Opioid Formulations Research Articles

Real-World Prescription Data for Intrathecal Drug Delivery: A Retrospective Analysis in 32,784 Patients

ObjectivesCurrently, there are three monotherapy drugs approved by the United States Food and Drug Administration (FDA) for use in intrathecal drug delivery systems (IDDS): morphine, ziconotide, and baclofen. In practice, use includes alternate drugs, drug combinations, and drug concentrations. There is a paucity of real-world data examining prescription patterns for IDDS. Our analysis explores a one-year sample of prescription intrathecal (IT) medications from a large pharmaceutical data base to characterize medication usage in IDDS. Materials and MethodsData were provided by an accredited pharmacy as a deidentified data base of IT drug prescriptions. Statistical analyses included rates of monotherapy vs combination therapies, frequencies of various IT prescriptions, use of on- vs off-label medications, and opioid vs nonopioid formulations. ResultsData were extracted from February 1, 2021 to February 14, 2022. No patients were excluded. The initial sample comprised 49,917 individual IT prescriptions for 32,784 patients. Monotherapies constituted 55.0% of all prescriptions (27,475/49,917). Of these, 23,257 prescriptions (84.6%) were opioid based, with the most common medications being morphine (46.5%), hydromorphone (39.4%), and fentanyl (13.5%). Although 29.3% of all prescriptions were for one of the FDA-approved medications, only 7.9% used FDA-approved concentrations; 9865 patients underwent ≥one prescription change in the study period—16.7% of whom were initially prescribed medications that met the approved, on-label indications for the pump before being switched to off-label concentrations or combinations to address clinical needs. ConclusionsDespite the prevalence of IDDS for managing chronic, intractable pain, minimal data exist on real-world prescription practices. Our study found that FDA-approved IT formulations accounted for the minority of prescriptions, indicating significant practice variation, with off-label prescriptions being common.

M98 - Comparisons Between Prescription Opioid Formulations and Risk for New-Onset Affective Disorders in Chronic Pain Patients

M98 - Comparisons Between Prescription Opioid Formulations and Risk for New-Onset Affective Disorders in Chronic Pain Patients

Persistent opioid use after hospital admission due to trauma: a population-based cohort study.

Persistent opioid use (POU) is a common marker of harm related to opioid use after trauma. This study determined the incidence and risk factors for POU after hospitalisation due to trauma in New Zealand, among opioid-naïve patients. This was a population-based, retrospective cohort study, using linked data, involving all trauma patients of any age admitted to all NZ hospitals between 2007 and 2019. We included all patients who received opioids after discharge and were considered opioid naïve, defined as not having received opioids or not having a prior diagnosis of opioid-use disorder up to 365 days preceding the discharge date. The primary outcome was the incidence of POU defined as opioid use after discharge between 91 and 365 days. We used a multivariable logistic regression to identify independent risk factors for POU. A total of 177,200 patients were included in this study. Of these, 15.3% (n = 27,060) developed POU based on criteria used for the primary analysis, with sensitivity analyses showing POU incidence ranging from 14.3% to 0.8%. The opioid exposure risk factors associated with POU included switching between different opioids (adjusted odds ratio [aOR] 2.62; 95% confidence interval [CI] 2.51-2.73), prescribed multiple opioids (vs codeine, aOR 1.44; 95% CI 1.37-1.53), slow-release opioid formulations (aOR 1.32; 95% CI 1.26-1.39), and dispensed higher total doses of on the initial discharge prescription (aOR 1.26; 95% CI 1.20-1.33). Overall, 1 in 7 opioid-naïve patients who were exposed to opioids after trauma developed POU. Our findings highlight clinicians should be aware of these factors when continuing opioids on discharge.

