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Abuse-deterrent opioids

Abuse-deterrent opioids
Author:
Richard Rosenquist, MD
Section Editor:
Scott Fishman, MD
Deputy Editor:
Marianna Crowley, MD
Literature review current through: Apr 2025. | This topic last updated: Apr 17, 2025.

INTRODUCTION — 

Prescription opioid misuse initially represented a large component of the opioid drug crisis in the United States. The rate of fatal overdoses due to oral formulations of semisynthetic opioids (eg, oxycodone, hydrocodone) rose steadily since 2000, and in 2017 was greater than that of heroin [1]. Beginning in 2013 there was rise in deaths related to synthetic opioids. This rise has continued unabated and now greatly exceeds deaths related to prescription opioids, heroin, and methadone. During this same time period, while opioid prescribing rates have decreased significantly [2], the rate of deaths related to prescription opioids has remained stable and those related to heroin have dropped [3-5].

Many individuals who misuse opioids progress from an initially legitimate, legal use of oral opioids to misuse, tolerance, and possible addiction. Those who misuse opioids may swallow many pills at once, but may also chew the tablets or crush them to facilitate smoking, inhalation, or intravenous (IV) injection, all of which increase the risks of overdose and addiction. Abuse-deterrent formulations (ADFs) of opioids are designed to prevent these altered routes of administration, while retaining efficacy with oral administration for legitimate pain relief. Prescription of ADF opioids is controversial because of unanswered questions about their ability to reduce overall opioid misuse, and their higher cost. ADFs neither prevent individuals from taking the drugs in higher doses than prescribed (which is the most common form of opioid misuse), change the addictive properties of the drug, nor prevent the other adverse, multisystem effects of opioids.

This topic will discuss the technologies used, available formulations, and efficacy of ADF opioids for reducing opioid misuse. Opioid use disorder and misuse of prescription opioids is discussed separately. (See "Opioid use disorder: Epidemiology, clinical features, health consequences, screening, and assessment" and "Prescription drug misuse: Epidemiology, prevention, identification, and management", section on 'Opioid analgesics'.)

GOALS FOR ABUSE-DETERRENT FORMULATION — 

The primary goal for an abuse-deterrent formulation (ADF) is to deter or dissuade an individual from chewing the drug or using it by inhalation or intravenous (IV) injection. These latter routes of administration are associated with an increased risk of respiratory depression and fatal overdose compared with oral administration [6], particularly because of the high dose of opioid that is concentrated in extended-release formulations. Chewing, inhalation, and IV routes of drug administration rapidly achieve a high blood level and greater degree of rewarding effects [7,8], and therefore may increase the risk of addiction and misuse. Non-oral routes of administration are also associated with a variety of other health consequences, including damage to nasal and oral structures [9,10] and blood-borne infections (eg, human immunodeficiency virus, hepatitis, and endocarditis) [11].

ABUSE-DETERRENT TECHNOLOGIES — 

One or more abuse-deterrent technologies are used for the abuse-deterrent formulations (ADFs) currently available in the United States and approved for ADF labeling by the US Food and Drug Administration (FDA) (table 1). There are several abuse-deterrent preparations available in Canada, none of which have been approved for tamper resistant labeling by Health Canada.

Physical/chemical barriers – The most common ADF technology employs either physical or chemical barriers, or both. Physical barriers are used to prevent chewing, crushing, cutting, or grinding of the tablet. Chemical barriers (eg, gelling agents) resist penetration and dissolution by water or other solvents, and may change the form of the active drug to render it difficult to inhale or inject. As an example, with one chemical barrier technology, the active drug turns into a viscous gel when exposed to a liquid, making it difficult to use a syringe to inject the drug [12].

Agonist/antagonist combinations An opioid antagonist can be added to the agonist drug. Opioid antagonists are not effectively absorbed when swallowed, and do not counteract the opioid agonist when taken as intended [13]. However, when the manipulated drug is injected or inhaled, the antagonist is effective at reducing or eliminating the euphoria associated with the agonist. The combination drug that includes buprenorphine and naloxone (Suboxone), used for pharmacotherapy of opioid use disorder, works by this mechanism. (See "Opioid use disorder: Pharmacologic management", section on 'Transmucosal formulations'.)

