Skip to main content
SpringerLink
Log in

Formulations of Fentanyl for the Management of Pain

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

Abstract

Fentanyl is an opioid initially developed for parenteral administration. While oral administration is not an option due to a high first-pass metabolism, its high potency and lipophilicity have made a number of new routes of administration feasible. The transdermal therapeutic system offers an excellent option for long-term treatment of cancer and chronic pain, achieving stable plasma concentrations over the treatment period. The recent change from reservoir to matrix systems has made these systems more convenient to wear and safer to use, while being bioequivalent. In contrast, the patient-controlled iontophoretic transdermal system has been developed to enable on-demand delivery of transdermal bolus doses of fentanyl to treat postoperative pain. It offers a needle-free system to provide patient-controlled analgesia otherwise offered by intravenous pumps. However, due to technical difficulties the system is currently not clinically available. Oral transmucosal fentanyl utilizes the rapid uptake through the buccal mucosa to achieve high plasma concentrations rapidly and is indicated to treat breakthrough pain in patients who are not opioid-naive. The recently introduced fentanyl buccal tablets offer slightly better pharmacokinetics for the same indication. The intranasal route is another option to achieve rapid uptake of fentanyl, and is currently being investigated to provide acute and breakthrough pain relief. Transpulmonary administration of fentanyl remains experimental and this route of administration is not yet in clinical use. Overall, the specific pharmacological and physicochemical properties of fentanyl have made this compound highly suitable for novel routes of administration in a range of clinical indications.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

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

    Article  PubMed  CAS  Google Scholar 

  2. Maguire P, Tsai N, Kamal J, et al. Pharmacological profiles of fentanyl analogs at mu, delta and kappa opiate receptors. Eur J Pharmacol 1992 Mar 24; 213(2): 219–25

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  6. 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

    PubMed  CAS  Google Scholar 

  7. Sathyan G, Guo C, Sivakumar K, et al. Evaluation of the bioequivalence of two transdermal fentanyl systems following single and repeat applications. Curr Med Res Opin 2005 Dec; 21(12): 1961–8

    Article  PubMed  CAS  Google Scholar 

  8. Gupta SK, Southam M, Gale R, et al. System functionality and physicochemical model of fentanyl transdermal system. J Pain Symptom Manage 1992; 7 (3 Suppl.): S17–26

    Article  PubMed  CAS  Google Scholar 

  9. Muijsers RB, Wagstaff AJ. Transdermal fentanyl: an updated review of its pharmacological properties and therapeutic efficacy in chronic cancer pain control. Drugs 2001; 61(15): 2289–307

    Article  PubMed  CAS  Google Scholar 

  10. Duthie DJ, Rowbotham DJ, Wyld R, et al. Plasma fentanyl concentrations during transdermal delivery of fentanyl to surgical patients. Br J Anaesth 1988 May; 60(6): 614–8

    Article  PubMed  CAS  Google Scholar 

  11. Skaer TL. Practice guidelines for transdermal opioids in malignant pain. Drugs 2004; 64(23): 2629–38

    Article  PubMed  CAS  Google Scholar 

  12. Varvel JR, Shafer SL, Hwang SS, et al. Absorption characteristics of transdermally administered fentanyl. Anesthesiology 1989 Jun; 70(6): 928–34

    Article  PubMed  CAS  Google Scholar 

  13. Ashburn MA, Ogden LL, Zhang J, et al. The pharmacokinetics of transdermal fentanyl delivered with and without controlled heat. J Pain 2003 Aug; 4(6): 291–7

    Article  PubMed  CAS  Google Scholar 

  14. Freynhagen R, von Giesen HJ, Busche P, et al. 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 Sep; 30(3): 289–97

    Article  PubMed  CAS  Google Scholar 

  15. Lehmann KA, Zech D. Transdermal fentanyl: clinical pharmacology. J Pain Symptom Manage 1992 Apr; 7 (3 Suppl.): S8–16

    Article  PubMed  CAS  Google Scholar 

  16. Gourlay GK, Kowalski SR, Plummer JL, et al. The transdermal administration of fentanyl in the treatment of postoperative pain: pharmacokinetics and pharmacodynamic effects. Pain 1989 May; 37(2): 193–202

