough pain. CNS Drugs. 2012;26(6):509–35. doi:10.2165/11630580-000000000-00000.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Jandhyala R, Fullarton J. Various formulations of oral transmucosal fentanyl for breakthrough cancer pain: an indirect mixed treatment comparison meta-analysis. BMJ Support Palliat Care. 2012;2(2):156–62. doi:10.1136/bmjspcare-2011-000139.

    Article  PubMed  Google Scholar 

  22. Scott LJ. Fentanyl iontophoretic transdermal system: a review in acute postoperative pain. Clin Drug Investig. 2016;36(4):321–30. doi:10.1007/s40261-016-0387-x.

    Article  CAS  PubMed  Google Scholar 

  23. Drug Approval Package: Actiq (oral transmucosal fentanyl citrate) NDA# 02747. In: US Food and Drug Administration. http://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20747_Actiq.cfm. Accessed 19 Mar 2017.

  24. Drug Approval Package: Fentota (fentanyl) NDA #021947. In: US Food and Drug Administration. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021947s000FentoraTOC.cfm. Accessed 19 Mar 2017.

  25. Drug Approval Package: Onsolis NDA #022266. In: US Food and Drug Administration. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022266_onsolis_toc.cfm. Accessed 19 Mar 2017.

  26. Drug Approval Package: Abstral (fentanyl) NDA #022510. In: US Food and Drug Administration. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022510_abstral_toc.cfm. Accessed 19 Mar 2017.

  27. Drug Approval Package: Subsys (fentanyl sublingual) NDA #202788. In: US Food and Drug Administration. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202788_subsys_toc.cfm. Accessed 19 Mar 2017.

  28. Moore N, Darwish M, Amores X, Schneid H. A review of the pharmacokinetic profile of transmucosal fentanyl formulations. Curr Med Res Opin. 2012;28(11):1781–90. doi:10.1185/03007995.2012.735227.

    Article  CAS  PubMed  Google Scholar 

  29. Streisand JB, Varvel JR, Stanski DR, Le Maire L, Ashburn MA, Hague BI, et al. Absorption and bioavailability of oral transmucosal fentanyl citrate. Anesthesiology. 1991;75(2):223–9.

    Article  CAS  PubMed  Google Scholar 

  30. Zhang H, Zhang J, Streisand JB. Oral mucosal drug delivery: clinical pharmacokinetics and therapeutic applications. Clin Pharmacokinet. 2002;41(9):661–80. doi:10.2165/00003088-200241090-00003.

    Article  CAS  PubMed  Google Scholar 

  31. Aronoff GM, Brennan MJ, Pritchard DD, Ginsberg B. Evidence-based oral transmucosal fentanyl citrate (OTFC) dosing guidelines. Pain Med. 2005;6(4):305–14.

    Article  PubMed  Google Scholar 

  32. Lichtor JL, Sevarino FB, Joshi GP, Busch MA, Nordbrock E, Ginsberg B. The relative potency of oral transmucosal fentanyl citrate compared with intravenous morphine in the treatment of moderate to severe postoperative pain. Anesth Analg. 1999;89(3):732–8.

    CAS  PubMed  Google Scholar 

  33. Farrar JT, Cleary J, Rauck R, Busch M, Nordbrock E. Oral transmucosal fentanyl citrate: randomized, double-blinded, placebo-controlled trial for treatment of breakthrough pain in cancer patients. J Natl Cancer Inst. 1998;90(8):611–6.

    Article  CAS  PubMed  Google Scholar 

  34. Payne R, Coluzzi P, Hart L, Simmonds M, Lyss A, Rauck R, et al. Long-term safety of oral transmucosal fentanyl citrate for breakthrough cancer pain. J Pain Symptom Manage. 2001;22(1):575–83.

    Article  CAS  PubMed  Google Scholar 

  35. Pinna MA, Bruera E, Moralo MJ, Correas MA, Vargas RM. A randomized crossover clinical trial to evaluate the efficacy of oral transmucosal fentanyl citrate in the treatment of dyspnea on exertion in patients with advanced cancer. Am J Hosp Palliat Care. 2015;32(3):298–304. doi:10.1177/1049909113513063.

    Article  PubMed  Google Scholar 

  36. Butler FK, Kotwal RS, Buckenmaier CC 3rd, Edgar EP, O’Connor KC, Montgomery HR, et al. A Triple-Option Analgesia Plan for Tactical Combat Casualty Care: TCCC Guidelines Change 13-04. J Spec Oper Med. 2014;14(1):13–25.

    Google Scholar 

  37. Blankenstein TN, Gibson LM, Claydon MA. Is intramuscular morphine satisfying frontline medical personnels’ requirement for battlefield analgesia in Helmand Province, Afghanistan? A questionnaire study. Br J Pain. 2015;9(2):115–21. doi:10.1177/2049463714535563.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Wedmore IS, Kotwal RS, McManus JG, Pennardt A, Talbot TS, Fowler M, et al. Safety and efficacy of oral transmucosal fentanyl citrate for prehospital pain control on the battlefield. J Trauma Acute Care Surg. 2012;73(6 suppl 5):S490–5. doi:10.1097/TA.0b013e3182754674.

    Article  CAS  PubMed  Google Scholar 

  39. Coluzzi PH, Schwartzberg L, Conroy JD, Charapata S, Gay M, Busch MA, et al. Breakthrough cancer pain: a randomized trial comparing oral transmucosal fentanyl citrate (OTFC) and morphine sulfate immediate release (MSIR). Pain. 2001;91(1–2):123–30.

    Article  CAS  PubMed  Google Scholar 

  40. Mandel L, Carunchio MJ. Rampant caries from oral transmucosal fentanyl citrate lozenge abuse. J Am Dent Assoc. 2011;142(4):406–9 ([pii] 142/4/406).

    Article  PubMed  Google Scholar 

  41. Gordon D, Schroeder M. Oral transmucosal fentanyl citrate–OTFC (ACTIQ) #103. J Palliat Med. 2008;11(4):633–4. doi:10.1089/jpm.2008.9922.

