Abuse-deterrent Opioid Formulations Research Articles

Review on Recent Development in Opioid Abuse-Deterrent Formulation Technologies and Regulatory Expectation

Chronic pain occurs as a result of several diseases and ailments. The problem of improper utilization of vital opioid medication has been a topic of substantial discourse during the last two decades, in conjunction with its application for the extended-term control of persistent pain. Abuse-deterrent formulations play a crucial role in comprehensive methods to manage the risks associated with opioids. These formulations diminish the allure and narcotic properties of opioids by restricting their capacity to be assimilated by the body. This diminishes the appeal and incentives for misusing altered opioid prescriptions, and also poses challenges in extracting the opioid substance for utilization in alternative manners. This article examines various regulatory measures, projected prerequisites for the licensing of abuse-deterrent formulations, and current activities aimed at producing opioid abuse-deterrent formulations as potential remedies to combat the opioid abuse pandemic. Considering the seriousness of the global opioid problem, it is crucial for various regulatory entities to come together to safeguard society from the opioid pandemic. This involves implementing a thorough policy on prescribing opioid medications to patients, conducting evaluations to determine the likelihood of addiction, and increasing efforts to approve only opioid drugs that are specifically tailored to prevent abuse.

Review of Opioid Abuse-Deterrent Formulations: Impact and Barriers to Access

Review of Opioid Abuse-Deterrent Formulations: Impact and Barriers to Access

Matching study design to prescribing intention: The prevalent new-user design for studying abuse-deterrent formulations of opioids.

In drug studies, research designs requiring no prior exposure to certain drug classes may restrict important populations. Since abuse-deterrent formulations (ADF) of opioids are routinely prescribed after other opioids, choice of study design, identification of appropriate comparators, and addressing confounding by "indication" are important considerations in ADF post-marketing studies. In a retrospective cohort study using claims data (2006-2018) from a North Carolina private insurer [NC claims] and Merative MarketScan [MarketScan], we identified patients (18-64 years old) initiating ADF or non-ADF extended-release/long-acting (ER/LA) opioids. We compared patient characteristics and described opioid treatment history between treatment groups, classifying patients as traditional (no opioid claims during prior six-month washout period) or prevalent new users. We identified 8415 (NC claims) and 147 978 (MarketScan) ADF, and 10 114 (NC claims) and 232 028 (MarketScan) non-ADF ER/LA opioid initiators. Most had prior opioid exposure (ranging 64%-74%), and key clinical differences included higher prevalence of recent acute or chronic pain and surgery among patients initiating ADFs compared to non-ADF ER/LA initiators. Concurrent immediate-release opioid prescriptions at initiation were more common in prevalent new users than traditional new users. Careful consideration of the study design, comparator choice, and confounding by "indication" is crucial when examining ADF opioid use-related outcomes.

The Importance of Drug Delivery in the Clinical Development and Lifecycle of Drug Products with Examples from Authorised Medicinal Products

Drug delivery systems (DDS) are formulations or devices that enable the introduction of a therapeutic into the body and its delivery to its target site, potentially enhancing its efficacy and safety. Advances in formulation approaches related to the enhancement of solubility, permeability and thus bioavailability of drugs have already been successfully implemented by the pharmaceutical industry. This review highlights the importance of formulations/DDS in the clinical development and the lifecycle of drug products. Examples from already authorised drug products have been used to showcase how the development of appropriate formulations/DDS could deliver drugs to the site of action (e.g., pulmonary and nasal drug delivery) and enhance patient adherence to medication (e.g., long-acting injectables, 3D-printed tablets). Moreover, examples from authorised products have been provided to highlight how formulation can improve safety (e.g., liposomes, abuse-deterrent opioid formulations) and efficacy (e.g., albumin-based nanoparticles, permeation enhancers for oral delivery of peptides).

