Extended-release Opioids Research Articles

Controlled Substance Prescribing Patterns--Prescription Behavior Surveillance System, Eight States, 2013.

Drug overdose is the leading cause of injury death in the United States. The death rate from drug overdose in the United States more than doubled during 1999-2013, from 6.0 per 100,000 population in 1999 to 13.8 in 2013. The increase in drug overdoses is attributable primarily to the misuse and abuse of prescription drugs, especially opioid analgesics, sedatives/tranquilizers, and stimulants. Such drugs are prescribed widely in the United States, with substantial variation by state. Certain patients obtain drugs for nonmedical use or resale by obtaining overlapping prescriptions from multiple prescribers. The risk for overdose is directly associated with the use of multiple prescribers and daily dosages of >100 morphine milligram equivalents (MMEs) per day. 2013. The Prescription Behavior Surveillance System (PBSS) is a public health surveillance system that allows public health authorities to characterize and quantify the use and misuse of prescribed controlled substances. PBSS began collecting data in 2012 and is funded by CDC and the Food and Drug Administration. PBSS uses standard metrics to measure prescribing rates per 1,000 state residents by demographic variables, drug type, daily dose, and source of payment. Data from the system can be used to calculate rates of misuse by certain behavioral measures such as use of multiple prescribers and pharmacies within specified time periods. This report is based on 2013 de-identified data (most recent available) that represent approximately one fourth of the U.S. Data were submitted quarterly by prescription drug monitoring programs (PDMPs) in eight states (California, Delaware, Florida, Idaho, Louisiana, Maine, Ohio, and West Virginia) that routinely collect data on every prescription for a controlled substance to help law enforcement and health care providers identify misuse or abuse of such drugs. In all eight states, opioid analgesics were prescribed approximately twice as often as stimulants or benzodiazepines. Prescribing rates by drug class varied widely by state: twofold for opioids, fourfold for stimulants, almost twofold for benzodiazepines, and eightfold for carisoprodol, a muscle relaxant. Rates for opioids and benzodiazepines were substantially higher for females than for males in all states. In most states, opioid prescribing rates peaked in either the 45-54 years or the 55-64 years age group. Benzodiazepine prescribing rates increased with age. Louisiana ranked first in opioid prescribing, and Delaware and Maine had relatively high rates of use of long-acting (LA) or extended-release (ER) opioids. Delaware and Maine ranked highest in both mean daily opioid dosage and in the percentage of opioid prescriptions written for >100 MMEs per day. The top 1% of prescribers wrote one in four opioid prescriptions in Delaware, compared with one in eight in Maine. For the five states whose PDMPs collected the method of payment, the percentage of controlled substance prescriptions paid for in cash varied almost threefold, and the percentage paid by Medicaid varied sixfold. In West Virginia, for 1 of every 5 days of treatment with an opioid, the patient also was taking a benzodiazepine. Multiple-provider episode rates were highest in Ohio and lowest in Louisiana. This report presents rates of population-based prescribing and behavioral measures of drug misuse in the general population that have not been available previously for comparison among demographic groups and states. The higher prescribing rates for opioids among women compared with men are consistent with a higher self-reported prevalence of certain common types of pain, such as lower back pain among women. The trend in opioid prescribing rates with age is consistent with an increase in the prevalence of chronic pain with age, but the increasing prescribing rates of benzodiazepines with age is not consistent with the fact that anxiety is most common among persons aged 30-44 years. The variation among states in the type of opioid or benzodiazepine of choice is unexplained. Most opioid prescribing occurs among a small minority of prescribers. Most of the prescriptions by top-decile prescribers probably are written by general, family medicine, internal medicine, and midlevel practitioners. The source of payment varied by state, for reasons that are unclear. Persons who are prescribed opioids also are commonly prescribed benzodiazepine sedatives despite the risk for additive depressant effects. States can use their prescription drug monitoring programs to generate population-based measures for the prescribing of controlled substances and for behaviors that suggest their misuse. Comparing data with other states and tracking changes in these measures over time can be useful in measuring the effect of policies designed to reduce prescription drug misuse.

Abuse-deterrent formulations: transitioning the pharmaceutical market to improve public health and safety.