    Article  PubMed  Google Scholar 

  42. Davies A. Current thinking in cancer breakthrough pain management. Eur J Palliat Care. 2005;12(suppl):4–6.

    Google Scholar 

  43. Jacobsen R, Møldrup C, Christrup L. Rationales behind the choice of administration form with fentanyl: Delphi survey among Danish general practitioners. J Opioid Manag. 2010;6(4):259–68.

    Article  PubMed  Google Scholar 

  44. Laverty D. Treating cancer-related breakthrough pain: the oral transmucosal route. Int J Palliat Nurs. 2007;13(7):326–31. doi:10.12968/ijpn.2007.13.7.24344.

    Article  PubMed  Google Scholar 

  45. Pather I, Siebert JM, Hontz J, Khankari R, Kumbale R, Gupte S. Enhanced buccal delivery of fentanyl using the OraVescent drug delivery system. Drug Deliv Technol. 2001;1(1):54–7.

    CAS  Google Scholar 

  46. Darwish M, Xie F. Pharmacokinetics of fentanyl buccal tablet: a pooled analysis and review. Pain Pract. 2012;12(4):307–14. doi:10.1111/j.1533-2500.2011.00491.x.

    Article  PubMed  Google Scholar 

  47. European Public Assessment Report (EPAR): Effentora. European Medicines Agency; 2008.

  48. Durfee S, Messina J, Khankari R. Fentanyl effervescent buccal tablets. Am J Drug Deliv. 2006;4(1):1–5. doi:10.2165/00137696-200604010-00001.

    Article  CAS  Google Scholar 

  49. FENTORA (fentanyl) buccal tablet [package insert]. Cephalon; 2013.

  50. Taylor DR. Fentanyl buccal tablet: rapid relief from breakthrough pain. Expert Opin Pharmacother. 2007;8(17):3043–51. doi:10.1517/14656566.8.17.3043.

    Article  CAS  PubMed  Google Scholar 

  51. Portenoy RK, Taylor D, Messina J, Tremmel L. A randomized, placebo-controlled study of fentanyl buccal tablet for breakthrough pain in opioid-treated patients with cancer. Clin J Pain. 2006;22(9):805–11. doi:10.1097/01.ajp.0000210932.27945.4a.

    Article  PubMed  Google Scholar 

  52. Slatkin NE, Xie F, Messina J, Segal TJ. Fentanyl buccal tablet for relief of breakthrough pain in opioid-tolerant patients with cancer-related chronic pain. J Support Oncol. 2007;5(7):327–34.

    CAS  PubMed  Google Scholar 

  53. Lister N, Warrington S, Boyce M, Eriksson C, Tamaoka M, Kilborn J. Pharmacokinetics, safety, and tolerability of ascending doses of sublingual fentanyl, with and without naltrexone. Japanese subjects. J Clin Pharmacol. 2011;51(8):1195–204. doi:10.1177/0091270010379410.

    Article  CAS  PubMed  Google Scholar 

  54. Vasisht N, Gever LN, Tagarro I, Finn AL. Single-dose pharmacokinetics of fentanyl buccal soluble film. Pain Med. 2010;11(7):1017–23. doi:10.1111/j.1526-4637.2010.00875.x.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Finn AL, Vasisht N, Stark JG, Gever LN, Tagarro I. Dose proportionality and pharmacokinetics of fentanyl buccal soluble film in healthy subjects: a phase I, open-label, three-period, crossover study. Clin Drug Investig. 2012;32(1):63–71. doi:10.2165/11594670-000000000-00000.

    Article  CAS  Google Scholar 

  56. Davies A, Finn A, Tagarro I. Intra- and interindividual variabilities in the pharmacokinetics of fentanyl buccal soluble film in healthy subjects: a cross-study analysis. Clin Drug Investig. 2011;31(5):317–24. doi:10.2165/11533540-000000000-00000.

    Article  CAS  PubMed  Google Scholar 

  57. Garnock-Jones KP. fentanyl buccal soluble film: a review in breakthrough cancer pain. Clin Drug Investig. 2016;36(5):413–9. doi:10.1007/s40261-016-0394-y.

    Article  CAS  PubMed  Google Scholar 

  58. Chwieduk CM, McKeage K. Fentanyl sublingual: in breakthrough pain in opioid-tolerant adults with cancer. Drugs. 2010;70(17):2281–8. doi:10.2165/11200910-000000000-00000.

    Article  CAS  PubMed  Google Scholar 

  59. Bredenberg S, Duberg M, Lennernäs B, Lennernäs H, Pettersson A, Westerberg M, et al. In vitro and in vivo evaluation of a new sublingual tablet system for rapid oromucosal absorption using fentanyl citrate as the active substance. Eur J Pharm Sci. 2003;20(3):327–34.

    Article  CAS  PubMed  Google Scholar 

  60. Nalamachu S. An evaluation of total disintegration time for three different doses of sublingual fentanyl tablets in patients with breakthrough pain. Pain Ther. 2013;2(2):121–8. doi:10.1007/s40122-013-0019-6.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Murphy A, O’Sullivan R, Wakai A, Grant TS, Barrett MJ, Cronin J, et al. Intranasal fentanyl for the management of acute pain in children. Cochrane Database Syst Rev. 2014;2014(10):CD009942. doi:10.1002/14651858.CD009942.pub2.

    Google Scholar 

  62. Abstral Sublingual Tablets—Summary of Product Characteristics. In: Electronic Medicines Compendium. http://www.medicines.org.uk/EMC/medicine/21371/SPC/Abstral%2BSublingual%2BTablets/.

  63. Davies A, Mundin G, Vriens J, Webber K, Buchanan A, Waghorn M. The influence of low salivary flow rates on the absorption of a sublingual fentanyl citrate formulation for breakthrough cancer pain. J Pain Symptom Manage. 2016;51(3):538–45. doi:10.1016/j.jpainsymman.2015.11.018.

    Article  PubMed  Google Scholar 

  64. Parikh N, Goskonda V, Chavan A, Dillaha L. Single-dose pharmacokinetics of fentanyl sublingual spray and oral transmucosal fentanyl citrate in healthy volunteers: a randomized crossover study. Clin Ther. 2013;35(3):236–43. doi:10.1016/j.clinthera.2013.02.017.

