Until this month, only buprenorphine in the sublingual form was FDA approved for the treatment of opioid addiction. This includes commonly known brands like Suboxone and Zubsolv, and generic buprenorphine both with and without naloxone added.
But earlier this month, the FDA approved Bunavail (B-YOU-na- vail), a buprenorphine product that is absorbed through the mucosa of the cheek. This method of delivery is termed “buccal.” The company making Bunavail says the product has an adhesive, which they call “BioErodible MucoAdhesive,” that improves absorption through the cheek mucosa. This product has twice the bioavailability of Suboxone film, and that’s the selling point for this new product.
Bioavailability is the percent of the drug that is absorbed into the bloodstream out of the total amount of the drug that is administered. If a drug is injected, by definition it has 100% bioavailability. Other routes of administration have less than 100% bioavailability because not all of the drug is absorbed orally, or due to the first-pass metabolism seen with some drugs like buprenorphine. When using a route of administration with lower bioavailability, more of the drug must be given to achieve the same blood level as when the drug is injected.
Buprenorphine has poor gastrointestinal availability. If a drug company made an oral tablet to be swallowed, less than 10% of the drug would be absorbed into the bloodstream. Sublingually (under the tongue), bioavailability of buprenorphine is said to be anywhere from 30 to 50%, and can be influenced by things like the pH of oral secretions (an acid environment interferes with absorption, which is why we tell patients not to drink any soft drinks, coffee, or tea for fifteen minutes prior to dosing).
So what does Bunavail’s higher bioavailability mean on a practical level? Bunavail’s films contain less buprenorphine than Suboxone, but deliver the same blood level. And if the blood level’s the same, the effect of the drug is the same. In other words, individual patients should feel the same.
Other than that, I can think of a few potential advantages. With higher bioavailability, fewer grams of buprenorphine would be prescribed, and fewer grams of buprenorphine that could make it to the black market.
Since less of the drug is needed per unit dose, perhaps the price will be lower. I have no information about the costs of this new product…but I’m going to make a wild prediction that Bunavail won’t be significantly cheaper than Suboxone. Zubsolv has higher bioavailability but I don’t think it’s significantly cheaper than its competitors.
The makers of Bunavail are making a big deal about the inconvenience of sublingual forms of buprenorphine compared to their new product, which sticks to the side of the cheek. In an interview on Bloomberg News, one of their scientists said patients taking Bunavail can talk and swallow while their medication is dissolving, something that can’t be done with their sublingual competitors.
OK, maybe that’s an advantage…but what are we talking about, five or ten minutes at most? I don’t know if patients will think that’s a big selling point, but time will tell.
On their website, the manufacturers caution, “Do not switch from BUNAVAIL to other medicines that contain buprenorphine without talking with your doctor. The amount of buprenorphine in a dose of BUNAVAIL is not the same as the amount of buprenorphine in other medicines. Your doctor will prescribe a dose of BUNAVAIL that may be different than other buprenorphine-containing medicines you may have been taking.”
To me this means I will have to be careful if I have a patient who wishes to switch buprenorphine products. However, the package insert says that 4.2/.7 mg of Bunavail is equal to Suboxone 8mg/2mg. The package insert goes on to say that patients should be started at 2.1mg and increased in increments of 2.1mg until a maintenance dose of 8.4mg is reached, though patients may go as high as 12.6mg
The insert also says not to tear or cut the film. Manufacturers of Suboxone say the same thing about their film, though cutting those films is fairly standard practice. I think that since the drug company hasn’t done any testing of their products when cut or torn, they can’t say for sure that it’s OK.
The company behind Bunavail, BioDelivery Sciences International Inc. (BDSI) has several other unique products. For example, they already market Onsolis, which is fentanyl also in a buccal (absorbed through the cheek) film. They’re also in phase 3 trials now with another buprenorphine product that uses the special mucoadhesive they developed, but it will be marketed for moderate to severe chronic pain. No information is available yet regarding the doses contained in this product.
Bunavail is expected to be marketed to doctors the last quarter of this year.