oxymorphone and Opioid-Related-Disorders

The United States Food and Drug Administration is tasked with ensuring the efficacy and safety of medications marketed in the United States. One of their primary responsibilities is to approve the entry of new drugs into the marketplace, based on the drug's perceived benefit-risk relationship. The Anesthetic and Analgesic Drug Product Advisory Committee is composed of experts in anesthesiology, pain management, and biostatistics, as well as consumer and industry representatives, who meet several times annually to review new anesthetic-related drugs, those seeking new indications, and nearly every opioid-related application for approval. The following report describes noteworthy activities of this committee since 2017, as it has grappled, along with the Food and Drug Administration, to balance the benefit-risk relationships for individual patients along with the overarching public health implications of bringing additional opioids to market. All anesthesia advisory committee meetings since 2017 will be described, and six will be highlighted, each with representative considerations for potential new opioid formulations or local anesthetics.

Topics: Advisory Committees; Analgesics; Analgesics, Opioid; Anesthetics; Congresses as Topic; Decision Making; Delayed-Action Preparations; Drug Approval; Humans; Opioid-Related Disorders; Oxymorphone; Spiro Compounds; Thiophenes; United States

Pain among the elderly is pervasive, under-treated and can be properly managed by judiciously using analgesics in the armamentarium. For severe pain, opioids generally provide the most effective pain relief, but concerns about safety and tolerability have limited, often unnecessarily, their utilization in the geriatric population.. It is common for geriatric patients to be taking more than one medicine. Oxymorphone might be particularly well suited for use in geriatric patients, in that its metabolism is mainly through non-CYPP450 pathways, thereby posing less risk of interaction with the many drugs that are metabolized by the CYPP450 system. However, oxymorphone is not as familiar to clinicians as morphine or some other opioids. We review here the clinical studies on oxymorphone to outline the key considerations for use of oxymorphone in the geriatric population.. Nine available clinical trials of oxymorphone alone or comparing oxymorphone with placebo or other active agents were analyzed with respect to the safety and tolerability findings. These studies included geriatric patients but were not designed to evaluate oxymorphone exclusively in this population.. Based on the results from nine published clinical studies, oxymorphone is an effective opioid analgesic with a safety profile at least comparable to other opioid drugs. At low starting doses and individual titration, oxymorphone should be considered for appropriate geriatric patients, particularly in whom there is concern about interaction with drugs that are metabolized by CYPP450 enzymes.

Topics: Aged; Aged, 80 and over; Arthralgia; Biotransformation; Clinical Trials as Topic; Constipation; Drug Interactions; Glucuronosyltransferase; Humans; Liver; Narcotics; Nausea; Neoplasms; Opioid-Related Disorders; Oxymorphone; Pain; Pain, Postoperative; Polypharmacy; Receptors, Opioid, mu; Sleep Stages; Vomiting

Intravenous (IV) misuse of the µ opioid analgesic oxymorphone has caused significant public health harms; however, no controlled data on its IV abuse potential are available. The primary aims of this pilot study were to directly compare IV oxymorphone to IV oxycodone, morphine, and hydromorphone on a subjective measure of drug liking and to assess relative potency.. Participants (n = 6) with opioid use disorder, physical dependence, and current IV use completed this two-site, within-subject, double-blind, placebo-controlled, inpatient pilot study. During each session, one IV dose (mg/70 kg) was administered: oxymorphone (1.8, 3.2, 5.6, 10, 18, 32), hydromorphone (1.8, 3.2, 5.6, 10, 18), oxycodone (18, 32, 56), morphine (18, 32), and placebo. Data were collected before and for 6 h after dosing. Primary outcomes included safety/physiological effects, subjective reports of drug liking, and relative potency estimates.. All active test drugs produced prototypical, dose-related µ opioid agonist effects (e.g., miosis). Oxymorphone was more potent than the comparator opioids on several measures, including drug liking and respiratory depression (p < 0.05). Across abuse-related subjective outcomes, oxymorphone was 2.3-2.8-fold more potent than hydromorphone and 12.5-14-fold more potent than oxycodone (p < 0.05).. Despite the relatively small sample size, this pilot study detected robust oxymorphone effects. Oxymorphone was far more potent than the comparator opioids, particularly on abuse potential outcomes. Overall, these findings may help explain surveillance reports that demonstrate, after adjusting for prescription availability, oxymorphone is injected at the highest frequency, relative to other prescription opioids.

