Langwirksame Buprenorphinpräparate als neue pharmakologische
                    Option bei Opiatabhängigkeit

Michael Soyka

doi:10.1055/a-1064-6188

Suchttherapie, Table of Contents

Suchttherapie 2020; 21(01): 13-18
DOI: 10.1055/a-1064-6188

Schwerpunktthema

Langwirksame Buprenorphinpräparate als neue pharmakologische Option bei Opiatabhängigkeit

Long-Acting Buprenorphine Medications as a Novel Pharmacological Option in Opioid Dependence

Michael Soyka

¹Medical Park Chiemseeblick, Bernau/Felden

²Psychiatrische Universitätsklinik LMU München

› Author Affiliations

Abstract

Zusammenfassung

Die Opioidsubstitution mit Methadon (oral) oder Buprenorphin (sublingual) ist eine etablierte weltweit praktizierte First-Line-Behandlung der Opiatabhängigkeit. Beide Substanzen müssen täglich oder zumindest alle 2 Tage (Buprenorphin) gegeben werden. Langwirksame Opioide standen zur Substitution nicht zur Verfügung. Das ändert sich jetzt mit dem bereits zugelassenen, wöchentlich oder monatlich subkutan injizierbaren Buprenorphin Depot CAM 2038 (Buvidal^®), dem monatlich zu applizierenden Depotpräparat RBP-6000 (Sublocade™) und dem 6-Monate wirkenden Buprenorphin Depot-Implantat (Probuphine™). Klinische Befunde und mögliche Indikationen dieser Medikamente werden diskutiert.

Abstract

Opioid maintenance treatment with oral methadone or sublingual buprenorphine is an established first-line treatment in opioid dependence. Both drugs must be taken daily (methadone) or at least every second day (buprenorphine). Apart from the novel subcutaneous weekly and monthly depot formulations CAM 2038 (Buvidal^®) 2 other long-acting buprenorphine formulations may be introduced in the near future: the monthly depot formulation RBP-6000 (Sublocade™) and a 6-month buprenorphine implant (Probuphine™). Clininical findings of these three medications are given and possible clinical indications are discussed.

