Prescription Opioids: Risk Management and Strategies for Safe Use _ _________________________________ manufacturer [138; 143]. These formulations use different strategies to prevent misuse, with varying advantages and disadvantages ( Table 11 ) [138]. While all ADF strategies may potentially deter tampering, physical barriers to crushing or chewing appear to be the only strategy that benefits nona- busers and abusers alike by preventing accidental crushing or chewing and not inducing adverse events. This contrasts with strategies that precipi- tate adverse events to deter inappropriate use, such as ADFs that use sequestered aversive agents that will induce adverse events in patients who chew or crush the tablets, accidentally or without intent of abuse. The extent of deterrence from these formula- tions is unclear because some persons are willing to endure discomfort from the aversive agent in order to obtain the more intense high from tampering. Sequestered opioid antagonists may offer a more effective approach in pharmacologic abuse deter- rence by rendering the opioid ineffective, but they can induce sudden and severe opioid withdrawal in physically dependent patients who accidentally chew the tablet [138]. ADF OUTCOME DATA Although opioid ADFs have been introduced into widespread clinical use relatively recently, several studies of their efficacy have already been pub- lished. These reports have documented significantly reduced abuse rates of ADF opioids after they have fully replaced the original formulations, but no effect on the overall rates of opioid abuse. For example, data were obtained on 140,496 persons assessed for substance abuse treatment, spanning from one year before ADF OxyContin (Oxy ADF) introduction to two years post-Oxy ADF introduction. Abuse of OxyContin was 41% lower with the ADF versus the original formulation, including a 17% decrease in oral abuse and a 66% decrease in abuse through non-oral routes. Meaningful reductions in ER mor- phine and ER oxymorphone abuse rates were not found. The authors concluded that conversion of OxyContin to an ADF formulation was successful in reducing non-oral administration that requires tampering [145]. Another study found that follow- ing OxyContin ADF introduction, poison center exposures for oxycodone ER abuse declined 38% per population and 32% per unique recipients of dis-
ADVANTAGES AND DISADVANTAGES OF ADF STRATEGIES
ADF Strategy Physical barriers
Advantages
Disadvantages
Prevents crushing or chewing to block rapid high-dose opioid release into the system Prevents accidental crushing or chewing in compliant patients No adverse events in compliant patients FDA-approved formulation available May prevent abuse by chewing or crushing the product May limit abuse of intact tablets because taking too much will amplify adverse events
Does not deter abuse of intact tablets Only one FDA-approved product available
Aversive components (e.g., niacin)
Potential adverse events in compliant patients taking product as intended Adverse events with intact tablets may prevent legitimate dose increase if pain increases or efficacy decreases over time Adverse events may not be sufficient to deter a motivated abuser No FDA-approved formulations Does not deter abuse of intact tablets Chewing or crushing the tablet may trigger severe withdrawal symptoms
Sequestered antagonist (e.g., naloxone, naltrexone) New molecular entities/ prodrugs
Prevents abuse by chewing or crushing opioids FDA-approved formulation available
Prevents abuse by providing a chemical barrier to the in vitro conversion to the parent opioid. —
Source: [138; 144]
Table 11
38
MDMS1526
Powered by FlippingBook