    Article  CAS  PubMed  Google Scholar 

  65. Rauck R, Reynolds L, Geach J, Bull J, Stearns L, Scherlis M, et al. Efficacy and safety of fentanyl sublingual spray for the treatment of breakthrough cancer pain: a randomized, double-blind, placebo-controlled study. Curr Med Res Opin. 2012;28(5):859–70. doi:10.1185/03007995.2012.683111.

    Article  CAS  PubMed  Google Scholar 

  66. Rauck RL, Tark M, Reyes E, Hayes TG, Bartkowiak AJ, Hassman D, et al. Efficacy and long-term tolerability of sublingual fentanyl orally disintegrating tablet in the treatment of breakthrough cancer pain. Curr Med Res Opin. 2009;25(12):2877–85. doi:10.1185/03007990903368310.

    Article  CAS  PubMed  Google Scholar 

  67. Uberall MA, Muller-Schwefe GH. Sublingual fentanyl orally disintegrating tablet in daily practice: efficacy, safety and tolerability in patients with breakthrough cancer pain. Curr Med Res Opin. 2011;27(7):1385–94. doi:10.1185/03007995.2011.583231.

    Article  PubMed  CAS  Google Scholar 

  68. Minkowitz H, Bull J, Brownlow RC, Parikh N, Rauck R. Long-term safety of fentanyl sublingual spray in opioid-tolerant patients with breakthrough cancer pain. Support Care Cancer. 2016;24(6):2669–75. doi:10.1007/s00520-015-3056-3.

    Article  PubMed  Google Scholar 

  69. Velazquez Rivera I, Munoz Garrido JC, Garcia Velasco P, de Enciso IEX, Clavarana LV. Efficacy of sublingual fentanyl vs. oral morphine for cancer-related breakthrough pain. Adv Ther. 2014;31(1):107–17. doi:10.1007/s12325-013-0086-4.

    Article  CAS  PubMed  Google Scholar 

  70. Paech MJ, Bloor M, Schug SA. New formulations of fentanyl for acute pain management. Drugs Today. 2012;48(2):119–32. doi:10.1358/dot.2012.48.2.1745275.

    Article  CAS  PubMed  Google Scholar 

  71. Fisher A, Watling M, Smith A, Knight A. Pharmacokinetics and relative bioavailability of fentanyl pectin nasal spray 100–800 µg in healthy volunteers. Int J Clin Pharmacol Ther. 2010;48(12):860–7.

    Article  CAS  PubMed  Google Scholar 

  72. European Public Assessment Report (EPAR): PecFent. European Medicines Agency; 2010.

  73. Gizurarson S. The relevance of nasal physiology to the design of drug absorption studies. Adv Drug Deliv Rev. 1993;11(3):329–47. doi:10.1016/0169-409X(93)90015-V.

    Article  CAS  Google Scholar 

  74. Crellin D, Ling RX, Babl FE. Does the standard intravenous solution of fentanyl (50 microg/ml) administered intranasally have analgesic efficacy? Emerg Med Australas. 2010;22(1):62–7. doi:10.1111/j.1742-6723.2010.01257.x.

    Article  PubMed  Google Scholar 

  75. Dale O, Hjortkjaer R, Kharasch ED. Nasal administration of opioids for pain management in adults. Acta Anaesthesiol Scand. 2002;46(7):759–70.

    Article  CAS  PubMed  Google Scholar 

  76. Illum L. Nanoparticulate systems for nasal delivery of drugs: a real improvement over simple systems? J Pharm Sci. 2007;96(3):473–83. doi:10.1002/jps.20718.

    Article  CAS  PubMed  Google Scholar 

  77. Dhuria SV, Hanson LR, Frey WH. Intranasal delivery to the central nervous system: mechanisms and experimental considerations. J Pharm Sci. 2010;99(4):1654–73. doi:10.1002/jps.21924.

    Article  CAS  PubMed  Google Scholar 

  78. Illum L, Davis SS, Pawula M, Fisher AN, Barrett DA, Farraj NF, et al. Nasal administration of morphine-6-glucuronide in sheep–a pharmacokinetic study. Biopharm Drug Dispos. 1996;17(8):717–24. doi:10.1002/(SICI)1099-081X(199611)17:8<717:AID-BDD985>3.0.CO;2-I.

    Article  CAS  PubMed  Google Scholar 

  79. Mercadante S. Pharmacotherapy for breakthrough cancer pain. Drugs. 2012;72(2):181–90. doi:10.2165/11597260-000000000-00000.

    Article  CAS  PubMed  Google Scholar 

  80. Moksnes K, Fredheim OM, Klepstad P, Kaasa S, Angelsen A, Nilsen T, et al. Early pharmacokinetics of nasal fentanyl: is there a significant arterio-venous difference? Eur J Clin Pharmacol. 2008;64(5):497–502. doi:10.1007/s00228-007-0444-8.

    Article  CAS  PubMed  Google Scholar 

  81. Panagiotou I, Mystakidou K. Intranasal fentanyl: from pharmacokinetics and bioavailability to current treatment applications. Expert Rev Anticancer Ther. 2010;10(7):1009–21. doi:10.1586/era.10.77.

    Article  CAS  PubMed  Google Scholar 

  82. Nave R, Schmitt H, Popper L. Faster absorption and higher systemic bioavailability of intranasal fentanyl spray compared to oral transmucosal fentanyl citrate in healthy subjects. Drug Deliv. 2013;20(5):216–23. doi:10.3109/10717544.2012.762435.

    Article  CAS  PubMed  Google Scholar 

  83. Mercadante S, Prestia G, Adile C, Casuccio A. Intranasal fentanyl versus fentanyl pectin nasal spray for the management of breakthrough cancer pain in doses proportional to basal opioid regimen. J Pain. 2014;15(6):602–7. doi:10.1016/j.jpain.2014.02.002.

    Article  CAS  PubMed  Google Scholar 

  84. Hansen MS, Mathiesen O, Trautner S, Dahl JB. Intranasal fentanyl in the treatment of acute pain—a systematic review. Acta Anaesthesiol Scand. 2012;56(4):407–19. doi:10.1111/j.1399-6576.2011.02613.x.

