Oral Transmucosal Fentanyl Citrate for Cancer Breakthrough Pain: A Review

Debra B. Gordon

ONF 2007, 33(2), 257-264. DOI: 10.1188/06.ONF.257-264

Purpose/Objectives: To review the dose titration, efficacy, and safety of oral transmucosal fentanyl citrate (OTFC).

Data Sources: Phase I and II clinical trial abstracts and evidencebased review articles.

Data Synthesis: OTFC has an onset, peak, and duration of action similar to that of an IV dose of an opioid and has been demonstrated to be effective and well tolerated for the management of breakthrough pain in patients with cancer.

Conclusions: Studies of OTFC demonstrate that it is easy to use, noninvasive, effective, safe, and acceptable to patients, caregivers, and healthcare providers. However, OTFC is expensive and approved for use only in opioid-tolerant patients with cancer.

Implications for Nursing: Breakthrough pain in patients with cancer is a common problem with characteristics that make it difficult to treat. Oncology nurses should familiarize themselves with OTFC's unique characteristics to be able to best help patients manage their therapy.

Jump to a section

    References

    Adelus, S., Rice, S., & Bruno, L. (2002, August). Titration and evaluation of oral transmucosal fentanyl citrate (OTFC-ACTIQ) for managing breakthrough pain (BTP) in clinical practice. Presentation at the International Conference on Cancer Nursing, London, UK.
    American Pain Society. (2003). Principles of analgesic use in the treatment of acute pain and cancer pain (5th ed.). Glenview, IL: Author.
    Ashburn, M.A., & Streisand, J.B. (1994). Oral transmucosal fentanyl: Help or hindrance? Drug Safety, 11, 295-300.
    Ashburn, M.A., Streisand, J.B., Tarver, S.D, Mears, S.L., Mulder, S.M., Floet Wilms, A.W., et al. (1990). Oral transmucosal fentanyl citrate for premedication in paediatric outpatients. Canadian Journal of Anaesthesia, 37, 857-866.
    Ashby, M.A., Fleming, B.G., Brooksbank, M., Rounsefell, B., Runciman, W.B., Jackson, K., et al. (1992). Description of a mechanistic approach to pain management in advanced cancer. Preliminary report. Pain, 52, 153-161.
    Basskin, L.E. (1999). Oral transmucosal fentanyl citrate: A new dosage form for breakthrough malignant pain. American Journal of Pain Management, 9, 129-138.
    Bennett, D., Burton, A.W., Fishman, S., Fortner, B., McCarberg, B., Miaskowski, C., et al. (2005a). Consensus panel recommendations for the assessment and management of breakthrough pain, part 1, assessment. Pharmacy and Therapeutics, 30, 296-301.
    Bennett, D., Burton, A.W., Fishman, S., Fortner, B., McCarberg, B., Miaskowski, C., et al. (2005b). Consensus panel recommendations for the assessment and management of pain, part 2, management. Pharmacy and Therapeutics, 30, 354-361.
    Bruera, E., Fainsinger, R., MacEachern, T., & Hanson, J. (1992). The use of methylphenidate in patients with incident cancer pain receiving regular opiates: A preliminary report. Pain, 50, 75-77.
    Burton, A.W., Driver, L.C., Mendoza, T.R., & Syed, G. (2004). Oral transmucosal fentanyl citrate in the outpatient management of severe cancer pain crises: A retrospective case series. Clinical Journal of Pain, 20, 195-197.
    Cephalon. (2004). Actiq® package insert. Frazer, PA: Author.
    Cephalon. (2005, May 5). Cephalon announces positive stage 3 clinical trial results for Oravescent® fentanyl. Retrieved July 21, 2005, from http://phx.corporate-ir.net/phoenix.zhtml?c=81709&p=irol-newsArticle&ID=706 033&highlight