Topics: Analgesics, Opioid; Humans; Opioid-Related Disorders; Oxycodone; Oxymorphone; Pilot Projects

Oxymorphone is a semisynthetic μ-opioid agonist, marketed as a prescription analgesic purported to be twice as potent as oxycodone for pain relief. Oral formulations of oxymorphone were reintroduced in the United States in 2006 and reports of abuse ensued; however, there are limited data available on its pharmacodynamic effects. The current study aimed to examine the direct physiologic effects, relative abuse liability, analgesic profile and overall pharmacodynamic potency of oxymorphone in comparison with identical doses of oxycodone. Healthy, non-dependent opioid abusers (n = 9) were enrolled in this within-subject, double-blind, placebo-controlled, 3-week inpatient study. Seven experimental sessions (6.5 hours) were conducted, during which an oral dose of immediate-release formulations of oxymorphone (10, 20 and 40 mg), oxycodone (10, 20 and 40 mg) or placebo was administered. An array of physiologic, abuse liability and experimental pain measures was collected. At identical doses, oxymorphone produced approximately twofold less potent effects on miosis, compared with oxycodone. Oxymorphone also produced lesser magnitude effects on measures of respiratory depression, two experimental pain models and observer-rated agonist effects. However, 40 mg of oxymorphone was similar to 40 mg of oxycodone on several abuse-related subjective ratings. Formal relative potency analyses were largely invalid because of the substantially greater effects of oxycodone. Overall, oxymorphone is less potent on most pharmacodynamic measures, although at higher doses, its abuse liability is similar to oxycodone. These data suggest that the published clinical equianalgesic estimates may not be consistent with the observed direct physiologic effects of opioids, results of experimental pain models or abuse liability measures, as assessed in the human laboratory.

Topics: Administration, Oral; Adult; Analgesics, Opioid; Blood Pressure; Cognition; Cold Temperature; Cross-Over Studies; Double-Blind Method; Female; Heart Rate; Humans; Male; Opioid-Related Disorders; Oxymorphone; Pain; Pain Measurement; Pressure

Urine drug testing (UDT) monitors prescription compliance and/or drug abuse. However, interpretation of UDT results obtained by liquid chromatography-tandem mass spectrometry (LC-MS-MS) can be complicated by the presence of drug impurities that are detected by highly sensitive methods. Hydrocodone is a drug impurity that can be found as high as 1% in oxycodone pills.. We evaluated the frequency and concentration of hydrocodone and its metabolite, hydromorphone, in patients taking oxycodone to check if the ratio of hydrocodone or hydromorphone to oxycodone could distinguish between oxycodone only use from those consuming additional opiates.. We correlated LC-MS/MS results with medication records of 319 patients with positive oxycodone results over 7 months (4/2021-11/2021).. Fifteen of 319 patients with positive oxycodone results were taking oxycodone only. For these 15 patients, the mean ratio of hydrocodone to oxycodone was 0.57% (range 0.05%-3.35%), and the mean ratio of hydromorphone to oxycodone was 0.81% (range 0.18-3.51%).. Hydrocodone and/or hydromorphone are detectable in patients taking only oxycodone and can likely be identified as an impurity if their calculated ratio to oxycodone is <1 %. Further validation of the ratios in a larger sample size is recommended.

Topics: Analgesics, Opioid; Chromatography, Liquid; Humans; Hydrocodone; Hydromorphone; Opioid-Related Disorders; Oxycodone; Oxymorphone; Tandem Mass Spectrometry

While the current landscape of opioid use disorder (OUD) is complicated by the increase in use of non-prescription opioids, prescription opioids continue to be frequently used in non-medical ways. In response to this abuse, pharmaceutical companies have developed abuse deterrent formulations (ADFs) for extended-release (ER) opioids. To test the effectiveness of Xtampza ER ADF (oxycodone myristate) at reducing tampering, its rate of tampering in a treatment-center population was compared to immediate release (IR) single entity (SE) oxycodone, other ER oxycodone opioids, and ER oxymorphone.. Data were collected between the third quarter of 2018 and the third quarter of 2021 from individuals entering nationally distributed opioid treatment programs. To determine odds of tampering with Xtampza ER compared to each comparator, a logistic model was fit with a random intercept allowing for multiple drugs in each subject. Within-subject correlation was assumed to have a compound symmetric relationship.. Overlap among the categories of drug tampering was high. Logistic regression analyses found that oxycodone myristate had lower odds of tampering when compared to both IR SE oxycodone (OR = 0.23 [95% CI 0.11, 0.50], p = 0.0002) and ER oxymorphone (OR = 0.30 [95% CI 0.14, 0.67], p = 0.0038). Oxycodone myristate was not significantly different from other ER oxycodone opioids (OR = 0.5 [95% CI 0.24, 1.03], p = 0.0612). These findings did not change when the estimates were adjusted for age and sex.. Drugs employing ADF technology may reduce the likelihood of tampering when compared to non-ADF formulations in a treatment-center population, which represents an opportunity for intervention in OUD among those still requiring pain management.