    Article  CAS  PubMed  Google Scholar 

  85. Saunders M, Adelgais K, Nelson D. Use of intranasal fentanyl for the relief of pediatric orthopedic trauma pain. Acad Emerg Med. 2010;17(11):1155–61. doi:10.1111/j.1553-2712.2010.00905.x.

    Article  PubMed  Google Scholar 

  86. Finn J, Wright J, Fong J, Mackenzie E, Wood F, Leslie G, et al. A randomised crossover trial of patient controlled intranasal fentanyl and oral morphine for procedural wound care in adult patients with burns. Burns. 2004;30(3):262–8. doi:10.1016/j.burns.2003.10.017.

    Article  PubMed  Google Scholar 

  87. Cole J, Shepherd M, Young P. Intranasal fentanyl in 1-3-year-olds: a prospective study of the effectiveness of intranasal fentanyl as acute analgesia. Emerg Med Australas. 2009;21(5):395–400. doi:10.1111/j.1742-6723.2009.01216.x.

    Article  PubMed  Google Scholar 

  88. Shelley K, Paech MJ. The clinical applications of intranasal opioids. Curr Drug Deliv. 2008;5(1):55–8.

    Article  CAS  PubMed  Google Scholar 

  89. Striebel HW, Oelmann T, Spies C, Rieger A, Schwagmeier R. Patient-controlled intranasal analgesia: a method for noninvasive postoperative pain management. Anesth Analg. 1996;83(3):548–51.

    Article  CAS  PubMed  Google Scholar 

  90. Toussaint S, Maidl J, Schwagmeier R, Striebel HW. Patient-controlled intranasal analgesia: effective alternative to intravenous PCA for postoperative pain relief. Can J Anaesth. 2000;47(4):299–302. doi:10.1007/BF03020941.

    Article  CAS  PubMed  Google Scholar 

  91. Christrup LL, Foster D, Popper LD, Troen T, Upton R. Pharmacokinetics, efficacy, and tolerability of fentanyl following intranasal versus intravenous administration in adults undergoing third-molar extraction: a randomized, double-blind, double-dummy, two-way, crossover study. Clin Ther. 2008;30(3):469–81. doi:10.1016/j.clinthera.2008.03.001.

    Article  CAS  PubMed  Google Scholar 

  92. Galinkin JL, Fazi LM, Cuy RM, Chiavacci RM, Kurth CD, Shah UK, et al. Use of intranasal fentanyl in children undergoing myringotomy and tube placement during halothane and sevoflurane anesthesia. Anesthesiology. 2000;93(6):1378–83.

    Article  CAS  PubMed  Google Scholar 

  93. Kerr D, Taylor D, Evans B. Patient-controlled intranasal fentanyl analgesia: a pilot study to assess practicality and tolerability during childbirth. Int J Obstet Anesth. 2015;24(2):117–23. doi:10.1016/j.ijoa.2014.11.006.

    Article  CAS  PubMed  Google Scholar 

  94. Karlsen AP, Pedersen DM, Trautner S, Dahl JB, Hansen MS. Safety of intranasal fentanyl in the out-of-hospital setting: a prospective observational study. Ann Emerg Med. 2014;63(6):699–703. doi:10.1016/j.annemergmed.2013.10.025.

    Article  PubMed  Google Scholar 

  95. Mercadante S, Radbruch L, Davies A, Poulain P, Sitte T, Perkins P, et al. A comparison of intranasal fentanyl spray with oral transmucosal fentanyl citrate for the treatment of breakthrough cancer pain: an open-label, randomised, crossover trial. Curr Med Res Opin. 2009;25(11):2805–15. doi:10.1185/03007990903336135.

    Article  CAS  PubMed  Google Scholar 

  96. Vissers D, Stam W, Nolte T, Lenre M, Jansen J. Efficacy of intranasal fentanyl spray versus other opioids for breakthrough pain in cancer. Curr Med Res Opin. 2010;26(5):1037–45. doi:10.1185/03007991003694340.

    Article  CAS  PubMed  Google Scholar 

  97. Portenoy RK, Burton AW, Gabrail N, Taylor D, Fentanyl Pectin Nasal Spray 043 Study G. A multicenter, placebo-controlled, double-blind, multiple-crossover study of fentanyl pectin nasal spray (FPNS) in the treatment of breakthrough cancer pain. Pain. 2010;151(3):617–24. doi:10.1016/j.pain.2010.07.028.

    Article  CAS  PubMed  Google Scholar 

  98. Mercadante S, Vellucci R, Cuomo A, Adile C, Cortegiani A, Valle A, et al. Long-term efficacy and tolerability of intranasal fentanyl in the treatment of breakthrough cancer pain. Support Care Cancer. 2015;23(5):1349–54. doi:10.1007/s00520-014-2491-x.

    Article  PubMed  Google Scholar 

  99. Jandhyala R, Fullarton JR, Bennett MI. Efficacy of rapid-onset oral fentanyl formulations vs. oral morphine for cancer-related breakthrough pain: a meta-analysis of comparative trials. J Pain Symptom Manage. 2013;46(4):573–80. doi:10.1016/j.jpainsymman.2012.09.009.

    Article  PubMed  Google Scholar 

  100. Zeppetella G, Davies AN. Opioids for the management of breakthrough pain in cancer patients. Cochrane Database Syst Rev. 2013;10:4311. doi:10.1002/14651858.CD004311.pub3.

    Google Scholar 

  101. Nalamachu SR, Parikh N, Dillaha L, Rauck R. Lack of correlation between the effective dose of fentanyl sublingual spray for breakthrough cancer pain and the around-the-clock opioid dose. J Opioid Manag. 2014;10(4):247–54. doi:10.5055/jom.2014.0212.

    Article  PubMed  Google Scholar 

  102. Alberts DS, Smith CC, Parikh N, Rauck RL. Fentanyl sublingual spray for breakthrough cancer pain in patients receiving transdermal fentanyl. Pain Manag. 2016;6(5):427–34. doi:10.2217/pmt-2015-0009.

    Article  PubMed  Google Scholar 

  103. Rauck R, Bull J, Parikh N, Dillaha L, Stearns L. Effective dose titration of fentanyl sublingual spray in patients with breakthrough cancer pain. Pain Pract. 2015. doi:10.1111/papr.12360.