    Chandler, S. (1999). Oral transmucosal fentanyl citrate: A new treatment for breakthrough pain. American Journal of Hospice and Palliative Care, 16, 489-491.
    Christie, J.M., Simmonds, M., Patt, R., Coluzzi, P., Busch, M.A., Nordbrock, E., et al. (1998). Dose-titration, multicenter study of oral transmucosal fentanyl citrate for the treatment for breakthrough pain in cancer patients using transdermal fentanyl for persistent pain. Journal of Clinical Oncology, 16, 3238-3245.
    Colleau, S.M. (2004). Breakthrough (episodic) vs. baseline (persistent) pain in cancer. Cancer pain Release, 17(4), 1-3.
    Coluzzi, P.H. (1998). Sublingual morphine: Efficacy reviewed. Journal of Pain and Symptom Management, 16, 184-192.
    Coluzzi, P.H., Schwartzberg, L., Conroy, J.D., Charapata, S., Gay, M., Busch, M.A., et al. (2001). Breakthrough cancer pain: A randomized trial comparing oral transmucosal fentanyl citrate (OTFC) and morphine sulfate immediate release (MSIR). Pain, 91, 123-130.
    Danjoux, C., Chow, E., Wong, R., Connolly, R., Andersson, L., Franssen, E., et al. (2000). Oral transmucosal fentanyl citrate (OTFC) for incidental pain in radiotherapy patients-an innovative approach [Abstract 144]. Clinical Investigator Medicine, 23(4, Suppl.), S23.
    Davis, T., Miser, A.W., Loprinzi, C.L, Kaur, J.S., Burnham, N.L., Dose, A.M., et al. (1993). Comparative morphine pharmacokinetics following sublingual, intramuscular, and oral administration in patients with cancer. Hospice Journal, 9, 85-90.
    Egan, T., Kern, S.E., & Vadiei, K.Q. (2002, Feburary). The pharmacokinetics and safety of oral transmucosal fentanyl administered to health volunteers as two 400-μg ACTIQ dosage units or as a single 800-μg ACTIQ dosage unit. Poster presentation at the American Academy of Pain Management Annual Scientific Meeting, San Francisco, CA.
    Ferrante, F.M. (1996). Principles of opioid pharmacotherapy: Practical implications of basic mechanisms. Journal of Pain and Symptom Management, 11, 265-273.
    Fine, P.G., & Busch, M.A. (1998). Characterization of breakthrough pain by hospice patients and their caregivers. Journal of Pain and Symptom Management, 16, 179-183.
    Fine, P.G., & Streisand, J.B. (1998). A review of oral transmucosal fentanyl citrate: Potent, rapid and noninvasive opioid analgesia. Journal of Palliative Medicine, 1, 55-63.
    Foley, K.M. (1993). Opioids. Neurologic Clinics, 11, 503-522.
    Fortner, B.V., Okon, T.A., & Portenoy, R.K. (2002). A survey of pain-related hospitalizations, emergency department visits, and physician office visits reported by cancer patients with and without history of breakthrough pain. Journal of Pain, 3, 38-44.
    Gomez-Batiste, X., Madrid, F., Moreno, F., Gracia, A., Trelis, J., Nabal, M., et al. (2002). Breakthrough cancer pain: Prevalence and characteristics in patients in Catalonia, Spain. Journal of Pain and Symptom Management, 24, 45-52.
    Kharasch, E.D., Hoffer, C., & Whittington, D. (2004). Influence of age on the pharmacokinetics and pharmacodynamics of oral transmucosal fentanyl citrate. Anesthesiology, 101, 738-743.
    Lee, M., Kern, S.E., Kisicki, J.C., & Egan, T.D. (2003). A pharmacokinetic study to compare two simultaneous 400 microg doses with a single 800 microg dose of oral transmucosal fentanyl citrate. Journal of Pain and Symptom Management, 26, 743-747.