Review on Recent Development in Opioid Abuse-Deterrent Formulation Technologies and Regulatory Expectation

Chronic pain occurs as a result of several diseases and ailments. The problem of improper utilization of vital opioid medication has been a topic of substantial discourse during the last two decades, in conjunction with its application for the extended-term control of persistent pain. Abuse-deterrent formulations play a crucial role in comprehensive methods to manage the risks associated with opioids. These formulations diminish the allure and narcotic properties of opioids by restricting their capacity to be assimilated by the body. This diminishes the appeal and incentives for misusing altered opioid prescriptions, and also poses challenges in extracting the opioid substance for utilization in alternative manners. This article examines various regulatory measures, projected prerequisites for the licensing of abuse-deterrent formulations, and current activities aimed at producing opioid abuse-deterrent formulations as potential remedies to combat the opioid abuse pandemic. Considering the seriousness of the global opioid problem, it is crucial for various regulatory entities to come together to safeguard society from the opioid pandemic. This involves implementing a thorough policy on prescribing opioid medications to patients, conducting evaluations to determine the likelihood of addiction, and increasing efforts to approve only opioid drugs that are specifically tailored to prevent abuse.

Trajectories of Opioid Use Before and After Cancer Diagnosis: A Population-Based Cohort Study

BackgroundOpioid use prior to cancer diagnosis increases the likelihood of long-term use during survivorship, however, patterns of use before and after diagnosis are not understood. MethodsWe used population-based dispensing data linked with cancer and death notifications to identify two cohorts of adults residing in New South Wales initiating opioids within 24 months prior to a first cancer diagnosed between 2014 and 2016: ‘survivors’ (alive 24 months following diagnosis) and ‘decedents’ (died within 24 months). We used group-based trajectory modelling to identify trajectories of monthly opioid dispensings and dispensed oral morphine equivalent milligrams (OMEmg) during the 24 months before/after cancer diagnosis. ResultsThere were 21,843 survivors with four prediagnosis opioid dispensing trajectories: infrequent (58% of the cohort), late increasing (26%), moderate (10%), and sustained dispensing (6%). We observed an overall increase in dispensed OMEmg of 83 OMEmg (95% CI: 76–91) during the month of diagnosis, with strong opioid formulations comprising most treatment postdiagnosis. Within each prediagnosis opioid trajectory group, we observed five to six postdiagnosis trajectory groups, including no opioid dispensing. Moderate and sustained prediagnosis groups had large proportions of people continuing or increasing opioid dispensing after diagnosis, while small proportions discontinued opioid treatment. We observed similar trajectories in the decedent cohort. ConclusionsThere is considerable heterogeneity in opioid use before and after cancer diagnosis. Our findings suggest noncancer factors drive a significant proportion of postdiagnosis opioid use, but use increased significantly from the month of cancer diagnosis and never returned to prediagnosis levels.

Review of Opioid Abuse-Deterrent Formulations: Impact and Barriers to Access

Review of Opioid Abuse-Deterrent Formulations: Impact and Barriers to Access

Payor denial after prior authorization request for long-acting pain medication: Provider and patient perspectives.

11004 Background: For patients with cancer, uncontrolled pain can reduce quality of life, lead to treatment breaks, and result in worse cancer outcomes. Guideline-concordant treatment for chronic, severe pain can include long-acting opioid formulations. Pain medications, however, often face prior authorization (PA), which requires providers to obtain payor pre-approval and may result in delayed or denied care. This analysis characterizes PA-related denials for pain medications for patients with cancer. Methods: At an urban comprehensive cancer center, we identified all PA requests for outpatient long-acting opioid (i.e., buprenorphine, fentanyl, hydromorphone, methadone, morphine, oxycodone, oxymorphone, tapentadol) prescriptions from 2023 and described frequency of PA approvals and denials. For denials, chart review 2 weeks post-PA was conducted of provider notes and patient communications with results summarized qualitatively. Results: 1752 new long-acting opioids prescriptions for 982 unique patients required PA. Of those, 1567 (89.4%) were approved after PA process, 99 (5.6%) were denied, 81 (4.6%) were cancelled after PA initiation, and 6 (0.3%) were unresolved. Most were prescribed by pain specialists including supportive care (n = 699, 40.0%) and anesthesia/pain medicine (n = 444, 25.3%) with most common indication: “Neoplasm related pain (chronic)” (61.1%). Oxycodone was the most common long-acting opioid requiring PA (n = 551, 31.4% of prescriptions), followed by fentanyl (n = 501, 28.6%), hydromorphone (n = 205, 11.7%), and methadone (n = 137, 7.8%). Long-acting morphine was denied most frequently (16.3% of n = 129 PA requests denied), followed by buprenorphine (12.1% of n = 33), and hydromorphone (7.3%). Fentanyl was denied the least (2.8%). The 99 denials affected 62 unique patients, including a patient with 7 denials. Chart review (n = 62) of the 2 weeks post-denial revealed a median of 2 (range 0-8) provider notes mentioning pain or PA barriers and median of 1 (range 0-5) patient calls or messages about the same. 22.6% (n = 14) patients ended up in the ER or admitted to the hospital for pain crisis or failure to thrive. Providers documented poor pain control, weight loss, need to “try and fail” other medications, and noted 11.3% (n = 7) patients ending up paying out of pocket for their medications. Patient messages document uncontrolled pain and unmanageable side effects with some literally begging for relief; one patient spoke of their fear of “dying in pain”. Conclusions: The vast majority of PA requests for long-acting pain medication result in approvals, suggesting that the process -which can delay essential pain management- is largely unnecessary. For the 1 in 20 requests that were denied, provider and patient concerns highlight the negative impact of uncontrolled pain. An improved, transparent PA process is essential for adequately treating chronic, cancer-related pain.

