FDA Creates New Class for Safer Opioids
Pain management drugs come with a risk of addiction that cannot be avoided. Even with careful monitoring, patients may increase their dosage or try to obtain more drugs than prescribed. The problem is made worse when pharmaceuticals reach the illegal market where those already dependent on narcotics modify the pills to get a stronger effect. Recently, the Food and Drug Administration addressed the problem head on.
The OxyContin Story
OxyContin was released in 1996 as a time-release formulation of the active ingredient, oxycodone. This is a powerful narcotic, used to treat severe pain. The idea was to formulate a tablet that would be difficult for addicts to abuse, since the oxycodone was bound into a matrix that would only slowly dissolve. The time-release characteristics also meant that pain patients could get extended relief, perhaps allowing them to sleep through the night.
Unfortunately, addicts quickly learned methods to get around the features of that formulation and within four years, the manufacturer, Purdue Pharma withdrew the highest strength tablet (160mg) from the market.
After an explosion in sales (2.5 billion in 2008) and the release of a cheaper generic version, it became obvious that “Oxy” was making its way onto the streets in a big way. In 2010, Purdue reformulated the product to make it more difficult to abuse, adding more ingredients (binders). Original formulations were removed from the market.
Finally, in 2013, the FDA decided that any generics equivalent to the original formulation were less safe than the current version and withdrew approval for generics based on that version.
The concept of abuse deterrence is a new one, outlined by the FDA in a news release about OxyContin.
In general, if a generic drug can deliver the same amount of active ingredient to a patient, over the same time period, it is considered bioequivalent and can be substituted for the name brand product. Other ingredients, as long as they are inert, do not matter. This is why colors, sizes and shapes of generics can vary from the brand product – the dyes and other changes don’t matter after the tablet is swallowed – so long as the active ingredient and delivery matches, there is no medical difference.
Abuse deterrence, however, is a property beyond what happens when a tablet is used properly by the patient for whom it is prescribed. The point here is to defend against misuse. With this idea, the focus is not on making sure a legitimate patient gets the proper amount of the narcotic, but that addicts cannot defeat the safety mechanisms built in.
Abuse of OxyContin
To get the effects sought, those who abuse OxyContin want to release all, or most of the dose immediately. They want the entire dose as fast as possible – defeating the time-release properties built into the tablet.
The most common method is to crush the tablet and either snort the powder or dissolve the active ingredient in water and then inject it. Abuse-deterrence formulations are designed to make these manipulations impractical or impossible.
In the case of the latest formulation of OxyContin (called extended release or ER) two methods are combined. The first is to bind the oxycodone into a matrix that dissolves slowly and releases the drug in gastrointestinal tract over an extended period. More significantly, other ingredients have been added to prevent crushing and injection. According to the FDA:
It’s important to note that oxycodone and OxyContin are still addictive and may still be abused. Taking the drug orally in higher amounts than prescribed will remain a problem and movement from legitimate medical use to “street” use will continue. However, by lowering the abuse potential, not only is the popularity of "Oxy" reduced, but the possibility of fatal overdose is lowered as well.
For Purdue, the benefits of the FDA decision mean they get a second bite at the patent apple. Since they own the rights to the latest formulation, no one can make a generic yet and previous generics don’t meet the new FDA standards. This is a huge incentive for other companies to follow the same path and come up with safer, abuse-deterrent version of their products as well.