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.

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.

Pronounced State-Level Disparities in Prescription of Cannabinoids to Medicaid Patients.

Introduction: Dronabinol is approved in the USA for chemotherapy-induced nausea as well as vomiting and HIV-induced anorexia, while cannabidiol is primarily approved for childhood epileptic disorders Lennox-Gastaut and Dravet syndrome. The use pattern for these prescription cannabinoids in the USA is unknown. This study examined Medicaid claims for two FDA-approved prescription cannabinoids, dronabinol and cannabidiol, approved in 1985 and 2018, respectively, from 2016-2020 to better understand the pharmacoepidemiologic trends and distribution of these drugs in US Medicaid amidst the increasing use of non-pharmaceutical formulations of cannabis. Methods: The longitudinal study analyzed Medicaid prescription claims that were calculated by extracting the prescriptions on a state level from 2016 to 2020 for two cannabinoids, dronabinol and cannabidiol, where outcomes over each year were calculated. Outcomes were (1) the number of prescriptions for each state corrected for the number of Medicaid enrollees and (2) dronabinol and cannabidiol spending. Spending refers to the amount reimbursed by the state Medicaid program. Results: Dronabinol prescriptions per state decreased by 25.3% from 2016 to 2020, while cannabidiol prescriptions increased by 16,272.99% from 2018 to 2020. The spending on these drugs parallels that of their prescription trend with a 66.3% decrease in reimbursement for dronabinol ($5.7 million in 2020), whereas cannabidiol increased by +26,582.0% ($233.3 million in 2020). Dronabinol prescriptions, when corrected for the number of enrollees, in Connecticut were 136.4 times larger than in New Mexico, and seventeen states had zero prescriptions. Idaho's prescriptions of cannabidiol (27.8/10,000 enrollees) were significantly elevated relative to the national average and were 15.4-fold higher than Washington, DC (1.8/10K enrollees). Conclusions: The prescriptions of pharmaceutical-grade tetrahydrocannabinol decreased while those of cannabidiol increased. This study also identified pronounced state-level variation in cannabinoid prescribing to Medicaid patients. State formularies and prescription drug list variation may contribute to the drug reimbursements in Medicaid, though further research is needed to identify the health policy or pharmacoeconomic origins of these disparities.

High Prescribing and State-Level Variation in Z-Drug Use Among Medicare Patients.

BACKGROUND: Z-drugs are nonbenzodiazepine hypnotics used for sleep initiation and maintenance; these drugs increase the risk of fall-related injuries in older adults. The American Geriatrics Society's Beers criteria classifies Z-drugs as high-risk and strongly recommends avoiding prescribing Z-drugs to older adults due to adverse effects. The study objectives were to determine the prevalence of Z-drug prescribing among Medicare Part D patients and identify state or specialty-dependent prescribing differences. This study also aimed to determine prescribing patterns of Z-drugs to Medicare patients. METHODS: Z-drug prescription data was extracted from the Centers for Medicare and Medicaid Services State Drug Utilization Data for 2018. For all 50 states, the number of prescriptions per 100 Medicare enrollees and days-supply per prescription was determined. The percentage of total prescriptions prescribed by each specialty and the average number of prescriptions per provider within each specialty was also determined. RESULTS: Zolpidem was the most prescribed Z-drug (95.0%). Prescriptions per 100 enrollees were significantly high in Utah (28.2) and Arkansas (26.7) and significantly low in Hawaii (9.3) relative to the national average (17.5). Family medicine (32.1%), internal medicine (31.4%), and psychiatry (11.7%) made up the largest percentages of total prescriptions. The number of prescriptions per provider was significantly high among psychiatrists. DISCUSSION: Contrary to the Beers criteria, Z-drugs are prescribed to older adults at high rates.

Reductions and pronounced regional differences in morphine distribution in the United States.

