By: Ada Seldin PharmD Candidate c/o 2015

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On April 16^th, 2013, the FDA approved the labeling change for the reformulated OxyContin^® (oxycodone hydrochloride controlled-release) tablets, made by Pharma L.P. This change reflects the abuse-deterrent properties of the reformulated OxyContin^®, which were not present in the original formulation approved by the FDA in 1995. OxyContin^® is intended to be used around-the-clock over an extended period of time for the relief of moderate to severe pain. The tablets must be swallowed whole to ensure the slow release of the drug. Breaking, chewing, crushing, or dissolving OxyContin^® tablets compromises their medicinal purpose and safety profile. However, OxyContin^® is often manipulated to bypass its extended release features.¹ In this case, the rapid release and absorption of the drug can lead to overdose and death.²

In an attempt to reduce abuse and misuse, Purdue came out with the reformulated OxyContin^®, which received FDA approval in April 2010. The new formulation is more difficult to crush, break, or dissolve, and it forms a viscous hydrogel that prevents abusers from attempting to directly inject or insufflate the drug. These chemical and physical properties of the drug have shown to substantially reduce abuse, prompting the FDA to approve the claim on the product labeling.¹ This action is the first of its kind, consistent with the FDA’s efforts to reduce prescription drug abuse, and may foreshadow a trend in the development of safety mechanisms for other commonly abused substances.³ The FDA released guidelines on the development of tamper-resistant characteristics for manufacturers in March and has offered its assistance in implementing them.⁴

In addition to this landmark approval, the FDA has determined that “the benefits of the original OxyContin^® no longer outweigh its risks, and that original OxyContin^® [will be] withdrawn from sale for reasons of safety and effectiveness.”¹ Logically, the FDA will no longer accept abbreviated drug applications that are based on the original OxyContin^® formulation. All generics of OxyContin^® must now possess abuse-deterrent properties to be granted FDA approval.

Interestingly, however, this does not apply to all cases of oft abused pain medicine. On May 10^th, 2013, the FDA made a decision regarding the painkiller Opana^® ER (oxymorphone). In response to a petition from Endo Pharmaceuticals Inc., the manufacturer of Opana^® ER, the FDA decided to keep the original Opana^® ER on the market for reasons of safety and effectiveness, and thus deemed generics that rely on the original formulation viable for approval upon submission of an abbreviated drug application. The FDA’s decision was based on review of experimental data that makes this case unique from that of OxyContin^®. The purportedly abuse-deterrent Opana^® ER is resistant to crushing, but not to cutting, grinding, or chewing. It can still be easily prepared for snorting using commonly available tools and methods. Contrary to Endo Pharmaceuticals’ claim that the new Opana^® ER tablets are resistant to “aqueous extraction,” the FDA’s evaluation concluded that these tablets can be readily prepared for injection. Furthermore, some studies suggest that the new Opana^® ER has a higher percentage of abuse via injection than the original. Although post-marketing surveillance is still inconclusive, these early findings are far from comforting.⁵

The FDA, in its public statement explaining its decision, announced that although the development of abuse-deterrent technologies to reduce opioid abuse is continuously encouraged, each new formulation that wants to make such a claim will be evaluated individually on its own merits.

SOURCES:

1. FDA approves abuse-deterrent labeling for reformulated Oxycontin. News and Events. U.S Food and Drug Administration Website. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm348252.htm Updated April 16, 2013. Accessed May 29, 2013.
2.  Oxycontin Prescribing Information. Purdue Pharma L.P. website. http://www.purduepharma.com/wpcontent/uploads/OxyContin_Prescribing_Information_2013_04_16.pdf Updated April 4, 2013. Accessed May 29, 2013.
3.  Cole EB, FDA bars generic version of OxyContin. Pharmacy Times. Published online April 17, 2013. http://www.pharmacytimes.com/news/FDA-Bars-Generic-Version-of-Oxycontin Accessed May 29, 2013.
4.  Weiss D, FDA refuses to remove generic Opana from market. Pharmacy Times. Published online May 21, 2013. http://www.pharmacytimes.com/news/FDA-Refuses-to-Remove-Generic-Opana-From-Market Accessed May 29, 2013.
5.  FDA statement: original Opana ER relisting determination. News and Events. U.S Food and Drug Administration Website. http://www.fda.gov/Drugs/DrugSafety/ucm351357.htm Updated May 10, 2013. Accessed May 29, 2013.

Published by Rho Chi Post