    Google Scholar 

  104. Kleeberg UR, Davies A, Jarosz J, Mercadante S, Poulain P, O’Brien T, et al. Pan-European, open-label dose titration study of fentanyl buccal tablet in patients with breakthrough cancer pain. Eur J Pain. 2015;19(4):528–37. doi:10.1002/ejp.577.

    Article  CAS  PubMed  Google Scholar 

  105. Mercadante S, Gatti A, Porzio G, Lo Presti C, Aielli F, Adile C, et al. Dosing fentanyl buccal tablet for breakthrough cancer pain: dose titration versus proportional doses. Curr Med Res Opin. 2012;28(6):963–8. doi:10.1185/03007995.2012.683112.

    Article  CAS  PubMed  Google Scholar 

  106. Mercadante S, Porzio G, Aielli F, Averna L, Ficorella C, Casuccio A. The use of fentanyl buccal tablets for breakthrough pain by using doses proportional to opioid basal regimen in a home care setting. Support Care Cancer. 2013;21(8):2335–9. doi:10.1007/s00520-013-1799-2.

    Article  PubMed  Google Scholar 

  107. Shimoyama N, Gomyo I, Teramoto O, Kojima K, Higuchi H, Yukitoshi N, et al. Efficacy and safety of sublingual fentanyl orally disintegrating tablet at doses determined from oral morphine rescue doses in the treatment of breakthrough cancer pain. Jpn J Clin Oncol. 2015;45(2):189–96. doi:10.1093/jjco/hyu182.

    Article  PubMed  Google Scholar 

  108. Bennett MI, Graham J, Schmidt-Hansen M, Prettyjohns M, Arnold S, Guideline Development G. Prescribing strong opioids for pain in adult palliative care: summary of NICE guidance. BMJ. 2012;344:e2806.

    Article  PubMed  Google Scholar 

  109. Gaertner J, Schiessl C. Cancer pain management: what’s new? Curr Pain Headache Rep. 2013;17(4):328. doi:10.1007/s11916-013-0328-9.

    Article  PubMed  Google Scholar 

  110. Ruggeri M, Turriziani A, Oradei M. Cost-effectiveness analysis of transnasal fentanyl citrate for the treatment of breakthrough cancer pain. Expert Rev Pharmacoecon Outcomes Res. 2014;14(3):459–64. doi:10.1586/14737167.2014.904750.

    Article  PubMed  Google Scholar 

  111. Vissers DC, Lenre M, Tolley K, Jakobsson J, Sendersky V, Jansen JP. An economic evaluation of short-acting opioids for treatment of breakthrough pain in patients with cancer. Value Health. 2011;14(2):274–81. doi:10.1016/j.jval.2010.09.007.

    Article  PubMed  Google Scholar 

  112. Kuo KL, Saokaew S, Stenehjem DD. The pharmacoeconomics of breakthrough cancer pain. J Pain Palliat Care Pharmacother. 2013;27(2):167–75. doi:10.3109/15360288.2013.787137.

    Article  PubMed  Google Scholar 

  113. American College of Medical T. ACMT Position Statement: safety issues regarding prescription fentanyl products. J Med Toxicol. 2016;12(2):211–2. doi:10.1007/s13181-016-0535-y.

    Article  Google Scholar 

  114. Warner M, Trinidad J, Bastian B. Drugs most frequently involved in drug overdose deaths: United States, 2010–2014. Hyattsville, MD: National Center for Health Statistics; 2016.

    Google Scholar 

  115. Marquardt KA, Tharratt RS, Musallam NA. Fentanyl remaining in a transdermal system following three days of continuous use. Ann Pharmacother. 1995;29(10):969–71.

    CAS  PubMed  Google Scholar 

  116. Zernikow B, Michel E, Anderson B. Transdermal fentanyl in childhood and adolescence: a comprehensive literature review. J Pain. 2007;8(3):187–207. doi:10.1016/j.jpain.2006.11.008.

    Article  CAS  PubMed  Google Scholar 

  117. Prodduturi S, Sadrieh N, Wokovich AM, Doub WH, Westenberger BJ, Buhse L. Transdermal delivery of fentanyl from matrix and reservoir systems: effect of heat and compromised skin. J Pharm Sci. 2010;99(5):2357–66. doi:10.1002/jps.22004.

    Article  CAS  PubMed  Google Scholar 

  118. Forsgren J, Jämstorp E, Bredenberg S, Engqvist H, Strømme M. A ceramic drug delivery vehicle for oral administration of highly potent opioids. J Pharm Sci. 2010;99(1):219–26. doi:10.1002/jps.21814.

    Article  CAS  PubMed  Google Scholar 

  119. Lilleng PK, Mehlum LI, Bachs L, Morild I. Deaths after intravenous misuse of transdermal fentanyl. J Forensic Sci. 2004;49(6):1364–6.

    Article  CAS  PubMed  Google Scholar 

  120. Marier J-F, Lor M, Potvin D, Dimarco M, Morelli G, Saedder EA. Pharmacokinetics, tolerability, and performance of a novel matrix transdermal delivery system of fentanyl relative to the commercially available reservoir formulation in healthy subjects. J Clin Pharmacol. 2006;46(6):642–53. doi:10.1177/0091270006286901.

    Article  CAS  PubMed  Google Scholar 

  121. Moore PW, Palmer RB, Donovan JW. Fatal fentanyl patch misuse in a hospitalized patient with a postmortem increase in fentanyl blood concentration. J Forensic Sci. 2015;60(1):243–6. doi:10.1111/1556-4029.12559.

    Article  CAS  PubMed  Google Scholar 

  122. Mrvos R, Feuchter AC, Katz KD, Duback-Morris LF, Brooks DE, Krenzelok EP. Whole fentanyl patch ingestion: a multi-center case series. J Emerg Med. 2012;42(5):549–52. doi:10.1016/j.jemermed.2011.05.017.

    Article  PubMed  Google Scholar 

  123. Schauer CK, Shand JA, Reynolds TM. The fentanyl patch boil-up—a novel method of opioid abuse. Basic Clin Pharmacol Toxicol. 2015;117(5):358–9. doi:10.1111/bcpt.12412.