Topics: Abuse-Deterrent Formulations; Analgesics, Opioid; Cross-Sectional Studies; Delayed-Action Preparations; Humans; Opioid-Related Disorders; Oxycodone; Oxymorphone

Diverted prescription opioids are significant contributors to drug overdose mortality. Street price has been suggested as an economic metric of the diverted prescription opioid black market. This study examined variables that may influence the street price of diverted oxycodone and oxymorphone.. A cross-sectional study was conducted utilizing data from the previously validated, crowdsourcing website StreetRx. Street price reports of selected oxycodone and oxymorphone products, between August 22, 2014 and June 30, 2016, were considered for analysis. Geometric means and 95% confidence intervals were calculated comparing prices per milligram of drug in US dollars. Univariate and multivariable regressions were used to examine the influence of dosage strength, drug formulation, and bulk purchasing on street price.. A total of 5611 oxycodone and 1420 oxymorphone reports were analyzed. Across various dosages and formulations, geometric mean prices per milligram ranged between $0.12 and $1.07 for oxycodone and $0.73 and $2.90 for oxymorphone. For a 2-fold increase in dosage strength, there is a 24.0% (95% CI: -28.1%, -19.6%, P < 0.001) and a 22.5% (95% CI: -24.2%, -20.8%, P < 0.001) decrease on average in price per milligram for oxycodone and oxymorphone, respectively. Lower potency, high dosage strength, crush-resistant opioids, and those purchased in bulk were significantly cheaper.. Street prices for diverted oxycodone and oxymorphone are influenced by multiple factors including potency, dosage, formulation, and bulk purchasing. Buyers who purchase large quantities of low potency, large dosage, crush-resistant formulation prescription opioids can expect to achieve the lowest price.

Topics: Commerce; Cross-Sectional Studies; Drug Overdose; Humans; Illicit Drugs; Narcotics; Opioid-Related Disorders; Oxycodone; Oxymorphone; Prescription Drug Diversion; Prospective Studies; United States

Prescription opioid abuse poses a serious problem in the United States, representing 615 per 100 000 deaths annually. Extended-release oxymorphone (Opana-ER) is an oral opioid pain medication that has recently been found to cause thrombotic microangiopathy when intravenously abused. In this retrospective study, we attempted to determine the prevalence and outcomes of acute kidney injury (AKI) among patients intravenously abusing extended-release oral oxymorphone.. A query of electronic medical records for 'drug abuse' at an academic medical centre during January 2012 to December 2015 was performed and yielded 2350 patients. Patients were further identified by documented intravenous abuse of extended-release oxymorphone. Patients were stratified based on multiple renal indices and outcomes. Potential confounders were also identified.. One hundred and sixty-five patients were found to have a documented history of intravenous abuse of extended-release oral oxymorphone. Prevalence of AKI in this population was a 47.8%. KDIGO stage-I patients consisted of 17.8% of patients with AKI, 40.5% were classified as KDIGO stage-II AKI, and 41.8% were classified as KDIGO stage-III AKI. Among patients with AKI, average age was found to be 37.5 years, 59.4% experienced renal recovery, 56.9% required intensive care unit admission, 13.9% progressed to end-stage renal disease (ESRD), and 7.6% expired during admission.. Clinicians should be educated to help recognize intravenous abuse of extended-release oral oxymorphone and its associated effects. Our data suggests AKI is common in these patients; higher KDIGO staging appears to be associated with slower rates of renal recovery, increased comorbidities and progression to both CKD and ESRD.

Topics: Acute Kidney Injury; Administration, Oral; Analgesics, Opioid; Comorbidity; Delayed-Action Preparations; Disease Progression; Drug Compounding; Female; Hospital Mortality; Humans; Injections, Intravenous; Kidney; Kidney Failure, Chronic; Male; Middle Aged; North Carolina; Opioid-Related Disorders; Oxymorphone; Prevalence; Recovery of Function; Renal Insufficiency, Chronic; Retrospective Studies; Risk Factors; Substance Abuse, Intravenous; Time Factors

Misuse of prescription opioid analgesics (POA) has increased dramatically in the US, particularly in non-urban areas. We examined injection practices among persons who inject POA in a rural area that experienced a large HIV outbreak in 2015.. Between August-September 2015, 25 persons who injected drugs within the past 12 months were recruited in Scott County, Indiana for a qualitative study. Data from in-depth, semi-structured interviews were analyzed.. We describe a high-risk injection practice that may have contributed to the rapid spread of HIV in this community. Efforts to prevent bloodborne infections among people who inject POA need to assess for MIPIE so that provision of sterile injection equipment and safer injection education addresses the MIPIE risk environment.

