Are Abuse-deterrent Opioids Working?

[[{"type":"media","view_mode":"media_crop","fid":"51785","attributes":{"alt":"","class":"media-image media-image-right","height":"222","id":"media_crop_6094005956477","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"6407","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"float: right; margin: 4px;","title":" ","typeof":"foaf:Image","width":"224"}}]]It may be a reflection of the current state of pain drug development and the extent of opioid abuse that the number of drug studies presented at PAINWeek 2016 which evaluated abuse-deterrent formulation (ADF) mechanisms exceeded the number of studies evaluating new compounds and formulations for greater efficacy or tolerability.

The reported investigations comprised category 1 ADF research (In-vitro dosage manipulation), category 2 (pharmacokinetics after release from manipulated dosage), and category 3 (clinical studies of abuse potential). Although no category 4, postmarketing studies have yet been conducted, the following four reports on the patterns of ADF product usage may give an early indication of how these products could impact abuse and overdose.

A key question is contained in the title of one new research report: Are immediate-release (IR) opioids really safer than extended-release (ER) opioids? The study by Laura Wallace, MPH and colleagues,¹ employees of Purdue Pharma LP, examined a healthcare claims database from 2010 to 2013 to assess patterns in rates of diagnosed abuse, addiction/dependence, and overdose/poisoning associated with oxycodone IR and ER products.

"Though safe prescribing is an area of increased focus," the investigators indicate, "there are limited data on differences in safety and utilization patterns between ER and IR opioids."

This study follows an earlier investigation that used North Carolina State Medical Examiner data to find that prescriptions for oxycodone IR 30mg had a 2-fold greater risk of overdose than prescriptions for 30 to 80 mgs of oxycodone ER. In the current investigation, Wallace and colleagues found that the rate of prescribing ER oxycodone has decreased, particularly for higher dosages, while the number of prescriptions for the IR opioid is increasing but for shorter durations than ER. The rate of diagnosed abuse among patients was found to be higher with IR (0.79 per 100 person-years [PY] of opioid use) than with ER (0.31 per 100 PY).

"Consistent with the study on overdose fatalities," Wallace and colleagues indicate, "rates of diagnosed abuse, addiction/dependence, and overdose/poisoning diagnoses were higher for IR oxycodone than for ER oxycodone, despite the higher average ER oxycodone dose and shorter duration of use for IR oxycodone.

"Practitioners should be thoughtful about the risks of all opioids, regardless of IR or ER formulation," they commented.

An additional study by this group², with lead author Angela DeVeaugh-Geiss, PhD, looked for changes in nonmedical use of OxyContin after it had been reformulated in 2010 with ADF properties. The investigators accessed data from the National Survey on Drug Use and Health, conducted annually by SAMHSA, to compare rates of nonmedical use in 2009 to each year post-reformulation from 2011 to 2014.

"Practitioners should be thoughtful about the risks of all opioids, regardless of IR or ER formulation."

The investigators found decreases in nonmedical use of OxyContin generally occurring for both past-year initiation and past-month use, with population-adjusted rates, and rates adjusted for OxyContin from data including generic forms.

A study³ lead by Stephen Butler, PhD, Inflexxion, Inc, and colleagues from Collegium Pharmaceutical considered the abuse potential of crush-resistant tablets (CRT) across several manufacturers, using self-reports from adults entering substance abuse treatment between 2009 and 2015, captured on the Addiction Severity Index Multimedia Version (ASI-MV) computerized clinical interview program (Inflexxion).

Among more than 360 00 patients entering their history onto the ASI-MV, 20.9% reported abuse of any prescription opioid and 7.7% reported abuse of the selected CRTs. Among abusers of any product, those using a CRT had a higher prevalence (26.3 per 100 abusers) of using an alternate oral mode of administration (eg, chewing, dissolving in mouth, or drinking after dissolving in liquid) than those using the comparators (5.6 to 20.6 per 100 abusers).  

"Previous data have shown that CRTs may reduce snorting and injecting," the investigators indicate. "Findings presented here suggest that, although CRT are less likely to be abused by swallowing whole (among oral abusers), they are more likely to be abused by alternate oral modes of administration that involve product manipulation prior to swallowing."

[[{"type":"media","view_mode":"media_crop","fid":"51788","attributes":{"alt":"","class":"media-image media-image-right","id":"media_crop_4346486757570","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"6409","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"height: 170px; width: 250px; margin: 4px; float: right;","title":" ","typeof":"foaf:Image"}}]]A study⁴ from the Rocky Mountain Poison and Drug Center, Denver, Colorado evaluated the tampering and medical outcomes from abuse of the crush-resistant product, Nucynta ER relative to other opioid formulations without tamper-resistant technology. Lead author Jody Green, PhD, and colleagues accessed data from the Researched Abuse, Diversion and Addiction Related Surveillance System (RADARS) Poison Center Program from 2011 to 2016.

The non-ADF ER opioid tablet/capsules were found to be approximately 2.5 times more likely to have been tampered than Nucynta ER. None of the Nucynta ER cases reported major medical outcome or death, while 13.3% of the non-ADF ER opioid tablet/capsule cases resulted in a major medical outcome or death.

"Prescription opioids with abuse-deterrent properties may reduce abuse and misuse as well as severity of medical outcomes and should be considered one approach to addressing this significant public health issue," the investigators concluded.

References:

1. Wallace L, Coplan P, DeVeaugh-Geiss A, Kadakia A. Are immediate-release (IR) opioids really safer than extended-release ER opioids: A case study using data on ER and IR oxycodone. Poster presented September 8 at the Painweek 2016 conference, September 6-10, 2016, Las Vegas, Nevada.

2. DeVeaugh-Geiss A, Coplan P, Chilcoate H, et al. Changes in nonmedical use of OxyContin after reformulation with abuse-deterrent properties. Poster presented September 8 at the Painweek 2016 conference, September 6-10, 2016, Las Vegas, Nevada.

3. Butler SF, Black RA, Kopecky EA, et al. Relative abuse of crush-resistant tablets of prescription opioids via alternative oral modes of administration. Poster presented September 8 at the Painweek 2016 conference, September 6-10, 2016, Las Vegas, Nevada.

4. Green JL, Le Lait, M-C, Severtson, SG, Dart RC. Tampering and medical outcomes in poison cneter abuse and misuse Nucynta ER exposures. Poster presented September 8 at the Painweek 2016 conference, September 6-10, 2016, Las Vegas, Nevada.