We read with great interest the article entitled ‘Abuse-deterrent formulations: transitioning the pharmaceutical market to improve public health and safety’ by Simon and colleagues, published in the April 2015 Issue of Therapeutic Advances in Drug Safety [Simon et al. 2015]. We agree with the authors that Federal abuse-deterrent formulation (ADF) policy does not reflect the urgency of the prescription drug abuse epidemic and does not go far enough toward changing the status quo. We also agree with the authors that policies must also require federal prescription drug benefit plans to cover ADFs to ensure consumers have access to such medications. However, we disagree with the statement ‘ADFs have been proven to reduce prescription drug abuse and its consequences, and even an incremental reduction in abuse can have a significant impact on the nation by reducing the costly social, physical, mental, and public health problems resulting from abuse’. The study by Coplan and colleagues [Coplan et al. 2013] was quoted as the main reference to support the argument by Simon and colleagues that ‘ADF have been proven to reduce prescription drug abuse and its consequences…’. However, in the study by Coplan and colleagues, what was additionally reported was a 20% increase in abuse exposure for other single-entity oxycodone, and 42% increase in abuse exposure for heroin, concomitant with the 36% decrease in abuse exposure for reformulated extended-release (ER) oxycodone (ADF). Coplan and colleagues also acknowledged that reformulating one product’s tablets will not treat opioid addiction, and substitution of other available opioids is likely to consequently occur. Michna and colleagues examined the degree of adherence to the ER opioid, following its switching to a reformulated ER opioid (ADF), and found some patients changed to other ER opioids without abuse-deterrent technology or discontinued ER opioids [Michna et al. 2014]. The conclusion of their study was that abusers may seek more easily abusive alternatives. These include prescription opioids without abuse deterrent technology. Preliminary data suggest that the reformulation of opioids to resist tampering may influence media attention, recreational user preferences, and opioid availability in ways that may in turn alter their attractiveness to recreational users [Romach et al. 2013]. ER oxymorphone abuse has been mentioned in popular media only since recreational users began to recognize it as an alternative to the reformulation of ER oxycodone (ADF), which is designed to be tamper-resistant. Increased public awareness of higher potency with oxymorphone ER and the difficulties of tampering with reformulated ER oxycodone may have lessened abuse of ER oxycodone and made ER oxymorphone a preferred choice for some recreational users [Romach et al. 2013]. Indeed, total oxymorphone prescriptions increased sharply from 268,000 in 2007 to 1.22 million in 2012. In the first quarter of 2011, 325,000 oxymorphone prescriptions were dispensed by retail pharmacies [Drug Enforcement Administration, 2013]. According to the Drug Abuse Warning Network (DAWN ED), total estimated emergency department visits associated with oxymorphone increased from 4599 in 2010 to 12,122 in 2011. The American Association of Poison Control Centers reported 1041 total oxymorphone exposures in 2011, an increase from 169 in 2010 [Drug Enforcement Administration, 2013]. To examine the change in prevalence of prescription opioid abuse after introduction of an abuse-deterrent formulation oxycodone ER in August 2010, Cassidy and colleagues conducted a cross-sectional study, and found significantly greater abuse of oxymorphone ER and buprenorphine, coinciding with the introduction of ADF oxycodone ER [Cassidy et al. 2014]. Cassidy and colleagues conclude that replacement of a widely prescribed opioid with ADF formulation may have had little effect on overall prescription opioid abuse as a class. Another issue of great concern is escalating heroin abuse since the introduction of reformulated ER oxycodone (ADF) to the market. There were 119,000 total users in 2003, but 281,000 by 2011. In addition, first-time past-year use nearly doubled between 2005 and 2011. The death rate of heroin overdose from the 28 states (surveyed) doubled, from 2010 to 2012, from 1.0 to 2.1 per 100,000 [Rudd et al. 2014]. Heroin overdose death rates increased significantly for both sexes, all age groups, all census regions, and all racial/ethnic groups other than American Indians/Alaska Natives. In conclusion, at this point, the introduction of ADF opioids has resulted in significantly reduced abuse of those specific ADF opioids after they have fully replaced the original formulations. However, this has resulted in merely a shift away from the ADF opioids to other traditional non-ADF opioids or heroin, and unfortunately, no effect on the overall rates of opioid abuse.