    Article  PubMed  CAS  Google Scholar 

  17. Portenoy RK, Southam MA, Gupta SK, et al. Transdermal fentanyl for cancer pain: repeated dose pharmacokinetics. Anesthesiology 1993 Jan; 78(1): 36–43

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  19. Sathyan G, Jaskowiak J, Evashenk M, et al. 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

    PubMed  CAS  Google Scholar 

  20. Gupta SK, Southam MA, Hwang SS. Evaluation of diurnal variation in fentanyl clearance. J Clin Pharmacol 1995 Feb; 35(2): 159–62

    PubMed  CAS  Google Scholar 

  21. Plezia PM, Kramer TH, Linford J, et al. Transdermal fentanyl: pharmacokinetics and preliminary clinical evaluation. Pharmacotherapy 1989; 9(1): 2–9

    PubMed  CAS  Google Scholar 

  22. Holdsworth MT, Forman WB, Killilea TA, et al. Transdermal fentanyl disposition in elderly subjects. Gerontology 1994; 40(1): 32–7

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  24. Thompson JP, Bower S, Liddle AM, et al. Perioperative pharmacokinetics of transdermal fentanyl in elderly and young adult patients. Br J Anaesth 1998; 81(2): 152–4

    Article  PubMed  CAS  Google Scholar 

  25. Heiskanen T, Matzke S, Haakana S, et al. Transdermal fentanyl in cachectic cancer patients. Pain 2009 Jul; 144(1–2): 218–22

    Article  PubMed  CAS  Google Scholar 

  26. Newshan G. Heat-related toxicity with the fentanyl transdermal patch. J Pain Symptom Manage 1998 Nov; 16(5): 277–8

    Article  PubMed  CAS  Google Scholar 

  27. Rose PG, Macfee MS, Boswell MV. Fentanyl transdermal system overdose secondary to cutaneous hyperthermia. Anesth Analg 1993 Aug; 77(2): 390–1

    PubMed  CAS  Google Scholar 

  28. Southam MA. Transdermal fentanyl therapy: system design, pharmacokinetics and efficacy. Anticancer Drugs 1995 Apr; 6 Suppl. 3: 29–34

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  30. Grond S, Radbruch L, Lehmann KA. Clinical pharmacokinetics of transdermal opioids: focus on transdermal fentanyl. Clin Pharmacokinet 2000; 38(1): 59–89

    Article  PubMed  CAS  Google Scholar 

  31. Sandler AN, Baxter AD, Katz J, et al. A double-blind, placebo-controlled trial of transdermal fentanyl after abdominal hysterectomy. Analgesic, respiratory, and pharmacokinetic effects. Anesthesiology 1994 Nov; 81(5): 1169–80; discussion 26A

    Article  PubMed  CAS  Google Scholar 

  32. Payne R, Chandler S, Einhaus M. Guidelines for the clinical use of transdermal fentanyl. Anticancer Drugs 1995 Apr; 6 Suppl. 3: 50–3

    Article  PubMed  CAS  Google Scholar 

  33. Sandler A. Transdermal fentanyl: acute analgesic clinical studies. J Pain Symptom Manage 1992 Apr; 7 (3 Suppl.): S27–35

    Article  PubMed  CAS  Google Scholar 

  34. Hanks GW, Fallon MT. Transdermal fentanyl in cancer pain: conversion from oral morphine. J Pain Symptom Manage 1995 Feb; 10(2): 87

    Article  PubMed  CAS  Google Scholar 

  35. Donner B, Zenz M, Tryba M, et al. Direct conversion from oral morphine to transdermal fentanyl: a multicenter study in patients with cancer pain. Pain 1996; 64(3): 527–34

    Article  PubMed  CAS  Google Scholar 

  36. Jeal W, Benfield P. Transdermal fentanyl. A review of its pharmacological properties and therapeutic efficacy in pain control. Drugs 1997; 53(1): 109–38

    Article  PubMed  CAS  Google Scholar 

  37. Radbruch L, Sabatowski R, Petzke F, et al. Transdermal fentanyl for the management of cancer pain: a survey of 1005 patients. Palliat Med 2001 Jul; 15(4): 309–21

