Abuse-deterrent formulations: transitioning the pharmaceutical market to improve public health and safety

We read with great interest the article entitled ‘Abuse-deterrent formulations: transitioning the pharmaceutical market to improve public health and safety’ by Simon and colleagues, published in the April 2015 Issue of Therapeutic Advances in Drug Safety [Simon et al. 2015]. We agree with the authors that Federal abuse-deterrent formulation (ADF) policy does not reflect the urgency of the prescription drug abuse epidemic and does not go far enough toward changing the status quo. We also agree with the authors that policies must also require federal prescription drug benefit plans to cover ADFs to ensure consumers have access to such medications.

However, we disagree with the statement ‘ADFs have been proven to reduce prescription drug abuse and its consequences, and even an incremental reduction in abuse can have a significant impact on the nation by reducing the costly social, physical, mental, and public health problems resulting from abuse’.

The study by Coplan and colleagues [Coplan et al. 2013] was quoted as the main reference to support the argument by Simon and colleagues that ‘ADF have been proven to reduce prescription drug abuse and its consequences…’. However, in the study by Coplan and colleagues, what was additionally reported was a 20% increase in abuse exposure for other single-entity oxycodone, and 42% increase in abuse exposure for heroin, concomitant with the 36% decrease in abuse exposure for reformulated extended-release (ER) oxycodone (ADF). Coplan and colleagues also acknowledged that reformulating one product’s tablets will not treat opioid addiction, and substitution of other available opioids is likely to consequently occur.

Michna and colleagues examined the degree of adherence to the ER opioid, following its switching to a reformulated ER opioid (ADF), and found some patients changed to other ER opioids without abuse-deterrent technology or discontinued ER opioids [Michna et al. 2014]. The conclusion of their study was that abusers may seek more easily abusive alternatives. These include prescription opioids without abuse deterrent technology.

Preliminary data suggest that the reformulation of opioids to resist tampering may influence media attention, recreational user preferences, and opioid availability in ways that may in turn alter their attractiveness to recreational users [Romach et al. 2013]. ER oxymorphone abuse has been mentioned in popular media only since recreational users began to recognize it as an alternative to the reformulation of ER oxycodone (ADF), which is designed to be tamper-resistant. Increased public awareness of higher potency with oxymorphone ER and the difficulties of tampering with reformulated ER oxycodone may have lessened abuse of ER oxycodone and made ER oxymorphone a preferred choice for some recreational users [Romach et al. 2013].

Indeed, total oxymorphone prescriptions increased sharply from 268,000 in 2007 to 1.22 million in 2012. In the first quarter of 2011, 325,000 oxymorphone prescriptions were dispensed by retail pharmacies [Drug Enforcement Administration, 2013]. According to the Drug Abuse Warning Network (DAWN ED), total estimated emergency department visits associated with oxymorphone increased from 4599 in 2010 to 12,122 in 2011. The American Association of Poison Control Centers reported 1041 total oxymorphone exposures in 2011, an increase from 169 in 2010 [Drug Enforcement Administration, 2013]. To examine the change in prevalence of prescription opioid abuse after introduction of an abuse-deterrent formulation oxycodone ER in August 2010, Cassidy and colleagues conducted a cross-sectional study, and found significantly greater abuse of oxymorphone ER and buprenorphine, coinciding with the introduction of ADF oxycodone ER [Cassidy et al. 2014]. Cassidy and colleagues conclude that replacement of a widely prescribed opioid with ADF formulation may have had little effect on overall prescription opioid abuse as a class.

Another issue of great concern is escalating heroin abuse since the introduction of reformulated ER oxycodone (ADF) to the market. There were 119,000 total users in 2003, but 281,000 by 2011. In addition, first-time past-year use nearly doubled between 2005 and 2011. The death rate of heroin overdose from the 28 states (surveyed) doubled, from 2010 to 2012, from 1.0 to 2.1 per 100,000 [Rudd et al. 2014]. Heroin overdose death rates increased significantly for both sexes, all age groups, all census regions, and all racial/ethnic groups other than American Indians/Alaska Natives.

In conclusion, at this point, the introduction of ADF opioids has resulted in significantly reduced abuse of those specific ADF opioids after they have fully replaced the original formulations. However, this has resulted in merely a shift away from the ADF opioids to other traditional non-ADF opioids or heroin, and unfortunately, no effect on the overall rates of opioid abuse.