PSY64 - Treatment patterns among Chronic users of immediate-release Oxycodone initiating treatment with extended-release Opioids

PSY64 - Treatment patterns among Chronic users of immediate-release Oxycodone initiating treatment with extended-release Opioids

A Retrospective Cohort Study of Long-Term Immediate-Release Hydrocodone/Acetaminophen Use and Acetaminophen Dosing Above the Food and Drug Administration Recommended Maximum Daily Limit Among Commercially Insured Individuals in the United States (2008–2013)

Immediate-release (IR) hydrocodone/acetaminophen is the most prescribed opioid in the United States; however, patterns of use, including long-term treatment and dose, are not well described. Duration of use, including the percentage of patients on long-term treatment (>90 days of continuous use), was assessed for patients newly prescribed IR hydrocodone/acetaminophen compared to other opioid analgesics in a national commercial insurance database (January 2008–September 2013). Though only a small percentage of IR hydrocodone/acetaminophen patients continued treatment long-term (1.7%), the number was large (104,839) and was nearly 5 times the number receiving extended-release (ER) morphine (n = 22,338) and nearly 4 times the number receiving ER oxycodone (n = 26,946) long-term. Using a less conservative allowable gap in treatment increased the number of patients meeting the criteria for long-term use (approximately 160,000 for IR hydrocodone/acetaminophen vs <30,000 for ER morphine and ER oxycodone). Most patients meeting these criteria received IR hydrocodone doses between >20 and ≤60 mg/d (n = 56,220, 53.6%) in month 4; 5.5% (n = 5,743) received doses >60 mg/d. Moreover, approximately 15% of IR hydrocodone/acetaminophen patients (n > 900,000) were prescribed total daily acetaminophen doses exceeding 4 g (the limit recommended by the U.S. Food and Drug Administration) at their initial IR hydrocodone/acetaminophen prescription or any time during therapy. PerspectiveAlthough most patients were prescribed IR hydrocodone/acetaminophen for acute pain, the number of patients prescribed long-term therapy exceeds the number of patients prescribed ER opioids. It is important to consider the benefits and risks inherent with long-term opioid therapy, whether with IR or ER opioids, to ensure safe use of these products.

Extended-Release Opioid Returns to Market

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Review of naloxone safety for opioid overdose: practical considerations for new technology and expanded public access.

Opioid overdose and mortality have increased at an alarming rate prompting new public health initiatives to reduce drug poisoning. One initiative is to expand access to the opioid antidote naloxone. Naloxone has a long history of safe and effective use by organized healthcare systems and providers in the treatment of opioid overdose by paramedics/emergency medicine technicians, emergency medicine physicians and anesthesiologists. The safety of naloxone in a prehospital setting administered by nonhealthcare professionals has not been formally established but will likely parallel medically supervised experiences. Naloxone dose and route of administration can produce variable intensity of potential adverse reactions and opioid withdrawal symptoms: intravenous administration and higher doses produce more adverse events and more severe withdrawal symptoms in those individuals who are opioid dependent. More serious adverse reactions after naloxone administration occur rarely and may be confounded by the effects of other co-intoxicants and the effects of prolonged hypoxia. One component of the new opioid harm reduction initiative is to expand naloxone access to high-risk individuals (addicts, abusers, or patients taking high-dose or extended-release opioids for pain) and their close family or household contacts. Patients or their close contacts receive a naloxone prescription to have the medication on their person or in the home for use during an emergency. Contacts are trained on overdose recognition, rescue breathing and administration of naloxone by intramuscular injection or nasal spraying of the injection prior to the arrival of emergency medical personnel. The safety profile of naloxone in traditional medical use must be considered in this new context of outpatient prescribing, dispensing and treatment of overdose prior to paramedic arrival. New naloxone delivery products are being developed for this prehospital application of naloxone in treatment of opioid overdose and prevention of opioid-induced mortality.