An evaluation method for developing abuse-deterrent opioid formulations with agonist and antagonist combinations using conditioned place preference

Although opioids are useful narcotic analgesics in clinical settings, their misuse and addiction in the United States of America and other countries are rapidly increasing. Therefore, the development of abuse-deterrent formulations is an urgent issue. We herein investigated how to select the ratio of an opioid and the opioid receptor antagonist, naloxone in abuse-deterrent formulations for mice. The conditioned place preference (CPP) test was used to evaluate the rewarding effects of abused drugs. The opioids morphine (30 μmol/kg), oxycodone (3 μmol/kg), fentanyl (0.4 μmol/kg), and buprenorphine (0.5 μmol/kg) significantly induced place preference in mice. We also examined the optimal ratio of naloxone and opioids to inhibit the rewarding effects of the latter. Naloxone (3–5 μmol/kg) effectively inhibited place preference induced by the opioids tested. We calculated theoretical drug doses that exerted the same pharmacodynamic effects based on two parameters: μ-opioid receptor binding affinity and blood-brain barrier (BBB) permeability. Theoretical doses were very close to the drug doses at which mice showed place preference. Therefore, the CPP test is useful as a behavioral method for evaluating abuse-deterrent formulations of opioids mixed with an antagonist. The ratio of naloxone with opioids, at which mice did not show place preference, may be an effective index for developing abuse-deterrent formulations. Ratios may be calculated for other opioids based on μ-opioid receptor binding affinity and BBB permeability.

A US Retrospective Claims Analysis Comparing Healthcare Costs of Patients Transitioning from Immediate-Release Oxycodone to Two Different Formulations of Extended-Release Oxycodone: Xtampza ER or OxyContin.

PurposeOpioid therapy for managing chronic pain remains a challenge, as providers must weigh the medical benefit to the patient with the risk of adverse events. Manipulation of many extended-release (ER) opioid formulations may lead to increased serious medical outcomes or death. The economic burden of opioid use disorders due to opioid misuse and abuse may vary depending on which abuse deterrent opioid formulation is prescribed. The study aimed to compare demographic and clinical characteristics and healthcare costs of chronic pain patients treated with two different abuse-deterrent opioid formulations, Xtampza ER and reformulated OxyContin.MethodsThe source of data was IBM® MarketScan® Commercial Claims and Encounters Medicare Supplemental database, from January 2016 through February 2020. Patients with chronic pain were assigned to either the Xtampza ER or the OxyContin cohort based on the initial ER opioid prescription set as the index date. Continuous healthcare coverage was required during a minimum 3-month pre-index and 9-month post-index periods. Pre-index patients’ characteristics were analyzed. Healthcare costs of Xtampza ER vs OxyContin were assessed in the post-index period.ResultsAfter applying selection criteria, 464 patients were observed in the Xtampza ER cohort versus 1927 patients in the OxyContin cohort. In unmatched patients, ER opioid costs were lower for Xtampza ER than OxyContin ($2645 vs $3141; p<0.001), which ultimately led to lower total prescription costs for the Xtampza ER cohort compared to the OxyContin cohort ($7492 vs $8754; p=0.016). In matched patients, the total healthcare costs were significantly lower in the Xtampza ER cohort than in the OxyContin cohort, $22,630 vs $28,386 (p=0.005), respectively.ConclusionThis study suggests that Xtampza ER may result in lower healthcare costs than OxyContin for a population of chronic pain patients switching from immediate release oxycodone based on real-world data.

Pharmaceutical opioid marketing and physician prescribing behavior.

Physicians' relationships with the pharmaceutical industry have recently come under public scrutiny, particularly in the context of opioid drug prescribing. This study examines the effect of doctor-industry marketing interactions on subsequent prescribing patterns of opioids using linked Medicare Part D and Open Payments data for the years 2014-2017. Results indicate that both the number and the dollar-value of marketing visits increase physicians' patented opioid claims. Furthermore, direct-to-physician marketing of safer abuse-deterrent formulations of opioids is the primary driver of positive and persistent spillovers on the prescribing of less safe generic opioids - a result that we show appears to be driven by insurance coverage policies. These findings suggest that pharmaceutical marketing efforts may have unintended public health implications.

Opioid Prescribing in United States Health Systems, 2015 to 2019

ObjectivesHealth systems (nonfederal hospitals and clinics) are the second major source for drug expenditure in the United States. Opioids prescribed in these healthcare settings are commonly short-acting opioids that can lead to persistent opioid use. Nevertheless, there are no national data that describe trends in opioid use and the associated expenditure in health systems. Therefore, the objective of this article was to describe opioid use and expenditures in US health systems from 2015 to 2019. MethodsWe used data from IQVIA National Sales Perspectives to describe prescription opioid expenditure and use in health systems (nonfederal hospitals and clinics). ResultsOver the 5-year study period, health systems dispensed a total of 6.55 billion units of opioids (26.88% decrease) with an associated expenditure of $3.33 billion (26.78% decrease). Relative to all opioid formulations in our study, oxycodone, hydrocodone, and fentanyl were the opioids with the highest use in US health systems. All opioid prescriptions decreased except fentanyl use, which increased by 29.80% in clinics. The use of abuse-deterrent formulations of opioids decreased by 51.00% over the study period, although the decrease seems to be driven mainly by long-acting oxycodone (brand name Oxycontin). ConclusionsOpioid use and expenditures in health systems have been decreasing following national trends from retail pharmacies. Nevertheless, fentanyl use increased in clinics and was prescribed at higher proportions in nonfederal hospitals than other opioids, which warrants further investigation.

