Opioids: What Role for Abuse-Deterrent Formulations?

The FDA recently made decisions on the approval of 2 new formulations of oxycodone that were developed in an attempt to reduce the abuse of this drug. One drug, Oxecta, received approval. Another, Remoxy, did not.

Oxecta, previously under development as Acurox, is an immediate-release form of oxycodone that is combined with other materials. If the pill is crushed, it turns into chunks instead of powder, making it difficult to snort or inject. If the drug is mixed with a liquid, it turns sudsy, which further reduces the likelihood that it can be injected.

Remoxy is a long-acting form of oxycodone in a specially designed gelatin capsule that resists crushing or melting. It appears to be similar to the new abuse-resistant formulation of OxyContin (see below). The FDA rejected its application based on inconsistencies among in vitro testing results. I am unaware of any research that shows whether or not its abuse potential is any less. Both Oxecta and Remoxy are Pfizer products.

What is the probable impact of these decisions on patients who require pain management?  Probably not much. In the past couple of years, 2 other opioid products meant to reduce abuse were introduced to the market. Embeda, a long-acting form of morphine combined with naltrexone, was on the market for only a little over a year before it was recalled because of problems with its manufacture. When -or if -it will be reintroduced is unclear. The other product, a new formulation of OxyContin, is supposed to be difficult to cut, break, crush, chew, or dissolve and is available.

The problems that became associated with OxyContin, a controlled-release form of oxycodone, are well known. Although there has never been any evidence to indicate that OxyContin, taken as prescribed (swallowed whole on a fixed schedule of q 12h), has greater abuse potential than other opioids, considerable negative publicity surrounded its misuse. People crushed the tablets and then swallowed, snorted, or injected the powdered form, bypassing the pill’s controlled-release mechanism and ingesting all at once a dose meant to be delivered over 12 hours. To reduce this possibility, the manufacturer (Purdue Pharma) added a resin-based material to the new formulation of OxyContin. Shortly afterward, Purdue stopped manufacturing the original OxyContin. Because a great deal of the original drug is probably still in inventory, it is difficult to know how much of an impact on opioid abuse the new formulation has had. 

OxyContin is the only long-acting form of oxycodone currently on the market in the US. Until a generic form is available, clinicians who feel that this agent is indicated do not have any choice as to formulation. When it comes to immediate-release oxycodone formulations, however, prescribers do have choices. These include oxycodone, either alone or in combination with another drug such as acetaminophen.  

So. How does the physician decide whether to prescribe Oxecta or one of the other drugs already on the market? Cost may be one determinant. Oxecta is only available as a brand-name drug. This will probably make it significantly more expensive than the many available generic formulations of oxycodone. To warrant this additional expense (to the patient or insurance carrier), there has to be a good reason for choosing Oxecta; I have yet to see any convincing evidence of this. First, neither Oxecta, the new OxyContin, Embeda (when it was available), or Remoxy (yet to be approved) do anything to reduce the risk of the most common form of abuse: taking doses that are higher than prescribed. And while reducing the alteration potential of these opioids might make them less desirable to social abusers, I would be very hesitant to prescribe any opioid to a patient whom I suspect is likely to alter the medication to get high, or who is likely to give or sell it to someone else.

There are situations where patients who need opioids have family members who are likely to steal their medications. Prescribing Oxecta might be considered in this instance but even here, there is no way to reduce the risk that the abuser(s) will simply take as much of the drug as they can get their hands on. Regarding the potential for the drugs to be stolen by someone outside of the family, I question whether it would be fair to make a patient bear an additional expense because a stranger might abuse the drug.

It is also important not to overstate the extent of improvement provided by Oxecta and the new OxyContin. Note that the prescribing information (PI) for Oxecta states “there is no evidence that Oxecta has a reduced abuse liability compared to immediate-release oxycodone” (http://pfizer. com/products/rx/prescription. jsp), while the PI for the new OxyContin says that it “can be abused in a manner similar to other opioid agonists, legal or illicit” (http://www.purduepharma. com/Products/Prescription/Pages/default. aspx).

One final point. As far as I know, the studies to determine the level of “abuse resistance” for Oxecta, the new OxyContin, and Remoxy were performed among non-abusers.  Anyone who works with drug abusers knows that they can find ways to get drugs into their bodies that would never occur to non-abusers. To put it another way, I know how to use a computer, but if someone wanted to determine how resistant a new program is to viruses, they would choose an expert from Google, Microsoft, or Apple over me.