    Article  CAS  PubMed  Google Scholar 

  124. Arroyo Plasencia AM, Mowry J, Smith J, Quigley K. In vitro release of fentanyl from transdermal patches in gastric and intestinal fluid. Clin Toxicol (Phila). 2014;52(9):945–7. doi:10.3109/15563650.2014.967399.

    Article  CAS  Google Scholar 

  125. Freynhagen R, von Giesen HJ, Busche P, Sabatowski R, Konrad C, Grond S. Switching from reservoir to matrix systems for the transdermal delivery of fentanyl: a prospective, multicenter pilot study in outpatients with chronic pain. J Pain Symptom Manage. 2005;30(3):289–97. doi:10.1016/j.jpainsymman.2005.03.015.

    Article  CAS  PubMed  Google Scholar 

  126. Gourlay GK, Kowalski SR, Plummer JL, Cherry DA, Gaukroger P, Cousins MJ. The transdermal administration of fentanyl in the treatment of postoperative pain: pharmacokinetics and pharmacodynamic effects. Pain. 1989;37(2):193–202.

    Article  CAS  PubMed  Google Scholar 

  127. Varvel JR, Shafer SL, Hwang SS, Coen PA, Stanski DR. Absorption characteristics of transdermally administered fentanyl. Anesthesiology. 1989;70(6):928–34.

    Article  CAS  PubMed  Google Scholar 

  128. Ross JR, Quigley C. Transdermal fentanyl: informed prescribing is essential. Eur J Pain. 2003;7(5):481–3. doi:10.1016/S1090-3801(02)00148-9.

    Article  CAS  PubMed  Google Scholar 

  129. Holley FO, van Steennis C. Postoperative analgesia with fentanyl: pharmacokinetics and pharmacodynamics of constant-rate i.v. and transdermal delivery. Br J Anaesth. 1988;60(6):608–13.

    Article  CAS  PubMed  Google Scholar 

  130. DURAGESIC (fentanyl transdermal system) for transdermal administration [package insert]. Janssen Pharmaceuticals; 2014.

  131. Carter KA. Heat-associated increase in transdermal fentanyl absorption. Am J Health Syst Pharm. 2003;60(2):191–2.

    PubMed  Google Scholar 

  132. Doris MK, Sandilands EA. Life-threatening opioid toxicity from a fentanyl patch applied to eczematous skin. BMJ Case Rep. 2015. doi:10.1136/bcr-2014-208945.

    PubMed  Google Scholar 

  133. Sindali K, Sherry K, Sen S, Dheansa B. Life-threatening coma and full-thickness sunburn in a patient treated with transdermal fentanyl patches: a case report. J Med Case Rep. 2012;6:220. doi:10.1186/1752-1947-6-220.

    Article  PubMed  PubMed Central  Google Scholar 

  134. Solassol I, Bressolle F, Caumette L, Garcia F, Poujol S, Culine S, et al. Inter- and intraindividual variabilities in pharmacokinetics of fentanyl after repeated 72-hour transdermal applications in cancer pain patients. Ther Drug Monit. 2005;27(4):491–8.

    Article  CAS  PubMed  Google Scholar 

  135. Solassol I, Caumette L, Bressolle F, Garcia F, Thézenas S, Astre C, et al. Inter- and intra-individual variability in transdermal fentanyl absorption in cancer pain patients. Oncol Rep. 2005;14(4):1029–36.

    PubMed  Google Scholar 

  136. Portenoy RK, Southam MA, Gupta SK, Lapin J, Layman M, Inturrisi CE, et al. Transdermal fentanyl for cancer pain. Repeated dose pharmacokinetics. Anesthesiology. 1993;78(1):36–43.

    Article  CAS  PubMed  Google Scholar 

  137. Reddy A, Yennurajalingam S, Reddy S, Wu J, Liu D, Dev R, et al. The opioid rotation ratio from transdermal fentanyl to “strong” opioids in patients with cancer pain. J Pain Symptom Manage. 2016;51(6):1040–5. doi:10.1016/j.jpainsymman.2015.12.312.

    Article  PubMed  Google Scholar 

  138. Bentley JB, Borel JD, Nenad RE, Gillespie TJ. Age and fentanyl pharmacokinetics. Anesth Analg. 1982;61(12):968–71.

    Article  CAS  PubMed  Google Scholar 

  139. Arnet I, Schacher S, Balmer E, Koeberle D, Hersberger KE. Poor adhesion of fentanyl transdermal patches may mimic end-of-dosage failure after 48 h and prompt early patch replacement in hospitalized cancer pain patients. J Pain Res. 2016;9:993–9. doi:10.2147/JPR.S116091.

    Article  PubMed  PubMed Central  Google Scholar 

  140. Hadley G, Derry S, Moore RA. Wiffen PJ (2013) Transdermal fentanyl for cancer pain. Cochrane Database Syst Rev. 2013;10:CD010270. doi:10.1002/14651858.CD010270.pub2.

    Google Scholar 

  141. Koyyalagunta D, Bruera E, Solanki DR, Nouri KH, Burton AW, Toro MP, et al. A systematic review of randomized trials on the effectiveness of opioids for cancer pain. Pain Phys. 2012;15(3 suppl):ES39–58.

    Google Scholar 

  142. Nelson L, Schwaner R. Transdermal fentanyl: pharmacology and toxicology. J Med Toxicol. 2009;5(4):230–41.

    Article  PubMed  PubMed Central  Google Scholar 

  143. Freynhagen R, Geisslinger G, Schug SA. Opioids for chronic non-cancer pain. BMJ. 2013;346:f2937. doi:10.1136/bmj.f2937.

    Article  PubMed  Google Scholar 

  144. Wolff RF, Aune D, Truyers C, Hernandez AV, Misso K, Riemsma R, et al. Systematic review of efficacy and safety of buprenorphine versus fentanyl or morphine in patients with chronic moderate to severe pain. Curr Med Res Opin. 2012;28(5):833–45. doi:10.1185/03007995.2012.678938.

    Article  CAS  PubMed  Google Scholar 

  145. Centers For Disease C, Prevention Public Health Service USDOH, Human S. Guideline for prescribing opioids for chronic pain. J Pain Palliat Care Pharmacother. 2016;30(2):138–40. doi:10.3109/15360288.2016.1173761.