Understanding multiple myeloma

Understanding multiple myeloma

Changes in attentional bias to drug cues and fMRI Stroop with behavioral treatment for cocaine dependence

Changes in attentional bias to drug cues and fMRI Stroop with behavioral treatment for cocaine dependence

Is opioid dose a strong predictor of the risk of opioid overdose? Important confounding factors that change the dose–overdose relationship

Is opioid dose a strong predictor of the risk of opioid overdose? Important confounding factors that change the dose–overdose relationship

Pre-military victimization and trauma among a sample of justice-involved veterans

s / Drug and Alcohol Dependence 146 (2015) e34–e117 e89 Brief guide to prevent overdose fatality for prescription opioid abusers: A harm reduction initiative Lauren E. Sandstrom1, Paul Coplan1, Howard Chilcoat1, Fred W. Brason2, Carl Leukefeld3, Louis A. Morris4 1 Purdue Pharma, Stamford, CT, United States 2 Project Lazarus, Moravian Falls, NC, United States 3 University of Kentucky, Lexington, KY, United States 4 Louis A Morris & Assoc., Dix Hills, NY, United States Aims: Pharmaceutical companies are required by FDA to distribute Medication Guides to patients with each pill bottle of extended-release opioids educating them on safe use. However, a large portion of overdoses occur among abusers without prescriptions. To fill this gap, a 1-page Guide was developed targeted to opioid abusers and friends/families, which provides information to reduce risk of fatal overdose. Methods:Adraft Guidewas developedwith input fromexperts. The draft addressed key risks and effective steps to intervene in 5 areas:What are the risks?What are the signs? How do I respond to an overdose in another person?What increases the risks? Help for drug treatment. Qualitative researchwas conducted usingmultiple diverse focus groups (FG) composed of 8–15daily non-medical opioid users. Phase I focused on version (concise versus detailed) and Phase II focused on participants’ understanding and acceptance of content. Results: Phase I testing determined a concise version was preferred over a detailed one (368 vs. 611words) but some items from the detailed version were considered valuable e.g., list of opioids. Phase II examined a single version of revised content in 2 diverse rural FG in KY and NC. Themes highlighted by both FG included the dangers of mixing drugs and alcohol and increasing doses to get high. The groups differed on preferred order of presentation of content. The recommendation to Call 911 was identified as risky in KY, but not in NC where Good Samaritan legislation was in place. FG participants highlighted key information in the Guide that was learned including <10breaths/minute and snoring as signs of overdose. However, there was strong adherence tomyth or actions that do not work and waste time in overdose response e.g., ice or cold showers. Conclusions: A simple guide to prevent opioid overdose and its consequences was found to be useful and was accepted by nonmedical opioid users. Financial support: Purdue Pharma L.P. http://dx.doi.org/10.1016/j.drugalcdep.2014.09.610 Pre-military victimization and trauma among a sample of justice-involved veterans Leon Sawh1,2,3, Debra A. Pinals4,2, David Smelson1,2, Carl Fulwiler2, Stephanie Singer2, Kathryn O’Connor2, William Fisher3, Stephanie Hartwell5, Gerardo Gonzalez2 1 Department of Veterans Affairs, Bedford, MA, United States 2 University of Massachusetts Medical School, Worcester, MA, United States 3 University of Massachusetts Lowell, Lowell, MA, United States 4 Massachusetts Department of Mental Health, Boston, MA, United States 5 University of Massachusetts Boston, Boston, MA,

Brief guide to prevent overdose fatality for prescription opioid abusers: A harm reduction initiative

