First approved in 2002, Suboxone, a sublingual pill, was undoubtedly a breakthrough in opiate addiction treatment—especially as compared to methadone. Unlike methadone, Suboxone could be prescribed in the office and filled at pharmacies, freeing patients from the shackles of the methodone lifestyle and its required daily clinic visits.
We’ve written about Suboxone before (CATR May 2014 and an overview in its sister publication, The Carlat Psychiatry Report May 2010) so for basic information about the medication, please see those articles. The picture changed in 2010, however, when Suboxone’s original marketing exclusivity protection expired, leading to the current confusing landscape of five different versions from which to choose. Keep in mind, however, all the formulations are bioequivalent—composed of the same two molecules—buprenorphine and naloxone, in a 4:1 ratio.
The Back Story
In 2010, Suboxone’s marketing exclusivity period expired. Reckitt Benckiser (RB) Pharmaceuticals, Suboxone’s manufacturer, was concerned about generic competition, which generally leads to an 80% loss of sales of the branded product within a year. However, RB was prepared, because it had already developed a Suboxone sublingual film for which it received approval from the US Food and Drug Administration (FDA) in August of 2010.
As is common practice in pharmaceutical marketing, RB reps tried to convince doctors to switch patients from the generic pill to the new film version. Their pitch had to do with safety—namely, that children were more able to access the pills than the film, which is wrapped in hard-to-open foil packaging. In addition, the company tried to convince the FDA to reject applications from generic drug companies seeking approval for their cheap versions of the buprenorphine/naloxone pill. RB’s tactic was to file a “Citizen’s Petition” to the FDA, arguing that these formulations (identical to the drug RB had marketed to doctors for years) were unsafe and should be blocked from entering the market. Luckily for cost-conscious patients, the FDA was unconvinced by RB’s argument and denied the petition. Furthermore, suspecting that the petition was a sham to discourage competitors, the FDA referred the case to the Federal Trade Commission, which led to an active investigation of potential antitrust activities (see http://bit.ly/1FbW7z0).
Comparing the Formulations
Table: Buprenorphine/Naloxone: Currently Available Formulations
There are a number of factors to consider in comparing the various formulations.
Bioavailability: This is the fraction of the drug that actually makes its way into the bloodstream and to the brain. Recall that after we ingest a regular pill, the molecules get absorbed by the microvilli of the intestine, and then go into the portal circulation and are sent directly to the liver. The liver metabolizes compounds before sending them into the systemic circulation. This passing through the liver is called the first pass effect, and it serves to remove some fraction of the drug from circulation. The degree of this effect varies significantly from drug to drug.
The only way to completely avoid the first pass effect is to administer drugs intravenously. That way, 100% of the drug gets into systemic circulation, meaning that the bioavailability is 100%. Another way to try to bypass the liver is to create sublingual drugs, which are supposed to dissolve under the tongue and get absorbed into the oral mucosa. These capillaries go directly to systemic circulation.
All buprenorphine/naloxone preparations exploit this route in some way or another, but they vary in how effectively they do it. The greater the bioavailability, the lower the dose required, which is why, for example, Bunavail (the citrus-flavored buccal film approved in June 2014) 4.2 mg is equivalent to sublingual bup/nal 8 mg.
Speed of onset: While all the formulations dissolve and get absorbed somewhere in the mouth, some get absorbed more quickly than others. A faster absorption means that a patient who is in withdrawal in your office will get somewhat faster relief from those symptoms—but we’re only talking about 10 or 15 minutes difference at most.
Side effects: Opiates tend to cause constipation and lowered libido. Manufacturers may claim side effect advantages depending on their safety data.
Dose required: The more bioavailable formulations require a lower number of milligrams to achieve the same effect. One theoretical advantage of fewer milligrams is that diversion will yield less milligrams of opiates on the streets. A possible disadvantage is a psychological one—patients who are used to taking 8 mg of Suboxone may erroneously believe they are getting too little by taking 4.2 mg of Bunavail. This “nocebo” effect can be significant when it comes to very subjective perceptions of opiate effects.
Now let’s take a look at the various formulations currently on the market (note that the doses indicate buprenorphine/naloxone; prices were retrieved in January 2015 from the Good Rx website and indicate prices available at Walmart):
At the time of this writing, there are two generic versions of the sublingual tablets, manufactured by Amneal Pharmaceuticals and Actavis.
Doses available: 2 mg/0.5 mg and 8 mg/2 mg
Cost for one month supply (30 pills) at 8 mg/2 mg dose/day: $185.22
Advantages: Long track record of use, cheap
Disadvantages: Some complain about the taste
Sublingual Tablets—Branded (Zubsolv)
Dose: 1.4 mg/0.36 mg, 5.7 mg/1.4 mg
Cost for one month supply (30 pills) at 5.7 mg/1.4 mg dose/day: $224.80
Advantage: Menthol flavor, higher bioavailability than generics (33% vs. 25% for generics)
Cost for one month supply (30 pills) at 8 mg/2 mg dose/day: $224.80
- Faster absorption, meaning faster onset of effect
- Easy to taper gradually because you can cut the film into very small sizes
- Packaging makes it more difficult for kids to open
- More diversion potential because you can easily mail the strips (this has been a problem in prisons, where inmates have received mail)
- High cost
Manufacturer: BioDelivery Sciences International Inc. (BDSI)
Bioavailability: Highest of all preparations, about 50%
Doses: 2.1 mg/0.3 mg, 4.2 mg/0.7 mg, 6.3 mg/1 mg
Cost for one month supply (30 pills) at 6.3 mg/1 mg dose/day: $440.90
- High bioavailability
- Faster absorption, faster onset of effect
- Less constipation
- Potentially more convenient to take then sublingual tablets or films, because bunavail sticks to the cheek while dissolving, allowing patient to talk. The company markets this as making the drug more “discrete.”
- Possibly more difficult to cut and taper than sublingual film, since cutting Bunavail may affect how well it sticks to the cheek mucosa
- High cost
A special thank you to Jeffrey Junig MD, PhD, who helped us find information for this article. See his blog, Suboxone Talk Zone (www.suboxonetalkzone.com) for an inexhaustible supply of Suboxone knowledge.