    Article  Google Scholar 

  146. Hostynek JJ, Maibach HI. Fentanyl transdermal patches: overview of cutaneous adverse effects in humans. Cutan Ocul Toxicol. 2010;29(4):241–6. doi:10.3109/15569527.2010.492487.

    Article  CAS  PubMed  Google Scholar 

  147. Catterall RA. Problems of sweating and transdermal fentanyl. Palliat Med. 1997;11(2):169–70.

    CAS  PubMed  Google Scholar 

  148. Roy SD, Flynn GL. Transdermal delivery of narcotic analgesics: pH, anatomical, and subject influences on cutaneous permeability of fentanyl and sufentanil. Pharm Res. 1990;7(8):842–7.

    Article  CAS  PubMed  Google Scholar 

  149. Collins JJ, Dunkel IJ, Gupta SK, Inturrisi CE, Lapin J, Palmer LN, et al. Transdermal fentanyl in children with cancer pain: feasibility, tolerability, and pharmacokinetic correlates. J Pediatr. 1999;134(3):319–23.

    Article  CAS  PubMed  Google Scholar 

  150. Grond S, Radbruch L, Lehmann KA. Clinical pharmacokinetics of transdermal opioids: focus on transdermal fentanyl. Clin Pharmacokinet. 2000;38(1):59–89. doi:10.2165/00003088-200038010-00004.

    Article  CAS  PubMed  Google Scholar 

  151. Neighbors DM, Bell TJ, Wilson J, Dodd SL. Economic evaluation of the fentanyl transdermal system for the treatment of chronic moderate to severe pain. J Pain Symptom Manage. 2001;21(2):129–43.

    Article  CAS  PubMed  Google Scholar 

  152. Schröder B, Nickel U, Meyer E, Lee G. Transdermal delivery using a novel electrochemical device, part 2: in vivo study in humans. J Pharm Sci. 2012;101(6):2262–8. doi:10.1002/jps.23108.

    Article  PubMed  CAS  Google Scholar 

  153. Chelly JE. An iontophoretic, fentanyl HCl patient-controlled transdermal system for acute postoperative pain management. Expert Opin Pharmacother. 2005;6(7):1205–14. doi:10.1517/14656566.6.7.1205.

    Article  CAS  PubMed  Google Scholar 

  154. Sathyan G, Jaskowiak J, Evashenk M, Gupta S. Characterisation of the pharmacokinetics of the fentanyl HCl patient-controlled transdermal system (PCTS): effect of current magnitude and multiple-day dosing and comparison with IV fentanyl administration. Clin Pharmacokinet. 2005;44(Suppl 1):7–15.

    Article  CAS  PubMed  Google Scholar 

  155. Phipps JB, Joshi N, Regal KA, Li J, Sinatra RS. Pharmacokinetic characteristics of fentanyl iontophoretic trandermal system over a range of applied current. Expert Opin Drug Metab Toxicol. 2015;11(4):481–9. doi:10.1517/17425255.2015.1020296.

    Article  CAS  PubMed  Google Scholar 

  156. IONSYS (fentanyl iontophoretic transdermal system) [package insert]. The Medicines Company; 2015.

  157. Schröder B, Nickel U, Meyer E, Lee G. Transdermal delivery using a novel electrochemical device, part 1: device design and in vitro release/permeation of fentanyl. J Pharm Sci. 2012;101(1):245–55. doi:10.1002/jps.22765.

    Article  PubMed  CAS  Google Scholar 

  158. Minkowitz HS, Danesi H, Ding L, Jones JB. Development of the fentanyl iontophoretic transdermal system (ITS) for patient-controlled analgesia of postoperative pain management. Pain Manag. 2015;5(5):327–37. doi:10.2217/pmt.15.26.

    Article  PubMed  Google Scholar 

  159. Joshi N, Lemke J, Danesi H. Design and functionality of a smart fentanyl iontophoretic transdermal system for the treatment of moderate-to-severe postoperative pain. Pain Manag. 2016;6(2):137–45. doi:10.2217/pmt.15.70.

    Article  PubMed  Google Scholar 

  160. Camu F, Van Aken H, Bovill JG. Postoperative analgesic effects of three demand-dose sizes of fentanyl administered by patient-controlled analgesia. Anesth Analg. 1998;87(4):890–5.

    CAS  PubMed  Google Scholar 

  161. Panchal SJ, Damaraju CV, Nelson WW, Hewitt DJ, Schein JR. System-related events and analgesic gaps during postoperative pain management with the fentanyl iontophoretic transdermal system and morphine intravenous patient-controlled analgesia. Anesth Analg. 2007;105(5):1437–41. doi:10.1213/01.ane.0000281442.36582.81 (table of contents).

    Article  CAS  PubMed  Google Scholar 

  162. European Public Assessment Report (EPAR): IonSys. European Medicines Agency; 2015.

  163. Gupta SK, Hwang S, Southam M, Sathyan G. Effects of application site and subject demographics on the pharmacokinetics of fentanyl HCl patient-controlled transdermal system (PCTS). Clin Pharmacokinet. 2005;44(Suppl 1):25–32.

    Article  CAS  PubMed  Google Scholar 

  164. Sathyan G, Phipps B, Gupta SK. Passive absorption of fentanyl from the fentanyl HCl iontophoretic transdermal system. Curr Med Res Opin. 2009;25(2):363–6. doi:10.1185/03007990802594941.

    Article  CAS  PubMed  Google Scholar 

  165. Viscusi ER, Reynolds L, Tait S, Melson T, Atkinson LE. An iontophoretic fentanyl patient-activated analgesic delivery system for postoperative pain: a double-blind, placebo-controlled trial. Anesth Analg. 2006;102(1):188–94. doi:10.1213/01.ane.0000183649.58483.77.

    Article  CAS  PubMed  Google Scholar 

  166. Sinatra RS, Viscusi ER, Ding L, Danesi H, Jones JB, Grond S. Meta-analysis of the efficacy of the fentanyl iontophoretic transdermal system versus intravenous patient-controlled analgesia in postoperative pain management. Expert Opin Pharmacother. 2015;16(11):1607–13. doi:10.1517/14656566.2015.1054279.