Schlüsselwörter

Opiatabhängigkeit - Substitutionsbehandlung - Buprenorphin - Depot - Implantat

Key words

opioid dependence - maintenance treatment - buprenorphine - depot - implant

Full Text

References

Literatur
1 Bell J. Pharmacological maintenance treatments of opiate addiction. Br J Clin Pharmacol 2014; 77: 253-263
2 Amato L, Minozzi S, Davoli M. et al. Psychosocial combined with agonist maintenance treatments versus agonist maintenance treatments alone for treatment of opioid dependence. Cochrane Database Syst Rev. 2011; 10 CD004147.
3 Mattick RP, Breen C, Kimber J. et al. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev. 2014; CD002207
4 Schuckit MA. Treatment of opioid-use disorders. N Engl J Med 2016; 375: 1596-1597
5 Soyka M, Strehle J, Rehm J. et al. Six-Year Outcome of Opioid Maintenance Treatment in Heroin-Dependent Patients: Results from a Naturalistic Study in a Nationally Representative Sample. Eur Addict Res 2017; 23: 97-105
6 Walter M, Soyka M. Opioide.In Soyka M, Batra A, Heinz A, Moggi F, Walter M , Hrsg. Suchtmedizin. München: Elsevier 2019; 177–202
7 Degenhardt L, Charlson F, Mathers B. et al. The global epidemiology and burden of opioid dependence: results from the global burden of disease 2010 study. Addiction 2014; 109: 1320-1333
8 Bell J, Strang J. Medication Treatment of opioid use disorder. Biol Psychiatry. 2019;
9 Volkow ND, Frieden TR, Hyde PS. et al. Medication-Assisted therapies: tackling the opioid-overdose epidemic. N Engl J Med 2014; 370: 2063-2066
10 Rehm J, Gschwend P, Steffen T. et al. Feasibility, safety, and efficacy of injectable heroin prescription for refractory opioid addicts: A follow-up study. Lancet 2001; 358: 1417-1423
11 Strang J, Groshkova T. Uchtenhagen et al. Heroin on trial: Systematic review and meta-analysis of randomised trials of diamorphine prescribing as treatment for refractory heroin addiction. Br J Psychiatry 2015; 207: 5-14
12 Atzendorf J, Rauschert L, Seitz NN. et al. Gebrauch von Alkohol, Tabak, illegalen Drogen und Medikamenten. Dtsch Ärzteblatt 2019; 116: 577-584
13 Center for Behavioral Health Statistics and Quality (CBHSQ). National Survey on Drug Use and Health: Detailed Tables. Substance Abuse and Mental Health Services Administrations. Rockville, MD; 2016
14 McLellan AT, McKay JR, Forman R. et al. Reconsidering the evaluation of addiction treatment: From retrospective follow-up to concurrent recovery monitoring. Addiction 2005; 100: 447-458
15 Russolillo A, Moniruzzaman A, McCandless LC. et al. Associations between methadone maintenance treatment and crime: A 17-year longitudinal cohort study of Canadian provincial offenders. Addiction 2018; 113: 656-667
16 Dennis ML, Scott CK, Funk R. et al. The duration and correlates of addiction and treatment careers. J Subst Abuse Treat 2005; 28: 51-62
17 Gossop M, Marsden J, Stewart D. et al. Outcomes after methadone maintenance and methadone reduction treatments: Two-year follow-up results from the National Treatment Outcome Research Study. Drug Alcohol Depend 2001; 62: 255-264
18 Teesson M, Mills K, Ross J. et al. The impact of treatment on 3 years’ outcome for heroin dependence: Findings from the Australian Treatment Outcome Study (ATOS). Addiction 2007; 103: 80-88
19 Kimber J, Larney S, Hickman M. et al. Mortality risk of opioid substitution therapy with methadone versus buprenorphine: A retrospective cohort study. Lancet Psychiat 2015; 2: 901-908
20 Bundesärztekammer. Richtlinie der Bundesärztekammer zur Durchführung der substitutionsgestützten Behandlung Opioidabhängiger. 2017; Im Internet: www.bundesaerztekammer.de/fileadmin/user_upload/downloads/pdf-Ordner/RL/Substitution.pdf; Stand: 18.11.2019
21 Bell J, Burrell T, Indig D. et al. Cycling in and out of treatment; participation in methadone treatment in NSW, 1990-2002. Drug Alcohol Depend 2006; 81: 55-61
22 Zhang L, Zou X, Zhang D. et al. Investigation of repeat client drop-out and re-enrolment cycles in fourteen methadone maintenance treatment clinics in Guangdong, China. PLoS One 2015; 10: e0139942
