Understanding transdermal buprenorphine and a practical guide to its use for chronic cancer and non-cancer pain management


  • Tony O’Brien, MB, FRCPI
  • Jin Seok Ahn, MD
  • Brian Le, MBBS (Hons), MPH, FRACP, FAChPM
  • Henry Lu, MD, DABPN, DPBPM
  • Gabriel Olarte, MD
  • Mariana Palladini, MD
  • Amar Salti, MD, EDRA
  • Yu-Yun Shao, MD, PhD
  • Hayati Yaakup, MBBS, MMED (UKM), PgDip
  • Kristal Cielo Buemio, MD
  • Consuelo Gutierrez Colin, MD
  • Yacine Hadjiat, MD




transdermal buprenorphine, practical guide, chronic pain management, cancer pain, non-cancer pain, neuropathic pain


Transdermal buprenorphine (TDB) has demonstrated effectiveness in treating a range of chronic pain conditions, including cancer pain, nociceptive pain, and neuropathic pain and has a favorable safety profile. Worldwide, clinical experience of its use is relatively limited. There is considerable misunderstanding about the pharmacology, mechanism of action, and safety of buprenorphine. There is also limited guidance on the appropriate use of TDB for chronic pain management. This article presents an overview of TDB and also provides practical recommendations for its use as part of a multifaceted strategy in chronic cancer and non-cancer pain.

Author Biographies

Tony O’Brien, MB, FRCPI

Department of Palliative Medicine, Marymount University Hospital & Hospice, University College Cork, Cork, Ireland

Jin Seok Ahn, MD

Department of Hematology and Oncology, Sungkyunkwan University School of Medicine Samsung Medical Center, Seoul, Republic of Korea


Department of Palliative Medicine, St. Vincent’s Hospital Sydney, New South Wales, Australia

Brian Le, MBBS (Hons), MPH, FRACP, FAChPM

Department of Palliative Care, Victorian Comprehensive Cancer Centre, The Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Victoria, Australia


Pain Management Center, St Luke’s Medical Center Global City, Makati Medical Center, Metro Manila, Philippines

Gabriel Olarte, MD

Diagnostic and Pain Treatment Service, Alexander Fleming Oncology Institute, Buenos Aires, Argentina

Mariana Palladini, MD

Centro Paulista De Dor, São Paulo, Brazil

Amar Salti, MD, EDRA

Department of Anesthesia & Pain Medicine, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates

Yu-Yun Shao, MD, PhD

Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan

Hayati Yaakup, MBBS, MMED (UKM), PgDip

Department of Palliative Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia

Kristal Cielo Buemio, MD

Medical Affairs, Mundipharma Singapore Holding Pte Ltd, Singapore

Consuelo Gutierrez Colin, MD

Medical Affairs, Mundipharma Singapore Holding Pte Ltd, Singapore

Yacine Hadjiat, MD

Medical Affairs, Mundipharma Singapore Holding Pte Ltd, Singapore


Kress HG, Aldington D, Alon E, et al.: A holistic approach to chronic pain management that involves all stakeholders: Change is needed. Curr Med Res Opin. 2015; 31(9): 1743-1754.

O’Brien T, Christrup LL, Drewes AM, et al.: European Pain Federation position paper on appropriate opioid use in chronic pain management. Eur J Pain. 2017; 21(1): 3-19.

National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology: Adult Cancer Pain. Version 1. Plymouth Meeting, PA: National Comprehensive Cancer Network, 2018. Available at https://www.nccn.org/professionals/physician_gls/pdf/pain.pdf. Accessed January 22, 2018.

Ripamonti CI, Santini D, Maranzano E, et al.: Management of cancer pain: ESMO clinical practice guidelines. Ann Oncol. 2012; 23(suppl 7): vii139-vii154.

Caraceni A, Hanks G, Kaasa S, et al.: Use of opioid analgesics in the treatment of cancer pain: Evidence-based recommendations from the EAPC. Lancet Oncol. 2012; 13(2): e58-e68.

World Health Organization: Cancer Pain Relief: With a Guide to Opioid Availability. 2nd ed. Geneva: WHO, 1996.

Busse JW, Craigie S, Juurlink DN, et al.: Guideline for opioid therapy and chronic noncancer pain. CMAJ. 2017; 189(18): E659-E666.