Abuse-Deterrent Opioid Formulations and the Opioid Crisis: A Pharmacist's Perspective.

For over 20 years, the United States has suffered the detrimental effects of an opioid epidemic. Extended-release opioid products are particularly prone to abuse due to the high amount of opioid present. By bypassing the controlled-release mechanisms and nonoral administration, individuals experience intense and dangerous "highs." Abuse-deterrent opioid formulations have been recommended as a potential solution to the crisis, but widespread utilization has been stunted and their role in therapy remains unclear owing to limited real-world efficacy data and affordability issues. This review discusses abuse-deterrent opioid formulations, the mechanisms and data underlying available products, and a pharmacist's perspective of their role in the opioid crisis. The authors reviewed PubMed, MEDLINE, and Google Scholar electronic databases for premarketing and postmarketing studies on OxyContin, Xtampza ER, and Hysingla ER. Studies showed lower rates of abuse (19% reduction), opioid use disorder (27%), overdose (34%), and fatalities (85%) with the reformulated OxyContin when compared with the original product and comparator opioids. However, these studies revealed the potential for bypassing abuse-deterrent mechanisms and diverting abuse to other drugs. Postmarketing studies are unavailable for Xtampza ER or Hysingla ER, although premarketing studies suggested that some controlled-release properties persist when the product is manipulated, indicating that abuse may be more difficult and less rewarding. Abuse-deterrent opioid products may lead to reductions in abuse, overdose, and overdose fatalities. However, cost, loopholes in deterrence mechanism, and possible diversion to other substances hinder their role in the opioid crisis. Multiple approaches must be used to improve opioid safety, and further postmarketing and real-world analyses should be performed on available opioid formulations to assess their impact on abuse-related adverse events.

Economic Evaluation in Opioid Modeling: Systematic Review

ObjectivesThe rapid increase in opioid overdose and opioid use disorder (OUD) over the past 20 years is a complex problem associated with significant economic costs for healthcare systems and society. Simulation models have been developed to capture and identify ways to manage this complexity and to evaluate the potential costs of different strategies to reduce overdoses and OUD. A review of simulation-based economic evaluations is warranted to fully characterize this set of literature. MethodsA systematic review of simulation-based economic evaluation (SBEE) studies in opioid research was initiated by searches in PubMed, EMBASE, and EbscoHOST. Extraction of a predefined set of items and a quality assessment were performed for each study. ResultsThe screening process resulted in 23 SBEE studies ranging by year of publication from 1999 to 2019. Methodological quality of the cost analyses was moderately high. The most frequently evaluated strategies were methadone and buprenorphine maintenance treatments; the only harm reduction strategy explored was naloxone distribution. These strategies were consistently found to be cost-effective, especially naloxone distribution and methadone maintenance. Prevention strategies were limited to abuse-deterrent opioid formulations. Less than half (39%) of analyses adopted a societal perspective in their estimation of costs and effects from an opioid-related intervention. Prevention strategies and studies’ accounting for patient and physician preference, changing costs, or result stratification were largely ignored in these SBEEs. ConclusionThe review shows consistently favorable cost analysis findings for naloxone distribution strategies and opioid agonist treatments and identifies major gaps for future research.