Matching study design to prescribing intention: The prevalent new-user design for studying abuse-deterrent formulations of opioids.

In drug studies, research designs requiring no prior exposure to certain drug classes may restrict important populations. Since abuse-deterrent formulations (ADF) of opioids are routinely prescribed after other opioids, choice of study design, identification of appropriate comparators, and addressing confounding by "indication" are important considerations in ADF post-marketing studies. In a retrospective cohort study using claims data (2006-2018) from a North Carolina private insurer [NC claims] and Merative MarketScan [MarketScan], we identified patients (18-64 years old) initiating ADF or non-ADF extended-release/long-acting (ER/LA) opioids. We compared patient characteristics and described opioid treatment history between treatment groups, classifying patients as traditional (no opioid claims during prior six-month washout period) or prevalent new users. We identified 8415 (NC claims) and 147 978 (MarketScan) ADF, and 10 114 (NC claims) and 232 028 (MarketScan) non-ADF ER/LA opioid initiators. Most had prior opioid exposure (ranging 64%-74%), and key clinical differences included higher prevalence of recent acute or chronic pain and surgery among patients initiating ADFs compared to non-ADF ER/LA initiators. Concurrent immediate-release opioid prescriptions at initiation were more common in prevalent new users than traditional new users. Careful consideration of the study design, comparator choice, and confounding by "indication" is crucial when examining ADF opioid use-related outcomes.

Evaluating the Risk Index for Serious Prescription Opioid-Induced Respiratory Depression or Overdose in Patients with Cancer

The Commercially Insured health Plan Risk Index for Overdose or Serious Opioid-induced Respiratory Depression (CIP-RIOSORD) is an evidence-based tool to determine serious opioid-induced respiratory depression (OIRD) or overdose risk. The CIP-RIOSORD total score determines a risk class and estimates the probability for an OIRD event within the next 6 months. We performed a single-center, retrospective analysis to determine CIP-RIOSORD baseline scores and the most common predictive factors in patients with cancer. Patients (n = 160) were split into new consultations (n = 83, Group 1) versus the first documented follow-up consultation (n = 77, Group 2). Most patients were Caucasian women with metastatic gastrointestinal cancer. CIP-RIOSORD scores for Group 1 patients were 14.8 ± 15.2 (mean ± SD, risk class 4). Group 2 patients had higher CIP-RIOSORD scores (16.6 ± 14.9, risk class 4). For Group 1, the most common CIP-RIOSORD predictive factors were use of a long-acting opioid formulation (n = 24, 29%) and daily oral morphine equivalent (OME) ≥100 (n = 20, 24%); for Group 2, predictive factors were use of an antidepressant (n = 34, 44%) and a long-acting opioid formulation (n = 27, 35%). Based on the CIP-RIOSORD, there is a 15% probability of experiencing a serious OIRD event or overdose within the next 6 months.

Conversion ratios: Why is it so challenging to construct opioid conversion tables?

