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Review of Formulations, Administration Methods and Misuse Potential of
Buprenorphine for Opioid Agonist Therapy
Stephanie T. Weiss, MD PhDWake Forest School of Medicine
Addiction Medicine ProgramNovember 19, 2019
Objectives
• Identify the formulations of buprenorphine currently available in the United States and Israel
•Compare their advantages and disadvantages (including possible diversion, misuse or abuse)
Buprenorphine Is a Semisynthetic Opioid
Canadian Journal of Chemistry, 2015, 93:492-501, https://doi.org/10.1139/cjc-2014-0552
https://doi.org/10.1139/cjc-2014-0552
Buprenorphine is Both an Agonist and an Antagonist
Khanna, I. K., & Pillarisetti, S. (2015). Buprenorphine - an attractive opioid with underutilized potential in treatment of chronic pain. Journal of pain research, 8, 859–870. doi:10.2147/JPR.S85951
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Grinnell, S. G., Ansonoff, M., Marrone, G. F., Lu, Z., Narayan, A., Xu, J., ... & Pintar, J. (2016). Mediation of buprenorphine analgesia by a combination of traditional and truncated mu opioid receptor splice variants. Synapse, 70(10), 395-407.
Summary of Buprenorphine and Naloxone Pharmacokinetic Properties
https://www.semanticscholar.org/paper/National-PBM-Drug-Monograph-Sublingual-%2F-Naloxone-(-Buprenorphine-Naloxone/87871680f9203edd042d6da63d4b258559f6820e
Buprenorphine/Naloxone Sublingual Films/Tablets (Suboxone, Zubsolv)
• Multiple brands and generics available in the US (Suboxone in Israel)• Formulated with naloxone
to reduce abuse potential • SL administration has
~30% bioavailability
• Indication: management of opioid use disorder
https://www.zubsolv.com/
Buprenorphine Sublingual Films/Tablets (Subutex)
•Multiple brands and generics available (Subutex in Israel)• Do not contain naloxone• SL administration has
~30% bioavailability
• Indication: management of opioid use disorder
https://www.opiate.com/wp-content/uploads/subutex.png
Buprenorphine/Naloxone Buccal Films (Bunavail)
• Buccal combination film approved in 2014• Buccal bioavailability
is ~60%, so doses are about half of SL doses
• Taken daily as with SL formulations
• Indicated for management of opioid use disorder in the US
http://www.biopharmartis.com/pipeline/core/bpp_b.jsp
Sublingual Buprenorphine Diversion
Cicero, T. J., Ellis, M. S., & Chilcoat, H. D. (2018). Understanding the use of diverted buprenorphine. Drug and Alcohol Dependence, 193, 117-123.
Buprenorphine Depot Injection (Sublocade)
• Injectable depot formulation that solidifies on contact w/ body fluids• Delivers buprenorphine over an extended period of time (one month)• Must be administered by a trained HCP
• Indication: management of opioid use disorder (approved in 2017 in US)
https://www.sublocade.com/ (Indivior Pharmaceuticals)
https://www.sublocade.com/
Buprenorphine Implant (Probuphine)
• Four “matchstick-sized” implants that go into the upper arm approved in May 2016 in US• Must be placed under local
anesthetic by a trained HCP• Provide buprenorphine release x
6 months• Should only be used in pts stable
on ≤8 mg/day buprenorphine
• Indication: management of OUD
https://probuphine.com/ (Titan Pharmaceuticals)
https://probuphine.com/
Transdermal Buprenorphine Patch (Butrans)
• Available in 5, 7.5, 10, 15, and 20 mcg/hr patches that are worn for a week each (US and Israel)
• Indication: approved in 2010 for management of severe pain
• “Abuse or misuse of Butrans by placing it in the mouth, chewing it, swallowing it, or using it in ways other than indicated may cause choking, overdose and death.” https://butrans.com/ (Purdue Pharmaceuticals)
https://butrans.com/
Anecdotal Abuse Potential of Buprenorphine Patch
https://www.bluelight.org/xf/threads/butrans-patch-extraction-any-help-please.859372/
Literature Abuse Potential of Buprenorphine Patch
Coplan, P.M., et al. (2017). Comparison of abuse, suspected suicidal intent, and fatalities related to the 7-day buprenorphine transdermal patch versus other opioid analgesics in the National Poison Data System. Postgraduate medicine, 129 1, 55-61 .
Wiegand, Timothy J. et al. (2016) Analysis of the Abuse and Diversion of the Buprenorphine Transdermal Delivery System, The Journal of Pain, 17(6): 745 - 752
Summary of Buprenorphine Formulations
https://www.practicalpainmanagement.com/treatments/addiction-medicine/opioid-use-disorder/buprenorphine-promising-yet-overlooked-tool