__________________________________ Prescription Opioids: Risk Management and Strategies for Safe Use pensed drug. Therapeutic error exposures declined 24% per population and 15% per unique recipients of dispensed drug, and diversion reports declined 53% per population and 50% per unique recipients of dispensed drug. The declines were greater than those observed for other prescription opioids in aggregate [146]. However, several published reports have documented the abandonment of opioid anal- gesics and a migration to heroin use by previous OxyContin abusers following the introduction of ADF OxyContin [147; 148]. REGULATORY MANDATES
In June 2017, the FDA requested that Endo Pharma remove the reformulated Opana ER from the market based on concerns that the benefits of the drug may no longer outweigh the risks [153]. This is the first time the FDA has taken steps to remove a currently marketed opioid pain medication. The agency’s decision was based on a review of avail- able postmarketing data, which demonstrated a significant shift in the route of abuse of Opana ER from nasal to injection following release of the ADF formulation. Injection abuse of reformulated Opana ER has been associated with a serious outbreak of HIV and hepatitis C and with cases of thrombotic microangiopathy [153].
The FDA has prohibited labeling or marketing claims of abuse resistance or abuse deterrence to be used in any ADF opioid product because supportive epidemiologic data have not yet been published [149]. Any future label claim of abuse deterrence must be supported by post-marketing data [138]. In 2013, Purdue Pharma and Endo Pharma, the makers of OxyContin and Opana ER, respec- tively, requested a ruling from the FDA that the original formulations were removed from market and replaced by ADFs because of safety or efficacy concerns. Such a ruling would render the original formulations ineligible for generic replication, thus protecting ADF OxyContin and Opana ER market share from generic non-ADF competition [150]. The FDA ruled in favor of this request for Purdue but not for Endo. The basis for the decision was the extent of abuse liability with the original OxyContin prepara- tion and insufficiency in the abuse deterrence with the ADF formulation to block future applications to produce generic versions of the non-ADF Opana ER [151]. Interestingly, this favorable ruling for Purdue Pharma was made on April 16, 2013, the exact date of patent expiration for OxyContin [150]. In 2013, the FDA issued a draft document to guide pharmaceutical companies in developing ADF opioid products. Although the FDA strongly encourages industry to employ ADFs in new opioid products, the guidance document fell short of a mandate [142]. Later that year, the FDA approved an ER formulation of hydrocodone (Zohydro) that lacks abuse-deterrent properties, which seemed contradictory to the FDA stance on ADF product development [152].
OTHER GOVERNMENT AND INDUSTRY EFFORTS
In response to increasing rates of opioid analgesic abuse, addiction, diversion, and overdose, the National Drug Control Policy created a multiagency Drug Abuse Prevention Plan in 2011 to reduce prescription drug abuse. The four key elements of the plan are expansion of PDMPs; responsible disposal of unused medications; reduction of pill mills through enhanced law enforcement efforts; and support for provider and patient education. Regarding provider education, several state medi- cal boards (e.g., California, West Virginia) require prescribers to obtain continuing education credit in pain management and prescription opioid use [154]. As noted, emerging trends and patterns of prescrip- tion opioid abuse, addiction, and overdose are moni- tored by several industry and government agencies through data collection from a variety of sources, including health insurance claims; the Automa- tion of Reports and Consolidated Orders System (ARCOS), a DEA-run program that monitors the flow of controlled substances from manufacturing through distribution to retail sale or dispensing; the Treatment Episode Data Set (TEDS), which monitors treatment admissions; National Center for Health Statistics state mortality data; and the Researched, Abuse, Diversion and Addiction- Related Surveillance (RADARS) System, which
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MDMS1526
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