23 Timko C, Schultz NR, Cucciare MA. et al. Retention in medication-assisted treatment for opiate dependence: A systematic review. J Addict Dis 2016; 35: 22-35
24 Kuhlman JJ, Levine B, Johnson RE. et al. Relationship of plasma buprenorphine and norbuprenorphine to withdrawal symptoms during dose induction, maintenance and withdrawal from sublingual buprenorphine. Addiction 1998; 93: 549-559
25 Greenwald MK, Comer SD, Fiellin DA. Buprenorphine maintenance and mu-opioid receptor availability in the treatment of opioid use disorder: implications for clinical use and policy. Drug Alcohol Depend 2014; 144: 1-11
26 Greenwald MK, Johanson CE, Moody DE. et al. Effects of buprenorphine maintenance dose on mu-opioid receptor availability, plasma concentrations, and antagonist blockade in heroin-dependent volunteers. Neuropsychopharmacol 2003; 28: 2000-2009
27 Fareed A, Vayalapalli S, Casarella J. et al. Effect of buprenorphine dose on treatment outcome. J Addict Dis 2012; 31: 8-18
28 Hser YI, Saxon AJ, Huang D. et al. Treatment retention among patients randomized to buprenorphine/naloxone compared to methadone in a multi-site trial. Addiction 2014; 109: 8-18
29 Hser YI, Evans E, Huang D. et al. Long-term outcomes after randomization to buprenorphine/naloxone versus methadone in a multi-site trial. Addiction 2016; 111: 695-705
30 Bell J, Butler B, Lawrance A. et al. Comparing overdose mortality associated with methadone and buprenorphine treatment. Drug Alcohol Depend 2009; 104: 73-77
31 Bell J, Trinh L, Butler B. et al. Comparing retention in treatment and mortality in people after initial entry to methadone and buprenorphine treatment. Addiction 2009; 104: 1193-1200
32 Sun EC, Dixit A, Humphreys K. et al. Association between concurrent use of prescription opioids and benzodiazepines and overdose: Retrospective analysis. BMJ. 2017; 356 j760
33 Krantz MJ, Lewkowiez L, Hays H. et al. Torsade de pointes associated with very-high-dose methadone. Ann Intern Med 2002; 137: 501-504
34 Treece JM, Al Madani M, El Khoury G. et al. Comprehensive review on methadone-induced QT prolongation and torsades. J Pharmacol Pharmacother 2018; 9: 66-75
35 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: 2469-2475
36 Bell J. The Global Diversion of Pharmaceutical Drugs: Opiate Treatment and the Diversion of Pharmaceutical Opiates: A Clinician’s Perspective. Addiction 2010; 105: 1531-1537
37 Coe MA, Lofwall MR, Walsh SL. Buprenorphine Pharmalogy Review: Update on Transmucosal and Long-Acting Formulations. J Addict Med. 2019; 13: 93-193 doi:10.1097/ADM.0000000000000457
38 Walsh SL, Comer SD, Lofwall MR. et al. Effect of buprenorphine weekly depot (CAM 2038) and hydromorphone blockade in individuals with opioid use disorder: a randomized clinical trial. JAMA Psychiat 2017; 74: 894-902
39 Albayaty M, Linden M, Olsson H. et al. Pharmacokinetic evaluation of one-weekly and once-monthly buprenorphine subcutaneous injection depots (CAM 2038) versus intravenous and sublingual buprenorphine in healthy volunteers under naltrexone blockade: an open-label phase 1 study. Adv Ther 2017; 34: 560-575
40 Haasen C, Linden M, Tiberg F. Pharmacokinetics and pharmacodynamics of a buprenorphine subcutaneous depot formulation (CAM2038) for once-weekly dosing in patients with opioid disorder. J Subst Abuse Treat 2017; 78: 22-29
41 Lofwall MR, Walsh SL, Nunes EV. et al. Weekly and Monthly Subcutaneous Buprenorhpine Depot Formulations vs Daily Sublingual Burpenorphine with Naloxone for Treatment of Opioid Use Disorder: A Randomized Clinical Trial. JAMA Intern Med 2018; 178: 764-773
42 Frost M, Bailey GL, Lintzeris L. et al. Longtime safety of weekly and monthly subcutanious Buprenorphindepot (CAM 2038) in the treatment of adult out-patients with Opiod Use disorders. Addiction 2019; 114: 1416-1426
43 Nasser AF, Greenwald MK, Vince B. et al. Sustained-Release Buprenorphine (RBP-6000) Blocks the Effects of Opioid Challenge with Hydromorphone in Subjects with Opioid Use Disorder. J Clin Psychopharmacol 2016; 36: 18-26. doi10.1097/JCP
