With more patients abusing opioid products and associated deaths rising, the pressure to bring abuse-deterrent opioid products to market is on. A new formulation of oxycodone approved in late July combines oxycodone and naloxone in extended-release tablets (Targiniq ER—Purdue Pharma). The formulation is designed to release naloxone if the tablets are crushed and snorted or crushed, dissolved, and injected, thereby blocking the euphoric effects of oxycodone.
This approval comes on the heels of the controversial approval of Zogenix’s single-entity hydrocodone product (Zohydro ER) that lacked abuse-deterrent properties. As noted in a December 2013 Pharmacy Today article, Zohydro ER has been viewed by some as a product with a high potential for abuse. Organizations have advocated for its removal from the market, and the state of Massachusetts even tried to override the FDA approval in an unsuccessful attempt to keep the product out of that state. In early July, Zogenix announced it is working to bring two abuse-deterrent formulations of Zohydro ER to market in the coming years.
Sales of prescription opioids have quadrupled over the last decade, CDC reported. This has contributed to a substantial rise in the number of opioid-related overdose deaths. From 1999 to 2010, the annual number of overdose deaths involving opioids rose from approximately 4,000 to more than 16,000. An estimated 75% of all prescription drug–related overdoses involve opioids.
CDC also reported that prescription opioid abuse costs in the United States were $55.7 billion in 2007, with 46% of this amount attributable to workplace costs (e.g., lost productivity), 45% to health care costs (e.g., abuse treatment), and 9% to criminal justice costs.
FDA has taken various steps to minimize risks of opioid-containing products. In July 2012, the agency initiated a classwide risk evaluation and mitigation strategy (REMS). It requires manufacturers of extended-release/long-acting opioid analgesics to make training available to health professionals about proper prescribing and to distribute educational materials to professionals and patients on the safe use of these medications. In September of last year, FDA required new safety labeling information and postmarketing studies for all extended-release/long-acting opioid analgesics.
FDA has also released two draft guidances relevant to the development of abuse-deterrent formulations of controlled prescription drugs: Abuse-Deterrent Opioids: Evaluation and Labeling (January 2013) and Assessment of Abuse Potential of Drugs (January 2010).
The first guidance provides manufacturers with information on the data needed to demonstrate that a formulation has abuse-deterrent properties. The second guidance provides manufacturers with information on the design and implementation of clinical studies that may help in assessing whether a proposed abuse-deterrent formulation will reduce abuse relative to an appropriate comparator.
Targiniq ER is a new oxycodone/naloxone combination product indicated for treatment of pain severe enough to require daily, around-the-clock, long-term opioid treatment for which alternative treatment options are inadequate. These extended-release tablets will be marketed in combination strengths of oxycodone/naloxone 10/5 mg, 20/10 mg, and 40/20 mg, with a recommended dosing interval of every 12 hours.
Approval was based on data from a 12-week, double-blind, randomized, placebo-controlled clinical trial with 600 opioid-experienced patients, as well as supporting data from other clinical studies. Purdue Pharma also submitted data from abuse-liability studies designed and conducted in accordance with FDA’s January 2013 draft guidance mentioned above. Data from these abuse-liability studies demonstrated the abuse-deterrent features of the product as they relate to certain types of abuse such as snorting and injecting.
In addition, as noted above, FDA is requiring Purdue Pharma to conduct postmarketing studies to further assess the effects of the abuse-deterrent features on the risk for abuse of the product.
Pharmacists can help reduce the opioid abuse epidemic by closely monitoring patients receiving opioids for potential signs of abuse (e.g., early refills, numerous prescribers), educating patients and caregivers on the serious risks associated with use of these products, and following up with other providers to inform them of any issues. Abuse-deterrent opioid products are a step in the right direction, but more work needs to be done to better select and educate patients who are going to take these medications.