    Lichtor, J.L., Sevarino, F.B., Joshi, G.P., Busch, M.A., Nordbrock, E., & Ginsberg, B. (1999). The relative potency of oral transmucosal fentanyl citrate compared with intravenous morphine in the treatment of moderate to severe postoperative pain. Anesthesia and Analgesia, 89, 732-738.
    Lu, J., & Bailey, P.L. (2003, October). Dose-related respiratory pharmacology of oral transmucosal fentanyl-citrate (OTFC) versus intravenous morphine: A randomized, double-blind, double-dummy study. Presentation at the American Society of Anesthesiologists Annual Meeting, San Francisco, CA.
    Marek, B., Qazi, F., Ghazal, H., Drinkard, L., Tzou, N., Livermore, M., et al. (2001, May). Evaluation of oral transmucosal fentanyl citrate titration practices in the clinical setting. Poster abstract presented at the American Society of Clinical Oncology Annual Meeting, San Francisco, CA.
    Mather, E.L., & Denson, D.D. (2000). General principles of pharmacological techniques. In R.P. Raj (Ed.), Practical management of pain (3rd ed., pp. 445-461). St Louis, MO: Mosby.
    Mercadante, S., Radbruch, L., Caraceni, A., Cherny, N., Kaasa, S., Nauck, F., et al. (2002). Episodic (breakthrough) pain: Consensus conference on an expert working group of the European Association of Palliative Care. Cancer, 94, 832-839.
    Mock, D.L., Streisand, J.B., Hague, B., Dzelzkalns, R.R., Bailey, P.L., Pace, N.L., et al. (1986). Transmucosal narcotic delivery: An evaluation of fentanyl (lollipop) premedication in man. Anesthesia and Analgesia, 65, S102.
    Moore, P.A., Cuddy, M.A., Magera, J.A., Caputo, A.C., Chen, A.H., & Wilkinson, L.A. (2000). Oral transmucosal fentanyl pretreatment for outpatient general anesthesia. Anesthesia Progress, 47(2), 29-34.
    Mystakidou, K., Katsouda, E., Parpa, E., Tsiatas, M.L., & Vlahos, L. (2005). Oral transmucosal fentanyl citrate for the treatment of breakthrough pain in cancer patients: An overview of the pharmacological and clinical characteristics. American Journal of Hospice and Palliative Care, 22, 228-232.
    Nelson, P.S., Streisand, J.B., Mulder, S.M., Pace, N.L., & Stanley, T.H. (1989). Comparison of oral transmucosal fentanyl citrate and oral solutions of meperidine, diazepam, and atropine for premedication in children. Anesthesiology, 70, 616-621.
    Osborne, R., Joel, S., Trew, D., & Slevin, M. (1990). Morphine and metabolite behavior after different routes of morphine administration: Demonstration of the importance of the active metabolite morphine-6-glucourinide. Clinical Pharmacology and Therapeutics, 47, 12-19.
    Pannuti, F., Rossi, A.P., Iafelice, G., Mararo, D., Camera, P., Cricca, A., et al. (1982). Control of chronic pain in very advanced cancer patients with morphine hydrochloride administered by oral, rectal, and sublingual routes: Clinical report and preliminary results on morphine pharmacokinetics. Pharmacological Research Communications, 14, 369-380.
    Payne, R., Coluzzi, P., Hart, L., Simmonds, M., Lyss, A., Rauck, R., et al. (2001). Long-term safety of oral transmucosal fentanyl citrate for breakthrough cancer pain. Journal of Pain and Symptom Management, 22, 575-583.
    Portenoy, R.K., & Hagen, N.A. (1990). Breakthrough pain: Definition, prevalence and characteristics. Pain, 41, 273-281.