Additional formulations for abuse-deterrence include aversion, whereby substances are added to produce unpleasant effects of the drug when misused; unconventional opioid delivery systems such as sustained-release depot injectable formulations or subcutaneous implants that are difficult to manipulate; prodrugs or new molecular entities that must undergo enzymatic activation or other chemical transformations in the gastrointestinal tract in order to release the active opioid [14,15]; combinations of two or more technologies; or novel approaches or new technologies.

ABUSE-DETERRENT FORMULATION APPROVAL PROCESS — 

The FDA strongly recommends three types of premarket studies plus postmarket evaluation for abuse-deterrent formulation (ADF) labeling [16]. The premarket studies use healthy, non-addicted, recreational drug users between 18 and 55 years of age, and are designed to evaluate the bio-equivalency of the active drug, integrity of the deterrent properties, the ease with which the altered drug can be drawn into and injected from a syringe for intravenous (IV) use, and the "likeability" of a manipulated ADF.

Postmarketing studies evaluate the real-world effect of the ADF on reduction of misuse, adverse clinical outcomes, overdose, and death. Postmarketing studies have been completed for the ADF of extended-release oxycodone (OxyContin), which was the first available ADF, but the results are inconclusive. (See 'Efficacy' below.)

The FDA approves abuse-deterrent labeling for specific routes of drug use (ie, oral, nasal, or IV) based on clinical studies. The routes of drug use approved for abuse-deterrent labeling for available ADF opioids are shown in a table (table 1).

ABUSE-DETERRENT OPIOID FORMULATIONS — 

Several opioid preparations with abuse-deterrent formulation (ADF) labeling are available in the United States and are shown in a table (table 1). They include generic equivalents for extended-release oxycodone and for extended-release hydrocodone, and one immediate release formulation of oxycodone (Roxybond). One of the US Food and Drug Administration (FDA) approved ADFs of oxycodone (Targin) is available in Canada but not the United States.

An ADF of extended-release oxycodone (OxyContin) was the first opioid approved for ADF labeling, and is the most widely prescribed ADF opioid. The available ADF opioids, the technology used for abuse-deterrence, and available doses are shown in a table (table 1).

An oxymorphone preparation with abuse-deterrent technology, reformulated Opana ER, was withdrawn from the market by the manufacturer in 2017 [17] because of reports of drug-induced thrombotic microangiopathy (DITMA) [18,19], and an outbreak of human immunodeficiency virus infection [20] associated with intravenous use of the manipulated preparation. Reformulated Opana ER never acquired FDA ADF labeling due to concerns about safety and efficacy [21]. (See "Drug-induced thrombotic microangiopathy (DITMA)", section on 'Illicit or misused drugs'.)

EFFICACY — 

Abuse-deterrent formulation (ADF) probably reduces the misuse of a specific opioid but may also drive individuals with opioid use disorder to select a different non-ADF opioid, an intravenous opioid (eg, heroin), or another type of illegal psychostimulant (eg, cocaine).

Efficacy of technology — ADF labeling requires demonstration that the abuse-deterrent technology makes it more difficult to extract the active drug, more difficult to draw the extracted drug into a syringe and inject it from a syringe, and that the manipulated drug is less "likeable" than the non-ADF equivalent [16]. (See 'Abuse-deterrent formulation approval process' above.)

Real world efficacy — Real world efficacy of ADF technology may be reduced for the following reasons:

ADF does not prevent patients from taking increased quantities of the ADF formulation and therefore higher doses than prescribed, which is the most common form of opioid misuse [22].

ADF does not change the addictive property of the active drug.

ADFs are not abuse-proof, and online forums for using opioids have posted instructions for subverting some ADF technologies [23-25].