Standardizing opioid management is challenging due to the absence of a ceiling dose, the unknown ideal therapeutic plasma level, and the lack of an clear relationship between dose and therapeutic response. Opioid rotation or conversion, which is switching from one opioid, route of administration, or both, to another, to improve therapeutic response and reduce toxicities, occurs in 20-40 percent of patients treated with opioids. Opioid conversion is often needed when there are adverse effects, toxicities, or inability to tolerate a certain opioid formulation. A majority of patients benefit from opioid conversion, leading to improved analgesia and less adverse effects. There are different published ways of converting opioids in the literature. This review of 20 years of literature is centered on opioid conversions and aims to discuss the complexity of converting opioids. We discuss study designs, outcomes and measures, pain phenotypes, patient characteristics, comparisons of equivalent doses between opioids, reconciling conversion ratios between opioids, routes, directional differences, half-lives and metabolites, interindividual variability, and comparison to package insert information. Palliative care specialists have not yet come to a consensus on the ideal opioid equianalgesic table; however, we discuss a recently updated table, based on retrospective evidence, that may serve as a gold standard for practical use in the palliative care population. More robust, well-designed studies are needed to validate and guide future opioid conversion data.

Opioid therapy trajectories of patients with chronic non-cancer pain over 1 year of follow-up after initiation of short-acting opioid formulations.

This study compared opioid utilization trajectories of persons initiating tramadol, short-acting hydrocodone, or short-acting oxycodone, and it characterized opioid dose trajectories and type of opioid in persistent opioid therapy subsamples. A retrospective cohort study of adults with chronic non-cancer pain who were initiating opioid therapy was conducted with the IQVIA PharMetrics® Plus for Academics data (2008-2018). Continuous enrollment was required for 6 months before ("baseline") and 12 months after ("follow-up") the first opioid prescription ("index date"). Opioid therapy measures were assessed every 7 days over follow-up. Group-based trajectory modeling (GBTM) was used to identify trajectories for any opioid and total morphine milligram equivalent measures, and longitudinal latent class analysis was used for opioid therapy type. A total of 40276 tramadol, 141023 hydrocodone, and 45221 oxycodone initiators were included. GBTM on any opioid therapy identified 3 latent trajectories: early discontinuers (tramadol 39.0%, hydrocodone 54.1%, oxycodone 61.4%), late discontinuers (tramadol 37.9%, hydrocodone 39.4%, oxycodone 33.3%), and persistent therapy (tramadol 6.7%, hydrocodone 6.5%, oxycodone 5.3%). An additional fourth trajectory, intermittent therapy (tramadol 16.4%), was identified for tramadol initiators. Of those on persistent therapy, 2687 individuals were on persistent therapy with tramadol, 9169 with hydrocodone, and 2377 with oxycodone. GBTM on opioid dose resulted in 6 similar trajectory groups in each persistent therapy group. Longitudinal latent class analysis on opioid therapy type identified 6 latent classes for tramadol and oxycodone and 7 classes for hydrocodone. Opioid therapy patterns meaningfully differed by the initial opioid prescribed, notably the presence of intermittent therapy among tramadol initiators and higher morphine milligram equivalents and prescribing of long-acting opioids among oxycodone initiators.

Advancement in Opioid Abuse-deterrent Formulation Technologies and Regulatory Expectation.

Chronic pain is a byproduct of many diseases and conditions. Along with long-term opioid medication use in chronic pain management, misuse of this vital medication has been a topic of much debate over the last two decades. Abuse-deterrent formulations play a critical role in comprehensive opioid risk management strategies, limiting the attractiveness and drug-liking qualities of an opioid drug by limiting their bioavailability, making abuse of the tampered opioid medication less appealing or rewarding, or impeding the extraction of the opioid drug and thus impeding the administration of the opioid formulation via alternative routes. The present article covers various regulatory actions, expectations in abuse-deterrent formulation approval, and emerging opioid abuse-deterrent formulation strategies, such as incorporating physical barriers, chemical barriers, aversion agents, pH modulating release properties, novel delivery systems, agonist/antagonist combinations, and prodrugs, as potential approaches to encountering the crisis of the opioid abuse epidemic. Looking at the severity of the opioid crisis across the globe now is the right time for various regulatory agencies to come under one roof to save society from the opioid epidemic, define the policy on how and when to prescribe opioid formulations to patients, perform abuse risk assessments, and make more efforts to approve only abusedeterrent opioid medication.