    Portenoy, R.K., Lapin, J., Shaiova, L.A., Manco, L.S., Shasha, D., Hu, K., et al. (2002, May). Tolerability and effects of two formulations of oral transmucosal fentanyl citrate (OTFC; ACTIQ) in patients with radiation-induced oral mucositis. Presentation at the 38th American Society of Clinical Oncology Annual Meeting, Orlando, FL.
    Portenoy, R.K., Payne, D., & Jacobsen, P. (1999). Breakthrough pain: Characteristics and impact in patients with cancer pain. Pain, 81, 129-134.
    Portenoy, R.K., Payne, R., Coluzzi, P., Raschko, J.W., Lyss, A., Busch, M.A., et al. (1999). Oral transmucosal fentanyl citrate (OTFC) for the treatment of breakthrough pain in cancer patients: A controlled dose titration study. Pain, 79, 303-312.
    Rees, E. (2002). The role of oral transmucosal fentanyl citrate in the management of breakthrough cancer pain. International Journal of Palliative Nursing, 8, 304-308.
    Rhiner, M., & Kedziera, P. (1999). Managing breakthrough cancer pain: A new approach. American Journal of Nursing, 99, S3-S15.
    Robison, J.M., Wilkie, D.J., & Campbell, B. (1995). Sublingual and oral morphine administration. Nursing Clinics of North America, 30, 725-743.
    Shaiova, L., Lapin, J., Manco, L.S., Shasha, D., Hu, K., Harrison, L., et al. (2004). Tolerability and effects of two formulations of oral transmucosal fentanyl citrate (OTFC; ACTIQ) in patients with radiation-induced oral mucositis. Supportive Care in Cancer, 12, 268-273.
    Simmonds, M.A. (1997). Oral transmucosal fentanyl citrate produces pain relief faster than medication typically used for breakthrough pain in cancer patients. Proceeding from the American Society of Clinical Oncology, 16, 52.
    Squier, C.A., & Johnson, N.W. (1975). Permeability of oral mucosa. British Medical Bulletin, 31, 169-175.
    Stanley, T.H., Hague, B., Mock, D.L., Streisand, J.B., Bubbers, S., Dzelzkalns, R.R., et al. (1989). Oral transmucosal fentanyl citrate (lollipop) medication in human volunteers. Anesthesia and Analgesia, 69, 21-27.
    Streisand, J.B., Busch, M.A., Egan, T.D., Smith, B.G., Gay, M., & Pace, N.L. (1998). Dose proportionality and pharmacokinetics of oral transmucosal fentanyl citrate. Anesthesiology, 88, 305-309.
    Streisand, J.B., Busch, M.A., Gaylord, B.A., Gay, M.A., & East, K.A. (1996). Dose proportionality of oral transmucosal fentanyl citrate in human volunteers [Abstract 322]. Anesthesiology, 85(3A), 443.
    Streisand, J.B., Rosenberg, J.A., Ashburn, M.A., Kessler, K.F., East, K.A., Keivit, J.K., et al. (1993). Oral transmucosal fentanyl citrate: Repeated dose pharmacokinetics [Abstract 369]. Anesthesiology, 79(3A), 444.
    Streisand, J.B., Varvel, J.R., Stanski, D.R., Le Marie, L., Ashburn, M.A., Hague, B.I., et al. (1991). Absorption and bioavailability of oral transmucosal fentanyl citrate. Anesthesiology, 75, 223-229.
    U.S. Food and Drug Administration. (1998). FDA approves ACTIQ for marketing: Drug offers cancer patients relief from breakthrough pain [FDA talk paper]. Retrieved July 21, 2005, from http://www.fda.gov/bbs/topics/ANSWERS/ANS00921.html
    Weinberg, D.S., Inturrisi, C.E., Reidenberg, B., Moulin, D.E., Nip, T.J., Wallenstein, S., et al. (1988). Sublingual absorption of selected opioid analgesics. Clinical Pharmacology and Therapeutics, 44, 335-342.
    World Health Organization. (1996). Cancer pain relief (2nd ed.). Geneva, Switzerland: Author.
    Zimmer, R., & Ashburn, M.A. (2001). Noninvasive drug delivery. Comprehensive Therapy, 27, 293-301.