Effect of abuse-deterrent formulation on opioid related harm — The postmarketing studies that have been completed for reformulated extended-release (ER) oxycodone (OxyContin) have been inconclusive and have reported mixed results. It is unclear whether prescription of an ADF opioid rather than a non-ADF opioid reduces the risk of misuse, addiction, or overdose in opioid naïve patients or in those who do not misuse opioids at the time of prescription [26].

Most studies of the effects of reformulated OxyContin have reported a reduction in the rate of OxyContin misuse after reformulation, with reported reductions of 12 to 75 percent [27-32]. However, one database study of cohorts of patients who received ADF oxycodone versus non-ADF oxycodone for an initial opioid prescription found an increase in opioid-related adverse outcomes in patients who received the abuse-deterrent formulation [33]. These studies are retrospective, and have been based on poison control center calls, reports from individuals in substance use disorder programs, population-based drug use surveys, medical claims databases, and data from drug diversion programs; this data has been collected over time periods in which other interventions aimed at opioid misuse may have occurred.

It appears that very few individuals who misused OxyContin prior to reformulation ceased opioid misuse because of the abuse-deterrent formulation. In one survey of patients with opioid use disorder, 3 percent of patients reported that they stopped drug misuse because of OxyContin reformulation, whereas 66 percent of patients either continued to misuse OxyContin (either orally or by manipulation) or switched to other drugs [27,34]. (See 'Switch to other opioids or heroin' below.)

An industry-sponsored retrospective database study compared opioid related adverse outcomes in approximately 4850 patients who were prescribed extended abuse-deterrent morphine (Embeda, extended-release morphine with sequestered naltrexone hydrochloride) with outcomes in 10,350 patients who received non-abuse-deterrent extended-release morphine [35]. Prescription of the abuse-deterrent formulation was associated with lower incidences of misuse or dependence and non-fatal opioid related overdose.

Efficacy for reducing overall opioid misuse — The impact of ADF technology on opioid misuse at the societal level is difficult to determine because these technologies are part of evolving multipronged strategies to combat the opioid epidemic.

ADFs represent only a small portion of the available and prescribed opioid products in the United States (US), and therefore may have a limited impact on overall rates of opioid misuse [36]. In 2015, 96 percent of all opioid products prescribed in the United States (predominantly immediate-release [IR] formulations) lacked abuse-deterrent properties. In 2016, prescriptions for ADF opioids represented about 20 percent of all dispensed extended-release opioids [16], though availability of ADFs in the US may increase as state legislatures or health insurance companies mandate or encourage ADF prescription. (See 'State legislation' below.)

However, even if all prescription opioids were changed to ADFs, illicit opioids including heroin, fentanyl, and other synthetic opioids would still be available, and this change could drive users from prescription to illicit drug misuse.

NEGATIVE CONSEQUENCES OF ABUSE-DETERRENT OPIOID FORMULATION

Switch to other opioids or heroin — As an alternative to abuse-deterrent formulations (ADFs), many individuals who misused opioids have switched to other prescription opioids or have chosen to use heroin or fentanyl. Heroin and fentanyl are increasingly available and less expensive than ADF pills [37], and misuse of these drugs is a more significant public health issue than misuse of prescription opioids. (See "Prevention of lethal opioid overdose in the community", section on 'Epidemiology'.)

Increase in non-ADF opioids A number of studies have reported an increase in the use of non-ADF opioids that are easier to misuse after introduction of reformulated OxyContin [27-31,38-40]. As an example, in one study, opioid use was assessed after introduction of the ADF oxycodone (reformulated OxyContin) in patients who were taking the ER preparation continuously prior to reformulation [39]. Thirty percent of patients avoided switching to ADF opioid and instead changed to non-ADF extended-release (ER) opioids or immediate-release/short acting opioids or stopped taking prescription opioids (presumably many of whom switched to illicit opioids). The diagnosed opioid misuse rates were higher in patients who avoided switching to ADFs than in patients who transitioned to ADFs (6.7 percent for those who switched to other ER opioids, 10.9 percent for those who discontinued ER prescription opioids, and 11.3 percent for those who switched to immediate-release opioids, compared with 3.5 percent in patients who transitioned to ADF oxycodone).