Topics: Adult; Analgesics, Opioid; Disease Outbreaks; Female; HIV Infections; Humans; Indiana; Interviews as Topic; Male; Middle Aged; Needle Sharing; Opioid-Related Disorders; Oxymorphone; Risk-Taking; Rural Population; Substance Abuse, Intravenous; Substance-Related Disorders; Syringes; Young Adult

Recent advances in analytical capabilities allowing for the identification and quantification of drugs and metabolites in small volumes at low concentrations have made oral fluid a viable matrix for drug testing. Oral fluid is an attractive matrix option due to its relative ease of collection, reduced privacy concerns for observed collections and difficulty to adulterate. The work presented here details the development and validation of a liquid chromatography tandem mass spectrometry (LC-MS-MS) method for the quantification of codeine, morphine, 6-acetylmorphine, hydrocodone, hydromorphone, oxycodone and oxymorphone in neat oral fluid. The calibration range is 0.4-150 ng/mL for 6-acetylmorphine and 1.5-350 ng/mL for all other analytes. Within-run and between-run precision were <5% for all analytes except for hydrocodone, which had 6.2 %CV between runs. Matrix effects, while evident, could be controlled using matrix-matched controls and calibrators with deuterated internal standards. The assay was developed in accordance with the proposed mandatory guidelines for opioid confirmation in federally regulated workplace drug testing. The use of neat oral fluid, as opposed to a collection device, enables collection of a single sample that can be split into separate specimens.

Topics: Analgesics, Opioid; Calibration; Chromatography, Liquid; Codeine; Humans; Hydrocodone; Hydromorphone; Morphine; Morphine Derivatives; Opioid-Related Disorders; Oxycodone; Oxymorphone; Predictive Value of Tests; Reference Standards; Reproducibility of Results; Saliva; Spectrometry, Mass, Electrospray Ionization; Substance Abuse Detection; Tandem Mass Spectrometry

Drug testing is recommended as part of comprehensive monitoring for medication-assisted treatment. Alternative matrices including oral fluid offer a number of advantages when compared with conventional urine testing but are not as well characterized. This study aims to compare positivity rates of drugs and drug classes in oral fluid and urine as a measure of the clinical utility of oral fluid in the evaluation and treatment of patients with opioid use disorders.. A retrospective review of paired oral fluid and urine test results from Millennium Health's laboratory database was performed for 2746 patients with reported prescriptions for buprenorphine products used in the treatment of opioid dependence. Specimens were tested using quantitative LC-MS/MS for 34 medications, metabolites and illicit drugs.. A number of medications and illicit drugs were detected at comparable or higher rates in oral fluid vs. urine such as cocaine (15.7% vs. 7.9%), opiates (13.4% vs. 10.0%), oxycodone (8.6% vs. 3.7%), hydrocodone (3.0% vs. 1.2%) and others. Lower detection rates were observed in oral fluid vs. urine for benzodiazepines (6.6% vs. 8.7%), cannabinoids (15.5% vs. 19.5%), oxymorphone (1.8% vs. 3.1%) and hydromorphone (0.8% vs. 4.5%).. Clinicians may find oral fluid advantageous for detection of specific drugs and medications in certain clinical situations. Understanding the relative differences between urine and oral fluid can help clinicians carefully select tests best suited for detection in their respective matrix. To our knowledge, this is the largest inter-matrix patient comparison study using paired collections and direct to definitive testing.

Topics: Buprenorphine; Cannabinoids; Chromatography, Liquid; Humans; Hydrocodone; Hydromorphone; Illicit Drugs; Narcotic Antagonists; Opioid-Related Disorders; Oxycodone; Oxymorphone; Retrospective Studies; Saliva; Substance Abuse Detection; Tandem Mass Spectrometry

We describe the case of a 35-year-old man presenting with thrombotic microangiopathy (TMA) and renal impairment following, as he later disclosed, intravenous injection of oral formulation tamper-resistant extended-release oxycodone hydrochloride (Oxycontin). Recurrent misuse of this agent was associated with relapsing TMA despite treatment with terminal complement inhibitor eculizumab. Cases of TMA have been reported in the USA in association with intravenous misuse of extended-release oxymorphone (Opana ER) after the introduction of a new non-crushable formulation in 2012. There are two reported accounts of TMA associated with tamper-resistant Oxycontin, which became available in Australia in 2014. This is the first documented case in which eculizumab was used. This case illustrates the practical diagnostic challenges in identifying TMA disorders, and the importance of a detailed drug history. It also highlights the need to clarify what role, if any, eculizumab therapy has in cases of drug-associated TMA.