Yoon DH, Bin SI, Chan SK, et al.: Effectiveness and tolerability of transdermal buprenorphine patches: A multicenter, prospective, open-label study in Asian patients with moderate to severe chronic musculoskeletal pain. BMC Musculoskelet Disord. 2017; 18(1): 337.

Melilli G, Samolsky Dekel BG, Frenquelli C, et al.: Transdermal opioids for cancer pain control in patients with renal impairment. J Opioid Manag. 2014; 10(2): 85-93.

Janecki M, Pakosz A: Management of cancer pain with neuropathic component using transdermal buprenorphine—Three clinical cases report. Medycyna Paliatywna. 2014; 6(4): 220-224.

Rothman R: Buprenorphine: A review of the binding literature. In Cowan A, Lewis J (eds.): Buprenorphine: Combatting Drug Abuse with a Unique Opioid. New York: Wiley-Liss, 1995: 19-29.

Khanna IK, Pillarisetti S: Buprenorphine—An attractive opioid with underutilized potential in treatment of chronic pain. J Pain Res. 2015; 8: 859-870.

Johnson RE, Fudala PJ, Payne R: Buprenorphine: Considerations for pain management. J Pain Symptom Manage. 2005; 29(3): 297-326.

Helm S, Trescot AM, Colson J, et al.: Opioid antagonists, #partial |agonists, and agonists/antagonists: The role of office-based detoxification. Pain Physician. 2008; 11(2): 225-235.

Induru RR, Davis MP: Buprenorphine for neuropathic pain—Targeting hyperalgesia. Am J Hosp Palliat Care. 2009-2010; 26(6): 470-473.

Dahan A, Yassen A, Bijl H, et al.: Comparison of the respiratory effects of intravenous buprenorphine and fentanyl in humans and rats. Br J Anaesth. 2005; 94(6): 825-834.

Davis MP: Twelve reasons for considering buprenorphine as a frontline analgesic in the management of pain. J Support Oncol. 2012; 10(6): 209-219.

Skaer TL: Dosing considerations with transdermal formulations of fentanyl and buprenorphine for the treatment of cancer pain. J Pain Res. 2014; 7: 495-503.

Elkader A, Sproule B: Buprenorphine: Clinical pharmacokinetics in the treatment of opioid dependence. Clin Pharmacokinet. 2005; 44(7): 661-680.

Böger RH: Renal impairment: A challenge for opioid treatment? The role of buprenorphine. Palliat Med. 2006; 20(suppl 1): s17-s23.

Hand CW, Sear JW, Uppington J, et al.: Buprenorphine disposition in patients with renal impairment: Single and continuous dosing, with special reference to metabolites. Br J Anaesth. 1990; 64(3): 276-282.

Kress HG: Clinical update on the pharmacology, efficacy and safety of transdermal buprenorphine. Eur J Pain. 2009; 13(3): 219-230.

Pergolizzi J, Böger RH, Budd K, et al.: Opioids and the management of chronic severe pain in the elderly: Consensus statement of an International Expert Panel with focus on the six clinically most often used World Health Organization Step III opioids (buprenorphine, #fentanyl, |hydromorphone, #methadone, |morphine, oxycodone). Pain Pract. 2008; 8(4): 287-313.

Foster B, Twycross R, Mihalyo M, et al.: Buprenorphine. J Pain Symptom Manage. 2013; 45(5): 939-949. 25. Likar R, Krainer B, Sittl R: Challenging the equipotency calculation for transdermal buprenorphine: Four case studies. Int J Clin Pract. 2008; 62(1): 152-156.

Koppert W, Ihmsen H, Körber N, et al.: Different profiles of buprenorphine induced analgesia and antihyperalgesia in a human pain model. Pain. 2005; 118(1-2): 15-22.

Yassen A, Olofsen E, Romberg R, et al.: Mechanism-based PK/PD modeling of the respiratory depressant effect of buprenorphine and fentanyl in healthy volunteers. Clin Pharmacol Ther. 2007; 81(1): 50-58.

