Clinical Drug Investigation

, Volume 30, Supplement 1, pp 21–26

Safety and Efficacy of Buprenorphine/Naloxone in Opioid-Dependent Patients

An Italian Observational Study
  • Fernanda Magnelli
  • Lorita Biondi
  • Roberto Calabria
  • Angelo Fiore
  • Eugenio Peluso
  • Domenico Vonella
  • Amerigo Giuseppe Rota
Original Research Article

Abstract

Background: Opioid dependence is a growing problem. Methadone is an established agent for the treatment of opioid dependence, but there is a risk of this agent being abused, a potential for interaction with antiretroviral agents and a risk of cardiac toxicity. Another option is the partial μ-opioid receptor opioid agonist buprenorphine, which has been used successfully to manage opioid dependence. While the risk of abuse is lower than that for methadone, there is still a risk. The sublingual combination formulation of buprenorphine and the opioid receptor antagonist naloxone (buprenorphine/naxolone) is a newer agent with reduced abuse potential, and has been shown to have promising efficacy for opioid dependence.

Objectives: We describe the results of an observational study investigating the safety and efficacy of buprenorphine/naloxone in opioid-dependent patients.

Methods: A total of 77 patients were included and were switched from buprenorphine to sublingual tables of buprenorphine/naloxone; the buprenorphine dosage was titrated to achieve good control of withdrawal symptoms. The prevalence of withdrawal symptoms, craving, constipation, cramps, insomnia, sexual activity, depression, sweating, distress, bone/joint pain and drowsiness were compared over the first 30 days of treatment (period 1) and the total 120-day study duration (period 2).

Results: The average buprenorphine/naloxone dose in period 1 was 7.3 mg/day and 12.7 mg/day in period 2. Most patients did not experience any withdrawal symptoms in either period 1 or period 2. Fewer than 20% of patients experienced any cravings over the 120-day study period. Importantly, the adverse effects observed were usually mild, with very few patients experiencing significant adverse effects.

Conclusions: This study shows that buprenorphine/naloxone is an effective and well tolerated treatment for opioid withdrawal when the dosage is titrated to achieve good control of withdrawal symptoms. Switching from buprenorphine alone to buprenorphine/naloxone was possible with very little discomfort for the patient and effective retained patients in treatment.

References

  1. 1.
    US Department of Health and Human Services. Clinical guidelines for the use of buprenorphine in the treatment of opioid addiction: a treatment improvement protocol TIP 40. 2004Google Scholar
  2. 2.
    National Institute on Drug Abuse. Principles of drug addiction treatment: a research based guide. Evidence-based approaches to drug addiction treatment. [cited 2009 21 Oct]; Available from: http://www.drugabuse.gov/PODAT/ Evidence.html#PharmGoogle Scholar
  3. 3.
    Goldman FR, Thistel CI. Diversion of methadone: illicit methadone use among applicants to two metropolitan drug abuse programs. Int J Addict 1978 Aug; 13(6): 855–62PubMedGoogle Scholar
  4. 4.
    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
  5. 5.
    Prescribing Information — Methadone (Italy). [cited 2009 14 Nov]; Available from: http://www.pharmamarketing.it/ cont/020ser/050pro/default.asp?method=Mostra_Contenuto &id_cont=61641Google Scholar
  6. 6.
    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
  7. 7.
    Best SE, Oliveto AH, Kosten TR. Opioid addiction: recent advances in detoxification and maintenance therapy. CNS Drugs 1996; 6(4): 301–14CrossRefGoogle Scholar
  8. 8.
    Chapleo CB, Walter DS. The buprenorphine-naloxone combination product. Res Clin Forums 1997; 19(2): 55–8Google Scholar
  9. 9.
    Law FD, Myles JS, Daglish MRC. The clinical use of buprenorphine in opiate addiction: evidence and practice. Acta Neuropsychiatria 2004; 16: 246–74CrossRefGoogle Scholar
  10. 10.
    Mendelson J, Jones RT. Clinical and pharmacological evaluation of buprenorphine and naloxone combinations: why the 4:1 ratio for treatment? Drug Alcohol Depend 2003 May21;70(2Suppl.): S29–37PubMedCrossRefGoogle Scholar
  11. 11.
    Johnson RE, Strain EC, Amass L. Buprenorphine: how to use it right. Drug Alcohol Depend 2003 May 21; 70(2 Suppl.): S59–77PubMedCrossRefGoogle Scholar
  12. 12.
    Bickel WK, Stitzer ML, Bigelow GE, et al. Buprenorphine: dose-related blockade of opioid challenge effects in opioid dependent humans. J Pharmacol Exp Ther 1988 Oct; 247(1): 47–53PubMedGoogle Scholar
  13. 13.
    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
  14. 14.
    Bell J, Byron G, Gibson A, et al. A pilot study of buprenorphine-naloxone combination tablet (Suboxone) in treatment of opioid dependence. Drug Alcohol Rev 2004 Sep;23(3): 311–7PubMedCrossRefGoogle Scholar
  15. 15.
    European Medicines Agency. Scientific discussion (Suboxone) [online]. [cited 2007 21 Oct]; Available from: http://www. emea.europa.eu/humandocs/PDFs/EPAR/suboxone/069706 en6.pdfGoogle Scholar
  16. 16.
    Robinson SE. Buprenorphine-containing treatments: place in the management of opioid addiction. CNS Drugs 2006; 20(9): 697–712PubMedCrossRefGoogle 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.
    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
  19. 19.
    Kamien JB, Branstetter SA, Amass LA. Buprenorphinenaloxone versus methadone maintenance therapy: a randomised double-blind trial with opioid dependent patients. Heroin Addict Relat Clin Probl 2008; 10(4): 5–18Google Scholar
  20. 20.
    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
  21. 21.
    Reckitt Benckiser Pharmaceuticals Inc. Suboxone (buprenorphine HCl and naloxone HCl dihydrate sublingual tablets)/Subutex (buprenorphine HCl sublingual tablets): US prescribing information [online]. [cited 2009 16 November]; Available from: http://http://www.suboxone.com/patients/pi
  22. 22.
    Healy R. Effectiveness of two opioid antagonists in treating opioid-induced constipation. Br J Nurs 2009 Sep 10–23; 18(16): 998–1002PubMedGoogle Scholar
  23. 23.
    Woody GE, Poole SA, Subramaniam G, et al. Extended vs short-term buprenorphine-naloxone for treatment of opioid-addicted youth: a randomized trial. JAMA 2008 Nov 5; 300(17): 2003–11PubMedCrossRefGoogle Scholar
  24. 24.
    Ling W, Amass L, Shoptaw S, et al. A multi-center randomized trial of buprenorphine-naloxone versus clonidine for opioid detoxification: findings from the National Institute on Drug Abuse Clinical Trials Network. Addiction 2005 Aug; 100(8): 1090–100PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2010

Authors and Affiliations

  • Fernanda Magnelli
    • 1
  • Lorita Biondi
    • 1
  • Roberto Calabria
    • 1
  • Angelo Fiore
    • 1
  • Eugenio Peluso
    • 1
  • Domenico Vonella
    • 1
  • Amerigo Giuseppe Rota
    • 1
  1. 1.U.O.C Ser.T Cosenza Provincial Health AgencyCosenzaItaly

Personalised recommendations