A patient-activated iontophoretic transdermal system for acute pain management with fentanyl hydrochloride: Overview and applications

Kevin T. Bain, PharmD, BCPS, CGP, FASCP

Abstract


Opioid administration by patient-controlled analgesia (PCA) is the standard therapy for acute postoperative pain. Despite its utility in this setting, limitations of this modality do exist. Consequently, noninvasive PCA systems, including an iontophoretic transdermal system (ITS) with fentanyl hydrochloride, are under development to circumvent many of these limitations. This preprogram med, self-contained, compact, needle-free system provides pain con trol superior to that of placebo and comparable to morphine PCA in the first 24 hours after major surgical procedures. The objectives of this article are to describe the method of transdermal iontophoretic medication administration and to review the literature pertaining to the fentanyl ITS.

Keywords


iontophoresis, transdermal, fentanyl, opioid analgesics, patient-controlled analgesia, noninvasive method, postoperative pain, acute pain, breakthrough pain

Full Text:

PDF

References


Austrup ML, Korean G: Analgesic agents for the postoperative period. Opioids. Surg Clin North Am. 1999; 79(2): 253-273.

Jain S, Datta S: Postoperative pain management. Chest Surg Clin N Am. 1997; 7(4): 773-799.

Bennett RL, Batenhorst RL, Bivins BA, et al.: Patient-controlled analgesia: A new concept of postoperative pain relief. Ann Surg. 1982; 195(6): 700-705.

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

Ballantyne JC, Carr DB, Chalmers TC, et al.: Postoperative patient-controlled analgesia: Meta-analyses of initial randomized control trials. J Clin Anesth. 1993; 5(3): 182-193.

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; 98(2): 427-433.

Macintyre PE: Safety and efficacy of patient-controlled analgesia. Br J Anaesth. 2001; 87(1): 36-46.

Viscusi ER, Reynolds L, Chung F, et al.: Patient-controlled transdermal fentanyl hydrochloride vs intravenous morphine pump for postoperative pain: A randomized controlled trial. JAMA. 2004; 291(11): 1333-1341.

Etches RC: Patient-controlled analgesia. Surg Clin North Am. 1999; 79(2): 297-312.

Vicente KJ, Kada-Bekhaled K, Hillel G, et al.: Programming errors contribute to death from patient-controlled analgesia: Case report and estimate of probability. Can J Anaesth. 2003; 50(4): 328-332.

Viscusi ER, Witkowski TA: Iontophoresis: The process behind noninvasive drug delivery. Reg Anesth Pain Med. 2005; 30(3): 292-294.

Alexander-Williams JM, Rowbotham DJ: Novel routes of opioid administration. Br J Anaesth. 1998; 81(1): 3-7.

Barry BW: Novel mechanisms and devices to enable successful transdermal drug delivery. Eur J Pharm Sci. 2001; 14(2): 101-114.

Kalia YN, Naik A, Garrison J, et al.: Iontophoretic drug delivery. Adv Drug Deliv Rev. 2004; 56(5): 619-658.

Wang Y, Thakur R, Fan Q, et al.: Transdermal iontophoresis: Combination strategies to improve transdermal iontophoretic drug delivery. Eur J Pharm Biopharm. 2005; 60(2): 179-191.

Curdy C, Kalia YN, Guy RH: Non-invasive assessment of the effects of iontophoresis on human skin in-vivo. J Pharm Pharmacol. 2001; 53(6): 769-777.

Gupta SK, Southam M, Sathyan G, et al.: Effect of current density on pharmacokinetics following continuous or intermittent input from a fentanyl electrotransport system. J Pharm Sci. 1998; 87(8): 976-981.

Gourlay GK, Kowalski SR, Plummer JL, et al.: Fentanyl blood concentration-analgesic response relationship in the treatment of postoperative pain. Anesth Analg. 1988; 67(4): 329-337.

Peng PW, Sandler AN: A review of the use of fentanyl analgesia in the management of acute pain in adults. Anesthesiology. 1999; 90(2): 576-599.

