A Cross-Sectional Study of Tampering in Xtampza ER, an Abuse-Deterrent Formulation of an Extended-Release Opioid, in a Treatment Center Population.

BACKGROUND AND OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Relative potency of intravenous oxymorphone compared to other µ opioid agonists in humans - pilot study outcomes.

AIMS: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Anesthetic and Analgesic Drug Products Advisory Committee Activity and Decisions in the Opioid-crisis Era.

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.

Online Conversation Monitoring to Understand the Opioid Epidemic: Epidemiological Surveillance Study.

BACKGROUND: Between 2016 and 2017, the national mortality rate involving opioids continued its escalation; opioid deaths rose from 42,249 to 47,600, bringing the public health crisis to a new height. Considering that 69% of adults in the United States use online social media sites, a resource that builds a more complete understanding of prescription drug misuse and abuse could supplement traditional surveillance instruments. The Food and Drug Administration has identified 5 key risks and consequences of opioid drugs-misuse, abuse, addiction, overdose, and death. Identifying posts that discuss these key risks could lead to novel information that is not typically captured by traditional surveillance systems. OBJECTIVE: The goal of this study was to describe the trends of online posts (frequency over time) involving abuse, misuse, addiction, overdose, and death in the United States and to describe the types of websites that host these discussions. Internet posts that mentioned fentanyl, hydrocodone, oxycodone, or oxymorphone were examined. METHODS: Posts that did not refer to personal experiences were removed, after which 3.1 million posts remained. A stratified sample of 61,000 was selected. Unstructured data were classified into 5 key risks by manually coding for key outcomes of misuse, abuse, addiction, overdose, and death. Sampling probabilities of the coded posts were used to estimate the total post volume for each key risk. RESULTS: Addiction and misuse were the two most commonly discussed key risks for hydrocodone, oxycodone, and oxymorphone. For fentanyl, overdose and death were the most discussed key risks. Fentanyl had the highest estimated number of misuse-, overdose-, and death-related mentions (41,808, 42,659, and 94,169, respectively). Oxycodone had the highest estimated number of abuse- and addiction-related mentions (3548 and 12,679, respectively). The estimated volume of online posts for fentanyl increased by more than 10-fold in late 2017 and 2018. The odds of discussing fentanyl overdose (odds ratios [OR] 4.32, 95% CI 2.43-7.66) and death (OR 5.05, 95% CI 3.10-8.21) were higher for social media, while the odds of discussing fentanyl abuse (OR 0.10, 95% CI 0.04-0.22) and addiction (OR 0.24, 95% CI 0.15-0.38) were higher for blogs and forums. CONCLUSIONS: Of the 5 FDA-defined key risks, fentanyl overdose and death has dominated discussion in recent years, while discussion of oxycodone, hydrocodone, and oxymorphone has decreased. As drug-related deaths continue to increase, an understanding of the motivations, circumstances, and consequences of drug abuse would assist in developing policy responses. Furthermore, content was notably different based on media origin, and studies that exclusively use either social media sites (such as Twitter) or blogs and forums could miss important content. This study sets out sustainable, ongoing methodology for surveilling internet postings regarding these drugs.

Model-based Meta-analysis to Compare Primary Efficacy-endpoint, Efficacy-time Course, Safety, and Tolerability of Opioids Used in the Management of Osteoarthritic Pain in Humans.

BACKGROUND: Despite recent therapeutic advances, osteoarthritis continues to be a challenging health problem, especially in the elderly population. Opioids, which are potent analgesics, have shown an extraordinary ability to reduce intense pain in many osteoarthritic clinical trials; however, there is an increased need for a study to integrate the reported outcomes and utilize them to achieve a better understanding. Herein, efficacy and safety aspects of opioids used to manage osteoarthritic pain were assessed and compared using a model-based meta-analysis (MBMA). METHODS: To perform the analysis, a comprehensive database consisting of pain relief compounds with information on summary-level of efficacy over time, adverse events and dropout rates was compiled from multiple sources. MBMA was conducted using a nonlinear mixed-effects modeling approach. RESULTS: The results of primary efficacy endpoint analysis indicated that the doses of oxycodone, oxymorphone, and tramadol required to produce 50% of the maximum effect were 47, 84, and 247 mg per day, respectively. Efficacytime course analysis showed that opioids had rapid time to efficacy onset, suggesting potentially powerful painrelieving effects. It was also found that gastrointestinal adverse events were the most opioid-associated and dosedependent adverse effects. In addition, the analysis revealed that opioids were well-tolerated at low to moderate doses. CONCLUSION: This MBMA provides clinically meaningful insights into the efficacy and safety profiles of oxycodone, oxymorphone, and tramadol. Resultantly, the presented framework analysis can have an impact in the clinic on drug development where it can guide: the optimization of doses of opioids required to manage osteoarthritic pain; the making of precise key decisions for the positioning of new drugs, and; the design of more efficient trials.