    Article  PubMed  CAS  Google Scholar 

  38. Ahmedzai S, Brooks D. Transdermal fentanyl versus sustained-release oral morphine in cancer pain: preference, efficacy, and quality of life. J Pain Symptom Manage 1997; 13(5): 254–61

    Article  PubMed  CAS  Google Scholar 

  39. Payne R, Mathias SD, Pasta DJ, et al. Quality of life and cancer pain: satisfaction and side effects with transdermal fentanyl versus oral morphine. J Clin Oncol 1998; 16(4): 1588–93

    PubMed  CAS  Google Scholar 

  40. Allan L, Hays H, Jensen NH, et al. Randomised crossover trial of transdermal fentanyl and sustained release oral morphine for treating chronic non-cancer pain. BMJ 2001 May 12; 322(7295): 1154–8

    Article  PubMed  CAS  Google Scholar 

  41. Berliner MN, Giesecke T, Bornhovd KD. Impact of transdermal fentanyl on quality of life in rheumatoid arthritis. Clin J Pain 2007 Jul–Aug; 23(6): 530–4

    Article  PubMed  Google Scholar 

  42. Agarwal S, Polydefkis M, Block B, et al. Transdermal fentanyl reduces pain and improves functional activity in neuropathic pain states. Pain Med 2007 Oct–Nov; 8(7): 554–62

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  44. Viscusi ER, Reynolds L, Tait S, et al. An iontophoretic fentanyl patient-activated analgesic delivery system for postoperative pain: a double-blind, placebo-controlled trial. Anesth Analg 2006 Jan; 102(1): 188–94

    Article  PubMed  CAS  Google Scholar 

  45. Panchal SJ, Damaraju CV, Nelson WW, et al. 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 Nov; 105(5): 1437–41

    Article  PubMed  CAS  Google Scholar 

  46. Viscusi ER, Siccardi M, Damaraju CV, et al. 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 Nov; 105(5): 1428–36

    Article  PubMed  CAS  Google Scholar 

  47. Chelly JE, Grass J, Houseman TW, et al. The safety and efficacy of a fentanyl patient-controlled transdermal system for acute postoperative analgesia: a multicenter, placebo-controlled trial. Anesth Analg 2004 Feb; 98(2): 427–33

    Article  PubMed  CAS  Google Scholar 

  48. European Medicines Agency. European Medicines Agency recommends the suspension of the marketing authorisation of Ionsys (fentanyl hydrochloride) [online]. Available from URL: http://www.emea.europa.eu/humandocs/PDFs/EPAR/ionsys/61385208en.pdf [Accessed 2009 Jun 10]

  49. Zhang H, Zhang J, Streisand JB. Oral mucosal drug delivery: clinical pharmacokinetics and therapeutic applications. Clin Pharmacokinet 2002; 41(9): 661–80

    Article  PubMed  CAS  Google Scholar 

  50. Lichtor JL, Sevarino FB, Joshi GP, et al. The relative potency of oral transmucosal fentanyl citrate compared with intravenous morphine in the treatment of moderate to severe postoperative pain. Anesth Analg 1999 Sep; 89(3): 732–8

    PubMed  CAS  Google Scholar 

  51. Streisand JB, Varvel JR, Stanski DR, et al. Absorption and bioavailability of oral transmucosal fentanyl citrate. Anesthesiology 1991 Aug; 75(2): 223–9

    Article  PubMed  CAS  Google Scholar 

  52. Streisand JB, Busch MA, Egan TD, et al. Dose proportionality and pharmacokinetics of oral transmucosal fentanyl citrate. Anesthesiology 1998 Feb; 88(2): 305–9

    Article  PubMed  CAS  Google Scholar 

  53. Zeppetella G, Ribeiro MD. Opioids for the management of breakthrough (episodic) pain in cancer patients. Cochrane Database Syst Rev 2006; (1): CD004311