Geopolymers: Advanced Materials in Medicine, Energy, Anticorrosion and Environmental Protection

The initial predictions of the importance of geopolymers primarily assumed use mainly in the construction sector. However, as research progresses, it is becoming clear that these versatile materials demonstrate the ability to greatly exceed their original applications, as characterized in detail in this review article. To the best of our knowledge, there is no literature review concerning geopolymer materials that compiles the diverse applications of these versatile materials. This paper focuses on geopolymer applications beyond the construction industry. The surprising application potential of geopolymers in medicine has become a topic of particular interest. Therefore, considerable attention in this paper is devoted to characterizing the utility of these materials in tissue engineering, dentistry and drug delivery systems. Geopolymers not only have exceptional heat resistance and compressive strength, making them durable and resistant to manipulation (over five times less drug released from the geopolymer carrier compared to the commercial formulation), but also provide a robust solution for extended-release drug delivery systems, especially in opioid formulations. Their chemical stability, porous structure and ability to maintain structure after repeated regeneration processes speak to their potential in water treatment. Geopolymers, which excel in the energy industry as refractory materials due to their resistance to high temperatures and refractory properties, also present potential in thermal insulation and energy storage. It was demonstrated that geopolymer-based systems may even be 35% cheaper than conventional ones and show 70% lower thermal conductivity. In terms of protection against microorganisms, the possibility of modifying geopolymers with antimicrobial additives shows their adaptability, maintaining their effectiveness even under high-temperature conditions. Research into their use as anticorrosion materials is targeting corrosion-resistant coatings, with geopolymers containing graphene oxide showing particularly promising results. The multitude of potential applications for geopolymers in a variety of fields reflects their enormous potential. As research progresses, the scope of their possibilities continues to expand, offering innovative solutions to pressing global challenges.

Inpatient Use of Extended-Release (ER) Opioids for Vaso-Occlusive Crisis Associated with Increased Length of Stay for ER Opioid-Naïve Patients

Background: The intermittent acute pain syndrome associated with sickle cell disease (SCD) is a poorly understood phenomenon with complex pathophysiology. Given the broad spectrum of analgesic interventions, including immediate-release (IR) and extended-release (ER) opioids, healthcare providers are challenged with the task of safely and effectively escalating inpatient opioid regimens, especially in the setting of limited guidelines outlining the combination of different opioid formulations. Despite SCD being the most common genetic disorder in the United States, more research is required to improve physician expertise with appropriate and timely pain management of vaso-occlusive crisis. Methods: This study was a retrospective chart review (n=200) of patients with known SCD requiring hospitalization for acute pain secondary to vaso-occlusive crisis without an alternative etiology of pain symptoms. The review included a patient population aged 18-67 years old with 43.5% males and 56.5% females hospitalized from 2/1/2022 to 5/6/2022. The primary outcome measure was hospital length of stay (LOS) for adequate pain control compared against varying factors of inpatient opioid-prescribing practices, including initiation or continuation (if prescribed within 6 months prior to admission encounter per PDMP review) of an ER opioid formulation, degree of morphine milligram equivalents (MME) escalation from outpatient regimen, utilization of a sickle cell analgesic order set, and initiation of patient-controlled analgesia pump (PCA). A secondary outcome measure investigated was the quantitative comparison of highest daily prescribed MME in relation to the aforementioned inpatient variables. Data analysis was completed using Wilcoxon Rank Summary analysis, with a significant p-value set to < 0.05. Results: Among the primary outcome analysis, the only significant factor affecting LOS was the introduction of an ER opioid. The results show that within the patient cohort naïve to an outpatient ER opioid (n=105), ER opioid-incorporated inpatient analgesic regimens resulted in a significantly increased mean LOS compared to IR opioid monotherapy regimens, with an average of 8.8 inpatient days as compared to 5.3 days, respectively (p-value < 0.001). For the patients prescribed an outpatient ER opioid at baseline (n=95), the continuation of an inpatient ER opioid did not result in a significant change in mean LOS, calculated as 6.7 days vs. 6.0 days in the continued and non-continued groups, respectively (p-value = 0.716). Among the secondary outcome measures, utilization of a sickle cell order set and PCA did not significantly affect degree of MME escalation. Conclusions: Limited evidence-based recommendations for the treatment of acute pain episodes in SCD has resulted in widely varying opioid regimens prescribed by inpatient providers and has created clinical challenges regarding the optimization of pain management. This study investigated inpatient opioid regimens utilized in treatment of vaso-occlusive crisis and found that the initiation of ER opioids resulted in increased length of stay for ER opioid-naïve patients as compared to treatment with IR opioids alone. These results question the benefit of inpatient ER opioids in relation to the risk of opioid dependence and MME escalation.