Economic Evaluation in Opioid Modeling: Systematic Review

Background: The opioid crisis is a complex problem associated with significant economic costs for healthcare systems and society. Simulation models have been developed to understand its complexity and to evaluate the potential costs of different strategies to address this problem. Methods: A systematic review of simulation-based economic evaluation (SBEE) studies in opioid research was initiated by searches in PubMed, EMBASE, and EbscoHOST. Extraction of a pre-defined set of items and a quality assessment were performed for each study. Results: The screening process resulted in 23 SBEE studies ranging by year of publication from 1999 to 2019. Methodological quality of the cost analyses was moderately high. The most frequently evaluated strategies were methadone and buprenorphine maintenance treatments; the only harm reduction strategy explored was naloxone distribution. These strategies were consistently found to be cost-effective, especially naloxone distribution and methadone maintenance. Prevention strategies were limited to abuse-deterrent opioid formulations. Most analyses (78%) assessed the cost-utility or cost-effectiveness of two or more interventions. Less than half (39%) adopted a societal perspective in their estimation of costs and effects from an opioid-related intervention. Consideration of patient and physician preference, changing costs, result stratification, or prevention was infrequent. High heterogeneity in study designs and outcomes precluded a meta-analysis. Conclusions: The review shows consistently favorable cost analysis findings for naloxone distribution strategies and opioid antagonist treatments (methadone or buprenorphine maintenance treatments against no naloxone distribution and no treatment, respectively). The review observes gaps in accounting for patient and physician preferences or major changes in medication prices.

Abuse-deterrent opioid analgesics: a guide for clinicians.

The US FDA has encouraged the development of abuse-deterrent formulations (ADFs) of opioid analgesics as one component in a comprehensive effort to combat prescription opioid abuse. Guidance issued by the FDA outlines three types of premarket studies for evaluating abuse deterrence: laboratory-based in vitro manipulation and extraction studies, pharmacokinetic studies and human abuse potential studies. After approval, postmarket studies are needed to evaluate the impact of an ADF product on abuse in real-world settings. This review summarizes the regulatory issues involved in the development of ADF opioids and clarifies abuse-deterrence claims in product labels, in order to assist clinicians in critically evaluating the available evidence pertaining to the abuse-deterrent features of opioid analgesics.

Key characteristics and habits of the recreational opioid user.

To identify key characteristics and habits of recreational opioid users. The data were compiled from volunteers who participated in clinical studies at a contract research organization in Toronto, Ontario, Canada. Data were collected from 5,018 male and female recreational opioid users via telephone and face-to-face screening interviews. Five recreational opioid users participated in a live interview broadcast on the internet. Demographic data, recreational drug use history, routes of recreational drug administration, alcohol use, and smoking status. A subset of the demographic information and recreational drug use history was summarized separately using data collected between 2013 and 2016 from 114 recreational opioid users who were not dependent on opioids. Interview excerpts were included from five recreational opioid users who described their real-world experiences with drug abuse, including the impact of abuse-deterrent opioid formulations on their drug abuse behavior. The preferred route of administration of opioids was oral (52 percent), followed by intranasal (36 percent), intravenous (10 percent), and buccal (chewing on a patch; 2 percent). Other substances used included nicotine, alcohol, and non-opioid psychoactive drugs (primarily cannabis). Oxycodone was the most frequently reported opioid of abuse. Recreational opioid users have distinct drug-related behaviors and preferences. Monitoring current trends and examining these behaviors is an important component to understand the potential safety risks associated with recreational opioid use.

Safety and tolerability of ALO-02 (oxycodone hydrochloride and sequestered naltrexone hydrochloride) extended-release capsules in older patients: a pooled analysis of two clinical trials

Objective: To assess the impact of age on the safety and tolerability of ALO-02, an abuse-deterrent opioid formulation consisting of oxycodone hydrochloride and sequestered naltrexone hydrochloride, in patients with chronic pain.Methods: Data from two clinical studies in patients with chronic low back pain or chronic non-cancer pain were analyzed. Patients aged ≥18 years who required continuous around-the-clock opioid analgesia for an extended period were grouped into ≥65 years and <65 years age groups. Treatment-emergent adverse events (TEAEs), use of concomitant medications, clinical laboratory measurements, and occurrences of opioid withdrawal using reported adverse events (AEs) and Clinical Opiate Withdrawal Scale (COWS) scores assessed safety. Data pooling was employed for the titration and maintenance phases of both studies.Results: Respectively 805 and 436 patients received ≥1 dose of ALO-02 in the titration and maintenance phases; 121 (15.0%) and 83 (14.6%) patients, respectively, were aged ≥65 years in the titration and maintenance phases. Average doses of ALO-02 were lower in the older patients in both phases. Incidences of TEAEs were comparable between age groups in both phases and generally lower in the maintenance phase. Concomitant medications were taken more often by patients aged ≥65 years. Incidences of potentially clinically significant laboratory results were low in both phases with no clinically important differences between age groups. There were few reports of opioid withdrawal events as assessed by reported AEs and COWS scores. One patient aged ≥65 years experienced an AE of opioid withdrawal.Conclusions: The safety and tolerability of ALO-02 is similar in those aged ≥65 years and those aged <65 years with chronic pain.ClinicalTrials.gov identifiers: NCT01571362, NCT01428583.