Banta CA: A prospective, nonrandomized study of iontophoresis, wrist splinting, and antiinflammatory medication in the treatment of early-mild carpal tunnel syndrome. J Occup Med. 1994; 36(2): 166-168.

Singh J, Roberts MS: Transdermal delivery of drugs by iontophoresis: A review. Drug Des Deliv. 1989; 4(1): 1-12.

Singh P, Maibach HI: Iontophoresis in drug delivery: Basic principles and applications. Crit Rev Ther Drug Carrier Syst. 1994; 11(2-3): 161-213.

Chelly JE: An iontophoretic, fentanyl HCl patient-controlled transdermal system for acute postoperative pain management. Expert Opin Pharmacother. 2005; 6(7): 1205-1214.

Ashburn MA, Stephen RL, Ackerman E, et al.: Iontophoretic delivery of morphine for postoperative analgesia. J Pain Symptom Manage. 1992; 7(1): 27-33.

Bezzant JL, Stephen RL, Petelenz TJ, et al.: Painless cauterization of spider veins with the use of iontophoretic local anesthesia. J Am Acad Dermatol. 1988; 19(5 Pt 1): 869-875.

Petelenz T, Axenti I, Petelenz TJ, et al.: Mini set for iontophoresis for topical analgesia before injection. Int J Clin Pharmacol Ther Toxicol. 1984; 22(3): 152-155.

Glass JM, Stephen RL, Jacobson SC: The quantity and distribution of radiolabeled dexamethasone delivered to tissue by iontophoresis. Int J Dermatol. 1980; 19(9): 519-525.

Su MH, Srinivasan V, Ghanem AH, et al.: Quantitative in vivo iontophoretic studies. J Pharm Sci. 1994; 83(1): 12-17.

Ashburn MA, Streisand J, Zhang J, et al.: The iontophoresis of fentanyl citrate in humans. Anesthesiology. 1995; 82(5): 1146-1153.

Vanbever R, LeBoulenge E, Preat V: Transdermal delivery of fentanyl by electroporation. I. Influence of electrical factors. Pharm Res. 1996; 13(4): 559-565.

Vanbever R, Morre ND, Preat V: Transdermal delivery of fentanyl by electroporation. II. Mechanisms involved in drug transport. Pharm Res. 1996; 13(9): 1360-1366.

Singh P, Maibach HI: Transdermal iontophoresis. Pharmacokinetic considerations. Clin Pharmacokinet. 1994; 26(5): 327-334.

Thysman S, Preat V: In vivo iontophoresis of fentanyl and sufentanil in rats: Pharmacokinetics and acute antinociceptive effects. Anesth Analg. 1993; 77(1): 61-66.

Thysman S, Tasset C, Preat V: Transdermal iontophoresis of fentanyl: Delivery and mechanistic analysis. Int J Pharm. 1994; 101(1-2): 105-113.

Gupta SK, Bernstein KJ, Noorduin H, et al.: Fentanyl delivery from an electrotransport system: Delivery is a function of total current, not duration of current. J Clin Pharmacol. 1998; 38(10): 951-958.

Gupta SK, Sathyan G, Phipps B, et al.: Reproducible fentanyl doses delivered intermittently at different time intervals from an electrotransport system. J Pharm Sci. 1999; 88(8): 835-841.

Sathyan G, Zomorodi K, Gidwani S, et al.: The effect of dosing frequency on the pharmacokinetics of a fentanyl HCl patient-controlled transdermal system (PCTS). Clin Pharmacokinet. 2005; 44 Suppl 1: 17-24.

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.

Gupta SK, Hwang S, Southam M, et al.: 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.

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; 37(2): 193-202.

Gourlay GK, Kowalski SR, Plummer JL, et al.: The efficacy of transdermal fentanyl in the treatment of postoperative pain: A double-blind comparison of fentanyl and placebo systems. Pain. 1990; 40(1): 21-28.