  54. Coluzzi PH, Schwartzberg L, Conroy JD, 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  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  56. Hanks GW, Nugent M, Higgs CM, et al. Oral transmucosal fentanyl citrate in the management of breakthrough pain in cancer: an open, multicentre, dose-titration and long-term use study. Palliat Med 2004 Dec; 18(8): 698–704

    Article  PubMed  CAS  Google Scholar 

  57. Burton AW, Driver LC, Mendoza TR, et al. Oral transmucosal fentanyl citrate in the outpatient management of severe cancer pain crises: a retrospective case series. Clin J Pain 2004 May–Jun; 20(3): 195–7

    Article  PubMed  Google Scholar 

  58. Tennant F, Hermann L. Self-treatment with oral transmucosal fentanyl citrate to prevent emergency room visits for pain crises: patient self-reports of efficacy and utility. J Pain Palliat Care Pharmacother 2002; 16(3): 37–44

    PubMed  Google Scholar 

  59. Landy SH. Oral transmucosal fentanyl citrate for the treatment of migraine headache pain in outpatients: a case series. Headache 2004 Sep; 44(8): 762–6

    Article  PubMed  Google Scholar 

  60. Shaiova L, Wallenstein D. Outpatient management of sickle cell pain with chronic opioid pharmacotherapy. J Natl Med Assoc 2004 Jul; 96(7): 984–6

    PubMed  Google Scholar 

  61. Sharar SR, Bratton SL, Carrougher GJ, et al. A comparison of oral transmucosal fentanyl citrate and oral hydromorphone for inpatient pediatric burn wound care analgesia. J Burn Care Rehabil 1998 Nov–Dec; 19(6): 516–21

    Article  PubMed  CAS  Google Scholar 

  62. Sharar SR, Carrougher GJ, Selzer K, et al. A comparison of oral transmucosal fentanyl citrate and oral oxycodone for pediatric outpatient wound care. J Burn Care Rehabil 2002 Jan–Feb; 23(1): 27–31

    Article  PubMed  CAS  Google Scholar 

  63. Darwish M, Kirby M, Robertson Jr P, et al. Single-dose and steady-state pharmacokinetics of fentanyl buccal tablet in healthy volunteers. J Clin Pharmacol 2007 Jan; 47(1): 56–63

    Article  PubMed  CAS  Google Scholar 

  64. Darwish M, Kirby M, Robertson Jr P, et al. Pharmacokinetic properties of fentanyl effervescent buccal tablets: a phase I, open-label, crossover study of single-dose 100, 200, 400, and 800 microg in healthy adult volunteers. Clin Ther 2006 May; 28(5): 707–14

    Article  PubMed  CAS  Google Scholar 

  65. Darwish M, Kirby M, Robertson Jr P, et al. Absolute and relative bioavailability of fentanyl buccal tablet and oral transmucosal fentanyl citrate. J Clin Pharmacol 2007 Mar; 47(3): 343–50

    Article  PubMed  CAS  Google Scholar 

  66. Darwish M, Tempero K, Kirby M, et al. Relative bioavailability of the fentanyl effervescent buccal tablet (FEBT) 1080 pg versus oral transmucosal fentanyl citrate 1600 pg and dose proportionality of FEBT 270 to 1300 microg: a single-dose, randomized, open-label, three-period study in healthy adult volunteers. Clin Ther 2006 May; 28(5): 715–24

    Article  PubMed  CAS  Google Scholar 

  67. Darwish M, Tempero K, Kirby M, et al. Pharmacokinetics and dose proportionality of fentanyl effervescent buccal tablets in healthy volunteers. Clin Pharmacokinet 2005; 44(12): 1279–86

    Article  PubMed  CAS  Google Scholar 

  68. Darwish M, Kirby M, Robertson Jr P, et al. Comparison of equivalent doses of fentanyl buccal tablets and arteriovenous differences in fentanyl pharmacokinetics. Clin Pharmacokinet 2006; 45(8): 843–50

    Article  PubMed  CAS  Google Scholar 

  69. Portenoy RK, Taylor D, Messina J, et al. A randomized, placebo-controlled study of fentanyl buccal tablet for breakthrough pain in opioid-treated patients with cancer. Clin J Pain 2006 Nov–Dec; 22(9): 805–11