Possible increase in heroin or fentanyl – Some, but not all, studies have found an association between the availability of ADF opioids and increased use of heroin or fentanyl [31,41,42]. Existing studies are highly subject to confounding, due to the studied patient population, the complex nature of opioid misuse, and changes in public health opioid initiatives over time.

Cost — For some opioids the ADF is significantly more expensive than the non-ADF equivalent, particularly for oxycodone preparations. Costs to patients for ADFs vary depending on the retail outlet, insurance coverage and copays, and availability of drug manufacturer, or pharmacy discounts. Some states have mandated insurance coverage for ADF opioids. Many insurance plans require preapproval for ADF prescription. (See 'State legislation' below.)

The high cost of some ADFs has prompted analyses of the overall value of these drugs, considering indirect cost savings such as emergency room visits, hospitalizations, overdoses, and substance use disorder treatment programs, in addition to ADF drug costs. Such analysis is necessarily based on assumptions about the efficacy of ADFs for deterring misuse and related clinical outcomes, without reliable supporting data. (See 'Real world efficacy' above.)

STATE LEGISLATION — 

State legislatures have enacted or are considering legislation requiring that clinicians prescribe or pharmacists dispense abuse-deterrent formulation (ADF) opioids where they are available [43]. In 2014, Massachusetts became the first state to pass legislation that requires pharmacies to substitute ADFs by default for chemically equivalent non-ADF opioid prescriptions unless specifically directed otherwise by the prescriber, and to require insurance carriers to cover these ADFs with no additional cost burden to patients [44]. Clinicians should be aware of the regulations that apply in their states.

Data on the impact of these state policy interventions are limited and inconsistent [45].

INDICATIONS FOR PRESCRIBING ABUSE-DETERRENT FORMULATIONS — 

We do not routinely prescribe abuse-deterrent formulation (ADF) opioids rather than non-ADF opioids. The decision to prescribe ADF opioids should be individualized, but data are not available that would stratify risk and determine which patients should receive these preparations [46]. Use of ADFs should never be a substitute for other relevant risk management approaches or risk mitigation tools. (See "Use of opioids in the management of chronic pain in adults", section on 'Monitoring and risk management strategies during trial'.)

Prescription of ADF opioids has declined since reformulated oxycontin became available in 2010, and remains a very small fraction of available opioids [47,48].

The clinician who is truly concerned about misuse by the intended recipient should reconsider prescribing an opioid at all. An ADF may be indicated if there is high risk of diversion, such as a debilitated patient in a living situation that allows others access to the patient’s medications.

Whereas ADFs make misuse more difficult for patients who are prescribed opioids for chronic pain, individuals already misusing opioids may switch to other illicit opioids (including heroin or fentanyl) if a specific opioid is replaced with an ADF. The added cost to the health care system (and possibly the patient) is substantial. The same heightened vigilance is required whether an ADF or non-ADF opioid is prescribed. (See 'Real world efficacy' above.)

Further real world studies are required to elucidate the role of ADF opioids in attempts to curb the opioid epidemic.

SUMMARY AND RECOMMENDATIONS

Rationale for abuse-deterrent technology Abuse-deterrent formulations (ADFs) of opioids are designed to prevent unintended routes of administration, while retaining efficacy with oral administration for legitimate pain relief. (See 'Introduction' above.)

Technologies ADF technologies are intended to either make manipulation of oral medications (eg, chewing, inhalation, or injection) more difficult, or to make the drug less rewarding once manipulated. Available ADF opioids employ the following technologies (see 'Abuse-deterrent technologies' above):

Physical barriers that prevent chewing, crushing, cutting, or grinding of the tablet

Chemical barriers that prevent dissolution with solvent and therefore make injection or inhalation more difficult

Incorporation of an opioid antagonist that is inactive when taken orally but antagonizes the agonist opioid when the drug is manipulated

Availability Several opioids with ADF labeling are available in the US and are shown in a table (table 1). (See 'Abuse-deterrent opioid formulations' above.)