OBJECTIVES: The purpose of this longitudinal study was to describe the temporal pattern of morphine distribution nationally and between states. METHODS: Drug weight was obtained from Report 5 of the US Drug Enforcement Administration's Automation of Reports and Consolidated Orders System (ARCOS) to characterize patterns in the distribution of morphine from 2012 to 2021. Morphine distribution amounts were separated by state and business type and corrected for population. States outside a 95% confidence interval relative to the national average were considered statistically significant. KEY FINDINGS: In 2012, there was a 4.6-fold difference in morphine distribution between the highest-prescribing state, Tennessee (180.2 mg/person), and the lowest-prescribing state, Texas (39.4 mg/person). By the end of 2021, national distribution of morphine had decreased by 59.9% when compared to the peak year 2012. In 2021, Tennessee (51.1 mg/person) remained the highest-prescribing state with a 3.0-fold difference relative to Texas (17.2 mg/person). The average hospital decrease (-73.9%) from 2012 to 2021 was larger than that of pharmacies (-58.2%). CONCLUSIONS: The national 59.9% decline in morphine in the last decade may be attributable to prioritization of the US opioid crisis as a public concern. Further research is necessary to understand the persistent regional difference between states.

Pronounced Declines in Meperidine in the US: Is the End Imminent?

Background: Once a widely used analgesic in the United States (US), meperidine offered an alternative opioid to other opioids as a pain reliever and was widely assumed to be safer with acute pancreatitis. However, within the last two decades meperidine, has gone from a frequently used drug to being used only when patients exhibit atypical reactions to opioids (e.g., morphine and hydromorphone), to being taken off the World Health Organization List of Essential Medications and receiving strong recommendations for overall avoidance. The aim of this study was to identify changes in meperidine distribution in the US, and regional disparities as reported to the Drug Enforcement Administration's Automation of Reports and Consolidated Orders System (DEA ARCOS) and Medicaid. Methods: Data related to meperidine distribution was obtained through ARCOS (2001−2021) and Medicaid public use files (2016−2021). Heat maps were used to visualize regional disparities in distribution by state. States outside a 95% confidence interval were statistically significant. Results: Meperidine distribution between 2001 and 2021 decreased by 97.4% (R = −0.97, p < 0.0001). There was a 34-fold state-level difference in meperidine distribution between Arkansas (16.8 mg/10 persons) and Connecticut (0.5 mg/10 persons) in 2020. Meperidine distribution in 2020 was elevated in Arkansas, Mississippi, and Alabama. In 2021, meperidine distribution was highest in Arkansas (16.7 mg/10 persons) and lowest in Connecticut (0.8 mg/10 persons). Total prescriptions of meperidine as reported by Medicaid decreased by 73.8% (R = −0.67, p = 0.045) between 2016 and 2021. Conclusion: We observed a decrease in the overall distribution of meperidine in the past two decades, with a similar recent decline in prescribing it to Medicaid enrollees. The shortage of some parenteral formulations is an important contributor to these declines, however, the most likely explanation for this global decline in use is related to an increased recognition of safety concerns related to important drug interactions and a neurotoxic metabolite. This data may reflect plans to phase out the use of this opioid, especially in the many situations where safer and more preferred opioids are available.

Pronounced declines in dispensed licit fentanyl, but not fentanyl derivatives.

BACKGROUND: Fentanyl and its derivatives are highly utilized opioid-based analgesics provided to patients in various formulations, but this agent has also been implicated in many overdoses when misused. The evolving opioid crisis has increased pressure on the healthcare industry to monitor opioid prescriptions. Different policies and procedures implemented to contain the crisis have impacted the utilization of some opioids. OBJECTIVE: A prior report identified three-fold differences between states in fentanyl use. This study explored fentanyl distribution patterns from 2010 to 2019. METHODS: The amount of fentanyl base distributed from 2010 to 2019 was obtained from the Drug Enforcement Administration. Sufentanil, alfentanil, and remifentanil were also analyzed from 2010 to 2017, the most recent year reported. Prescriptions, units, and reimbursement for 2010 and 2019 were obtained from Medicaid and fentanyl prescriber specialty from Medicare Part D. RESULTS: There was a 65.5% decrease in the overall milligrams of fentanyl per person distributed corrected for population. Ohio had the greatest decrease (-79.3%), while Mississippi saw the smallest (-44.5%). There was a 6.8-fold regional difference in the quantity of fentanyl distributed per person in 2010 from hospitals (South Dakota = 775.2, Alabama = 113.2 µg/person). The regional difference was also sizeable for pharmacies (6.2-fold, Mississippi = 1,025.3, Washington DC = 165.6). Medicaid reimbursement in 2019 was $165 million for over eight hundred-thousand prescriptions with the majority for generic (99.7%) and injectable (77.6%) formulations. Interventional pain management and anesthesia were over-represented, and hematology/oncology significantly under-represented for fentanyl prescriptions in Medicare. CONCLUSION: The distribution of fentanyl-based substances decreased, although not uniformly, in the US over the last decade. Additionally, the most prescribed formulations of fentanyl have transitioned away from transdermal, potentially in an effort to regulate its availability. The considerable state-level disparities observed for fentanyl distribution from pharmacies and hospitals warrant further attention as there may be regional practices which are incongruent with evidence-based medicine.

