Probuphine® (buprenorphine implant): a promising candidate in opioid dependence

Abstract

Opioid dependence leads to physical dependence and addiction which finally results in profound medical, psychological and social dysfunction. One of the useful medications for opioid dependence is buprenorphine, the partial opioid agonist, which is used alone or in combination with naloxone. However, buprenorphine is the victim of its own success due to its illicit use and accidental poisoning in children. Also, buprenorphine typically requires daily self-administration and its effectiveness heavily depends on patient adherence. So, poor treatment adherence results in ineffective treatment manifesting as craving and withdrawal symptoms. Short-term use of buprenorphine in opioid dependence is also often followed by relapse. Buprenorphine when used sublingually often results in inadequate or fluctuating blood concentrations and poorer treatment retention compared with methadone. All of these led to the development of Probuphine®, a polymeric matrix composed of ethylene vinyl acetate and buprenorphine in the form of implants, that are implanted subdermally in office practice and deliver the active drug over 6 months. Buprenorphine release from such implant is fairly consistent, avoiding plasma peaks and troughs, and the implant is also reported to be safe. In this review article, we have highlighted these aspects of treatment of opioid addiction, stressing on the pharmacology of buprenorphine and Probuphine®, and relevant clinical trials addressing the efficacy and safety of Probuphine®. This sustained-release implantable formulation of buprenorphine has the potential to be a suitable alternative to daily or alternate day sublingual buprenorphine which can thereby eliminate the need for daily supervision, minimizing fluctuations in plasma concentrations, and allowing these patients to reduce clinic or pharmacy visits.

Opioid users' willingness to receive prolonged-release buprenorphine depot injections for opioid use disorder

“…Oral (sublingual) buprenorphine lasts around 24-60 h. As a partial agonist, buprenorphine activates the mu-opioid receptors in the brain, but to a lesser extent than full opioid agonists (Walsh & Eissenberg, 2003). In so doing, it latches onto opioid receptors with high receptor affinity, and reduces or 'blocks' the rewarding effects of illicit opioid use (Barnwal et al, 2017;Walsh & Eissenberg, 2003). In the UK, daily supervised dosing is recommended and sometimes required by regulators or treating clinicians, at least until good adherence is established.…”

“…After which time, supervised dosing should be reduced or stopped providing that stability is not jeopardised (Clinical Guidelines on Drug Misuse and Dependence (Update), 2017). Nonetheless, as with oral methadone, the burden and perceived stigma of having to constantly attend services can undermine patient satisfaction and compliance (Barnwal et al, 2017;Neale, Tompkins, McDonald, & Strang, 2018a). Further, there is evidence that patients sometimes forget or choose to miss oral buprenorphine doses; divert, snort or inject the tablets; 'misuse' the medication in other ways; or drop out of treatment prematurely and then return to illicit opioid use (Awgu, Magura, & Rosenblum, 2010;Fareed et al, 2014;Itzoe & Guarnieri, 2017;Middleton, Nuzzo, Lofwall, Moody, & Walsh, 2011;Rosenthal & Goradia, 2017;Sordo et al, 2017).…”

“…Since 2016, various prolonged-release buprenorphine products have been licensed. First, the United States (US) Food and Drug Administration (FDA) approved Probuphine® (Titan Pharmaceuticals, San Francisco and Braeburn Pharmaceuticals, Inc. Princeton, NJ, USA), a 6-month buprenorphine sub-dermal implant (Barnwal et al, 2017;Sigmon & Bigelow, 2016;Voelker, 2016). The FDA then approved Sublocade™ (investigational name RBP-6000) (Indivior, Richmond, VA, USA), a monthly subcutaneous depot buprenorphine (Lorman, 2018).…”

Factors influencing recruitment to a randomised placebo-controlled trial of oral naltrexone and extended release implant naltrexone: Qualitative study

“…Indeed, suspicion of implantable formulations seems to have received little attention outside of our own empirical qualitative research (Neale et al, 2018b), and appears to contrast with studies on the acceptability of injectable XR-NTX (Ahamad et al, 2015;Haase et al, 2016;Marcus et al, 2017;Marcus et al, 2018;Zaaijer et al, 2016). Given that the market of long-acting extended-release medications for OUD is expanding (Barnwal et al, 2017;Hegde, Singh & Sarkar, 2013;Lorman, 2018;Sigmon & Bigelow, 2016;Walsh et al, 2017), attitudes to such medications require further investigation, not least in light of concerns regarding the uptake of Probuphine® implants in the US (Titan Pharmaceuticals, 2018).…”

Langwirksame Buprenorphinpräparate als neue pharmakologische Option bei Opiatabhängigkeit

“…Smith et al [48] konnten Effekte von RBP-6000 auf das EKG und andere kardiologische Nebenwirkungen ausschließen. Eine weitere Untersuchung [54] wurde an Patienten, die stabil auf 8 mg oder weniger Buprenorphin eingestellt waren, durchgeführt.…”