I am writing in response to the article “Buprenorphine Explained, And Opioid Addiction Treatment Tips” published in the June 2018 edition of ACEP Now.

As an emergency physician with a special interest in the identification and treatment of opioid use disorder among our patients, I was overjoyed to learn that ACEP Now was publishing a series of articles centered around buprenorphine and its potential as a treatment for emergency patients.

I found that this article in particular was concise yet accurate in its description of buprenorphine’s pharmacology and avoided many of the common misunderstandings surrounding the drug (especially the idea that the naloxone included in Suboxone provides the opioid antagonist property).

However, I believe that it’s critical to correct two misunderstandings that could result in either serious legal trouble or patient harm.

First is the implication of the statement that “…we have a medication we can give 8 mg of sublingually or 0.3 mg of subcutaneously or via IV…” which suggests that the formulation of buprenorphine administered is inconsequential. In the context of treating opioid use disorder and acute opioid withdrawal, this is incorrect, and it is illegal for a physician to prescribe or administer an opioid drug for these purposes unless that drug carries an FDA approval for the treatment of opioid use disorder.

Although there exists an increasing number of buprenorphine formulations on the market, we are limited to those that are FDA approved specifically for the treatment of addiction, such as Suboxone, Subutex, Zubsolv, Sublocade (implant), or the generics thereof when treating opioid withdrawal and dependency. It would be against federal law to administer a buprenorphine formulation that does not carry this FDA approval such as Buprenex (IM/IV) or Butrans (transdermal); even Belbuca, which is a sublingual tablet nearly identical to Subutex, is disallowed for use.

The difference between these two groups is that the latter medications are only approved for the treatment of pain, while the former carry an indication for the treatment of opioid use disorder. Unfortunately, this seeming triviality could mean risking a felony conviction for violating the Controlled Substances Act. Institutions and providers have been investigated and fined in the past for their use of injected buprenorphine to treat their patients in opioid withdrawal.

The second troublesome statement is the suggestion that, “I could give them buprenorphine…and instead of causing precipitated withdrawal, it would cause precipitated breathing.” Although the author is trying to illustrate pharmacology rather than give us clinical advice, this implied clinical scenario is implausible. As described previously in the same article, buprenorphine has an extremely high affinity for the mu-receptor, higher than heroin and even higher than naloxone. You can titrate the dosage of naloxone so that it binds just enough receptors to reverse the overdose but still leaves some receptors available for agonists; this way, you create a happy median between apnea and agony.

In contrast, buprenorphine binds mu-receptors so avidly that it will come to occupy nearly all in the brain, leaving no open receptors for an agonist to bind. This creates legendarily severe precipitated withdrawal. There is no equilibrium between agonism and antagonism. As an analogy, it is the difference between walking down a staircase and jumping out the window; both reduce your altitude. However, with the first you can gradually move up or down, but once you defenestrate yourself, there’s no way back up and only one destination, ground level. Naloxone also has a much shorter half-life, so the agony of its precipitated withdrawal is over in about an hour or less. The half-life of buprenorphine is anywhere from 24 to 48 hours, which ensures ongoing misery for the patient, and with its avid binding, there is no way to titrate with another agonist.

I should also mention that although buprenorphine itself is unlikely to precipitate apnea (due to the “respiratory ceiling” from its partial mu-agonism), it can cause fatal overdoses in combination with other respiratory depressants. Since we often administer naloxone to unconscious patients with no knowledge of their recent drug consumption, it would be dangerous to give buprenorphine to such patients. The patient we assume overdosed on heroin might have actually taken a few Xanax, and the buprenorphine we administer might very well push them from hypoventilation to full respiratory arrest. Not to mention that the long half-life of buprenorphine means that they will be on the ventilator while the drug is metabolized over days.

I felt it was important to clear up these implied misunderstandings since most emergency physicians are unfamiliar with buprenorphine and its applications. I hope that this serves to educate rather than frighten physicians from adopting buprenorphine in their practice, and I look forward to more coverage of emergency addiction management. 

Jack C. McGeachy, MD
Tampa, Florida