s / Drug and Alcohol Dependence 146 (2015) e34–e117 e89 Brief guide to prevent overdose fatality for prescription opioid abusers: A harm reduction initiative Lauren E. Sandstrom1, Paul Coplan1, Howard Chilcoat1, Fred W. Brason2, Carl Leukefeld3, Louis A. Morris4 1 Purdue Pharma, Stamford, CT, United States 2 Project Lazarus, Moravian Falls, NC, United States 3 University of Kentucky, Lexington, KY, United States 4 Louis A Morris & Assoc., Dix Hills, NY, United States Aims: Pharmaceutical companies are required by FDA to distribute Medication Guides to patients with each pill bottle of extended-release opioids educating them on safe use. However, a large portion of overdoses occur among abusers without prescriptions. To fill this gap, a 1-page Guide was developed targeted to opioid abusers and friends/families, which provides information to reduce risk of fatal overdose. Methods:Adraft Guidewas developedwith input fromexperts. The draft addressed key risks and effective steps to intervene in 5 areas:What are the risks?What are the signs? How do I respond to an overdose in another person?What increases the risks? Help for drug treatment. Qualitative researchwas conducted usingmultiple diverse focus groups (FG) composed of 8–15daily non-medical opioid users. Phase I focused on version (concise versus detailed) and Phase II focused on participants’ understanding and acceptance of content. Results: Phase I testing determined a concise version was preferred over a detailed one (368 vs. 611words) but some items from the detailed version were considered valuable e.g., list of opioids. Phase II examined a single version of revised content in 2 diverse rural FG in KY and NC. Themes highlighted by both FG included the dangers of mixing drugs and alcohol and increasing doses to get high. The groups differed on preferred order of presentation of content. The recommendation to Call 911 was identified as risky in KY, but not in NC where Good Samaritan legislation was in place. FG participants highlighted key information in the Guide that was learned including <10breaths/minute and snoring as signs of overdose. However, there was strong adherence tomyth or actions that do not work and waste time in overdose response e.g., ice or cold showers. Conclusions: A simple guide to prevent opioid overdose and its consequences was found to be useful and was accepted by nonmedical opioid users. Financial support: Purdue Pharma L.P. http://dx.doi.org/10.1016/j.drugalcdep.2014.09.610 Pre-military victimization and trauma among a sample of justice-involved veterans Leon Sawh1,2,3, Debra A. Pinals4,2, David Smelson1,2, Carl Fulwiler2, Stephanie Singer2, Kathryn O’Connor2, William Fisher3, Stephanie Hartwell5, Gerardo Gonzalez2 1 Department of Veterans Affairs, Bedford, MA, United States 2 University of Massachusetts Medical School, Worcester, MA, United States 3 University of Massachusetts Lowell, Lowell, MA, United States 4 Massachusetts Department of Mental Health, Boston, MA, United States 5 University of Massachusetts Boston, Boston, MA,

Long- and short-acting opioids in cancer pain management: What is the best ratio?

206 Background: Many cancer patients experience chronic and breakthrough pain necessitating the use of both immediate release (IR) and extended release (ER) opioids. The common strategy in treating chronic cancer pain is using ER opioids with the addition of IR opioids for breakthrough pain. The National Comprehensive Cancer Network recommends IR dosing at 0.1-0.2 times the daily ER dose as needed every 1 hour for breakthrough pain, though data is lacking to validate this recommendation. The aim of this exploratory study was to review the current practice in prescribing IR and ER opioids and the IR/ER ratio used in cancer pain management at one comprehensive cancer center (CCC). Methods: We performed a retrospective chart review of 54 consecutive patients at a CCC over a 6 month period. IR/ER doses, dose adjustments and satisfaction with analgesia were recorded. Adjustments in treatment plans were made based on patients' report of effectiveness and side effects associated with ER and IR opioids. Results: 19 of 54 (35%) patients reported adequate analgesia, with the average daily prescribed IR/ER ratio of 0.6 (range 0 to 3.75). In this group, IR opioids were unchanged during the clinic visit. The ER opioids, on average, were also unchanged, though decreased by 25% and increased by 50% in a few cases over serial clinic visits. Of those patients reporting suboptimal analgesia during the clinic visit (65%), 80% had their ER opioids increased, 6% had IR opioids increased, and 9% had both IR and ER increased. The ER opioids were increased by 40% on average and IR by 11% with the average IR/ER ratio changing from 0.5 (range 0-2) to 0.37 (range 0-1.13). Conclusions: These preliminary data highlight the great variability between patient preferences and clinician decisions in terms of IR/ER opioid ratios. In this retrospective study, analgesia was better in the group using higher IR doses with a higher IR/ER ratio. At the same time, patients with suboptimal analgesia had their ER opioids titrated faster and higher than the IR opioids. More studies are needed to determine best practice in the prescribing of long and short acting opioids for management of chronic cancer pain.

