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