Therapeutic failure reported with HIV long-acting injectables: An analysis of the FDA Adverse Event Reporting System from 2021 to 2024.

OBJECTIVES: We examined adverse event (AE) reports relating to cabotegravir/rilpivirine (CAB/RPV) in the US FDA Adverse Event Reporting System (FAERS), focusing on therapeutic failure (TF) and non-therapeutic failure (NTF) outcomes. METHODS: FAERS is a database of AE and medication error reports from post-marketing surveillance. The study was granted exempt approval by the Binghamton University Institutional Review Board. We queried reports for CAB/RPV in the FAERS system from 1 January 2021 to 31 March 2024. TFs were defined as involving any of the following terms: viral load increased, virological failure, pathogen resistance, blood HIV RNA increased, treatment failure, drug ineffective, viral mutation identified, viraemia, and therapy non-responder. The top 20 most common AEs were also identified. Means, standard deviations, and percentages were used to characterize the sample. RESULTS: The study cohort consisted of 2605 reports. The reported sex of the study cohort was 50% male (n = 1295), 19% female (n = 505), and 31% unspecified (n = 805), with a mean ± standard deviation (SD) age of 46.9 ± 12.4 years (n = 378). The top three most reported AEs were TFs, product dose omissions, and injection site pain, with 377 (14.5%), 354 (13.6%), and 331 (12.7%) cases, respectively. The mean ± SD weight of people with a report of TF versus NTF was 101.8 ± 33.4 kg and 87.7 ± 26.7 kg, respectively (p = 0.0175). CONCLUSION: Our findings suggest that healthcare professionals should have a heightened awareness of potential challenges with CAB/RPV administration, including TFs and dose omissions in real-world settings.

Dynamic Changes in the Distribution of Hydrocodone and Oxycodone in Florida from 2006 to 2021.

BACKGROUND: Florida, which led the country in terms of its number of opioid-prescribing physicians, was unique during the height of the opioid epidemic because of its lax prescribing laws and high number of unregulated pain clinics. Here, we address differences in the distribution rates of oxycodone and hydrocodone across Florida counties during the peak years of the opioid epidemic using an under-utilized database. METHODS: The Washington Post and the United States Drug Enforcement Administration's Automation of Reports and Consolidated Orders System (ARCOS) databases provided longitudinal oxycodone and hydrocodone distribution data in grams per county (2006-2014) and state (2006-2021). Grams of oxycodone and hydrocodone were converted into morphine milligram equivalents (MMEs). RESULTS: There was a steep increase in oxycodone from 2006 to 2010, with a subsequent decline. In 2010, the average MME per person across Florida was 729.4, a 120.6% increase from 2006. The three counties with the highest MMEs per person in 2010 were Hillsborough (2271.3), Hernando (1915.3), and Broward (1726.9), and they were significantly (p < 0.05) elevated relative to the average county. CONCLUSIONS: The data demonstrated pronounced differences in opioid distribution, particularly oxycodone, between Florida counties during the height of the opioid epidemic. Legislative action taken between 2009 and 2011 aligns with the considerable decline in opioid distribution after 2010.

Utilization of Lower-Dose Cyclobenzaprine in the Older Inpatient.

Background In older inpatients, anticholinergic medications can increase the risk of complications that may increase length of stay (LOS). Cyclobenzaprine is an anticholinergic medication associated with mental status changes, falls, and injuries in older patients. Objective The purpose of this study is to determine whether use of a lower cyclobenzaprine dose (5 mg) compared with higher dosing (10 mg) will affect LOS, 30-day readmission rates, and need for injectable psychotropic agents in inpatients 65 years of age and older. Methods This was a retrospective cohort analysis comparing outcomes in patients 65 years of age and older who received either a 5 mg or 10 mg cyclobenzaprine dose during their inpatient admission over a 2.5-year period. The primary outcome was hospital LOS, adjusted using multivariate linear regression. Secondary outcomes included 30-day readmission rate adjusted using logistic regression and use of injectable antipsychotics or benzodiazepines. A sub-analysis evaluated the impact of the institution's implementation of a geriatric prescribing context (GEM-CON) on cyclobenzaprine dose selection. Results The adjusted LOS was 32.7% longer (95% CI 25.9%-39.9%) for patients exposed to higher-dose cyclobenzaprine. Use of injectable antipsychotics or benzodiazepines was also significantly greater in the higher-dose group (P < 0.001; P = 0.025). Cyclobenzaprine dose was not significantly associated with readmission on multivariate analysis (OR = 0.93, 95% CI 0.45-1.93). After GEM-CON implementation, there was a significant increase in use of the recommended lower cyclobenzaprine dose (P < 0.001). Conclusion Use of lower cyclobenzaprine dosing in older inpatients is associated with reduced hospital LOS and need for injectable antipsychotics and benzodiazepines.