Chevillard L, Mégarbane B, Risède P, et al.: Characteristics and comparative severity of respiratory response to toxic doses of fentanyl, #methadone, |morphine, and buprenorphine in rats. Toxicol Lett. 2009; 191(2-3): 327-340.

Wedam EF, Bigelow GE, Johnson RE, et al.: QT-interval effects of methadone, levomethadyl, and buprenorphine in a randomized trial. Arch Intern Med. 2007; 167(22): 2469-2475.

Anchersen K, Clausen T, Gossop M, et al.: Prevalence and clinical relevance of corrected QT interval prolongation during methadone and buprenorphine treatment: A mortality assessment study. Addiction. 2009; 104(6): 993-999.

Aloisi AM, Ceccarelli I, Carlucci M, et al.: Hormone replacement therapy in morphine-induced hypogonadic male chronic pain patients. Reprod Biol Endocrinol. 2011; 9: 26.

Hallinan R, Byrne A, Agho K, et al.: Hypogonadism in men receiving methadone and buprenorphine maintenance treatment. Int J Androl. 2009; 32(2): 131-139.

Aurilio C, Ceccarelli I, Pota V, et al.: Endocrine and behavioural effects of transdermal buprenorphine in pain-suffering women of different reproductive ages. Endocr J. 2011; 58(12): 1071-1078.

Sittl R, Nuijten M, Nautrup BP: Changes in the prescribed daily doses of transdermal fentanyl and transdermal buprenorphine during treatment of patients with cancer and noncancer pain in Germany: Results of a retrospective cohort study. Clin Ther. 2005; 27(7): 1022-1031.

Soyka M, Hock B, Kagerer S, et al.: Less impairment on one portion of a driving-relevant psychomotor battery in buprenorphine-maintained than in methadone-maintained patients: Results of a randomized clinical trial. J Clin Psychopharmacol. 2005; 25(5): 490-493.

Giacomuzzi S, Haaser W, Pilsz L, et al.: Driving impairment on buprenorphine and slow-release oral morphine in drug-dependent patients. Forensic Sci Int. 2005; 152(2-3): 323-324.

Tassinari D, Sartori S, Tamburini E, et al.: Adverse effects of transdermal opiates treating moderate-severe cancer pain in comparison to long-acting morphine: A meta-analysis and systematic review of the literature. J Palliat Med. 2008; 11(3): 492-501.

Pace MC, Passavanti MB, Grella E, et al.: Buprenorphine in long-term control of chronic pain in cancer patients. Front Biosci. 2007; 12: 1291-1299.

Franchi S, Panerai AE, Sacerdote P: Buprenorphine ameliorates the effect of surgery on hypothalamus-pituitary-adrenal axis, natural killer cell activity, and metastatic colonization in rats in comparison with morphine or fentanyl treatment. Brain Behav Immun. 2007; 21(6): 767-774.

Martucci C, Panerai AE, Sacerdote P: Chronic fentanyl or buprenorphine infusion in the mouse: Similar analgesic profile but different effects on immune responses. Pain. 2004; 110(1-2): 385-392.

Sacerdote P, Franchi S, Gerra G, et al.: Buprenorphine and methadone maintenance treatment of heroin addicts preserves immune function. Brain Behav Immun. 2008; 22(4): 606-613.

Filitz J, Griessinger N, Sittl R, et al.: Effects of intermittent hemodialysis on buprenorphine and norbuprenorphine plasma concentrations in chronic pain patients treated with transdermal

buprenorphine. Eur J Pain. 2006; 10(8): 743-748.

Likar R, Lorenz V, Korak-Leiter M, et al.: Transdermal buprenorphine patches applied in a 4-day regimen versus a 3-day regimen: A single-site, Phase III, randomized, open-label, crossover comparison. Clin Ther. 2007; 29(8): 1591-1606.

Cachia E, Ahmedzai SH: Transdermal opioids for cancer pain. Curr Opin Support Palliat Care. 2011; 5(1): 15-19.

Butrans 5, 10 and 20 microgram/hr patch [package insert]: Summary of product characteristics. Cambridge, UK: Napp Pharmaceuticals Limited, 2017. Available at https://www.medicines.org.uk/emc/medicine/16787/SPC/. Accessed January 22, 2018.