    Article  PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  71. Portenoy RK, Messina J, Xie F, et al. Fentanyl buccal tablet (FBT) for relief of breakthrough pain in opioid-treated patients with chronic low back pain: a randomized, placebo-controlled study. Curr Med Res Opin 2007 Jan; 23(1): 223–33

    Article  PubMed  CAS  Google Scholar 

  72. Simpson DM, Messina J, Xie F, et al. Fentanyl buccal tablet for the relief of breakthrough pain in opioid-tolerant adult patients with chronic neuropathic pain: a multicenter, randomized, double-blind, placebo-controlled study. Clin Ther 2007 Apr; 29(4): 588–601

    Article  PubMed  CAS  Google Scholar 

  73. Portenoy RK, Payne D, Jacobsen P. Breakthrough pain: characteristics and impact in patients with cancer pain. Pain 1999 May; 81(1–2): 129–34

    Article  PubMed  CAS  Google Scholar 

  74. Fine PG. Pain-final common pathways: pathophysiology and pragmatism. Reg Anesth Pain Med 2000 Jan–Feb; 25(1): 1–2

    PubMed  CAS  Google Scholar 

  75. Mercadante S, Arcuri E. Breakthrough pain in cancer patients: pathophysiology and treatment. Cancer Treat Rev 1998 Dec; 24(6): 425–32

    Article  PubMed  CAS  Google Scholar 

  76. Caraceni A, Martini C, Zecca E, et al. Breakthrough pain characteristics and syndromes in patients with cancer pain. An international survey. Palliat Med 2004 Apr; 18(3): 177–83

    Article  PubMed  Google Scholar 

  77. Fine PG, Busch MA. Characterization of breakthrough pain by hospice patients and their caregivers. J Pain Symptom Manage 1998; 16(3): 179–83

    Article  PubMed  CAS  Google Scholar 

  78. Portenoy RK, Hagen NA. Breakthrough pain: definition, prevalence and characteristics. Pain 1990 Jun; 41(3): 273–81

    Article  PubMed  CAS  Google Scholar 

  79. Zeppetella G, O’Doherty CA, Collins S. Prevalence and characteristics of breakthrough pain in cancer patients admitted to a hospice. J Pain Symptom Manage 2000 Aug; 20(2): 87–92

    Article  PubMed  CAS  Google Scholar 

  80. FDA. Important Safety Information for Fentora [online]. Available from URL: http://www.fda.gov/downloads/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/UCM154439.pdf [Accessed 2009 Oct 19]

  81. Diaz del Consuelo I, Falson F, Guy RH, et al. Ex vivo evaluation of bioadhesive films for buccal delivery of fentanyl. J Control Release 2007 Sep 26; 122(2): 135–40

    Article  Google Scholar 

  82. Vasisht N, Gever LN, Tagarro I, et al. Formulation selection and pharmacokinetic comparison of fentanyl buccal soluble film with oral transmucosal fentanyl citrate: a randomized, open-label, single-dose, crossover study. Clin Drug Investig 2009; 29(10): 647–54

    Article  PubMed  CAS  Google Scholar 

  83. Bredenberg S, Duberg M, Lennernas B, 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 Nov; 20(3): 327–34

    Article  PubMed  CAS  Google Scholar 

  84. Lennernas B, Hedner T, Holmberg M, et al. Pharmacokinetics and tolerability of different doses of fentanyl following sublingual administration of a rapidly dissolving tablet to cancer patients: a new approach to treatment of incident pain. Br J Clin Pharmacol 2005 Feb; 59(2): 249–53

    Article  PubMed  CAS  Google Scholar 

  85. Striebel HW, Kramer J, Luhmann I, et al. Pharmacokinetics of intranasal fentanyl. Schmerz 1993 Jun; 7(2): 122–5

    Article  PubMed  CAS  Google Scholar 

  86. Striebel HW, Wessel A, Rieger A. Intranasal fentanyl for breakthrough cancer pain. A pilot study. Schmerz 1993 Sep; 7(3): 174–7

    Article  PubMed  CAS  Google Scholar 

  87. Paech MJ, Lim CB, Banks SL, et al. A new formulation of nasal fentanyl spray for postoperative analgesia: a pilot study. Anaesthesia 2003 Aug; 58(8): 740–4

