Abuse-Deterrent Formulations in the Treatment of Chronic Pain

2017 ◽  
Author(s):  
Sanford M Silverman

Prescription drug abuse is the fastest growing problem in the United States. According to the Centers for Disease Control and Prevention (CDC), enough opioid pain relievers were sold in 2010 to provide every adult in the United States with the equivalent of a typical dose of 5 mg of hydrocodone every 4 hours for 1 month. Many solutions have been proposed to address this problem, including treatment guidelines, political solutions (statutory changes), Risk Evaluation and Mitigation Strategy (REMS), and technological innovations. Many opioid products are manipulated (crushed, snorted, injected, etc.) to facilitate abuse. Since extended-release/long-acting (ER/LA) opioids contain a large amount of opioid contained in a single delivery system, they are a favorite target of abusers. In short, the goal of an abuser is to convert an ER/LA opioid into an immediate-release one. Abuse-deterrent formulations (ADFs) are intended to make manipulation more difficult or to make abuse of the manipulated product less attractive or less rewarding. One such technological solution is the development of ADFs for opioid pain medications. The Food and Drug Administration's (FDA) guidelines for industry released in 2015 establish the rationale and methodology for the development of ER/LA opioids that contain abuse-deterrent properties. The goal is to deter abuse, realizing that it is impossible to prevent abuse. Key words: abuse-deterrent formulations, abuse-deterrent opioids, CDC guidelines, FDA opioid guidelines, opioid abuse, opioid deaths, opioid diversion, opioid overdose, prescription drug abuse, REMS 

Author(s):  
John J. Coleman

This chapter discusses how the pharmaceutical industry’s actions affected the accomplishments of the Decade of Pain Control and Research, which began on January 1, 2001, following almost two decades of rising concern over the inadequate treatment of chronic pain in the United States. To tell the story of this decade we must describe the accompanying problem of drug diversion and abuse. The development in 1995 of a new opioid product called OxyContin, its aggressive marketing, the morbidity and mortality associated with its misuse, and the eventual felony conviction in 2007 of the drug’s sponsor for fraudulent claims and marketing practices, affected the Decade in unexpected ways. The response by Congress and the regulatory community to what they termed an “epidemic” of prescription drug abuse produced long-lasting policy changes. The chapter also touches on the peculiar and sometimes troubling relationship between the regulators and the regulated.


2014 ◽  
Vol 40 (1) ◽  
pp. 85-112 ◽  
Author(s):  
Joanna Shepherd

Prescription painkiller abuse is the fastest growing drug problem in the United States. In the past year, approximately one out of twenty Americans reported misuse or abuse of prescription painkillers. Several factors contribute to the prescription painkiller epidemic. Drug abusers use various methods—such as doctor shopping, paying with cash, and filling prescriptions in different states—to avoid detection and obtain prescription painkillers for illegitimate uses. A few rogue physicians and pharmacists, lured by substantial profits, enable drug abusers by illegally prescribing or supplying controlled substances. Even ethical physicians rarely have adequate training to recognize and address prescription drug abuse, and as a result, prescribe painkillers to patients who are not using them for legitimate medical purposes. Similarly, although the majority of pharmacies have taken steps to combat drug abuse and reduce prescription painkiller dispensing, under current reporting systems, pharmacists lack visibility into several important indicators of drug abuse. As a result, even the most vigilant pharmacists find it extremely difficult to identify and detect drug abuse with certainty.While state governments have established prescription drug monitoring programs (PDMPs) to crack down on prescription drug abuse, these programs have proven to be inadequate. The programs currently suffer from inadequate data collection, ineffective utilization of data, insufficient interstate data sharing, and constraints on sharing data with law enforcement and state agencies. By contrast, third-party prescription payment systems run by pharmacy benefit managers (PBMs) or health insurers have been effective in detecting prescription drug abuse. This paper suggests that a national prescription drug reporting program building on existing PBM networks could be significantly more effective than existing state PDMPs in detecting prescription drug abuse.