Topics: Adult; Analgesics, Opioid; Antibodies, Monoclonal, Humanized; Complement Inactivating Agents; Delayed-Action Preparations; Humans; Injections, Intravenous; Male; Opioid-Related Disorders; Oxycodone; Oxymorphone; Renal Insufficiency; Substance Abuse, Intravenous; Thrombotic Microangiopathies

Prescription drug abuse is a major public health problem in the United States, with the rate of opioid-related deaths nearly quadrupling between 2000 and 2014. Extended-release oral oxymorphone hydrochloride (Opana ER) is a long-acting opioid prescribed for chronic pain; however, it also has the potential to be abused via intravenous injection. This retrospective review sought to analyze specific complications and sequelae requiring intensive care unit resources for patients intravenously abusing extended-release oral oxymorphone.. We retrospectively reviewed the medical records of patients identified for drug abuse between January 2012 and December 2015, identifying patients who intravenously abused extended-release oral oxymorphone. Medical charts were reviewed to identify associated sequelae and patients requiring an intensive care unit level of care.. We identified 53 patients who required treatment in an intensive care unit setting as a consequence of intravenously abusing extended-release oral oxymorphone. Twenty-eight patients (52.8%) required endotracheal intubation with mechanical ventilation for either acute hypoxic respiratory failure or protection of airway. Acute kidney injury developed in 48 patients (90.6%); 28.3% of these patients failed to regain renal function and required renal replacement therapy. Bacteremia was diagnosed in 36 patients (67.9%) and 30 patients (56.6%) were diagnosed as having acute infective bacterial endocarditis.. Our patients demonstrated a great need for critical care resources and severe sequelae related to intravenous drug abuse. Clinicians should be vigilant for the possibility for clinical decompensation when initially evaluating patients reporting intravenous abuse of extended-release oral oxymorphone.

Topics: Abscess; Acute Kidney Injury; Adult; Analgesics, Opioid; Bacteremia; Cellulitis; Delayed-Action Preparations; Endocarditis, Bacterial; Female; Humans; Intensive Care Units; Intubation, Intratracheal; Male; Middle Aged; North Carolina; Opioid-Related Disorders; Oxymorphone; Patient Admission; Prescription Drug Misuse; Renal Replacement Therapy; Respiration, Artificial; Respiratory Insufficiency; Retrospective Studies; Substance Abuse, Intravenous; Young Adult

The introduction of extended-release opioid analgesics helped initiate an epidemic of prescription opioid abuse in the United States. To make access to the drug by crushing or dissolution more difficult, abuse-deterrent formulations (ADFs) of OxyContin (Purdue Pharma, Stamford, CT) and Opana ER (Endo Pharmaceuticals Inc., Malvern, PA), which use the same foundation technology (Intac, Grunenthal, Aachen, Germany), were introduced in 2010 and 2012, respectively. To examine their relative effectiveness, we used a structured survey of 12,124 individuals entering treatment for opioid use disorder followed by a more focused online survey with a subset of these patients (N = 129) using both structured and open-ended questions. Data showed that the OxyContin ADF was highly effective in reducing nonoral abuse (91.4% before the ADF, 47.9% afterwards), particularly with insufflation (78%-28.8%) and intravenous injection of the active drug (42.7%-21.4%). However, although the Opana ER ADF was effective in reducing insufflation (80%-37.1%), injection (60.0%-51.4%), and overall nonoral abuse (94.3%-77.1%), it showed no significant decrease over time. Bearing in mind that the Opana ER sample was smaller in size than that for OxyContin, our results nonetheless suggest disparate outcomes resulting from the introduction of the ADFs, which could indicate that an ADF's effectiveness may be drug-specific. Given the public health impact of prescription opioids and the considerable effort being expended to develop ADFs as a partial solution to the problem, our preliminary studies suggest that each ADF must be evaluated on its own merits even if the same proprietary technology is used.