ADFs in the US are branded drugs that are significantly more expensive than non-ADF counterparts, and may or may not be paid for by health insurance. (See 'Cost' above.)

Efficacy ADF probably reduces the misuse of a specific opioid but may also drive individuals who misuse opioids to select a different non-ADF opioid, fentanyl, or heroin. Real world efficacy of ADFs may be reduced for the following reasons (see 'Real world efficacy' above):

ADFs do not prevent individuals from taking multiple pills

ADF does not change the addictive properties of the active drug

ADF technology can be subverted

As an alternative to ADFs, many individuals who misuse opioids have switched to using other opioids or heroin

ADFs represent a small portion of prescribed opioids

Legislation regarding ADF opioids Some state legislatures have enacted or are considering regulations that govern the prescription of ADF opioids. (See 'State legislation' above.)

Indications We do not routinely prescribe ADF opioids rather than non-ADF opioids, unless required by law. Use of ADFs should never be a substitute for other relevant risk management approaches or risk mitigation tools. (See 'Indications for prescribing abuse-deterrent formulations' above.)

ACKNOWLEDGMENT — 

The UpToDate editorial staff acknowledges Ronald S Litman, DO, ML, who contributed as an author to earlier versions of this topic review.

  1. Scholl L, Seth P, Kariisa M, et al. Drug and Opioid-Involved Overdose Deaths - United States, 2013-2017. MMWR Morb Mortal Wkly Rep 2018; 67:1419.
  2. Overdose epidemic report 2024. American Medical Association. https://www.ama-assn.org/system/files/ama-overdose-epidemic-report.pdf (Accessed on June 05, 2024).
  3. Drug Overdose Deaths in the United States, 2002-2022, NCHS Data Brier No. 491, March 2024 https://www.cdc.gov/nchs/products/databriefs/db491.htm#:~:text=The%20age%2Dadjusted%20rate%20of,those%20age%2035%20and%20older. (Accessed on May 01, 2024).
  4. Understanding the opioid overdose epidemic. Centers for Disease Control and Prevention. https://www.cdc.gov/overdose-prevention/about/understanding-the-opioid-overdose-epidemic.html?CDC_AAref_Val=https://www.cdc.gov/opioids/basics/epidemic.html (Accessed on May 21, 2024).
  5. Drug overdose deaths in the United States, 2002-2022. Centers for Disease Control and Prevention (Spencer MR, Garnett MF, Minino AM). https://stacks.cdc.gov/view/cdc/135849 (Accessed on January 08, 2025).
  6. Green JL, Bucher Bartelson B, Le Lait MC, et al. Medical outcomes associated with prescription opioid abuse via oral and non-oral routes of administration. Drug Alcohol Depend 2017; 175:140.
  7. Katz N, Dart RC, Bailey E, et al. Tampering with prescription opioids: nature and extent of the problem, health consequences, and solutions. Am J Drug Alcohol Abuse 2011; 37:205.
  8. McAnally HB. Attenuating the Agent: Reducing Opioid “Virulence”. In: Opioid Dependence, Springer, 2018.
  9. Yewell J, Haydon R, Archer S, Manaligod JM. Complications of intranasal prescription narcotic abuse. Ann Otol Rhinol Laryngol 2002; 111:174.
  10. Alexander D, Alexander K, Valentino J. Intranasal hydrocodone-acetaminophen abuse induced necrosis of the nasal cavity and pharynx. Laryngoscope 2012; 122:2378.
  11. Powell D, Alpert A, Pacula RL. A Transitioning Epidemic: How The Opioid Crisis Is Driving The Rise In Hepatitis C. Health Aff (Millwood) 2019; 38:287.
  12. Purdue Pharma LP. Hysingla ER (hydrocodone bitartrate) Extended-Release tablets https://hysinglaer.com/opioid-abuse-deterrence-studies.html.