44 Laffont CM, Gomeni R, Heidbreder C. et al. Population Pharmacokinetic Modeling After Repeated Administrations of RBP-6000, a New, Subcutaneously Injectable, Long-Acting, Sustained-Release Formulation of Buprenorphine, for the treatment of Opioid Use Disorder. J Clin Pharmacol 2016; 56: 806-815
45 Nasser AF, Heidbreder C, Gomeni R. et al. A population pharmacokinetic and pharmacodynamic modelling approach to support the clinical development of RBP-6000, a new, subcutaneously injectable, long-acting, sustained-release formulation of buprenorphine, for the treatment of opioid dependence. Clin Pharmacokinet 2014; 53: 813-824
46 Haight BR, Learned SM, Laffont CM. et al. Fudala J, Zhao Y, Garofalo AS, Greenwald MK, Nadipelli VR, Ling W, Heidbrder C; RB-US-13-0001 Study Investigators. Efficacy and safety of a monthly buprenorphine depot injection for opioid use disorder: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2019; 393: 778-790 doi:10.1016/S0140-6736(18)32259-1
47 Ling W, Nadipelli VR, Solem CT. et al. Patient-centered Outcomes in Participants of a Buprenorphine Monthly Depot (BUP-XR) Double-blind, Placebo-controlled, Multicenter, Phase 3 Study. J Addict Med 2019; 13: 442-449 doi:10.1097/ADM.0000000000000517
48 Smith VD, Curd L, Lohmer LRL. et al. Evaluation of the effects of a monthly buprenorphine depot subcutaneous injection on qt interval during treatment for opioid use disorder. Clin Pharmacol Ther 2019; 106: 576-584 doi:10.1002/cpt.1406
49 Barnwal P, Das S, Mondal S. et al. Probuphine^® (buprenorphine implant): A promising candidate in opioid dependence. Ther Adv Psychopharmacol 2017; 7: 119-134. doi:10.1177/2045125316681984
50 Itzoe M, Guarnieri M. New developments in managing opioid addiction: impact of a subdermal buprenorphine implant. Drug Des Devel Ther 2017; 11: 1429-1437. doi:10.2147/DDDT.S109331
51 White J, Bell J, Saunders JB. et al. Open-label dose-finding trial of buprenorphine implants (Probuphine) for treatment of heroin dependence. Drug Alcohol Depend 2009; 103: 37-43 10.1016/j.drugalcdep.2009.03.008
52 FDA, US Food and Drug Administration. Probuphine™ prescribing information; 2016. Im Internet: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/204442Orig1s000lbl.pdf Stand: 18.11.2019
53 Rosenthal RN, Ling W, Casadonte P. et al. Buprenorphine implants for treatment of opioid dependence: randomized comparison to placebo and sublingual buprenorphine/naloxone. Addiction 2013; 108: 2141-2149
54 Rosenthal RN, Lofwall MR, Kim S. et al. Effect of buprenorphine implants on illicit opioid use among abstinent adults with opioid dependence treated with sublingual buprenorphine: a randomized clinical trial. JAMA 2016; 316: 282-290
55 Kenney SR, Anderson BJ, Bailey GL. et al. Buprenorphine treatment formulations: Preferences among persons in opioid withdrawal management. J Subst Abuse Treat. 2018; 94: 55-59 doi:10.1016/j.jsat.2018.08.011
56 Tompkins CNE, Neale J, Strang J. Opioid Users Willingness to reeive prolonged-release Buprenorphine Depot injections for Opioid use disorder. J Subst Abuse treatment 2019; 104: 64-71
57 Neale J, Tompkins CNE, Strang J. Prolanged-release opoid agonist therapy: Qualitative study exploring patients views of 1-week, 1-month and 6-month Buprenorphine formulations. Harm Reduct J 2019; 16: 25 doi:10.1186/s12954-019-0296-4
58 Deamer RL, Wilson DR, Clark DS. et al. Torsades de pointes associated with high dose levomethadyl acetate (ORLAAM). J Addict Dis 2001; 20: 7-14 doi:10.1300/J069v20n04_02
59 European Agency for the Evaluation of Medical Products. EMEA public statement to suspend the marketing authorisation for Orlaam (levoacetylmethadol) in the European Union. 2001 EMEA/8776/01. Im Internet: https://www.ema.europa.eu/en/documents/public-statement/public-statement-recommendation-suspend-marketing-authorisation-orlaam-levacetylmethadol-european_en.pdf; Stand: 18.11.2019
60 Wieneke H, Conrads H, Wolstein J. et al. Levo-alpha-acetylmethadol (LAAM) induced QTc-prolongation-results from a controlled clinical trial. Eur J Med Res 2009; 14: 7-12