    Article  PubMed  CAS  Google Scholar 

  88. Striebel HW, Koenigs D, Kramer J. Postoperative pain management by intranasal demand-adapted fentanyl titration. Anesthesiology 1992 Aug; 77(2): 281–5

    Article  PubMed  CAS  Google Scholar 

  89. Striebel HW, Oelmann T, Spies C, et al. Patient-controlled intranasal analgesia: a method for noninvasive postoperative pain management. Anesth Analg 1996; 83: 548–51

    PubMed  CAS  Google Scholar 

  90. Toussaint S, Maidl J, Schwagmeier R, et al. Patient-controlled intranasal analgesia: effective alternative to intravenous PCA for postoperative pain relief. Can J Anaesth 2000 Apr; 47(4): 299–302

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  92. Rickard C, O’Meara P, McGrail M, et al. A randomized controlled trial of intranasal fentanyl vs intravenous morphine for analgesia in the prehospital setting. Am J Emerg Med 2007 Oct; 25(8): 911–7

    Article  PubMed  Google Scholar 

  93. Finn J, Wright J, Fong J, 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 May; 30(3): 262–8

    Article  PubMed  Google Scholar 

  94. 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 Oct; 20(4): 253–8

    Article  PubMed  CAS  Google Scholar 

  95. Borland M, Jacobs I, King B, et al. A randomized controlled trial comparing intranasal fentanyl to intravenous morphine for managing acute pain in children in the emergency department. Ann Emerg Med 2007 Mar; 49(3): 335–40

    Article  PubMed  Google Scholar 

  96. Manjushree R, Lahiri A, Ghosh BR, et al. Intranasal fentanyl provides adequate postoperative analgesia in pediatric patients. Can J Anaesth 2002 Feb; 49(2): 190–3

    Article  PubMed  Google Scholar 

  97. Worsley MH, MacLeod AD, Brodie MJ, et al. Inhaled fentanyl as a method of analgesia. Anaesthesia 1990 Jun; 45(6): 449–51

    Article  PubMed  CAS  Google Scholar 

  98. Hung OR, Whynot SC, Varvel JR, et al. Pharmacokinetics of inhaled liposome-encapsulated fentanyl. Anesthesiology 1995 Aug; 83(2): 277–84

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

No funding was received for the preparation of this article. The editorial assistance of Peta Gjedsted (employed by University of Western Australia, assisted with reference management), Mandy Burkert (employed by Socratec R&D, assisted in preparation of figures) and Maximilian Pohland (employed by Socratec R&D, assisted in preparation of figures) is acknowledged.

The department of Dr Stephan Schug receives research and consultancy funding from Janssen Pharmaceuticals, which manufacture some of the products mentioned in the review. The company of Dr Barbara Schug, Socratec R&D GmbH, has performed several bioavailability and bioequivalence studies of fentanyl preparations for Ratiopharm, Spirit and Haupt, and has acted as consultants for these companies as well as for Stada. Drs Grape and Lauer have no conflicts that are directly relevant to the content of this review.

Author information

Authors and Affiliations

  1. Department of Anaesthesia and Pain Medicine, Royal Perth Hospital, Perth, Western Australia, Australia

    Sina Grape &  Stephan A. Schug

  2. Pharmacology and Anaesthesiology Unit, University of Western Australia, Perth, Western Australia, Australia

    Stephan A. Schug

  3. Department of Anaesthesiology and Intensive Care Medicine, University of Muenster, Muenster, Germany

    Stephan A. Schug & Stefan Lauer

  4. SocraTec R&D GmbH, Oberursel, Germany

    Barbara S. Schug

Authors
  1. Sina Grape
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stephan A. Schug
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stefan Lauer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Barbara S. Schug
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Stephan A. Schug.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Grape, S., Schug, S.A., Lauer, S. et al. Formulations of Fentanyl for the Management of Pain. Drugs 70, 57–72 (2010). https://doi.org/10.2165/11531740-000000000-00000

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/11531740-000000000-00000

Keywords

Search

Navigation