Decline and Pronounced Regional Disparities in Medical Cocaine Usage in the United States.

Background: Cocaine is a stimulant and Schedule II drug used as a local anesthetic and vasoconstrictor. Objective: This descriptive study characterized medical cocaine use in the United States. Methods: Retail drug distribution data from 2002 to 2017 were extracted for each state from the Drug Enforcement Administration, which reports on medical, research, and analytical chemistry use. The percentage of buyers (pharmacies, hospitals, and providers) was obtained. Use per state, corrected for population, was determined. Available cross-sectional data on cocaine use as reported by the Medicare and Medicaid programs for 2013-2017 and electronic medical records were examined. Results: Medical cocaine use decreased by -62.5% from 2002 to 2017. Hospitals accounted for 84.9% and practitioners for 9.9% of cocaine distribution in 2017. The number of pharmacies carrying cocaine dropped by -69.4%. The percentages of hospitals, practitioners, and pharmacies that carried cocaine in 2017 were 38.4%, 2.3%, and 0.3%, respectively. There was a 7-fold difference in 2002 (South Dakota, 76.1 mg/100 persons; Delaware, 10.1 mg/100 persons). Relative to the average state in 2017, those reporting the highest values (Montana, 20.1; North Dakota, 24.1 mg/100 persons) were significantly elevated. Cocaine use within the Medicare and Medicaid programs was negligible. Cocaine use within the Geisinger system was rare from 2002 to 2007 (<4 orders/100 000 patients per year) but increased to 48.7 in 2018. Conclusion and Relevance: If these pharmacoepidemiological patterns continue, licit cocaine may soon become a historical relic. The pharmacology and pharmacotherapeutics education of health care providers may need to be adjusted accordingly.

Opioid Mortality Following Implementation of Medical Cannabis Programs in the United States.

INTRODUCTION: The United States is in the midst of an opioid overdose epidemic. Emerging evidence suggests that medical cannabis (MC) may reduce use of opioids for pain in some individuals, with potential impacts on opioid-related overdose. However, there may be other important differences between states that did, and did not, adopt MC. METHODS: This study evaluated differences following legal MC sales on US opioid-related overdose deaths, corrected for population, from 1999 to 2017 using an interrupted time series. Comparisons by MC status were also made for Medicaid expansion and the Centers for Disease Control death certificate reporting quality (0:

Rise and regional disparities in buprenorphine utilization in the United States.

PURPOSE: Buprenorphine is an opioid partial agonist used to treat opioid use disorder. While several policy changes have attempted to increase buprenorphine availability, access remains well below optimal levels. This study characterized how buprenorphine utilization in the United States has changed over time and whether there are regional disparities in distribution of the medication. METHODS: The amount of buprenorphine distributed from 2007 to 2017 was obtained from the Drug Enforcement Administration's Automated Reports and Consolidated Ordering System. Data were expressed as the percent change and milligrams per person in each state. The formulations and cost for prescriptions covered by Medicaid (2008 to 2018) were also examined. RESULTS: Buprenorphine distributed to pharmacies increased about 7-fold (476.8 to 3179.9 kg) while the quantities distributed to hospitals grew 5-fold (18.6 to 97.6 kg) nationally from 2007 to 2017. Buprenorphine distribution per person was almost 20-fold higher in Vermont (40.4 mg/person) relative to South Dakota (2.1 mg/person). There was a strong association between the number of physicians authorized to prescribe buprenorphine and distribution per state (r[49] = +0.94, P < .0005). The buprenorphine/naloxone sublingual film (Suboxone) was the predominant formulation (92.6% of 0.31 million Medicaid prescriptions) in 2008 but accounted for less than three-fifth (57.3% of 6.56 million prescriptions) in 2018. CONCLUSIONS: Although buprenorphine availability has substantially increased over the last decade, distribution was very nonhomogeneous across the United States.

