Clinical Drug Investigation

, Volume 30, Supplement 1, pp 13–19

Therapeutic Switch to Buprenorphine/Naloxone from Buprenorphine Alone

Clinical Experience in an Italian Addiction Centre
  • Franco Montesano
  • Domenico Zaccone
  • Egidio Battaglia
  • Felice Genco
  • Vincenzo Mellace
Original Research Article

Abstract

Background}: Pharmacological therapy has an important place in the management of opioid dependence. Methadone has been the mainstay of therapy but has a number of limitations. Buprenorphine monotherapy is another option, but misuse and diversion can have negative consequences. The opioid receptor antagonist, naloxone, has been added to buprenorphine to create a combination product with a reduced potential for misuse and diversion.

Objectives: This study evaluated the use of buprenorphine/naloxone for 24 weeks as a pharmacological management of opioid-dependent patients after therapeutic switch from buprenorphine alone.

Methods: Patients (n = 43) received sublingual tablets of buprenorphine/naloxone. The buprenorphine dose was 2–24 mg (mean 16). Patients saw a physician, including an interview using a structured data sheet, and had counselling each week. Assessments were performed at week 2 (period 1), week 6 (period 2), week 16 (period 3) and week 24 (period 4). Laboratory immunoenzymatic testing was performed weekly to detect drugs in the urine.

Results: The management of withdrawal symptoms was rated as ‘satisfactory’ by 67% of patients during period 1 and 91% during period 4. The majority of patients was highly satisfied with therapy and considered that buprenorphine/naloxone provided good control of cravings. Two patients dropped out of therapy, but all others continued to receive buprenorphine throughout the study. Approximately 50% of patients stated that they disliked the sensory properties (taste, colour, odour and feel) of buprenorphine/naloxone. Adverse effects were as would be expected on the basis of the mechanism of action of buprenorphine (i.e. opioid-induced constipation) and for patients undergoing drug withdrawal. Only 2% of patients attempted the intravenous misuse of buprenorphine/naloxone, none of whom experienced any gratifying effects.

Conclusions: Opioid-dependent patients maintained on buprenorphine monotherapy can be safely switched to a sublingual buprenorphine/naloxone tablet without any loss of treatment effectiveness. Buprenorphine/naloxone can be administered in an outpatient or primary care setting, and effectively controls cravings and withdrawal symptoms. Patient satisfaction was high, making retention in treatment more likely.