A multicenter, 12-month, open-label, single-arm safety study of oxycodone-hydrochloride/naltrexone-hydrochloride extended-release capsules (ALO-02) in patients with moderate-to-severe chronic noncancer pain

To evaluate the long-term safety of oxycodone-hydrochloride and sequestered naltrexone-hydrochloride (ALO-02) administered for up to 12 months. Open-label, single-arm safety study. Thirty-two US research centers (ClinicalTrials.gov identifier NCT01428583). Three hundred ninety-five adults (opioid experienced and opioid naïve) with moderate-to-severe chronic noncancer pain (CNCP). Open-label, oral ALO-02 capsules, daily dose ranging from 20 to 160 mg oxycodone for up to 12 months. Number and type of adverse events (AEs) and drugrelated AEs, including assessments of withdrawal (Clinical Opiate Withdrawal Scale; COWS), pharmacokinetics, efficacy, and aberrant behaviors (Current Opioid Misuse Measure). A total of 193 (48.9 percent) patients received ALO-02 for ≥181 days and 105 (26.6 percent) patients for ≥361 days. The most common treatment-emergent AEs were nausea (25.3 percent), constipation (21.3 percent), vomiting (13.9 percent), and headache (11.6 percent). The most common drug-related AEs were constipation (18.0 percent), nausea (14.9 percent), somnolence (8.4 percent), fatigue (6.8 percent), dizziness (5.6 percent), and vomiting (5.1 percent). A majority of patients (86.6 percent) had a maximum COWS total score below the level for mild withdrawal symptoms at every visit throughout the study. Pain severity scores as measured by the short Form of the Brief Pain Inventory (BPI-SF) decreased over time. Repeat dosing of ALO-02 for up to 12 months is safe and well tolerated in a CNCP population of both opioid-experienced and opioid-naïve patients. ALO-02 demonstrated a safety profile consistent with extended-release opioids and the expected analgesic efficacy. The addition of sequestered naltrexone had no significant clinical effect on patients when taken as directed.

The US FDA Draft Guidance for Developing Abuse-Deterrent Opioid Analgesics: 2014 and Beyond

Prescription medication abuse, particularly of opioids, remains a serious public health problem. Many socioeconomic and healthcare system factors have contributed to the resulting epidemic of prescription opioid abuse. As the scope of this epidemic became evident, efforts to make abuse-deterrent formulations (ADFs) began, and many ADFs are under development. In January 2013, the US Food and Drug Administration (FDA) issued a Draft Guidance outlining the categories of studies needed for evaluating the abuse-deterrent properties of ADF opioids (e.g., pre-market in vitro, pharmacokinetic and abuse potential studies, and post-marketing studies) and the four potential label claims that might be made about the products. Studies to be conducted are those required for approval, those that might be included as data in the label (implicit claims), and those that would be required to merit a specific explicit claim—Tier 1, 2, 3, or 4. In the context of the Guidance, new ADFs need to consider the unique features of their technology, market size, comparator products, actual routes and methods of abuse, the targeted health consequences of abuse, pricing and reimbursement, the impact of other interventions to decrease abuse, and the challenges in doing post-market studies. ADFs will not stop prescription opioid drug abuse; however, easily tampered formulations should not contribute to the problem. All extended-release (ER) opioids and other abusable drugs should have abuse-deterrent properties. Immediate-release (IR) opioids should also be formulated with abuse-deterrent properties, because abuse of IR opioids is a more common and serious problem than that of ER opioids. Maximum dosage strengths of ER opioids should also be limited. Finally, the current situation, where non-abuse-deterrent ER opioids exist concurrently on the market is extremely problematic from a public health policy perspective.

Societal economic benefits associated with an extended-release opioid with abuse-deterrent technology in the United States.