  13. Davis M, Goforth HW, Gamier P. Oxycodone combined with opioid receptor antagonists: efficacy and safety. Expert Opin Drug Saf 2013; 12:389.
  14. Kirkpatrick DL, Schmidt WK, Morales R, et al. In vitro and in vivo assessment of the abuse potential of PF614, a novel BIO-MD™ prodrug of oxycodone. J Opioid Manag 2017; 13:39.
  15. Maincent J, Zhang F. Recent advances in abuse-deterrent technologies for the delivery of opioids. Int J Pharm 2016; 510:57.
  16. US Food and Drug Administration. Abuse-deterrent opioids—evaluation and labeling. Guidance for industry. 2015. https://www.fda.gov/downloads/Drugs/Guidances/UCM334743.pdf (Accessed on June 19, 2017).
  17. US Food and Drug Administration. FDA requests removal of Opana ER for risks related to abuse, 2017. https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm562401.htm (Accessed on June 19, 2017).
  18. Hunt R, Yalamanoglu A, Tumlin J, et al. A mechanistic investigation of thrombotic microangiopathy associated with IV abuse of Opana ER. Blood 2017; 129:896.
  19. Centers for Disease Control and Prevention (CDC). Thrombotic thrombocytopenic purpura (TTP)-like illness associated with intravenous Opana ER abuse--Tennessee, 2012. MMWR Morb Mortal Wkly Rep 2013; 62:1.
  20. Peters PJ, Pontones P, Hoover KW, et al. HIV Infection Linked to Injection Use of Oxymorphone in Indiana, 2014-2015. N Engl J Med 2016; 375:229.
  21. US Food and Drug Administration: Postmarketing safety issues related to reformulated Opana ER®. 2017. https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/AnestheticAndAnalgesicDrugProductsAdvisoryCommittee/UCM545760.pdf (Accessed on June 20, 2017).
  22. Butler SF. Reply to commentary. J Pain 2013; 14:361.
  23. Vosburg SK, Haynes C, Besharat A, Green JL. Changes in drug use patterns reported on the web after the introduction of ADF OxyContin: findings from the Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS) System Web Monitoring Program. Pharmacoepidemiol Drug Saf 2017; 26:1044.
  24. McNaughton EC, Coplan PM, Black RA, et al. Monitoring of internet forums to evaluate reactions to the introduction of reformulated OxyContin to deter abuse. J Med Internet Res 2014; 16:e119.
  25. McNaughton EC, Black RA, Zulueta MG, et al. Measuring online endorsement of prescription opioids abuse: an integrative methodology. Pharmacoepidemiol Drug Saf 2012; 21:1081.
  26. DiPrete BL, Dasgupta N, Oh GY, et al. Abuse-deterrent formulations and opioid-related harms in North Carolina, 2010-2018. Am J Epidemiol 2025; 194:680.
  27. Cicero TJ, Ellis MS. Abuse-Deterrent Formulations and the Prescription Opioid Abuse Epidemic in the United States: Lessons Learned From OxyContin. JAMA Psychiatry 2015; 72:424.
  28. Butler SF, Cassidy TA, Chilcoat H, et al. Abuse rates and routes of administration of reformulated extended-release oxycodone: initial findings from a sentinel surveillance sample of individuals assessed for substance abuse treatment. J Pain 2013; 14:351.
  29. Sessler NE, Downing JM, Kale H, et al. Reductions in reported deaths following the introduction of extended-release oxycodone (OxyContin) with an abuse-deterrent formulation. Pharmacoepidemiol Drug Saf 2014; 23:1238.
  30. Severtson SG, Bartelson BB, Davis JM, et al. Reduced abuse, therapeutic errors, and diversion following reformulation of extended-release oxycodone in 2010. J Pain 2013; 14:1122.