Pediatric Drug Labeling and Imperfect Information.

I first became aware of bioethics in the spring of 1980. I had spent a thirty-six-hour shift shadowing a medical resident, and I was struck that many of the resident's decisions had ethical dimensions. The next day, I came across the Hastings Center Report, and I realized I wanted to explore ethical issues I found implicit in clinical care, even though I still wanted to become a pediatrician. In September 2019, when I attended my first meeting of the U.S. Food and Drug Administration's Pediatric Advisory Committee, as a pediatric pulmonologist, I had the same sense of awe and curiosity that I had forty years ago. What had appeared initially as somewhat technical decisions about the regulation of drug labeling was suffused with ethical questions. The committee was asked to discuss possible changes to the labeling of two previously approved drugs.

Scoring the best deal: Quantity discounts and street price variation of diverted oxycodone and oxymorphone.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Acute kidney injury is common with intravenous abuse of extended-release oral oxymorphone and delayed renal recovery rates are associated with increased KDIGO staging.

AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Oxymorphone Hydrochloride Extended-Release (OPANA®) Associated With Acute Kidney Injury in a Chronic Pain Patient: A Case Report.

Oxymorphone hydrochloride extended-release (OPANA®) is an opioid prescribed for the treatment of moderate-to-severe chronic pain. Kidney injury related to its use has not previously been reported. We present a case of a chronic pain patient with underlying chronic renal insufficiency who developed superimposed acute kidney injury when his opioid analgesic was changed from morphine sulfate extended-release to OPANA. Electron microscopy of his renal tissue revealed lamellated podocytes typically seen with drug-induced phospholipidosis.

A Phase I study of the pharmacokinetics, safety and tolerability of a novel tocopheryl phosphate mixture/oxymorphone transdermal patch system.

AIM: Characterize the pharmacokinetic profile and tolerability of two tocopheryl phosphate mixture/oxymorphone patch formulations in healthy subjects, and the active metabolite (6-OH-oxymorphone). MATERIALS & METHODS: Fifteen participants received a single application of oxymorphone patches +/- capsaicin for 72 h and were crossed-over for another 72 h. RESULTS: Plasma oxymorphone was detected approximately 7 h and 6-OH-oxymorphone after approximately 18-19 h postapplication of both formulations, respectively. For oxymorphone, median tmax was 24 h, and Cmax/Cmin ratio was approximately 2.4. The most frequently reported treatment-related adverse event was application site reaction, mainly with capsaicin formulation. CONCLUSION: Tocopheryl phosphate mixture/oxymorphone transdermal patches can successfully deliver therapeutic amounts of oxymorphone in a sustained manner over 72 h and are well tolerated. ANZCTR registration number: ACTRN12614000613606.

Thrombotic microangiopathy associated with intravenous injection of extended-release oxycodone.

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.

Ketorolac, Oxymorphone, Tapentadol, and Tramadol: A Comprehensive Review.

Pain remains a tremendous burden on patients and for the health care system, with uncontrolled pain being the leading cause of disability in this country. There are a variety of medications that can be used in the treatment of pain, including ketorolac, oxymorphone, tapentadol, and tramadol. Depending on the clinical situation, these drugs can be used as monotherapy or in conjunction with other types of medications in a multimodal approach. A strong appreciation of pharmacologic properties of these agents and potential side effects is warranted for clinicians.

Analysis of Intensive Care Unit Admission and Sequelae in Patients Intravenously Abusing Extended-Release Oral Oxymorphone.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Abuse of reformulated OxyContin: Updated findings from a sentinel surveillance sample of individuals assessed for substance use disorder.

