why the naloxone?  photo credit belowI will take a moment to clarify the difference between the two major forms of buprenorphine on the market, namely Suboxone and Subutex.

Suboxone is a medication that contains buprenorphine plus naloxone, an antagonist at the mu receptor used clinically to reverse opioid overdose.  Subutex and the generic equivalent of Subutex contain only buprenorphine.

The role of naloxone is difficult to understand without knowing a couple facts about the GI system. The human body is designed in a way that allows close monitoring and control of the things that we ingest.  Food or medication that reaches the stomach passes into the small intestine, where the bulk of digestion occurs.  From the small intestine, molecules are absorbed into the circulation and transported to the liver through the portal vein.

Some molecules are broken down very efficiently when they reach the liver; so efficiently that very little of the substance reaches the general circulation.  This efficient destruction of certain substances is called the ‘first pass effect,’ and applies to the two ingredients in Suboxone—buprenorphine and naloxone.

Because of the first pass effect, buprenorphine is largely ineffective if swallowed, and so is typically administered intravenously, transdermal (through the skin), or sublingual (under the tongue).  Tablets of Suboxone are intended to be taken sublingually; buprenorphine is a fat-soluble molecule that gains entry into the general circulation via tiny capillaries that lie under the surface of the delicate membranes lining the mouth.

Similarly, naloxone is inactive if swallowed.  But unlike buprenorphine, naloxone is a water-soluble molecule that does not pass through the membranes lining the mouth.  When a tablet of Suboxone dissolves under the tongue, buprenorphine passes into the circulation, but naloxone remains behind in the saliva, is eventually swallowed, and is destroyed by first pass metabolism at the liver.

So why add naloxone?

Buprenorphine has been used for thirty years as an intravenous pain medication.  There were concerns that buprenorphine intended to treat opioid dependence would be diverted and abused intravenously.   Naloxone was added to buprenorphine as a deterrent, so that if Suboxone was injected, the naloxone would precipitate withdrawal.

The naloxone in Suboxone has no action when the medication is used properly, and is not responsible in any way for the ‘ceiling effect’ of Suboxone. There is considerable confusion over this issue, and I have read comments by otherwise-intelligent physicians stating that naloxone is necessary to provide a ‘cap’ on the actions of buprenorphine.  Such a statement is incorrect; the actions of buprenorphine alone, as a partial agonist with a ceiling effect, are responsible for ALL of the effects of Suboxone on cravings for opioids.

Generic buprenorphine provides considerable cost savings over brand-name Suboxone.  Some prescribers are reluctant to prescribe the generic, however, out of fear that the patient will dissolve and inject the buprenorphine.  I find this fear to be unfounded for several reasons.

First, the large majority of opioid addicts ingest substances by insufflations (nasally), and I find it unlikely that addicts who avoided needles when using oxycodone or heroin would cross that barrier and take up injecting for the sake of using buprenorphine, an opioid with a far-lesser reward  than that of agonists.  Second, intravenous buprenorphine has a lower potency than would satisfy the tolerance of almost all of the addicts who have come to my practice for treatment; buprenorphine injected intravenously would precipitate withdrawal in anyone using more than about 60 mg of oxycodone per day, and the typical patient in my practice was using 120-600 mg of oxycodone per day at presentation.

Third, studies of diversion demonstrate that most cases consist of self-medication by addicts attempting to treat their own opioid dependence, to break free of their addictions.  Finally, heroin is much more plentiful, and much less expensive, than diverted generic buprenorphine.  If an addict is looking for a high, he/she will unfortunately have less trouble finding an agonist than finding buprenorphine.

New formulations of buprenorphine are entering the market, or in some cases at the verge of entering the market.  People who work with buprenorphine and who spend time talking to opioid addicts know, without a doubt, that buprenorphine is saving tens of thousands of lives every year—and will save countless more going forward.

Photo by Niels Heidenreich, available under a Creative Commons attribution, non-commercial license.