Dancing with Deterrents: Understanding the Role of Abuse-Deterrent Opioid Formulations and Naloxone in Managing Cancer Pain.

Prescription opioids are commonly prescribed for the relief of many kinds of pain syndromes, including cancer pain. In order to combat the growing rates of abuse and misuse of prescription opioids, the Centers for Disease Control and Prevention, along with the U.S. Food and Drug Administration and multiple pharmaceutical companies, have implemented many risk mitigation strategies. Abuse-deterrent drug delivery technology and more consistent prescribing of the opioid antagonist, naloxone, are two of the mechanisms of reducing harm in patients on chronic opioid therapy. Abuse-deterrent technology is implemented into different commercially available opioid products with the intent of discouraging manipulation of the opioid or making the use of the manipulated opioid less appealing. Use of the opioid antagonist, naloxone, for reversal of intentional or unintentional opioid overdose is a safe and effective means to reduce potential risk in patients who are on opioids for pain management. These mechanisms have multiple advantages and limitations that influence their practical use specifically in patients with cancer pain. Patients with cancer pain have unique therapeutic needs and goals, and their balance of treatment risks and benefits differs from that of other kinds of chronic pain disorders. This article provides an overview of the advantages and limitations of these specific harm-reduction strategies and provides guidance on how to practically utilize them when caring for patients with cancer pain. IMPLICATIONS FOR PRACTICE: Treating cancer pain has important and unique considerations compared with other chronic, noncancer pain disorders. The use of risk mitigation strategies for opioid prescribing as promoted by the Centers for Disease Control and Prevention does not translate seamlessly to patients with cancer. It is crucial to be wary of the advantages and pitfalls of all risk mitigation strategies related to opioid use in patients with cancer pain. Careful examination of patient-specific risks and benefits should always be considered when implementing pharmacologic treatment and harm-reduction strategies for the management of cancer pain.

Impact of Abuse Deterrent Formulations of Opioids in Patients With Chronic Pain in the United States: A Cost-Effectiveness Model

ObjectiveOpioid abuse is a significant public health problem in the United States. We evaluate the clinical effectiveness and economic impact of abuse-deterrent formulations (ADF) of opioids relative to non-ADF opioids in preventing abuse. MethodsWe developed a cost-effectiveness model simulating 2 cohorts of 100 000 noncancer, chronic-pain patients newly prescribed either ADF or non-ADF extended-release (ER) opioids and followed them over 5 years, tracking new events of opioid abuse and opioid-related overdose deaths in addition to tracking 5-year cumulative costs of therapeutic use and abuse of ADF and non-ADF opioids. Patients in each cohort entered the model for therapeutic opioid use from where they could continue in that pathway, discontinue opioid use, or abuse opioids or die of opioid overdose-related or unrelated causes. In addition, one-way sensitivity and scenario analysis were conducted. ResultsOver a 5-year time period, using ADF opioids prevented an additional 2300 new cases of opioid abuse at an additional cost of approximately $535 million to the healthcare sector. Threshold analyses showed that a 40% decrease in ADF opioid costs was required to attain cost neutrality between the 2 cohorts, whereas a 100% effectiveness in abuse reduction still did not result in cost neutrality. A 43% decrease in diversion with ADFs relative to non-ADFs was required to attain cost neutrality. Including a societal perspective produced results directionally similar to the base-case analysis findings. ConclusionADF opioids have the potential to prevent new cases of opioid abuse, but at substantially higher costs to the health system.

Mitigation of IV Abuse Through the Use of Abuse-Deterrent Opioid Formulations: An Overview of Current Technologies.