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

Gourlay GK: Treatment of cancer pain with transdermal fentanyl. Lancet Oncol. 2001; 2(3): 165-172.

Varvel JR, Shafer SL, Hwang SS, et al.: Absorption characteristics of transdermally administered fentanyl. Anesthesiology. 1989; 70(6): 928-934.

Sinatra R: The fentanyl HCl patient-controlled transdermal system (PCTS): An alternative to intravenous patient-controlled analgesia in the postoperative setting. Clin Pharmacokinet. 2005; 44 Suppl 1: 1-6.

Welchew EA: On-demand analgesia. A double-blind comparison of on-demand intravenous fentanyl with regular intramuscular morphine. Anaesthesia. 1983; 38(1): 19-25.

Lehmann KA, Heinrich C, van Heiss R: Balanced anesthesia and patient-controlled postoperative analgesia with fentanyl: Minimum effective concentrations, accumulation and acute tolerance. Acta Anaesthesiol Belg. 1988; 39(1): 11-23.

Glass PS, Estok P, Ginsberg B, et al.: Use of patient-controlled analgesia to compare the efficacy of epidural to intravenous fentanyl administration. Anesth Analg. 1992; 74(3): 345-351.

Ginsberg B, Gil KM, Muir M, et al.: The influence of lockout intervals and drug selection on patient-controlled analgesia following gynecological surgery. Pain. 1995; 62(1): 95-100.

Koo PJ: Postoperative pain management with a patient-controlled transdermal delivery system for fentanyl. Am J Health Syst Pharm. 2005; 62(11): 1171-1176.

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): 890-895.

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; 102(1): 188-194.

Schumann R, Shikora S, Weiss JM, et al.: A comparison of multimodal perioperative analgesia to epidural pain management after gastric bypass surgery. Anesth Analg. 2003; 96(2): 469-474.

Howell PR, Gambling DR, Pavy T, et al.: Patient-controlled analgesia following caesarean section under general anaesthesia: A comparison of fentanyl with morphine. Can J Anaesth. 1995; 42(1): 41-45.

Jadoul A, Bouwstra J, Preat VV: Effects of iontophoresis and electroporation on the stratum corneum. Review of the biophysical studies. Adv Drug Deliv Rev. 1999; 35(1): 89-105.

Cullander C, Guy RH: Sites of iontophoretic current flow into the skin: Identification and characterization with the vibrating probe electrode. J Invest Dermatol. 1991; 97(1): 55-64.

Burnette RR, Ongpipattanakul B: Characterization of the pore transport properties and tissue alteration of excised human skin during iontophoresis. J Pharm Sci. 1988; 77(2): 132-137.

Grimnes S: Pathways of ionic flow through human skin in vivo. Acta Derm Venereol. 1984; 64(2): 93-98.

Burnette RR, Marrero D: Comparison between the iontophoretic and passive transport of thyrotropin releasing hormone across excised nude mouse skin. J Pharm Sci. 1986; 75(8): 738-743.

Clemessy M, Couarraze G, Bevan B, et al.: Mechanisms involved in iontophoretic transport of angiotensin. Pharm Res. 1995; 12(7): 998-1002.

Hill AC, Baker GF, Jansen GT: Mechanism of action of iontophoresis in the treatment of palmar hyperhidrosis. Cutis. 1981; 28(1): 69-70, 72.

Karakoc Y, Aydemir EH, Kalkan MT, et al.: Safe control of palmoplantar hyperhidrosis with direct electrical current. Int J Dermatol. 2002; 41(9): 602-605.

Bath BD, Scott ER, Phipps JB, et al.: Scanning electrochemical microscopy of iontophoretic transport in hairless mouse skin. Analysis of the relative contributions of diffusion, migration, and electroosmosis to transport in hair follicles. J Pharm Sci. 2000; 89(12): 1537-1549.

Bath BD, White HS, Scott ER: Visualization and analysis of electroosmotic flow in hairless mouse skin. Pharm Res. 2000; 17(4): 471-475.