Retrospective study investigating naloxone prescribing and cost in US Medicaid and Medicare patients.

BACKGROUND: Opioid overdoses in the USA have increased to unprecedented levels. Administration of the opioid antagonist naloxone can prevent overdoses. OBJECTIVE: This study was conducted to reveal the pharmacoepidemiologic patterns in naloxone prescribing to Medicaid patients from 2018 to 2021 as well as Medicare in 2019. DESIGN: Observational pharmacoepidemiologic study SETTING: US Medicare and Medicaid naloxone claims INTERVENTION: The Medicaid State Drug Utilisation Data File was utilised to extract information on the number of prescriptions and the amount prescribed of naloxone at a national and state level. The Medicare Provider Utilisation and Payment was also utilised to analyse prescription data from 2019. OUTCOME MEASURES: States with naloxone prescription rates that were outliers of quartile analysis were noted. RESULTS: The number of generic naloxone prescriptions per 100 000 Medicaid enrollees decreased by 5.3%, whereas brand naloxone prescriptions increased by 245.1% from 2018 to 2021. There was a 33.1-fold difference in prescriptions between the highest (New Mexico=1809.5) and lowest (South Dakota=54.6) states in 2019. Medicare saw a 30.4-fold difference in prescriptions between the highest (New Mexico) and lowest states (also South Dakota) after correcting per 100 000 enrollees. CONCLUSIONS: This pronounced increase in the number of naloxone prescriptions to Medicaid patients from 2018 to 2021 indicates a national response to this widespread public health emergency. Further research into the origins of the pronounced state-level disparities is warranted.

Rising cases of drug-induced pulmonary fibrosis: Analysis of the Food and Drug Administration Adverse Event Reporting System (FAERS) database, 2000-2022.

PURPOSE: Pulmonary fibrosis (PF) is a severe, progressive disease, which may be caused by exposure to certain medications. METHODS: We queried the U.S. FDA Adverse Event Reporting System (FAERS) from 2000 to 2022, using the search terms "pulmonary fibrosis" and "idiopathic pulmonary fibrosis" and excluded reports with patients under the age of 18 years, and patients with unknown sex or age. Reports were sorted by generic drug names, counted, and plotted over time using a best-fit trendline based on an exponential function. RESULTS: From 2000 to 2022, there were 24 095 935 adverse drug events reported in FAERS, of which 17 520 (0.07%) were reported as PF. After excluding reports containing patients with unknown age (5255, 30%), sex (122, 0.7%), and age below 18 years old (155, 0.9%), our study included 11 988 reports. The mean age of the study sample was 66.5 ± 13.1 years, and 6248 patients (52.1%) were male. Plotting the 11 988 reports by year revealed an exponential best fit line (R2 = 0.88) with a positive slope over time. The top five drug classes associated with PF were disease modifying antirheumatic drugs (DMARDs, 39.4%), antineoplastic agents (26.4%), cardiovascular agents (12.6%), corticosteroids (4.6%), and immunosuppressive agents (4.0%). CONCLUSION: A 23-year analysis of the FAERS database revealed exponentially increasing adverse event reports of PF. Significant annual increases in reporting of PF suspected with DMARDs and antineoplastic agents were identified. Our study highlights important trends, which should be used to guide PF research related to drugs of potential importance.

State-level variation in distribution of oxycodone and opioid-related deaths from 2000 to 2021: an ecological study of ARCOS and CDC WONDER data in the USA.