Topics: Adult; Analgesics, Opioid; Delayed-Action Preparations; Drug Compounding; Female; Humans; Male; Opioid-Related Disorders; Oxycodone; Oxymorphone; Pain; Treatment Outcome

While the risk of opioid overdose is widely accepted, the dangers of opioid withdrawal are far less clearly defined. The purpose of this publication is to provide evidence against the erroneous clinical dictum that opioid withdrawal is never life-threatening.. This case report (N = 1) illustrates an unfortunate, common scenario of a man abusing prescription opioids and heroin. His attempt at self-detoxification with buprenorphine-naloxone resulted in life-threatening opioid withdrawal. A detailed account of each day of his withdrawal period was documented by patient and family report and review of all medical records. The patient was contacted three months after hospitalization to verify information and determine progress in treatment and abstinence from drugs and alcohol.. A review of the literature was completed on severe cases of precipitated and spontaneous opioid withdrawal followed by a discussion of the significance as it relates to this case.. Given the widespread use of prescription opioids and opioid maintenance treatment, physicians should be aware of the complications of acute opioid withdrawal and should be equipped to treat these complications.

Topics: Acute Kidney Injury; Administration, Intranasal; Administration, Oral; Administration, Sublingual; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Follow-Up Studies; Heroin; Heroin Dependence; Humans; Intensive Care Units; Male; Opioid-Related Disorders; Oxycodone; Oxymorphone; Prescription Drugs; Rhabdomyolysis; Self Medication; Substance Withdrawal Syndrome; Young Adult

Oxymorphone, a semisynthetic μ-opioid receptor agonist, is the major active metabolite of oxycodone. It is a highly potent narcotic analgesic due to its high lipid solubility, which allows it to readily cross the blood-brain barrier and enter the central nervous system. It is available as both an immediate-release and extended-release (ER) formulation. Oxymorphone can be abused by injection or inhalation of crushed tablets; thus, in 2011, the manufacturer of ER oxymorphone reformulated the drug with crush-resistant technology to deter its misuse and abuse. We describe the case of a previously healthy, 24-year-old male who experienced reproducible acute subjective bilateral temporary hearing loss that occurred after inhalation of oxymorphone. He presented to the emergency department complaining of acute bilateral hearing loss after he reported snorting a crushed oxymorphone ER 30-mg tablet. Emergency department evaluation revealed obvious bilateral hearing loss as well as coincidental aspiration pneumonia. The patient's medical history revealed that he had experienced a similar episode of hearing loss after a previous episode of oxymorphone inhalation. His hearing loss began to improve 3 hours after presentation to the emergency department and was completely resolved by the following day. Use of the Naranjo adverse drug reaction probability scale revealed oxymorphone to be a probable cause of this patient's acute hearing loss (score of 6). The mechanism of action of opioid-associated hearing loss (OAHL) is not completely understood, but it is thought to be due to disturbances within the cochlea, such as cochlear ischemia. To our knowledge, this is only the second published case report of acute reversible hearing loss following oxymorphone inhalation and the first published case report of reproducible OAHL. Since opioid misuse continues to be prevalent despite attempts at reformulations to make the drugs crush resistant, a high degree of clinical suspicion is needed to evaluate and treat patients who present with unique findings after episodes of substance abuse, especially those related to tamper-resistant formulations.

Topics: Administration, Inhalation; Delayed-Action Preparations; Hearing Loss, Sensorineural; Humans; Male; Narcotics; Opioid-Related Disorders; Oxymorphone; Receptors, Opioid, mu; Young Adult

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.

Topics: Adolescent; Adult; Analgesics, Opioid; Cross-Sectional Studies; Female; Humans; Male; Opioid-Related Disorders; Oxycodone; Oxymorphone; Prevalence; Young Adult

We report the case of a 22 year-old-woman who presented with upper extremity cellulitis secondary to an infiltration of illicit intravenous drug use. She confessed to the intravenous use of Opana ER (an extended release oral formulation of oxymorphone) which is an opioid drug approved only for oral use. She was found to have clinical evidence of profound thrombotic microangiopathy which resulted due to the intravenous use of Opana ER. She showed full clinical improvement after withholding drug and supportive clinical care. Recent report of Opana ER intravenous abuse was published from Tennessee county and has now been increasingly recognised as one of the causes of thrombocytopenia which mimicks clinically as thrombotic thrombocytopenic purpura. Physicians should be aware of this association as the lack of familiarity to this can pose serious management dilemmas for our patients (especially the polysubstance abusers).

