Rise of Buprenorphine May Signal Move Toward More Responsible Prescribing

Typically, the increased utilization of a brand drug – particularly an opioid – is cause for heightened awareness by workers’ compensation claims payors/adjusters. The brand opioids Belbuca® and Butrans® have been making a steady climb up the rankings on top opioid reports of late (with Butrans® cracking the top 10 among some of our customers’ top opioids in 2017), but that rise may in fact signal a shift in the prescribing environment toward more responsible, less addictive entities.


The active chemical in both Belbuca® and Butrans® is buprenorphine, a high-affinity opioid with mixed agonist-antagonist efficacy at standard opioid sub-receptors. Buprenorphine partially activates mu opioid sub-receptors and partially inactivates kappa opioid sub-receptors – meaning that increasing doses of buprenorphine appear to produce a subdued or bridled effect compared to opioid full agonists (i.e. morphine, oxycodone, and fentanyl) which elicit a correlating, complete response. (See Figure 1, following.)


Inverse agonist 2

Image Credit: Wikimedia Commons

Buprenorphine’s increasing appeal to prescribers may also be the result of recent studies suggesting that, with respect to analgesia, it acts more like a full agonist (increasing pain relief with increased dosage). At the same time, the drug appears to have a dose ceiling effect on respiratory depression exhibiting partial agonist activity in relation to this potentially lethal adverse effect, which is normally the dose-limiting factor in opioid prescribing.1,2

Buprenorphine, moreover, has such affinity for opioid receptors that when it binds, it effectively acts as an antagonist to full agonist opioids when administered together rather than induce an additive dose response. This protective antagonist effect is another appealing benefit, since blocking effects of unknown illicit or misused (alternate source, etc.) opioids may prevent injured workers from the serious adverse effects of respiratory depression and overdose.


Where opioids are indicated for the treatment of injured workers, appropriate formulations containing buprenorphine offer unique benefits. As with all opioids, while the risk of abuse and/or misuse must still be weighed, the consideration of a buprenorphine medication with an FDA-approved indication for the management of pain may be warranted for a growing number of injured worker populations.


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  1. Dahan A, Yassen A, Romberg R et al (2006) Buprenorphine induces ceiling in respiratory depression but not in analgesia. Br J Anaesth 96:627–632
  2. Lutfy K, Cowan A. Buprenorphine: a unique drug with complex pharmacology. Curr Neuropharmacol. 2004 Oct;2(4):395-402. doi: 10.2174/1570159043359477.