Temporal trends and patterns in initial opioid prescriptions after hospital discharge following colectomy in England over 10 years.

While opioid analgesics are often necessary for the management of acute postoperative pain, appropriate prescribing practices are crucial to avoid harm. The aim was to investigate the changes in the proportion of people receiving initial opioid prescriptions after hospital discharge following colectomy, and describe trends and patterns in prescription characteristics. This was a retrospective cohort study. Patients undergoing colectomy in England between 2010 and 2019 were included using electronic health record data from linked primary (Clinical Practice Research Datalink Aurum) and secondary (Hospital Episode Statistics) care. The proportion of patients having an initial opioid prescription issued in primary care within 90 days of hospital discharge was calculated. Prescription characteristics of opioid type and formulation were described. Of 95 155 individuals undergoing colectomy, 15 503 (16.3%) received opioid prescriptions. There was a downward trend in the proportion of patients with no prior opioid exposure (opioid naive) who had a postdischarge opioid prescription (P <0.001), from 11.4% in 2010 to 6.7% in 2019 (-41.3%, P <0.001), whereas the proportions remained stable for those prescribed opioids prior to surgery, from 57.5% in 2010 to 58.3% in 2019 (P = 0.637). Codeine represented 44.5% of all prescriptions and prescribing increased by 14.5% between 2010 and 2019. Prescriptions for morphine and oxycodone rose significantly by 76.6% and 31.0% respectively, while tramadol prescribing dropped by 48.0%. The most commonly prescribed opioid formulations were immediate release (83.9%), followed by modified release (5.8%) and transdermal (3.2%). There was a modest decrease in the prescribing of immediate-release formulations from 86.0% in 2010 to 82.0% in 2019 (P <0.001). Over the 10 years studied, there was a changing pattern of opioid prescribing following colectomy, with a decrease in the proportion of opioid-naive patients prescribed postdischarge opioids.

The Importance of Drug Delivery in the Clinical Development and Lifecycle of Drug Products with Examples from Authorised Medicinal Products

Drug delivery systems (DDS) are formulations or devices that enable the introduction of a therapeutic into the body and its delivery to its target site, potentially enhancing its efficacy and safety. Advances in formulation approaches related to the enhancement of solubility, permeability and thus bioavailability of drugs have already been successfully implemented by the pharmaceutical industry. This review highlights the importance of formulations/DDS in the clinical development and the lifecycle of drug products. Examples from already authorised drug products have been used to showcase how the development of appropriate formulations/DDS could deliver drugs to the site of action (e.g., pulmonary and nasal drug delivery) and enhance patient adherence to medication (e.g., long-acting injectables, 3D-printed tablets). Moreover, examples from authorised products have been provided to highlight how formulation can improve safety (e.g., liposomes, abuse-deterrent opioid formulations) and efficacy (e.g., albumin-based nanoparticles, permeation enhancers for oral delivery of peptides).

Predictors of persistent postoperative opioid use following colectomy: a population-based cohort study from England.

This retrospective cohort study on adults undergoing colectomy from 2010 to 2019 used linked primary (Clinical Practice Research Datalink), and secondary (Hospital Episode Statistics) care data to determine the prevalence of persistent postoperative opioid use following colectomy, stratified by pre-admission opioid exposure, and identify associated predictors. Based on pre-admission opioid exposure, patients were categorised as opioid-naïve, currently exposed (opioid prescription 0-6 months before admission) and previously exposed (opioid prescription within 7-12 months before admission). Persistent postoperative opioid use was defined as requiring an opioid prescription within 90 days of discharge, along with one or more opioid prescriptions 91-180 days after hospital discharge. Multivariable logistic regression analyses were conducted to obtain odds ratios for predictors of persistent postoperative opioid use. Among the 93,262 patients, 15,081 (16.2%) were issued at least one opioid prescription within 90 days of discharge. Of these, 6791 (45.0%) were opioid-naïve, 7528 (49.9%) were currently exposed and 762 (5.0%) were previously exposed. From the whole cohort, 7540 (8.1%) developed persistent postoperative opioid use. Patients with pre-operative opioid exposure had the highest persistent use: 5317 (40.4%) from the currently exposed group; 305 (9.8%) from the previously exposed group; and 1918 (2.5%) from the opioid-naïve group. The odds of developing persistent opioid use were higher among individuals who used long-acting opioid formulations in the 180 days before colectomy than those who used short-acting formulations (odds ratio 3.41 (95%CI 3.07-3.77)). Predictors of persistent opioid use included: previous opioid exposure; high deprivation index; multiple comorbidities; use of long-acting opioids; white race; and open surgery. Minimally invasive surgical approaches were associated with lower odds of persistent opioid use and may represent a modifiable risk factor.

