Originally posted 1/26/2013
Readers of this blog know that I have often questioned whether there is any clinical difference between Suboxone and generic buprenorphine. Naloxone is an opioid-blocking chemical added to buprenorphine, supposedly in order to reduce intravenous diversion of the medication. The combination of buprenorphine plus naloxone is branded as Suboxone. I’ve pointed out over the years that the high affinity of buprenorphine at the opioid receptor is too great to be overcome by the amount of naloxone in a tablet or two of Suboxone, making naloxone unnecessary for anything except to create profits from Suboxone.
Because of the low number of doctors who obtain certification to prescribe buprenorphine and the limits on number of patients per doctor, many people who want treatment with buprenorphine are unable to find it. While sitting on wait lists, some people opt to treat themselves with ‘street Suboxone, rather than continue to use oxycodone or heroin.
When taken through the proper sublingual route, about 25-33% of the buprenorphine in Suboxone reaches the bloodstream. Because of the scarcity and high cost of Suboxone, patients who engage in self-treatment sometimes choose to inject the medication, since doing so reduces their costs by 70%.
I have treated patients who described injecting buprenorphine or Suboxone while waiting for a treatment spot to open up. The patients always claim the same thing; that they could detect no difference between injecting Suboxone, with the medication’s naloxone component, vs. injecting plain buprenorphine.
I am not advocating injecting Suboxone by any means; injecting any substance not intended to be used intravenously is very dangerous, particularly in people who are not clinically monitored, by people who are not trained in aseptic techniques. My point is that in an era of limited healthcare resources, should insurers and state health agencies use a medication that costs four times more than the clinically-identical generic?
The reasoning behind Suboxone makes sense on the surface. Naloxone is poorly absorbed from the mouth, whereas buprenorphine dissolves through cell membranes and enters the circulation when Suboxone is placed under the tongue. Naloxone is swallowed, absorbed by the intestine, and destroyed at the liver. But if injected, the naloxone is not destroyed, and instead binds to opioid receptors, blocking the effects of buprenorphine.
But what if naloxone doesn’t do what everybody thinks? I’ve done binding studies of other neural receptors back in my grad school years, and I’ve wondered, from those experiences, just how well a loose-binding drug like naloxone would interfere with the binding of a very tightly-binding drug like buprenorphine?
A study in human volunteers from 2006 does nothing to reduce my curiosity (1). In the study, adult volunteers received 0.2 mg of intravenous buprenorphine and the respiratory effects were measured. The volunteers then received different doses of intravenous naloxone, and the ability of varying doses of naloxone to block the effects from buprenorphine were measured.
The study found that 2 mg of naloxone, the amount in a standard tablet of Suboxone, blocked the respiratory effects of 0.2 mg of buprenorphine. But the study found that lower ratios of naloxone had no effect on buprenorphine. A tablet of Suboxone contains 40 times more buprenorphine than was used in the study.
According to the 2006 study, naloxone had no effect on buprenorphine when administered intravenously in the ratio of 4:1. In fact, naloxone became effective only at doses over 10:1. But when a person injects Suboxone, the ratio of naloxone to buprenorphine is much, much smaller— equal to 0.25:1. According to the 2006 study, a dose of Suboxone would have to include 80 mg of naloxone in order to block the respiratory effects of 8 mg of buprenorphine!
To restate the findings, blocking the effects of buprenorphine requires a dose of naloxone ten times higher than the dose of buprenorphine. Suboxone contains only 2.5% of the naloxone that would be necessary—-an amount that isn’t even in the ballpark of what is needed to block the effects of buprenorphine.
If naloxone isn’t doing anything, why do insurers demand that people spend the insurers’ money on it?
- Van Dorp E, Yassen A, Sarton E, et al. Naloxone reversal of buprenorphine-induced respiratory depression. Anesthesiology. 2006;105(1):51–57