Topics: Analgesics, Opioid; Female; Humans; Opioid-Related Disorders; Oxymorphone; Purpura, Thrombotic Thrombocytopenic; Substance Abuse, Intravenous; Thrombotic Microangiopathies; Young Adult

The development of new formulations of extended-release (ER) opioids with abuse-deterrent technology attempts to deter prescription opioid abuse while maintaining appropriate access to care for pain patients. This study examined the degree to which some patients may avoid switching to reformulated ER opioids with abuse-deterrent technology and the extent to which those patients are more likely to be abusers.. We analyzed Truven MarketScan pharmacy and medical claims data following the introduction of two reformulated ER opioids with abuse-deterrent technology. Adults aged 18-64 who were continuous users of extended-release oxycodone HCl (ER oxycodone) or extended-release oxymorphone HCl (ER oxymorphone) in a 6 month period prior to the introduction of the respective reformulations of those products were identified and categorized based on whether they switched to the reformulation, switched to other ER/long-acting (LA) opioids (without abuse-deterrent technology), or discontinued ER/LA opioid treatment in a 6 month post-reformulation period. Abusers were identified using ICD-9-CM diagnosis codes for opioid abuse/dependence. Pearson's chi-squared tests and Fisher's exact tests were then used to compare rates of abuse between patients who avoided switching to a reformulated ER opioid. Sensitivity analyses examined several definitions used in this analysis.. ER/LA opioid utilization; rates of diagnosed opioid abuse.. A total of 31%-50% of patients avoided switching to reformulated ER opioids. Rates of diagnosed opioid abuse were higher among these patients compared to patients who transitioned to the reformulated ER opioids.. Due to the observational research design, caution is warranted in causal interpretation of the findings. The study was conducted among commercially insured continuous ER oxycodone or ER oxymorphone users; future research should consider additional patient populations, such as non-continuous users and those without commercial insurance (i.e., Medicare, Medicaid, uninsured).. Some patients switched to other ER/LA opioids without abuse-deterrent technology or discontinued ER/LA opioid treatment when their existing ER treatment was reformulated. Rates of opioid abuse were higher among patients who switched to other ER/LA opioids or discontinued ER/LA opioid treatment, suggesting that abusers may seek more easily abuseable alternatives such as prescription opioids without abuse-deterrent technology.

Topics: Adolescent; Adult; Analgesics, Opioid; Chronic Pain; Delayed-Action Preparations; Female; Humans; Male; Middle Aged; Opioid-Related Disorders; Oxycodone; Oxymorphone; Patient Acceptance of Health Care; United States; Young Adult

The extent of prescription opioid abuse has led to the development of formulations that are difficult to crush. The purpose of the present studies was to examine whether experienced prescription opioid abusers (individuals using prescription opioids for non-medical purposes regardless of how they were obtained) were able to prepare a formulation of oxymorphone hydrochloride ER 40 mg designed to be crush-resistant (DCR) for intranasal (study 1) or intravenous abuse (study 2), utilizing a non-crush-resistant formulation of oxymorphone (40 mg; OXM) as a positive control.. No drug was administered in these studies. Participants were provided with DCR and OXM tablets in random order and asked to prepare them for abuse with tools/solutions that they had previously requested. The primary outcome for study 1 was particle size distribution, and the primary outcome for study 2 was percent yield of active drug in the extracts. Other descriptive variables were examined to better understand potential responses to these formulations.. Fewer DCR than OXM particles were smaller than 1.705 mm (9.8% vs. 97.7%), and thus appropriate for analyses. Percent yield of active drug in extract was low and did not differ between the two formulations (DCR: 1.95%; OXM: 1.29%). Most participants were not willing to snort (92%) or inject (84%) the tampered products. Participants indicated that they found less relative value in the DCR than the OXM formulation across both studies.. These data suggest that the oxymorphone DCR formulations may be a promising technology for reducing opioid abuse.

Topics: Administration, Intranasal; Adult; Analgesics, Opioid; Chemistry, Pharmaceutical; Data Interpretation, Statistical; Delayed-Action Preparations; Demography; Excipients; Female; Hardness Tests; Humans; Hydrogels; Male; Middle Aged; Opioid-Related Disorders; Oxymorphone; Particle Size; Polysaccharides; Powders; Substance Abuse, Intravenous; Treatment Outcome; Young Adult

Because rates of both opioid prescribing and opioid abuse have increased, drug companies have responded by considering strategies to make opioid formulations less attractive for abuse without compromising safety or efficacy for patients with legitimate pain management needs. The emergence of tamper-resistant opioid formulations is intended to deter abuse by creating obstacles to crushing or dissolving opioid tablets and capsules. At present, 2 long-acting and 1 immediate-release (IR) opioids are available in tamper-resistant formulations. Oxycodone controlled-release and oxymorphone extended-release tablets have each been reformulated with a hardened matrix that resists crushing or dissolution in liquids, making them difficult to prepare for nasal insufflation or intravenous use. Oxycodone IR has been reformulated with aversive ingredients that create nasal discomfort if the tablet is crushed and insufflated. Tamper-resistant opioid formulations are likely to be selected for patients who are identified as being at risk for abuse. However, patients vary in their response to individual opioids and may require rotation to a series of alternative opioids before finding one that is effective and sufficiently well tolerated. With only a few tamper-resistant opioid formulations currently available, switching and rotation may become difficult. As a result, patients who do not respond to a tamper-resistant opioid formulation or experience intolerable adverse events may require rotation to a formulation without tampering safeguards. Prescribers will need to be on guard for patients who may make false claims of poor response or adverse events to avoid tamper-resistant opioid formulations. Moreover, prescribers need to be aware of any tamper-resistance mechanisms that may affect efficacy or tolerability in patients with legitimate pain management needs compared with formulations without tampering safeguards.