Long-Acting Opioid Analgesics for Acute Pain: Pharmacokinetic Evidence Reviewed.

Long-acting injectable (LAI) opioid formulations mitigate the harm profiles and management challenges associated with providing effective analgesia for animals. A single dose of a long-acting opioid analgesic can provide up to 72 h of clinically relevant pain management. Yet, few of these new drugs have been translated to products for veterinary clinics. Regulatory pathways allow accelerated drug approvals for generic and biosimilar drugs. These pathways depend on rigorous evidence for drug safety and pharmacokinetic evidence demonstrating bioequivalence between the new and the legacy drug. This report reviews the animal PK data associated with lipid and polymer-bound buprenorphine LAI formulations. Buprenorphine is a widely used veterinary opioid analgesic. Because of its safety profile and regulatory status, buprenorphine is more accessible than morphine, methadone, and fentanyl. This review of PK studies coupled with the well-established safety profile of buprenorphine suggests that the accelerated approval pathways may be available for this new family of LAI veterinary pharmaceuticals.

O128 Time trends in opioid prescribing after discharge following colectomy in england: a cross-sectional study

Abstract Introduction Opioid prescribing patterns after discharge following colectomy within a population from England are not well characterised. This study aimed to report changes in opioid prescribing prevalence, formulation choices and opioid analgesics over time. Methods This cross-sectional analysis included people undergoing colectomy between 2010 and 2019 using primary (Clinical Practice Research Datalink) and linked secondary care (Hospital Episode Statistics) data. The prevalence of initial opioid prescription within 90 days of surgical discharge was calculated, and prescription characteristics in terms of analgesics and formulation were described. Trend analysis was performed using the Cochran Armitage test, and percentage change between 2010 and 2019 was tested using univariate logistic regression. Results Of the 95,155 individuals undergoing colectomy within the study period, 15,503 (16.3%) received opioid prescriptions. There was a decreasing trend in the prevalence of post-discharge opioids for opioid naïve people (P&amp;lt;0.001), with a decrease from 11.4% in 2010 to 6.7% in 2019 (-41.3%, p&amp;lt;0.001). Whereas the prevalence remained stable for patients prescribed opioids prior to surgery (p=0.637). The prescribing of immediate release formulations decreased from 86% in 2010 to 82% in 2019 (-4.65%). Codeine represented 44.5% of all prescriptions and prescribing increased by 14.5% between 2010 and 2019. Moreover, morphine and oxycodone prescriptions rose significantly by 76.6% and 131%, respectively, while tramadol prescribing dropped by 48%. Conclusion This study identified a changing pattern of opioid prescribing following colectomy, with prescribing prevalence decreasing for opioid naïve people. Trends suggested decreased tramadol prescribing, but a shift toward increasing codeine, oxycodone and morphine prescriptions.

Specific Pharmacology of Long-Acting, Extended-Release, and Sustained-Release Opioids for the Treatment of Chronic Nonmalignant Pain

Opioid products, specifically long-acting (LA), extended-release (ER), and sustained-release (SR) formulations, are used for the treatment of a subset of patients with chronic noncancer pain (CNCP). This article will review the specific pharmacology and risks associated with specific LA, ER, and SR opioid formulations that have been used in the treatment of chronic pain. This article will not address the indications for, evidence for and against, or general controversy regarding the use of any form of long-term opioid therapy for the treatment of chronic nonmalignant pain (CNMP), as this has been presented in other published works.