References

  1. 1.
    National Institute on Drug Abuse. Principles of drug addiction treatment: a research based guide. Evidence-based approaches to drug addiction treatment. [cited 2009 Oct21]; Available from: http://www.drugabuse.gov/PODAT/ Evidence.html#PharmGoogle Scholar
  2. 2.
    Wedam EF, Bigelow GE, Johnson RE, et al. QT-interval effects of methadone, levomethadyl, and buprenorphine in a randomized trial. Arch Intern Med 2007 Dec 10; 167(22): 2469–75PubMedCrossRefGoogle Scholar
  3. 3.
    Prescribing Information — Methadone (Italy). [cited 2009 Nov14]; Available from: http://www.pharmamarketing.it/cont/ 020ser/050pro/default.asp?method=Mostra_Contenuto&id_ cont=61641Google Scholar
  4. 4.
    European Medicines Agency. Scientific discussion (Sub-oxone) [online]. [cited 2007 Oct 21]; Available from: http://www.emea.europa.eu/humandocs/PDFs/EPAR/suboxone/ 069706en6.pdfGoogle Scholar
  5. 5.
    Law FD, Myles JS, Daglish MRC. The clinical use of buprenorphine in opiate addiction: evidence and practice. Acta Neuropsychiatria 2004; 16: 246–74CrossRefGoogle Scholar
  6. 6.
    Best SE, Oliveto AH, Kosten TR. Opioid addiction: recent advances in detoxification and maintenance therapy. CNS Drugs 1996; 6(4): 301–14CrossRefGoogle Scholar
  7. 7.
    Chapleo CB, Walter DS. The buprenorphine-naloxone combination product. Res Clin Forums 1997; 19(2): 55–8Google Scholar
  8. 8.
    Mattick RP, Kimber J, Breen C, et al. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev 2003; (2): CD002207Google Scholar
  9. 9.
    Mendelson J, Jones RT. Clinical and pharmacological evaluation of buprenorphine and naloxone combinations: why the 4: 1 ratio for treatment? Drug Alcohol Depend 2003 May 21; 70(2 Suppl.): S29–37PubMedCrossRefGoogle Scholar
  10. 10.
    Johnson RE, Strain EC, Amass L. Buprenorphine: how to use it right. Drug Alcohol Depend 2003 May 21; 70(2 Suppl.): S59–77PubMedCrossRefGoogle Scholar
  11. 11.
    Lange WR, Fudala PJ, Dax EM, et al. Safety and side-effects of buprenorphine in the clinical management of heroin addiction. Drug Alcohol Depend 1990 Aug; 26(1): 19–28PubMedCrossRefGoogle Scholar
  12. 12.
    Walsh SL, Preston KL, Stitzer ML, et al. Clinical pharmacology of buprenorphine: ceiling effects at high doses. Clin Pharmacol Ther 1994 May; 55(5): 569–80PubMedCrossRefGoogle Scholar
  13. 13.
    Zubieta J, Greenwald MK, Lombardi U, et al. Buprenor-phine-induced changes in mu-opioid receptor availability in male heroin-dependent volunteers: a preliminary study. Neuropsychopharmacology 2000 Sep; 23(3): 326–34PubMedCrossRefGoogle Scholar
  14. 14.
    Alho H, Sinclair D, Vuori E, et al. Abuse liability of buprenorphine-naloxone tablets in untreated IV drug users. Drug Alcohol Depend 2007 Apr 17; 88(1): 75–8PubMedCrossRefGoogle Scholar
  15. 15.
    Carrieri MP, Amass L, Lucas GM, et al. Buprenorphine use: the international experience. Clin Infect Dis 2006 Dec 15; 43(Suppl. 4): S197–215PubMedCrossRefGoogle Scholar
  16. 16.
    Degenhard t L, Larance BK, Bell JR, et al. Injection of medications used in opioid substitution treatment in Australia after the introduction of a mixed partial agonist-antagonist formulation. Med J Aust 2009 Aug 3; 191(3): 161–5Google Scholar
  17. 17.
    Harris DS, Jones RT, Welm S, et al. Buprenorphine and naloxone co-administration in opiate-dependent patients stabilized on sublingual buprenorphine. Drug Alcohol Depend 2000 Dec 22; 61(1): 85–94PubMedCrossRefGoogle Scholar
  18. 18.
    Robinson SE. Buprenorphine-containing treatments: place in the management of opioid addiction. CNS Drugs 2006; 20(9): 697–712PubMedCrossRefGoogle Scholar
  19. 19.
    Fudala PJ, Bridge TP, Herbert S, et al. Office-based treatment of opiate addiction with a sublingual-tablet formulation of buprenorphine and naloxone. N Engl J Med 2003 Sep 4; 349(10): 949–58PubMedCrossRefGoogle Scholar
  20. 20.
    Kamien JB, Branstetter SA, Amass LA. Buprenorphine-naloxone versus methadone maintenance therapy: a randomised double-blind trial with opioid dependent patients. Heroin Addict Relat Clin Probl 2008; 10(4): 5–18Google Scholar
  21. 21.
    Kakko J, Gronbladh L, Svanborg KD, et al. A stepped care strategy using buprenorphine and methadone versus conventional methadone maintenance in heroin dependence: a randomized controlled trial. Am J Psychiatry 2007 May; 164(5): 797–803PubMedCrossRefGoogle Scholar
  22. 22.
    Gunderson EW, Fiellin DA. Office-based maintenance treatment of opioid dependence: how does it compare with traditional approaches? CNS Drugs 2008; 22(2): 99–111PubMedCrossRefGoogle Scholar
  23. 23.
    Amass L, Kamien JB, Mikulich SK. Efficacy of daily and alternate-day dosing regimens with the combination buprenorphine-naloxone tablet. Drug Alcohol Depend 2000 Feb 1; 58(1-2): 143–52PubMedCrossRefGoogle Scholar
  24. 24.
    Amass L, Kamien JB, Mikulich SK. Thrice-weekly supervised dosing with the combination buprenorphine-naloxone tablet is preferred to daily supervised dosing by opioid-dependent humans. Drug Alcohol Depend 2001 Jan 1; 61(2): 173–81PubMedCrossRefGoogle Scholar
  25. 25.
    Fiellin DA, Pantalon MV, Chawarski MC, et al. Counseling plus buprenorphine-naloxone maintenance therapy for opioid dependence. N Engl J Med 2006 Jul 27; 355(4): 365–74PubMedCrossRefGoogle Scholar
  26. 26.
    Italian Ministry of Health. [Accessed 2010 Mar 18]; Available from: http://www.salute.gov.it/Google Scholar
  27. 27.
    Daulouede JP, Caer Y, Galland P, et al. Preference for buprenorphine/naloxone and buprenorphine among patients receiving buprenorphine maintenance therapy in France: a prospective, multicenter study. J Subst Abuse Treat 2010; 38(1): 83–9PubMedCrossRefGoogle Scholar
  28. 28.
    Healy R. Effectiveness of two opioid antagonists in treating opioid-induced constipation. Br J Nurs 2009 Sep 10–23; 18(16): 998–1002PubMedGoogle Scholar
  29. 29.
    Schering Plough Italy. Suboxone. Riassunto delle caratteristiche del prodottoGoogle Scholar

Copyright information

© Adis Data Information BV 2010

Authors and Affiliations

  • Franco Montesano
    • 1
  • Domenico Zaccone
    • 1
  • Egidio Battaglia
    • 1
  • Felice Genco
    • 1
  • Vincenzo Mellace
    • 1
  1. 1.Drug Addiction Service, U.O.C. SerT SoveratoAzienda Sanitaria ProvincialeMontepaoneItaly

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