Advertisement

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

      This paper is only available as a PDF. To read, Please Download here.

      Abstract

      Background: Buprenorphine is a potent opioid analgesic that is available in sublingual and parenteral formulations. A new formulation, buprenorphine transdermal delivery system (TDS), has been developed.
      Objective: The aim of this study was to compare the analgesic efficacy and tolerability of the 3 available dosages of buprenorphine TDS (35.0, 52.5, and 70.0 μg/h) with placebo.
      Methods: This was a randomized, double-blind, placebo-controlled, multicenter study. Patients with chronic, severe pain related to cancer or other diseases and inadequately controlled with weak opioids were randomized to receive buprenorphine TDS 35.0, 52.5, or 70.0 μg/h or placebo patch for up to 15 days. A new patch was applied every 72 hours, for a total of 5 patches. All patients were permitted rescue analgesia with sublingual buprenorphine tablets (0.2 mg) as required for breakthrough pain.
      Results: A total of 157 patients (86 women, 71 men; mean [SD] age, 58.7 [11.8] years) were initially enrolled in the study. Buprenorphine TDS was associated with significantly higher response rates than was placebo at the 35.0- and 52.5-μg/h dosages (36.6% and 47.5%, respectively, vs 16.2%; P=0.032 and P=0.003, respectively) and a numerically higher response rate at 70.0 μg/h (33.3%), although this difference did not reach statistical significance. Patients treated with buprenorphine TDS experienced a 56.7% reduction in use of sublingual rescue analgesic during the study compared with an 8% reduction with the placebo patch. A total of 43.5% of patients treated with buprenorphine TDS reported good or complete pain relief compared with 32.4% in the placebo group. Pain intensity decreased in a dose-dependent manner with buprenorphine TDS, and the duration of sleep uninterrupted by pain was improved by the end of the study. More than three fourths (78.8%) of patients in the placebo and buprenorphine TDS groups reported at least 1 adverse event (AE) during the study. The most common AEs were central nervous system and gastrointestinal symptoms. The majority of treatment-related AEs were mild or moderate in intensity and were typical of those occurring at the beginning of therapy with a strong opioid.
      Conclusions: Buprenorphine TDS was shown to be an effective analgesic against chronic, severe pain in this study population. Patients treated with this new formulation of buprenorphine showed improved duration of sleep and reduced need for additional oral analgesics.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Clinical Therapeutics
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • World Health Organization
        Cancer Pain Relief: With a Guide to Opioid Availability.
        2nd ed. WHO, Geneva, Switzerland1996
      1. Anesthesiology. 1997; 86: 995-1004
        • American Geriatrics Society
        AGS Panel on Chronic Pain in Older Persons. The management of chronic pain in older persons.
        J Am Geriatr Soc. 1998; 46: 635-661
        • American College of Rheumatology
        Subcommittee on Osteoarthritis Guidelines. Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update.
        Arthritis Rheum. 2000; 43: 1905-1915
        • Zech D.F
        • Grond S
        • Lynch J
        • et al.
        Validation of World Health Organization guidelines for cancer pain relief: A 10-year prospective study.
        Pain. 1995; 63: 65-76
        • Schug S.A
        • Merry A.F
        • Acland R.H
        Treatment principles for the use of opioids in pain of nonmalignant origin.
        Drugs. 1991; 42: 228-239
        • Zenz M
        • Strumpf M
        • Tryba M
        Long-term oral opioid therapy in patients with chronic nonmalignant pain.
        J Pain Symptom Manage. 1992; 7: 69-77
        • Portenoy R.K
        Opioid therapy for chronic nonmalignant pain: A review of the critical issues.
        J Pain Symptom Manage. 1996; 11: 203-217
        • Arner S
        • Meyerson B.A
        Lack of analgesic effect of opioids on neuropathic and idiopathic forms of pain.
        Pain. 1988; 33: 11-23
        • Heel R.C
        • Brogden R.N
        • Speight T.M
        • et al.
        Buprenorphine: A review of its pharmacological properties and therapeutic efficacy.
        Drugs. 1979; 17: 81-110
        • Leander J.D
        Buprenorphine has potent kappa opioid receptor antagonist activity.
        Neuropharmacology. 1987; 26: 1445-1447
        • Wnendt S
        • Kruger T
        • Janocha E
        • et al.
        Agonistic effect of buprenorphine in a nociceptin/OFQ receptor-triggered reporter gene assay.
        Mol Pharmacol. 1999; 56: 334-338
        • Masson A.H
        Sublingual buprenorphine versus oral dihydrocodeine in post-operative pain.
        J Int Med Res. 1981; 9: 506-510
        • Hanks G.W
        The clinical usefulness of agonist-antagonist opioid analgesics in chronic pain.
        Drug Alcohol Depend. 1987; 20: 339-346
        • Caplan R.A
        • Ready L.B
        • Oden R.V
        • et al.
        Transdermal fentanyl for postoperative pain management: A double-blind placebo study.
        JAMA. 1989; 261: 1036-1039
        • Zech D.F
        • Grond S.U
        • Lynch J
        • et al.