OBJECTIVES: This study aims to characterise oxycodone's distribution and opioid-related overdoses in the USA by state from 2000 to 2021. DESIGN: This is an observational study. SETTING: More than 80 000 Americans died of an opioid overdose in 2021 as the USA continues to struggle with an opioid crisis. Prescription opioids play a substantial role, introducing patients to opioids and providing a supply of drugs that can be redirected to those seeking to misuse them. METHODS: The Drug Enforcement Administration annual summary reports from the Automation of Reports and Consolidated Orders System provided weights of oxycodone distributed per state by business type (pharmacies, hospitals and practitioners). Weights were converted to morphine milligram equivalents (MME) per capita and normalised for population. The Centers for Disease Control and Prevention Wide-ranging ONline Data for Epidemiologic Research provided mortality data for heroin, other opioids, methadone, other synthetic narcotics and other/unspecified narcotics. RESULTS: There was a sharp 280.13% increase in total MME/person of oxycodone from 2000 to 2010, followed by a slower 54.34% decrease from 2010 to 2021. Florida (2007-2011), Delaware (2003-2020) and Tennessee (2012-2021) displayed consistent and substantial elevations in combined MME/person compared with other states. In the peak year (2010), there was a 15-fold difference between the highest and lowest states. MME/person from only pharmacies, which constituted >94% of the total, showed similar results. Hospitals in Alaska (2000-2001, 2008, 2010-2021), Colorado (2008-2021) and DC (2000-2011) distributed substantially more MME/person over many years compared with other states. Florida stood out in practitioner-distributed oxycodone, with an elevation of almost 15-fold the average state from 2006 to 2010. Opioid-related deaths increased +806% from 2000 to 2021, largely driven by heroin, other opioids and other synthetic narcotics. CONCLUSIONS: Oxycodone distribution across the USA showed marked differences between states and business types over time. Investigation of opioid policies in states of interest may provide insight for future actions to mitigate opioid misuse.

First generation antipsychotic-associated serious adverse events in women: a retrospective analysis of a pharmacovigilance database.

BACKGROUND: Women have been under-represented in trials of antipsychotic medications. AIM: Our primary objective was to evaluate five adverse events (AE) associated with first-generation antipsychotics (FGAs) among women relative to men through an analysis of the FDA Adverse Event Reporting System (FAERS). METHOD: We queried 24.6 million AE reports from 2000 to 2023 involving FGAs. The study cohort consisted of chlorpromazine (n = 3317), fluphenazine (n = 1124), haloperidol (n = 16,709), loxapine (n = 3151), perphenazine (n = 816), thioridazine (n = 665), thiothixene (n = 244), and trifluoperazine (n = 360). Cases of neuroleptic malignant syndrome (NMS), tardive dyskinesia (TD), Torsades de Pointes (TdP), agranulocytosis (AG), and cerebrovascular adverse events (CVAE) were identified. Reporting odds ratios (ROR) and associated 95% confidence intervals (CI) were calculated with logistic regression for each AE among women relative to men. RESULTS: A total of 2,857 serious AEs were evaluated in the study cohort (NMS = 1810, TD = 434, TdP = 260, AG = 149, CVAE = 204). The ROR for women compared to men was 0.79 (95% CI, 0.71-0.87) for NMS, 0.83 (0.68-1.01) for TD, 1.21 (0.94-1.53) for TdP, 0.71 (0.51-0.98) for AG, and 0.91 (0.68-1.19) for CVAE. A secondary analysis revealed a higher odds in women compared to men of hospitalization associated with reports of TD (ROR = 1.95, 1.29-2.94) and death associated with reports of AG (ROR = 2.46, 1.15-5.24). A subgroup analysis of haloperidol revealed an ROR = 1.67 (1.26-2.21) for women relative to men for TdP. CONCLUSION: The subgroup analysis of haloperidol AEs revealed a significantly higher reporting odds ratio for TdP. Additionally, the secondary study findings suggest that women were more vulnerable to worse outcomes associated with certain AEs of FGAs.

Declining but Pronounced State-Level Disparities in Prescription Opioid Distribution in the United States.