Sandler A: Transdermal fentanyl: Acute analgesic clinical studies. J Pain Symptom Manage. 1992; 7(3 Suppl): S27-S35.

Kosinski MR, Schein JR, Vallow SM, et al.: An observational study of health-related quality of life and pain outcomes in chronic low back pain patients treated with fentanyl transdermal system. Curr Med Res Opin. 2005; 21(6): 849-862.

Clark AJ, Ahmedzai SH, Allan LG, et al.: Efficacy and safety of transdermal fentanyl and sustained-release oral morphine in patients with cancer and chronic non-cancer pain. Curr Med Res Opin. 2004; 20(9): 1419-1428.

Mystakidou K, Parpa E, Tsilika E, et al.: Pain management of cancer patients with transdermal fentanyl: A study of 1828 step I, II, & III transfers. J Pain. 2004; 5(2): 119-132.

Shaiova L, Wallenstein D: Outpatient management of sickle cell pain with chronic opioid pharmacotherapy. J Natl Med Assoc. 2004; 96(7): 984-986.

Lorvidhaya V, Katanyoo K, Srisomboon J, et al.: Evaluation of safety and efficacy of transdermal therapeutic system-fentanyl in adult patients with gynecological cancer-related pain. J Med Assoc Thai. 2004; 87(3): 319-325.

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; 322(7295): 1154-1158.

Donner B, Zenz M, Strumpf M, et al.: Long-term treatment of cancer pain with transdermal fentanyl. J Pain Symptom Manage. 1998; 15(3): 168-175.

Levy MH, Rosen SM, Kedziera P: Transdermal fentanyl: Seeding trial in patients with chronic cancer pain. J Pain Symptom Manage. 1992; 7(3 Suppl): S48-S50.

Patt RB, Hogan LA: Transdermal fentanyl for chronic cancer pain: Detailed case reports and the influence of confounding factors. J Pain Symptom Manage. 1992; 7(3 Suppl): S51-S53.

Sinatra R: Opioid analgesics in primary care: Challenges and new advances in the management of noncancer pain. J Am Board Fam Med. 2006; 19(2): 165-177.

Miaskowski C: Patient-controlled modalities for acute postoperative pain management. J Perianesth Nurs. 2005; 20(4): 255-267.

Apfelbaum JL, Chen C, Mehta SS, et al.: Postoperative pain experience: Results from a national survey suggest postoperative pain continues to be undermanaged. Anesth Analg. 2003; 97(2): 534-540.

Summers S: Evidence-based practice part 3: Acute pain management of the perianesthesia patient. J Perianesth Nurs. 2001; 16(2): 112-120.

Filos KS, Lehmann KA: Current concepts and practice in postoperative pain management: Need for a change? Eur Surg Res. 1999; 31(2): 97-107.

Kuhn S, Cooke K, Collins M, et al.: Perceptions of pain relief after surgery. BMJ. 1990; 300(6741): 1687-1690.

Lewis KS, Whipple JK, Michael KA, et al.: Effect of analgesic treatment on the physiological consequences of acute pain. Am J Hosp Pharm. 1994; 51(12): 1539-1554.

Oates JD, Snowdon SL, Jayson DW: Failure of pain relief after surgery. Attitudes of ward staff and patients to postoperative analgesia. Anaesthesia. 1994; 49(9): 755-758.

Chauvin M: State of the art of pain treatment following ambulatory surgery. Eur J Anaesthesiol Suppl. 2003; 28: 3-6.

Shang AB, Gan TJ: Optimising postoperative pain management in the ambulatory patient. Drugs. 2003; 63(9): 855-867.

Zimberg SE: Reducing pain and costs with innovative postoperative pain management. Manag Care Q. 2003; 11(1): 34-36.

Rawal N: Treating postoperative pain improves outcome. Minerva Anestesiol. 2001; 67(9 Suppl 1): 200-205.




DOI: https://doi.org/10.5055/jom.2006.0047

Refbacks

  • There are currently no refbacks.