    Article  CAS  PubMed  Google Scholar 

  167. Hartrick CT, Pestano CR, Ding L, Danesi H, Jones JB. Patient considerations in the use of transdermal iontophoretic fentanyl for acute postoperative pain. J Pain Res. 2016;9:215–22. doi:10.2147/JPR.S89278.

    Article  PubMed  PubMed Central  Google Scholar 

  168. Hartrick CT, Abraham J, Ding L. Ease-of-care from the physical therapists’ perspective comparing fentanyl iontophoretic transdermal system versus morphine intravenous patient-controlled analgesia in postoperative pain management. J Comp Eff Res. 2016;5(6):529–37. doi:10.2217/cer-2016-0038.

    Article  PubMed  Google Scholar 

  169. Viscusi ER. Patient-controlled drug delivery for acute postoperative pain management: a review of current and emerging technologies. Reg Anesth Pain Med. 2008;33(2):146–58. doi:10.1016/j.rapm.2007.11.005.

    PubMed  Google Scholar 

  170. Chelly JE, Grass J, Houseman TW, Minkowitz H, Pue A. The safety and efficacy of a fentanyl patient-controlled transdermal system for acute postoperative analgesia: a multicenter, placebo-controlled trial. Anesth Analg. 2004;98(2):427–33 (table of contents).

    Article  CAS  PubMed  Google Scholar 

  171. Langford RM, Chang KY, Ding L, Abraham J. Comparison of fentanyl iontophoretic transdermal system and routine care with morphine intravenous patient-controlled analgesia in the management of early postoperative mobilisation: results from a randomised study. Br J Pain. 2016;10(4):198–208. doi:10.1177/2049463716668905.

    Article  PubMed  PubMed Central  Google Scholar 

  172. Oliashirazi A, Wilson-Byrne T, Shuler FD, Parvizi J. Patient-controlled fentanyl iontophoretic transdermal system improved postoperative mobility compared to intravenous patient-controlled analgesia morphine: a pooled analysis of randomized, controlled trials. Pain Pract. 2016. doi:10.1111/papr.12432.

    PubMed  Google Scholar 

  173. Brown CR, Moodie JE, Bisley EJ, editors. Safety and efficacy of Transfenta in the treatment of post-operative pain: a double-blind, single-center, placebo-controlled trial. In: 17th Annual Scientific Meeting of the American Pain Society. San Diego, CA; 1998 (1998/11/05/8).

  174. Viscusi ER, Siccardi M, Damaraju CV, Hewitt DJ, Kershaw P. The safety and efficacy of fentanyl iontophoretic transdermal system compared with morphine intravenous patient-controlled analgesia for postoperative pain management: an analysis of pooled data from three randomized, active-controlled clinical studies. Anesth Analg. 2007;105(5):1428–36. doi:10.1213/01.ane.0000281913.28623.fd.

    Article  CAS  PubMed  Google Scholar 

  175. Viscusi ER, Grond S, Ding L, Danesi H, Jones JB, Sinatra RS. A comparison of opioid-related adverse events with fentanyl iontophoretic transdermal system versus morphine intravenous patient-controlled analgesia in acute postoperative pain. Pain Manag. 2016;6(1):19–24. doi:10.2217/pmt.15.49.

    Article  PubMed  Google Scholar 

  176. Lemke J, Sardariani E, Phipps JB, Patel N, Itri LM, Caravelli J, et al. Fentanyl iontophoretic transdermal system (IONSYS((R))) can be Safely used in the Hospital Environment with X-Rays, computerized tomography and radiofrequency identification devices. Adv Ther. 2016;33(9):1649–59. doi:10.1007/s12325-016-0381-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Wong P, Chadwick FD, Karovits J. Intranasal fentanyl for postoperative analgesia after elective Caesarean section. Anaesthesia. 2003;58(8):818–9.

    Article  CAS  PubMed  Google Scholar 

  178. Rickard C, O’Meara P, McGrail M, Garner D, McLean A, Le Lievre P. A randomized controlled trial of intranasal fentanyl vs intravenous morphine for analgesia in the prehospital setting. Am J Emerg Med. 2007;25(8):911–7. doi:10.1016/j.ajem.2007.02.027.

    Article  PubMed  Google Scholar 

  179. Worsley MH, MacLeod AD, Brodie MJ, Asbury AJ, Clark C. Inhaled fentanyl as a method of analgesia. Anaesthesia. 1990;45(6):449–51.

    Article  CAS  PubMed  Google Scholar 

  180. Hung OR, Whynot SC, Varvel JR, Shafer SL, Mezei M. Pharmacokinetics of inhaled liposome-encapsulated fentanyl. Anesthesiology. 1995;83(2):277–84.

    Article  CAS  PubMed  Google Scholar 

  181. Zeppetella G. An assessment of the safety, efficacy, and acceptability of intranasal fentanyl citrate in the management of cancer-related breakthrough pain: a pilot study. J Pain Symptom Manage. 2000;20(4):253–8.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The editorial assistance of Ms. Peta Gjedsted, Anaesthesiology Unit of UWA, is kindly acknowledged.

Author information

Authors and Affiliations

  1. Chair of Anaesthesiology, Pharmacology, Pharmacy and Anaesthesiology Unit, School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia

    Stephan A. Schug

  2. Department of Anaesthesia and Pain Medicine, Royal Perth Hospital, Level 2, MRF Building G Block, GPO Box X2213, Perth, WA, 6847, Australia

    Stephan A. Schug

  3. Department of Anaesthesia, Sir Charles Gairdner Hospital, Hospital Avenue, Perth, Nedlands, WA, 6009, Australia

    Sonya Ting

Authors
  1. Stephan A. Schug
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sonya Ting
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Stephan A. Schug.

Ethics declarations

Conflicts of interest

Both authors (SAS and ST) have no conflicts of interest that are directly relevant to the content of this review.

Funding

No funding or assistance was received for the preparation of this review.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Schug, S.A., Ting, S. Fentanyl Formulations in the Management of Pain: An Update. Drugs 77, 747–763 (2017). https://doi.org/10.1007/s40265-017-0727-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40265-017-0727-z

Keywords

Search

Navigation