        Transdermal fentanyl and initial dose-finding with patient-controlled analgesia in cancer pain: A pilot study with 20 terminally ill cancer patients.
        Pain. 1992; 50: 293-301
        • Southam M.A
        Transdermal fentanyl therapy: System design, pharmacokinetics and efficacy.
        Anticancer Drugs. 1995; 6: 29-34
        • 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 (for the TTS-Fentanyl Comparative Trial Group): 254-261
        • Kongsgaard U.E
        • Poulain P
        Transdermal fentanyl for pain control in adults with chronic cancer pain.
        Eur J Pain. 1998; 2: 53-62
        • Grond S
        • Radbruch L
        • Lehmann K.A
        Clinical pharmacokinetics of transdermal opioids: Focus on transdermal fentanyl.
        Clin Pharmacokinet. 2000; 38: 59-89
        • Allan L
        • Hays H
        • Jensen N.H
        • et al.
        Randomised crossover trial of transdermal fentanyl and sustained release oral morphine for treating chronic non-cancer pain.
        BMJ. 2001; 322: 1154-1158
        • Berner B
        • John V.A
        Pharmacokinetic characterisation of transdermal delivery systems.
        Clin Pharmacokinet. 1994; 26: 121-134
        • Steering Committee, Transdermal Nitroglycerin Cooperative Study
        Acute and chronic antianginal efficacy of continuous twenty-four-hour application of transdermal nitro-glycerin.
        Am J Cardiol. 1991; 68: 1263-1273
        • Ardissino D
        • Merlini P.A
        • Savonitto S
        • et al.
        Effect of transdermal nitroglycerin or N-acetylcysteine, or both, in the long-term treatment of unstable angina pectoris.
        J Am Coll Cardiol. 1997; 29: 941-947
        • Gordon S.F
        Clinical experience with a seven-day estradiol transdermal system for estrogen replacement therapy.
        Am J Obstet Gynecol. 1995; 173: 998-1004
        • Ly L.P
        • Jimenez M
        • Zhuang T.N
        • et al.
        A double-blind, placebo-controlled, randomized clinical trial of transdermal dihydrotesterone gel on muscular strength, mobility, and quality of life in older men with partial androgen deficiency.
        J Clin Endocrinol Metab. 2001; 86: 4078-4088
        • Payne R
        • Mathias S.D
        • Pasta D.J
        • et al.
        Quality of life and cancer pain: Satisfaction and side effects with transdermal fentanyl versus oral morphine.
        J Clin Oncol. 1998; 16: 1588-1593
        • Lehmann K.A
        • Gordes B
        Postoperative on-demand analgesia with buprenorphine [in German].
        Anaesthesist. 1988; 37: 65-70
        • Gralow I
        • von Hornstein W.F
        • Schleyer E
        • Hiddemann W
        Pharmacokinetics of buprenorphine in subcutaneous administration [in German].
        Anasthesiol Intensivmed Notf Med Schmerzther. 1995; 30: 412-416
        • Armitage P
        • Berry G
        Statistical Methods in Medical Research.
        in: Blackwell Scientific Publications, Oxford, United Kingdom1987: 391-453
      2. 5th ed. Statistical Methods in Cancer Research, Vol. I: The Analysis of Case-Control Studies. IARC Scientific Publications, Lyon, France1980: 296-338
        • Bauer P
        Multiple testing in clinical trials.
        Stat Med. 1991; 10: 871-889
        • Agresti A
        Categorical Data Analysis.
        in: Wiley & Sons, New York1990: 287-315
        • Pereira J
        • Lawlor P
        • Vigano A
        • et al.
        Equianalgesic dose ratios for opioids: A critical review and proposals for long-term dosing.
        J Pain Symptom Manage. 2001; 22: 672-687
        • Bullingham R.E
        • McQuay H.J
        • Moore R.A
        Clinical pharmacokinetics of narcotic agonist-antagonist drugs.
        Clin Pharmacokinet. 1983; 8: 332-343
        • Böhme K
        Buprenorphine transdermal system (TDS) (delivery rates 35/52.5/70 μg/h) in comparison to sublingual buprenorphine in chronic pain patients.
        J Pain Symptom Manage. 2002; 20 (Abstract): S54
        • Walsh S.L
        • Preston K.L
        • Bigelow G.E
        • Stitzer M.L
        Acute administration of buprenorphine in humans: Partial agonist and blockade effects.
        J Pharmacol Exp Ther. 1995; 274: 361-372
        • Sorge J
        Buprenorphine transdermal system (TDS) (delivery rate 35 μg/h) in comparison to sublingual tablets in chronic pain patients.
        J Pain Symptom Manage. 2002; 20 (Abstract): S78
        • Kopp M
        Buprenorphine transdermal system (TDS) in an open long-term study with chronic pain patients.
        J Pain Symptom Manage. 2002; 20 (Abstract): S78
        • Brema F
        • Pastorino G
        • Martini M.C
        • et al.
        Oral tramadol and buprenorphine in tumour pain. An Italian multicentre trial.
        Int J Clin Pharmacol Res. 1996; 16: 109-116
        • Bach V
        • Kamp-Jensen M
        • Jensen N.H
        • et al.
        Buprenorphine and sustained release morphine—effect and side-effects in chronic use.
        Pain Clinic. 1991; 4: 87-93
        • Nasar M.A
        • McLeavy M.A
        • Knox J
        An open study of sub-lingual buprenorphine in the treatment of chronic pain in the elderly.
        Curr Med Res Opin. 1986; 10: 251-255
        • Raisch D.W
        • Fye C.L
        • Boardman K.D
        • Sather M.R
        Opioid dependence treatment, including buprenorphine/naloxone.
        Ann Pharmacother. 2002; 36: 312-321