2012 ◽  
Vol 3S;15 (3S;7) ◽  
pp. S67-S116
Author(s):  
ASIPP ASIPP

Results: Part 2 of the guidelines on responsible opioid prescribing provides the following recommendations for initiating and maintaining chronic opioid therapy of 90 days or longer. 1. A) Comprehensive assessment and documentation is recommended before initiating opioid therapy, including documentation of comprehensive history, general medical condition, psychosocial history, psychiatric status, and substance use history. (Evidence: good) B) Despite limited evidence for reliability and accuracy, screening for opioid use is recommended, as it will identify opioid abusers and reduce opioid abuse. (Evidence: limited) C) Prescription monitoring programs must be implemented, as they provide data on patterns of prescription usage, reduce prescription drug abuse or doctor shopping. (Evidence: good to fair) D) Urine drug testing (UDT) must be implemented from initiation along with subsequent adherence monitoring to decrease prescription drug abuse or illicit drug use when patients are in chronic pain management therapy. (Evidence: good) 2. A) Establish appropriate physical diagnosis and psychological diagnosis if available prior to initiating opioid therapy. (Evidence: good) B) Caution must be exercised in ordering various imaging and other evaluations, interpretation and communication with the patient; to avoid increased fear, activity restriction, requests for increased opioids, and maladaptive behaviors. (Evidence: good) C) Stratify patients into one of the 3 risk categories – low, medium, or high risk. D) A pain management consultation, may assist non-pain physicians, if high-dose opioid therapy is utilized. (Evidence: fair) 3. Essential to establish medical necessity prior to initiation or maintenance of opioid therapy. (Evidence: good) 4. Establish treatment goals of opioid therapy with regard to pain relief and improvement in function. (Evidence: good) 5. A) Long-acting opioids in high doses are recommended only in specific circumstances with severe intractable pain that is not amenable to short-acting or moderate doses of long-acting opioids, as there is no significant difference between long-acting and short-acting opioids for their effectiveness or adverse effects. (Evidence: fair) B) The relative and absolute contraindications to opioid use in chronic non-cancer pain must be evaluated including respiratory instability, acute psychiatric instability, uncontrolled suicide risk, active or history of alcohol or substance abuse, confirmed allergy to opioid agents, coadministration of drugs capable of inducing life-limiting drug interaction, concomitant use of benzodiazepines, active diversion of controlled substances, and concomitant use of heavy doses of central nervous system depressants. (Evidence: fair to limited) 6. A robust agreement which is followed by all parties is essential in initiating and maintaining opioid therapy as such agreements reduce overuse, misuse, abuse, and diversion. (Evidence: fair) 7. A) Once medical necessity is established, opioid therapy may be initiated with low doses and short-acting drugs with appropriate monitoring to provide effective relief and avoid side effects. (Evidence: fair for short-term effectiveness, limited for long-term effectiveness) B) Up to 40 mg of morphine equivalent is considered as low dose, 41 to 90 mg of morphine equivalent as a moderate dose, and greater than 91 mg of morphine equivalence as high dose. (Evidence: fair) C) In reference to long-acting opioids, titration must be carried out with caution and overdose and misuse must be avoided. (Evidence: good) 8. A) Methadone is recommended for use in late stages after failure of other opioid therapy and only by clinicians with specific training in the risks and uses. (Evidence: limited) B) Monitoring recommendation for methadone prescription is that an electrocardiogram should be obtained prior to initiation, at 30 days and yearly thereafter. (Evidence: fair) 9. In order to reduce prescription drug abuse and doctor shopping, adherence monitoring by UDT and PMDPs provide evidence that is essential to the identification of those patients who are non-compliant or abusing prescription drugs or illicit drugs. (Evidence: fair) 10. Constipation must be closely monitored and a bowel regimen be initiated as soon as deemed necessary. (Evidence: good) 11. Chronic opioid therapy may be continued, with continuous adherence monitoring, in well-selected populations, in conjunction with or after failure of other modalities of treatments with improvement in physical and functional status and minimal adverse effects. (Evidence: fair) Disclaimer: The guidelines are based on the best available evidence and do not constitute inflexible treatment recommendations. Due to the changing body of evidence, this document is not intended to be a “standard of care.” Key words: Chronic pain, persistent pain, non-cancer pain, controlled substances, substance abuse, prescription drug abuse, dependency, opioids, prescription monitoring, drug testing, adherence monitoring, diversion


Author(s):  
Victor Puac-Polanco ◽  
Stanford Chihuri ◽  
David S Fink ◽  
Magdalena Cerdá ◽  
Katherine M Keyes ◽  
...  