Butrans - Buprenorphine patch, extended release [package insert]: Full prescribing information. Stamford, CT: Purdue Pharma LP, 2014. Available at http://app.purduepharma.com/xmlpublishing/pi.aspx?id=b. Accessed January 22, 2018.

Norspan [package insert]: Full prescribing information. Metro Manila, Philippines: Mundipharma (Philippines) Limited. Available at http://www.mims.com/philippines/drug/info/norspan/?type=full. Accessed February 19, 2018.

Sovenor [package insert]: Full prescribing information. Metro Manila, Philippines: Mundipharma Pharmaceuticals Pte Ltd. Available at http://www.mims.com/singapore/drug/info/sovenor/?type=full. Accessed February 19, 2018.

Restiva [package insert]: Patient information leaflet. Cambridge, UK: Mundipharma GmbH, 2008. Available at http://www.raffo.com.ar/prospectos/RESTIVA_PAT_PIL_6509583_V1.pdf. Accessed May 5, 2018.

Transtec 35, 52.5 and 70 micrograms transdermal patch [package insert]: Summary of product characteristics. Cambridge, UK: Napp Pharmaceuticals Limited, 2015. Available at https://www.medicines.org.uk/emc/medicine/8864. Accessed January 22, 2018.

Ahn JS, Lin J, Ogawa S, et al.: Transdermal buprenorphine and fentanyl patches in cancer pain: A network systematic review. J Pain Res. 2017; 10: 1963-1972.

Corli O, Montanari M, Deandrea S, et al.: An exploratory analysis on the effectiveness of four strong opioids in patients with cancer pain. Pain Med. 2012; 13(7): 897-907.

Griessinger N, Sittl R, Likar R: Transdermal buprenorphine in clinical practice—A post-marketing surveillance study in 13,179 patients. Curr Med Res Opin. 2005; 21(8): 1147-1156.

Gordon A, Rashiq S, Moulin DE, et al.: Buprenorphine transdermal system for opioid therapy in patients with chronic low back pain. Pain Res Manag. 2010; 15(3): 169-178.

Rodriguez MJ, The Opioid Study Group of the Spanish Pain Society: Transdermal buprenorphine in neuropathic pain. Rev Soc Esp Dolor. 2004; 11 (suppl 5): 11-21.

Simpson RW, Wlodarczyk JH: Transdermal buprenorphine relieves neuropathic pain: A randomized, double-blind, parallel-group, placebo-controlled trial in diabetic peripheral neuropathic pain. Diabetes Care. 2016; 39(9): 1493-1500.

Sittl R, Griessinger N, Likar R: Analgesic efficacy and tolerability of transdermal buprenorphine in patients with inadequately controlled chronic pain related to cancer and other disorders: A multicenter, randomized, double-blind, placebo-controlled trial. Clin Ther. 2003; 25(1): 150-168.

Munera C, Drehobl M, Sessler NE, et al.: A randomized, placebo-controlled, double-blinded, parallel-group, 5-week study of buprenorphine transdermal system in adults with osteoarthritis. J Opioid Manag. 2010; 6(3): 193-202.

Karlsson J, Söderström A, Augustini BG, et al.: Is buprenorphine transdermal patch equally safe and effective in younger and elderly patients with osteoarthritis-related pain? Results of an age-group controlled study. Curr Med Res Opin. 2014; 30(4): 575-587.

Butler S: Buprenorphine—Clinically useful but often misunderstood. Scand J Pain. 2013; 4: 148-152.

Raffa RB, Pergolizzi JVJr: Is buprenorphine a ‘partial agonist’? Preclinical and clinical evidence. Pract Pain Manag. 2013; 13(8): 33-39.

Sessler NE, Walker E, Chickballapur H, et al.: Disproportionality analysis of buprenorphine transdermal system and cardiac arrhythmia using FDA and WHO postmarketing reporting system data. Postgrad Med. 2017; 129(1): 62-68.

Raffa RB, Haidery M, Huang HM, et al.: The clinical analgesic efficacy of buprenorphine. J Clin Pharm Ther. 2014; 39(6): 577-583.

Mercadante S, Villari P, Ferrera P, et al.: Safety and effectiveness of intravenous morphine for episodic breakthrough pain in patients receiving transdermal buprenorphine. J Pain Symptom Manage. 2006; 32(2): 175-179.