  31. Cicero TJ, Ellis MS, Surratt HL. Effect of abuse-deterrent formulation of OxyContin. N Engl J Med 2012; 367:187.
  32. Rodriguez RD, Dailey Govoni T, Rajagopal V, Green JL. Evaluating the effectiveness of reformulated extended-release oxycodone with abuse-deterrent properties on reducing non-oral abuse among individuals assessed for substance abuse treatment with the Addiction Severity Index-Multimedia Version (ASI-MV). Curr Med Res Opin 2023; 39:579.
  33. Paljarvi T, Strang J, Quinn PD, et al. Abuse-deterrent extended-release oxycodone and risk of opioid-related harm. Addiction 2021; 116:2409.
  34. DiNardi M. The release of abuse-deterrent OxyContin and adolescent heroin use. Drug Alcohol Depend 2021; 229:109114.
  35. Cicero TJ, Mendoza M, Cattaneo M, et al. Real-world misuse, abuse, and dependence of abuse-deterrent versus non-abuse-deterrent extended-release morphine in Medicaid non-cancer patients. Postgrad Med 2019; 131:225.
  36. Tufts Center for the Study of Drug Development. ADF opioid development, uptake tied to efficacy, regulatory/payer policies, 2017. http://static1.squarespace.com/static/5a9eb0c8e2ccd1158288d8dc/t/5aa2b259f9619afb7edc688d/1520611929389/Summary_JulyAugustIR17.pdf.
  37. Cicero TJ, Ellis MS, Kasper ZA. Increased use of heroin as an initiating opioid of abuse. Addict Behav 2017; 74:63.
  38. Cassidy TA, DasMahapatra P, Black RA, et al. Changes in prevalence of prescription opioid abuse after introduction of an abuse-deterrent opioid formulation. Pain Med 2014; 15:440.
  39. Michna E, Kirson NY, Shei A, et al. Use of prescription opioids with abuse-deterrent technology to address opioid abuse. Curr Med Res Opin 2014; 30:1589.
  40. Jauncey M, Livingston M, Salmon AM, Dietze P. The impact of OxyContin reformulation at the Sydney Medically Supervised Injecting Centre: Pros and cons. Int J Drug Policy 2018; 53:17.
  41. Coplan PM, Kale H, Sandstrom L, et al. Changes in oxycodone and heroin exposures in the National Poison Data System after introduction of extended-release oxycodone with abuse-deterrent characteristics. Pharmacoepidemiol Drug Saf 2013; 22:1274.
  42. Alpert A, Powell D, Pacula RL. Supply-side drug policy in the presence of substitutes: Evidence from the introduction of abuse-deterrent opioids, NBER Working Paper 23031, RAND Corporation, 2017. http://www.nber.org/papers/w23031 (Accessed on July 15, 2017).
  43. Multistate Insider: States Have Stalled on Potential Opioid Abuse Solution: Deterrent Formulation Drugs. 2017. https://www.multistate.us/blog/state-efforts-have-stalled-on-potential-opioid-abuse-solution-deterrent-formulation-drugs (Accessed on July 21, 2017).
  44. https://malegislature.gov/Laws/SessionLaws/Acts/2016/Chapter52.
  45. Haegerich TM, Paulozzi LJ, Manns BJ, Jones CM. What we know, and don't know, about the impact of state policy and systems-level interventions on prescription drug overdose. Drug Alcohol Depend 2014; 145:34.
  46. https://www.cdc.gov/mmwr/volumes/65/rr/rr6501e1.htm#T1_down.
  47. Report on abuse-deterrent opioid formulations and access barriers under Medicare. US Food and Drug Administration. https://www.fda.gov/media/140805/download#:~:text=ER%20opioid%20analgesics%20however%2C%20represent,the%20overall%20opioid%20analgesic%20market. (Accessed on November 06, 2023).
  48. Brown JR, Oh G, Wang Y, et al. Variation in Abuse-Deterrent Formulation Opioid Prescribing in California, Florida, and Kentucky in 2018. J Rural Health 2021; 37:23.
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