Common chronic pain conditions affect approximately 100 million U.S. adults and result in costs of $560–635 billion annually in direct medical treatment costs and lost productivity [1]. In addition, pain is a common cause of disability in the United States [2]. The Food and Drug Administration (FDA) has noted that prescription opioids (RxOs) are an important component of modern pain management [3]. At the same time, the agency has acknowledged that RxO abuse is a serious public health problem. The National Survey on Drug Use and Health (NSDUH) reported that 1.8 million of the U.S. population ages 12 and up had prescription painkiller abuse or dependence in 2011 [4]. In 2007, RxO abuse accounted for an estimated $55.7 billion (US$ 2009) in annual societal costs in the United States [5]. These costs include health care, workplace, and criminal justice costs. Extended-release opioids (EROs) provide a longer period of drug release and can thus be taken less frequently than immediate-release opioids [6]. However, EROs can be manipulated and tampered with in an attempt to overcome their extended-release properties. Because of their higher drug dosages, EROs may be more attractive to some abusers than immediate-release formulations [7]. Manufacturers of EROs have attempted to address the problem of RxO abuse by developing formulations with abuse-deterrent properties. For example, reformulated extended-release oxycodone HCl with abuse-deterrent technology (reformulated ER oxycodone) was introduced in August 2010 and replaced the original formulation of ER oxycodone without abuse-deterrent technology. Several studies have examined the impact of reformulated ER oxycodone among abusers. A study on the attractiveness of reformulated ER oxycodone relative to other opioid formulations among recreational opioid abusers found that reformulated ER oxycodone was rated the least attractive, least valuable, least desirable, and least likely to be tampered with among …

Consequences of patient access restrictions to branded oxycodone hydrochloride extended-release tablets on healthcare utilization and costs in US health plans

Objective:To evaluate the impact of increased access restrictions to branded oxycodone hydrochloride extended-release tablets (oxycodone HCl ER), on healthcare utilization and costs in patients using extended-release and long-acting opioids (ER/LA opioids) from the health plan perspective during the period from 1/1/2009 to 6/30/2012.Methods:This retrospective cohort study analyzed claims data for adult patients from US plans that increased oxycodone HCl ER access restrictions. Study groups were segmented into commercial and Medicare payers, and by prior authorization (PA) and tier change (TC) restrictions. Six-month outpatient visits and prescription utilization and costs were evaluated during the pre- and post-access restriction periods using a bootstrapped t-test and regression to test the differences.Results:Mean 6-month post-restriction combined pharmacy and outpatient visit costs were $1131 (p < 0.001), $660 (p = 0.009), $699 (p < 0.001), and $564 (p < 0.001) higher than pre-restriction costs in commercial PA, commercial TC, Medicare PA, and Medicare TC groups, respectively. Outpatient visits accounted for the greatest proportion of increased costs in the access restriction groups.Conclusions:The results of this study suggest that oxycodone HCl ER access restrictions such as PA and TC may increase medical costs without an offsetting savings in pharmacy costs.

(453) The risk of cardiovascular events in opioid agonist/antagonist combination products compared to other ER opioids

There have been theoretical concerns that opioid antagonists used in combination with opioid agonists might precipitate opioid withdrawal and thus increase the risk of cardiovascular (CV) events. However, there is little literature to support or refute this. The objective of this study was to estimate and compare incidence rates for CV events (stratified as any ischemic CV events and major CV events) among patients prescribed the opioid agonist/antagonist combination extended-release (ER) oxycodone-naloxone (OXN) vs.

Medical cost savings associated with an extended-release opioid with abuse-deterrent technology in the US