Topics: Analgesics, Opioid; Chronic Pain; Delayed-Action Preparations; Drug Combinations; Drug Compounding; Drug Tolerance; Humans; Morphine; Naltrexone; Opioid-Related Disorders; Oxycodone; Oxymorphone; Patient Selection

Topics: Analgesics, Opioid; Cross Reactions; Diagnosis; Drug Overdose; Enzyme-Linked Immunosorbent Assay; Humans; Opioid-Related Disorders; Oxycodone; Oxymorphone; Substance Abuse Detection

Oxymorphone, a semi-synthetic opioid analgesic, has been available as Numorphan since the 1950s in the form of injectable solutions and a suppository. Recently, in 2006, oxymorphone was approved by the Federal Drug Administration for use in the form of immediate and extended release tablets under the trade name Opana. Since the advent of Opana, the number of deaths involving oxymorphone has risen considerably in the State of North Carolina. To date, there are very few reported values for postmortem concentrations of oxymorphone in the literature to aid in the interpretation of these cases. We report 33 medical examiner cases involving oxymorphone and provide the distribution of oxymorphone in postmortem blood, liver, and urine samples. Oxymorphone was detected in blood by enzyme immunoassay and confirmed by gas chromatography- mass spectrometry utilizing a solid-phase extraction procedure. Calibration curves from 0.025 to 0.50 mg/L were established with a limit of quantitiation of 0.025 mg/L. The mean concentration for oxymorphone in postmortem central (n = 28) and peripheral (n = 23) blood samples was 0.15 mg/L. The median values for the central and peripheral samples were 0.10 mg/L (range: 0.011-0.59) and 0.075 mg/L (range: 0.017-0.82), respectively. Liver concentrations ranged from "none detected" to > 2.0 mg/kg, with mean and median values of 0.36 and 0.30 mg/kg, respectively. The majority of urine samples were > 0.50 mg/L.

Topics: Adolescent; Adult; Analgesics, Opioid; Autopsy; Female; Forensic Medicine; Gas Chromatography-Mass Spectrometry; Humans; Immunoenzyme Techniques; Liver; Male; Middle Aged; North Carolina; Opioid-Related Disorders; Oxymorphone; Reference Values; Substance Abuse Detection

Topics: Administration, Oral; Analgesics, Opioid; Biological Availability; Clinical Trials as Topic; Delayed-Action Preparations; Drug Administration Schedule; Drug Interactions; Humans; Low Back Pain; Neoplasms; Opioid-Related Disorders; Osteoarthritis; Oxymorphone; Pain; Pain, Postoperative

We studied the effect of peripheral opioid receptor antagonist methylnaloxone on the development of withdrawal syndrome in morphine-dependent rats. Intraperitoneal injections of methylnaloxone iodide in a daily dose of 2 mg/kg over 3 days after morphine withdrawal reduced the severity of withdrawal symptoms. The mean total score of withdrawal syndrome in treated rats (3.20 +/- 0.13) was 2-fold lower compared to the control, mainly due to less pronounced wet dog shake behavior, limb and head shakes, dyspnea, ptosis, and teeth chattering. Methylnaloxone iodide in the specified dose had no effect on such symptoms of withdrawal syndrome as diarrhea and writhing. Our results indicate that modulation of the peripheral opioid system can reduce the severity of opioid withdrawal syndrome. Methylnaloxone-induced variations in the function of peripheral opioid receptors are probably accompanied by changes in the central nervous system, which prevents the development of withdrawal syndrome.

Topics: Animals; Male; Morphine; Opioid-Related Disorders; Oxymorphone; Rats; Rats, Wistar; Substance Withdrawal Syndrome

Topics: Comorbidity; Depressive Disorder; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Narcotics; Opioid-Related Disorders; Oxycodone; Oxymorphone; Treatment Outcome

Topics: Animals; Anti-Anxiety Agents; Benzodiazepines; Cocaine; Dogs; Guinea Pigs; Humans; Kinetics; Male; Nicotine; Opioid-Related Disorders; Oxymorphone; Phenazocine; Phencyclidine; Rats; Self Administration; Stereoisomerism