Providers who treat patients with chronic pain face a dual challenge: providing adequate access to opioid therapies for appropriate pain management while adopting strategies to minimize the risk for abuse. Commonly prescribed opioids have substantial abuse potential when administered intravenously, and extended‐release (ER)/long‐acting (LA) opioids may be targeted for intravenous (IV) abuse because of the higher per‐dose medication level. The consequences of IV opioid abuse are severe and increase the risks for adverse outcomes, including mortality due to acute health events, serious infections, and deep vein thrombosis, to name a few. To reduce the potential for abuse of prescription opioids by both recreational and experienced drug abusers, abuse‐deterrent formulations (ADFs) of opioid medications employ either physical/chemical barriers or agonist‐antagonist combinations. Here we review the development and use of opioid ADFs as a harm‐reduction strategy, and their potential for mitigating IV opioid abuse. The approved ER/LA opioids with ADF labeling in the United States include formulations of oxycodone, hydrocodone, and morphine. Findings from in vitro laboratory tests of abuse deterrence for opioid ADFs are described herein, as are data from human abuse potential studies for IV abuse of those ADF products, for which such studies are feasible (ie, abuse‐deterrent agonist‐antagonist formulations). The available ADF opioids may decrease both the attractiveness and the feasibility of IV abuse. The adoption of ADF opioids represents one tactic for providing access to needed medication for patients with chronic pain, while potentially reducing the risk for opioid abuse, in a comprehensive effort to combat the opioid epidemic.

Beta-glucan and arabinogalactan-based xerogels for abuse-deterrent opioid formulations

Novel polysaccharide hydrogels based on Methocel and beta-glucan or arabinogalactan and corresponding xerogels were prepared and described. Phase stability of hydrogels was confirmed over multiple freeze–thaw cycles. Binary beta-glucan:Methocel hydrogels showed the highest freeze–thaw stability in terms of their syneresis. The viscosity of binary hydrogels was further increased by adding water-soluble resin. Freeze drying of polysaccharide gels yields xerogels suitable as abuse-deterrent vehicles for opioid delivery. The xerogels were characterized by infrared spectroscopy, X-ray diffraction, differential scanning calorimetry, scanning electron microscopy and by their swelling behavior. As a model opioid, tramadol hydrochloride formulations were prepared with various xerogel matrices and dissolution-release profiles were determined. The xerogel matrix acts as a functional excipient that forms a viscous gel barrier with decreased rate of tramadol release. Moreover, slower drug release with no dose dumping is observed in the presence of ethanol. The release kinetics demonstrated that hydrophilic gels with beta-glucan or arabinogalactan are effective for controlling and prolonging the drug release for 12 h which could reduce the required number of administrations.

Effects of intravenous oxycodone alone or in combination with naltrexone on measures of respiratory depression: a randomized placebo-controlled study.

Background:Abuse of prescription opioids, particularly by intravenous (IV) administration, can cause respiratory depression and death. ALO-02, an abuse-deterrent opioid formulation, is designed to release sequestered naltrexone upon manipulation by crushing, thereby antagonizing the pharmacologic effects of oxycodone. This exploratory post-hoc analysis examined the effects of IV administration of simulated crushed ALO-02 on end-tidal carbon dioxide (EtCO2), a surrogate marker of respiratory depression.Methods:Data were obtained from a randomized, double-blind, placebo-controlled, three-way crossover study in nondependent recreational opioid users that evaluated the abuse potential of IV administered oxycodone 20 mg + naltrexone 2.4 mg (simulating crushed ALO-02) versus oxycodone 20 mg or placebo. EtCO2 was measured as a secondary endpoint using noninvasive capnography at baseline and postdose intervals, up to 24 h.Results:Baseline EtCO2 (mean ± standard error of the mean (SEM)) values (n = 33) were similar across treatments: 33.5 ± 0.9, 33.5 ± 0.8, and 34.0 ± 0.7 mmHg for oxycodone 20 mg + naltrexone 2.4 mg, oxycodone 20 mg, and placebo, respectively. After dosing, mean ± SEM of the maximum effect (Emax) on EtCO2 was 37.5 ± 0.6, 40.5 ± 0.8, and 36.9 ± 0.6 mmHg for oxycodone 20 mg + naltrexone 2.4 mg, oxycodone 20 mg, and placebo, respectively. Emax values were significantly lower for oxycodone 20 mg + naltrexone 2.4 mg versus oxycodone 20 mg (p = 0.0005), and not different from placebo (p > 0.05).Conclusions:This abuse-potential study suggests that naltrexone released from ALO-02 tampering by crushing attenuates oxycodone-induced increase of EtCO2 in nondependent recreational opioid users.

Are abuse-deterrent opioid formulations all they are crushed up to be?

Are abuse-deterrent opioid formulations all they are crushed up to be?