Objectives:In the US, prescription opioids with technology designed to deter abuse have been introduced to deter drug abuse without hindering appropriate access for pain patients. The objective of this study was to estimate changes in medical costs following the introduction of a new formulation of extended-release (ER) oxycodone HCl (oxycodone) with abuse-deterrent technology in the US.Methods:Health insurance claims data were used to estimate changes in rates of diagnosed opioid abuse among continuous users of extended-release opioids (EROs) following the introduction of reformulated ER oxycodone in August 2010. This study also calculated the excess medical costs of diagnosed opioid abuse using a propensity score matching approach. These findings were integrated with published government reports and literature to extrapolate the findings to the national level. All costs were inflated to 2011 US dollars.Results:The introduction of reformulated ER oxycodone was associated with relative reductions in rates of diagnosed opioid abuse of 22.7% (p < 0.001) and 18.0% (p = 0.034) among commercially-insured and Medicaid patients, respectively. There was no significant change among Medicare-eligible patients. The excess annual per-patient medical costs associated with diagnosed opioid abuse were $9456 (p < 0.001), $10,046 (p < 0.001), and $11,501 (p < 0.001) for commercially-insured, Medicare-eligible, and Medicaid patients, respectively. Overall, reformulated ER oxycodone was associated with annual medical cost savings of ∼$430 million in the US.Limitations:Because of the observational research design of this study, caution is warranted in any causal interpretation of the findings. Portions of the study relied on prior literature, government reports, and assumptions to extrapolate the national medical cost savings.Conclusions:This study provides evidence that reformulated ER oxycodone has been associated with reductions in abuse rates and substantial medical cost savings. Payers and policy-makers should consider these benefits as they devise and implement new guidelines and policies in this therapeutic area.

Changes in Prevalence of Prescription Opioid Abuse after Introduction of an Abuse-Deterrent Opioid Formulation

The reformulation of oxycodone hydrochloride controlled-release (CR) tablets in August 2010 created a natural experiment at a national scale, providing an opportunity to evaluate patterns of abuse of prescription opioids and other drugs before and after introduction of this abuse-deterrent formulation (ADF). Observational, cross-sectional study Sentinel sample of adults assessed for substance abuse treatment within the NAVIPPRO® surveillance system Two hundred thirty-two thousand and eight hundred seventy-four adults at 437 facilities during January 1, 2008 through December 31, 2011. Time-series analysis using logistic regression to estimate quarterly prevalence of past 30-day abuse (adjusted for covariates and prescription volume) and changes in abuse pre-and post-ADF introduction. Increases in abuse prevalence occurred for all prescription opioids as a class and for extended-release (ER) opioids. Significantly greater abuse of ER oxymorphone and buprenorphine occurred in the post-ADF period (relative risk [RR] = 2.91, 95% confidence interval [CI] = 2.59-3.27 and RR = 1.85, 95% CI = 1.74-1.96). Increases in abuse for these two compounds were significant among groups who reported abuse via preferential routes of administration (oral only, snorting only, injection only) post-ADF introduction. Replacement of a widely prescribed opioid formulation known for its abuse potential alone may have had little impact on overall rates of prescription opioids as a class. However, changes in abuse levels of certain opioids coinciding with ADF introduction suggest possible switching of abuse among this study sample to specific long-acting opioid analgesics. Additional follow-up studies will be important to monitor changing abuse patterns and their public health impact as new opioid formulations are developed and introduced to market.

Prescription histories and dose strengths associated with overdose deaths.

Misuse, abuse, and diversion of prescription drugs are large and growing public health problems that have resulted in an overdose epidemic. We investigated whether short-acting or extended-release opioids were more frequently prescribed to those who died of an overdose and whether there was a linear relationship between dose strength and associated overdose deaths. The study population was North Carolina residents in 2010. We conducted a retrospective, population-based, descriptive study of medication histories of overdose decedents using data from vital statistics, medical examiner records, and a prescription drug monitoring program. Unintentional or undetermined drug overdoses were responsible for 892 deaths. Out of 191 deaths involving methadone, only two were patients in opioid treatment programs. Immediate-release oxycodone was involved in the greatest number of opioid-related deaths. Out of 221 oxycodone deaths, 134 (61%) of the decedents filled a prescription for oxycodone in the 60 days prior to death. The most common strength dispensed within 60 days to a decedent who died of an oxycodone overdose was 10 mg for immediate-release (72 prescriptions). Immediate-release oxycodone products (rho = 1.00, P < 0.01) and extended-release fentanyl products (rho = 1.00, P < 0.01) showed strong increasing linear trends between dose strength and proportion of prescriptions dispensed to decedents. A significant proportion of overdose decedents had been prescribed the same type of drugs that contributed to their death, especially for decedents who died from overdoses involving oxycodone, hydrocodone, and alprazolam. Higher dose strengths for certain opioids had higher associated mortality, and certain immediate-release opioids may be considered for public health prevention efforts.