Another Head for the Hydra

© Vladimir Korostyshevskiy | 123rf.com

© Vladimir Korostyshevskiy | 123rf.com

Belbuca sounds like it is the name for new Italian recipe from a famous chef. Bel Buca sounds like the name of an Italian pop star. But Belbuca is actually the name of a new FDA approved pain medication for chronic pain management from Endo International and BioDelivery Sciences.  And “Bel Buca” actually has a twitter account, with the picture of an attractive blue-eyed dark-haired woman posing as Bel. She doesn’t seem to tweet much, but she follows Dr. Oz and several health and medical accounts, probably to see what they say about the medication she was named after.

The FDA just accepted the New Drug Application for Belbuca in February 2015 and approved it on October 23, 2015. The fast turn around was because the opioid analgesic used for pain relief and the drug delivery mechanism were both approved by the FDA and used for other medications. The opioid is buprenorphine and the drug delivery technology is BioErodible MucoAdhesive (BEMA). BEMA technology is used with buprenorphine in Bunavail, a buprenorphine-BEMA drug from—no surprise—BioDelivery Sciences (BDSI).  Belbuca contains .05 and .1 the amount of buprenorphine in Suboxone and other buprenorphine products like Bunavail used to treat opioid addiction.

Chronic pain relief is a much wider (and more lucrative) market for BioDelivery Sciences, so the sales from Belbuca should easily outpace Bunavail in a short time. BDSI only recorded $1.5 million in sales through the first six months of 2015, according to Jason deBruyn of the Triangle Business Journal. Endo will commercialize, market and sell Belbuca. BDSI is a relatively small company without the sales force to effectively market a drug like Belbuca, which has a large target market. Herein lies the potential problem, from my point of view.

Methadone, the first opioid maintenance medication, began to be used for chronic pain relief in the mid-1990s. By 2009, methadone accounted for almost 1 of every 3 prescription pain medication deaths. Six times as many people died from methadone overdoses in 2009 as did in 1999. The problem seems to have been the result of the length of time it takes methadone to be converted into inactive metabolites within opioid-naïve individuals. See “The Consequences of Ignoring the Past” for more on the problems with methadone as a pain reliever.

While there are some supposed biochemical advantages of buprenorphine over methadone, there is still a real potential for abuse, overdose and death with buprenorphine. It is a partial opioid agonist, meaning it binds to the mu opioid receptor and activates them, but not to the same degree as full agonists like heroin and methadone. It is by activating the mu opioid receptor that opioids exert their analgesic, euphoric and addictive effects. At a certain point, the effects of burprenorphine is said to reach a ceiling and not increase further. Nevertheless, buprenorphine has the potential for abuse and misuse.  See “Is Buprenorphine Just Another Head for the Hydra of Opiate Addiction?” Also see the FDA medication guide for Belbuca.

At lower doses and in individuals who are not dependent on opioids, full agonists (like heroin or methadone) and partial agonists (like buprenorphine) produce effects that are indistinguishable. As doses are increased, both full and partial agonists produce increasing effects.

The adverse reactions highlighted in the Belbuca medication guide include nausea, constipation, headache, vomiting, dizziness and somnolence (drowsiness). Using them along with central nervous system (CNS) depressants may cause “profound sedation, respiratory depression and death.” Benzodiazepines may increase buprenorphine-induced respiratory depression.

The medication guide distinguishes between “CNS depressants” and “benzodiazepines” when they actually fall within the same category as CNS depressants. Benzodiazepines such as diazepam (Valium) and alprazolam (Xanax) and non-benzo sleep medications such as zolpidem (Ambien), eszopicione (Lunesta) and zalepon (Sonata) are all CNS depressants. And by the way, respiratory depression is what happens when someone overdoses on opioids, opiates or a combination of these drugs and the other CNS depressants like benzodiazepines. The accidental overdose potential of buprenorphine does not have a ceiling effect if it is used in conjunction with other CNS depressants like Ambien or Xanax.

When the target market for buprenorphine is dramatically increased from that of individuals seeking medication assisted treatment (MAT) for opioid/opiate addiction to that of individuals with chronic pain issues, there will be an increase in individuals with “buprenorphine-induced respiratory depression,” overdose and death. I expect that what happened when methadone was released to the wider market of chronic pain to be replicated with buprenorphine. Additionally, the discontinuation (withdrawal) syndrome from burprenorphine is anecdotally more severe than heroin and methadone. Regularly over the years I’ve worked with opioid/opiate addicts who have told me they had a much harder time coming off of buprenorphine than heroin or methadone.

The FDA is also looking to approve buprenorphine to treat depression. At this time, the buprenorphine drug formula is only designated as “ALKS-5461” by Alkermes. See “The Coming Depression Apocalypse” for more on this issue. Be aware of the potential adverse reactions and negative consequences from using buprenorphine for chronic pain relief or depression. As bad as the pain or depression can be, don’t jump from the frying pan into the fire with buprenorphine. If you think I’m overstating the risk, go to an open Narcotics Anonymous meeting and strike up a conversation with someone who has misused burprenorphine or who has simply tried to taper off of it after an extended time of using it for MAT.

We now have two approved medical uses for buprenorphine and it’s likely we’ll soon have a third. “Is Buprenorphine Just Another Head for the Hydra of Opiate Addiction?” is looking prophetic. Buprenorphine had just grown a second head and is the process of adding a third head for the Hydra of opiate addiction.