Atkinson RE, Schofield P, Mellor P: The efficacy in sequential use of buprenorphine and morphine in advanced cancer pain. In Doyle D (ed.): Opioids in the Treatment of Cancer Pain. London: Royal Society of Medicine Services, 1990: 81-87.

Mercadante S, Porzio G, Fulfaro F, et al.: Switching from transdermal drugs: An observational “N of 1” study of fentanyl and buprenorphine. J Pain Symptom Manage. 2007; 34(5): 532-538.

Poole SA, Pecoraro A, Subramaniam G, et al.: The presence or absence of QTc prolongation in buprenorphine-naloxone among youth with opioid dependence. J Addict Med. 2016; 10(1): 26-33.

UK NHS: Position statement: Buprenorphine and fentanyl patches for pain. 2015. Available at http://www.lancsmmg.nhs.uk/download/position%20statements/Position%20Statement.%20Fentanyl%20&%20Buprenorphine%20Patches%20for%20Pain%20(Version%201.0).pdf. Accessed January 22, 2018.

Vithlani RH, Baranidharan G: Transdermal opioids for cancer pain management. Rev Pain. 2010; 4(2): 8-13.

James IG, O’Brien CM, McDonald CJ: A randomized, double-blind, double-dummy comparison of the efficacy and tolerability of low-dose transdermal buprenorphine (BuTrans sevenday patches) with buprenorphine sublingual tablets (Temgesic) in patients with osteoarthritis pain. J Pain Symptom Manage. 2010; 40(2): 266-278.

Twycross R, Wilcock A, Howard P (eds.): Palliative Care Formulary. 6th ed. Nottingham: Palliativedrugs.com Ltd., 2018.

Mercadante S, Casuccio A, Tirelli W, et al.: Equipotent doses to switch from high doses of opioids to transdermal buprenorphine. Support Care Cancer. 2009; 17(6): 715-718.

Cheshire and Merseyside Palliative and End of Life Care Network Audit Group: Standards and guidelines for the use of transdermal opioids in palliative care. July 2014. Available at https://www.nwcscnsenate.nhs.uk/files/5214/0742/3954/Transdermal_Opioids_-_Standards_and_Guidelines_-_July_2014_Final.pdf. Accessed January 22, 2018.

Rudowska J: Management of breakthrough pain due to cancer. Contemp Oncol. 2012; 16(6): 498-501.

Chou R, Fanciullo GJ, Fine PG, et al.: Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. J Pain. 2009; 10(2): 113-130.

Onofrio S, Vartan CM, Nazario M, et al.: The use of transdermal buprenorphine in complex regional pain syndrome: A report of two cases. J Pain Palliat Care Pharmacother. 2016; 30(2): 124-127.

Serpell M, Tripathi S, Scherzinger S, et al.: Assessment of transdermal buprenorphine patches for the treatment of chronic pain in a UK observational study. Patient. 2016; 9(1): 35-46.

Pergolizzi JV, Raffa RB, Pappagallo M, et al.: Peripherally acting μ-opioid receptor antagonists as treatment options for constipation in noncancer pain patients on chronic opioid therapy. Patient Prefer Adherence. 2017; 11: 107-119.

Nelson AD, Camilleri M: Opioid-induced constipation: Advances and clinical guidance. Ther Adv Chronic Dis. 2016; 7(2): 121-134.




How to Cite

O’Brien, MB, FRCPI, T., J. S. Ahn, MD, R. Chye, MBBS, FRACP, FFPMANZCA, FAChPM, B. Le, MBBS (Hons), MPH, FRACP, FAChPM, H. Lu, MD, DABPN, DPBPM, G. Olarte, MD, M. Palladini, MD, A. Salti, MD, EDRA, Y.-Y. Shao, MD, PhD, H. Yaakup, MBBS, MMED (UKM), PgDip, K. C. Buemio, MD, C. G. Colin, MD, and Y. Hadjiat, MD. “Understanding Transdermal Buprenorphine and a Practical Guide to Its Use for Chronic Cancer and Non-Cancer Pain Management”. Journal of Opioid Management, vol. 15, no. 2, Mar. 2019, pp. 147-58, doi:10.5055/jom.2019.0496.