The United States (US) opioid epidemic is a persistent and pervasive public health emergency that claims the lives of over 80,000 Americans per year as of 2021. There have been sustained efforts to reverse this crisis over the past decade, including a number of measures designed to decrease the use of prescription opioids for the treatment of pain. This study analyzed the changes in federal production quotas for prescription opioids and the distribution of prescription opioids for pain and identified state-level differences between 2010 and 2019. Data (in grams) on opioid production quotas and distribution (from manufacturer to hospitals, retail pharmacies, practitioners, and teaching institutions) of 10 prescription opioids (codeine, fentanyl, hydrocodone, hydromorphone, meperidine, methadone, morphine, oxycodone, oxymorphone, and tapentadol) for 2010 to 2019 were obtained from the US Drug Enforcement Administration. Amounts of each opioid were converted from grams to morphine milligram equivalent (MME), and the per capita distribution by state was calculated using population estimates. Total opioid production quotas increased substantially from 2010 to 2013 before decreasing by 41.5% from 2013 (87.6 MME metric tons) to 2019 (51.3). The peak year for distribution of all 10 prescription opioids was between 2010 and 2013, except for codeine (2015). The largest quantities of opioid distribution were observed in Tennessee (520.70 MME per person) and Delaware (251.45) in 2011 and 2019. There was a 52.0% overall decrease in opioid distribution per capita from 2010 to 2019, with the largest decrease in Florida (-61.6%) and the smallest in Texas (-18.6%). Southern states had the highest per capita distribution for eight of the ten opioids in 2019. The highest to lowest state ratio of total opioid distribution, corrected for population, decreased from 5.25 in 2011 to 2.78 in 2019. The mean 95th/5th ratio was relatively consistent in 2011 (4.78 ± 0.70) relative to 2019 (5.64 ± 0.98). This study found a sustained decline in the distribution of ten prescription opioids during the last five years. Distribution was non-homogeneous at the state level. Analysis of state-level differences revealed a fivefold difference in the 95th:5th percentile ratio between states, which has remained unchanged over the past decade. Production quotas did not correspond with the distribution, particularly in the 2010-2016 period. Future research, focused on identifying factors contributing to the observed regional variability in opioid distribution, could prove valuable to understanding and potentially remediating the pronounced disparities in prescription opioid-related harms in the US.

Pronounced State-Level Disparities in Medicaid Prescribing of Buprenorphine for Opioid Use Disorder (2019-2020).

OBJECTIVE: The purpose of this study was to analyze buprenorphine prescribing across states in Medicaid patients during 2019-2020. METHOD: Buprenorphine prescriptions per Medicaid enrollee per state were calculated for 2019 and 2020. Data analysis was conducted with buprenorphine formulations that are approved by the U.S. Food & Drug Administration for opioid use disorder (OUD; including generic and brand name formulations of buprenorphine mono product and buprenorphine/naloxone combination products) using Microsoft Excel. The totals of mono product buprenorphine were divided over the total of combination buprenorphine/naloxone in 2019 and 2020 to obtain the ratio of mono/combo. Formulations of buprenorphine indicated for pain were excluded. States outside 95% confidence intervals (1.96 standard deviations above and below the mean) were considered statistically significant. RESULTS: The overall change in buprenorphine prescribing between 2019 and 2020 was modest (+3.6%) but highly variable, with more than a 10% increase in 17 states (Iowa = +100.5%, p < .05) but more than a 10% decrease in 9 states (Alabama = -68.5%, p < .05). Total amount reimbursed in 2019 increased (+9.9%) to $1.42 billion in 2020. Branded formulations accounted for two fifths (39.5%) of prescribing but more than two thirds (66.8%) of spending in 2020. CONCLUSIONS: The COVID-19 pandemic exacerbated state-level disparities in buprenorphine prescribing for OUD among Medicaid patients. Legislation expanding buprenorphine-waivered providers and Medicaid expansion may have contributed to the statistically significant changes in state buprenorphine prescriptions.

Dynamic changes in methadone utilisation for opioid use disorder treatment: a retrospective observational study during the COVID-19 pandemic.

OBJECTIVES: Opioid use disorder (OUD) is a major public health concern in the USA, resulting in high rates of overdose and other negative outcomes. Methadone, an OUD treatment, has been shown to be effective in reducing the risk of overdose and improving overall health and quality of life. This study analysed the distribution of methadone for the treatment of OUD across the USA over the past decade and through the COVID-19 pandemic. DESIGN: Retrospective observational study using secondary data analysis of the Drug Enforcement Administration and Medicaid Databases. SETTING: USA. PARTICIPANTS: Patients who were dispensed methadone at US opioid treatment programmes (OTPs). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcomes were the overall pattern in methadone distribution and the number of OTPs in the USA per year. The secondary outcome was Medicaid prescriptions for methadone. RESULTS: Methadone distribution for OUD has expanded significantly over the past decade, with an average state increase of +96.96% from 2010 to 2020. There was a significant increase in overall distribution of methadone to OTP from 2010 to 2020 (+61.00%, p<0.001) and from 2015 to 2020 (+26.22%, p<0.001). However, the distribution to OTPs did not significantly change from 2019 to 2021 (-5.15%, p=0.491). There was considerable state-level variation in methadone prescribing to Medicaid patients with four states having no prescriptions. CONCLUSIONS: There have been dynamic changes in methadone distribution for OUD. Furthermore, pronounced variation in methadone distribution among states was observed, with some states having no OTPs or Medicaid coverage. New policies are urgently needed to increase access to methadone treatment, address the opioid epidemic in the USA and reduce overdose deaths.