OBJECTIVE: To examine abuse prevalence for OxyContin and comparator opioids over a 6-year period prior to and following market entry of reformulated OxyContin and assess consistency in abuse across treatment settings and geographic regions. DESIGN: An observational study examining longitudinal changes using cross-sectional data from treatment centers for substance use disorder. SETTING: A total of 874 facilities in 39 states in the United States within the National Addictions Vigilance Intervention and Prevention Program (NAVIPPRO®) surveillance system. PARTICIPANTS: Adults (72,060) assessed for drug problems using the Addiction Severity Index-Multimedia Version (ASI-MV®) from January 2009 through December 2015 who abused prescription opioids. MAIN OUTCOME MEASURE(S): Percent change in past 30-day abuse. RESULTS: OxyContin had significantly lower abuse 5 years after reformulation compared to levels for original OxyContin. Consistency of magnitude in OxyContin abuse reductions across geographic regions, ranging from 41 to 52 percent with differences in abuse reductions in treatment setting categories occurred. Changes in geographic region and treatment settings across study years did not bias the estimate of lower OxyContin abuse through confounding. CONCLUSION: In the postmarket setting, limitations and methodologic challenges in abuse measurement exist and it is difficult to isolate singular impacts of any one intervention given the complexity of prescription opioid abuse. Expectations for a reasonable threshold of abuse for any one ADF product or ADF opioids as a class are still uncertain and undefined. A significant decline in abuse prevalence of reformulated OxyContin was observed 5 years after its reformulation among this treatment sample of individuals assessed for substance use disorder that was lower historically for the original formulation of this product.

A mechanistic investigation of thrombotic microangiopathy associated with IV abuse of Opana ER.

Since 2012, a number of case reports have described the occurrence of thrombotic microangiopathy (TMA) following IV abuse of extended-release oxymorphone hydrochloride (Opana ER), an oral opioid for long-term treatment of chronic pain. Here, we present unique clinical features of 3 patients and investigate IV exposure to the tablet's inert ingredients as a possible causal mechanism. Guinea pigs were used as an animal model to understand the hematopathologic and nephrotoxic potential of the inert ingredient mixture (termed here as PEO+) which primarily contains high-molecular-weight polyethylene oxide (HMW PEO). Microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury were found in a group of 3 patients following recent injection of adulterated extended-release oxymorphone tablets. Varying degrees of cardiac involvement and retinal ischemia occurred, with TMA evident on kidney biopsy. A TMA-like state also developed in guinea pigs IV administered PEO+. Acute tubular and glomerular renal injury was accompanied by nonheme iron deposition and hypoxia-inducible factor-1α upregulation in the renal cortex. Similar outcomes were observed following dosing with HMW PEO alone. IV exposure to the inert ingredients in reformulated extended-release oxymorphone can elicit TMA. Although prescription opioid abuse shows geographic variation, all physicians should be highly inquisitive of IV drug abuse when presented with cases of TMA.

New Initiation of Long-Acting Opioids in Long-Stay Nursing Home Residents.

OBJECTIVES: To estimate the prevalence of new initiation of long-acting opioids since introduction of national efforts to increase prescriber and public awareness on safe use of transdermal fentanyl patches. DESIGN: Cross-sectional. SETTING: U.S. nursing homes (NHs). PARTICIPANTS: Medicare-enrolled long-stay NH residents (N = 22,253). MEASUREMENTS: Minimum Data Set 3.0 was linked with Medicare enrollment, hospital claims, and prescription drug transaction data (January-December 2011) and used to determine the prevalence of new initiation of a long-acting opioid prescribed to residents in NHs. RESULTS: Of NH residents prescribed a long-acting opioid within 30 days of NH admission (n = 12,278), 9.4% (95% confidence interval = 8.9-9.9%) lacked a prescription drug claim for a short-acting opioid in the previous 60 days. The most common initial prescriptions of long-acting opioids were fentanyl patch (51.9% of opioid-naïve NH residents), morphine sulfate (28.1%), and oxycodone (17.2%). CONCLUSION: New initiation of long-acting opioids-especially fentanyl patches, which have been the subject of safety communications-persists in NHs.

THROMBOTIC MICROANGIOPATHY ASSOCIATED WITH OPANA ER INTRAVENOUS ABUSE A Case Report.

Thrombotic microangiopathy is characterized by endothelial changes and microvascular stenosis. Several entities such as pregnancy, infection, connective tissue diseases, and drugs are associated with secondary thrombotic microangiopathy. Recently, new reformulation of Opana ER had been associated with thrombotic microangiopathy when injected intravenously. Here, we report the case of a 37-year-old man who developed renal failure and hemolytic anemia secondary to Opana ER intravenous abuse. Renal biopsy pathology was consistent with thrombotic microangiopathy likely caused by Opana ER intravenous abuse.

A tale of 2 ADFs: differences in the effectiveness of abuse-deterrent formulations of oxymorphone and oxycodone extended-release drugs.

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.

A case of rhabdomyolysis associated with severe opioid withdrawal.

BACKGROUND AND OBJECTIVE: 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. METHODS AND RESULTS: 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. DISCUSSION AND CONCLUSION: 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. SCIENTIFIC SIGNIFICANCE: 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.

Acute Sensorineural Hearing Loss After Abuse of an Inhaled, Crushed Oxymorphone Extended-Release Tablet.

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.