Abstract Prescription drug monitoring programs (PDMPs) are a crucial component of federal and state governments’ response to the opioid epidemic. Evidence about the effectiveness of PDMPs in reducing prescription opioid–related adverse outcomes is mixed. We conducted a systematic review to examine whether PDMP implementation within the United States is associated with changes in 4 prescription opioid–related outcome domains: opioid prescribing behaviors, opioid diversion and supply, opioid-related morbidity and substance-use disorders, and opioid-related deaths. We searched for eligible publications in Embase, Google Scholar, MEDLINE, and Web of Science. A total of 29 studies, published between 2009 and 2019, met the inclusion criteria. Of the 16 studies examining PDMPs and prescribing behaviors, 11 found that implementing PDMPs reduced prescribing behaviors. All 3 studies on opioid diversion and supply reported reductions in the examined outcomes. In the opioid-related morbidity and substance-use disorders domain, 7 of 8 studies found associations with prescription opioid–related outcomes. Four of 8 studies in the opioid-related deaths domain reported reduced mortality rates. Despite the mixed findings, emerging evidence supports that the implementation of state PDMPs reduces opioid prescriptions, opioid diversion and supply, and opioid-related morbidity and substance-use disorder outcomes. When PDMP characteristics were examined, mandatory access provisions were associated with reductions in prescribing behaviors, diversion outcomes, hospital admissions, substance-use disorders, and mortality rates. Inconsistencies in the evidence base across outcome domains are due to analytical approaches across studies and, to some extent, heterogeneities in PDMP policies implemented across states and over time.


2020 ◽  
Vol 1;23 (1;1) ◽  
pp. 1-16 ◽  
Author(s):  
Alaa Abd-Elsayed

Background: The cost of chronic pain in the United States is extremely high. Opioids are one of the most common medications prescribed for the treatment of chronic pain, and their misuse and addiction have been of concern. It has been found that opioids are frequently abused and negatively impact the American workforce. Objectives: The objective of this study was to obtain data on US employers’ concerns and priorities, perceptions of prescription drug abuse, perceived impact of prescription drug use on the workplace, identification of and response to drug abuse, perceived ability to handle prescription drug abuse in the workplace, and workplace initiatives, employee assistance programs, employee drug testing, workplace prescription drug training, insurance coverage of alternative treatment, and overall preparedness to deal with the issue. Study Design: This research used an employer proprietary questionnaire created by members of the National Safety Council in cooperation with market research experts at B2B International. Setting: Employers surveyed via an online survey represent diverse industries and geographical areas. Methods: The research was conducted using a proprietary questionnaire. Participants were recruited from a sample of verified panelists through Research Now, and fieldwork was conducted online by B2B International. This report is on 501 interviews that each represent a US employer with 50 or more employees. The employers sampled are extremely diverse in not only size and industry, but also geography and centralization. Results: Our results showed that 67% of employers reported concerns related to prescription drug misuse, which was comparable to workplace violence and more concerning than the use of illegal drugs. Sixty-one percent reported concerns related to prescription opioids, which was a higher concern than using anti-anxiety medications, stimulants, and even heroin. Limitations: Survey study with descriptive analysis with limited sample. Conclusions: Prescription drug misuse and abuse concern American employers. Their side effects are clear, but employers are less likely to acknowledge their detrimental business effect. Employers report being unprepared for dealing with issues related to this; however, the firms with programs in place feel more prepared to deal with misuse and abuse. Key words: Prescription drugs, US workforce, chronic pain


Pain Medicine ◽  
2019 ◽  
Vol 21 (5) ◽  
pp. 1005-1009
Author(s):  
Michael A Fishman ◽  
Ashley Scherer ◽  
Jacob Topfer ◽  
Philip S H Kim

Abstract Importance Buprenorphine is a Schedule III analgesic that is recommended as the firstline long-acting opioid for the treatment of chronic pain due to its ceiling effect on respiratory depression, adverse effect profile, and analgesic efficacy. However, prescription drug coverage policies commonly require that patients try and fail multiple Schedule II conventional opioids before approval of on-label use of buprenorphine for chronic pain. Design A retrospective review was performed looking at coverage of buprenorphine in the forms of Butrans and Belbuca. Patient denial letters, web searches of insurance and pharmacy benefit managers (PBMs), and an online tool (formularylookup.com) were used to assess the coverage and availability of buprenorphine for chronic pain. Results Unrestricted access to Butrans was reported for 42% of commercial lives and 11% of Medicare lives in all locations. Unrestricted access to Belbuca was reported for 53% of commercial lives and 23% of Medicare lives in all locations. Oxycodone immediate-release has unrestricted access for 84% of commercial plans and 97% of Medicare plans. Morphine extended-release has unrestricted access for 62% of commercial lives and 65% of Medicare lives. Conclusions and Relevance There are >17,000 prescription opioid–involved deaths each year in the United States. By substituting buprenorphine as the firstline treatment for chronic and even acute pain, there may be fewer prescribed conventional opioids in the United States. Schedule III buprenorphine formulations for chronic pain should be given unrestricted access for appropriate patients before considering a Schedule II opioid as a public health priority.


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