Assessment of Controlled Substance Distribution to U.S. Veterinary Teaching Institutions From 2006 to 2019.

Objective: To evaluate the changing pattern of distribution of Schedule II and III opioids, barbiturates, and stimulants to veterinary educational institutions in the United States. Design: Longitudinal study. Sample: Veterinary teaching institutions that use Schedule II and III drugs. Procedures: Distribution of controlled substances to veterinary teaching institutions was obtained from the Drug Enforcement Administration's Automated Reports and Consolidated Orders System (ARCOS) for opioids (e.g., methadone, fentanyl, codeine), barbiturates (pentobarbital, butalbital), and stimulants (amphetamine, methylphenidate, lisdexamfetamine) from 2006-2019. Opioids were converted to their morphine milligram equivalents (MME) for evaluation over time. Results: Controlled substance distribution to veterinary schools exhibited dynamic, and agent specific, changes. The total MME for 11 opioids peaked in 2013 and decreased by 17.3% in 2019. Methadone accounted for two-fifths (42.3%) and fentanyl over one-third (35.4%) of the total MME in 2019. Pentobarbital distribution was greatest by weight of all substances studied and peaked in 2011 at 69.4 kg. Stimulants underwent a pronounced decline and were very modest by 2014. Conclusions and Clinical Relevance: Opioids by total MME in veterinary teaching practice have undergone more modest changes than opioids used with humans. Hydrocodone, codeine and recently fentanyl use have declined while methadone increased. Stimulant distribution decreased to become negligible. Together, this pattern of findings warrant continued monitoring.

Trends in Medical Use of Opioids in the U.S., 2006-2016.

INTRODUCTION: The U.S. is experiencing an opioid epidemic which is at least partially iatrogenic and fueled by both prescription and illicit misuse. This study provides a nationwide examination of opioid distribution patterns during the last decade. METHODS: Data were obtained from the U.S. Drug Enforcement Administration's Automation of Reports and Consolidated Orders System for 2006-2016. Analyses include quantities of ten opioids legally dispensed nationwide by weight and converted to Morphine Milligram Equivalents. Geospatial and state-level analyses were also completed in 2017. RESULTS: The total for ten opioids peaked in 2011 (389.5 metric tons Morphine Milligram Equivalents) relative to both 2006 (286.1) and 2016 (364.6). Changes in the volume of opioids by weight over the decade were agent specific. Since 2011, there were decreases in hydrocodone (-28.4%); oxymorphone (-28.0%); fentanyl (-21.4%); morphine (-18.9%); oxycodone (-13.8%); and meperidine (-58.0%) and an increase in buprenorphine (75.2%) in 2016. There were substantial inter-state variations in rates with a fivefold difference between the highest Morphine Milligram Equivalents in 2016 (Rhode Island=2,623.7 mg/person) relative to the lowest (North Dakota=484.7 mg/person). An association was identified between state median age and per capita Morphine Milligram Equivalents (r =0.49, p<0.0005). CONCLUSIONS: With the exception of buprenorphine, used to treat an opioid use disorder, prescription opioid use has been decreasing over the past 5 years in the U.S. Further efforts are needed to continue to optimize the balance between appropriate opioid access for acute pain while minimizing diversion and treating opioid addiction.

Using Controlled Substance Receipt Patterns to Predict Prescription Overdose Death.

BACKGROUND: This study evaluates complete state data from controlled substance prescribing trends in the prescription monitoring program (PMP) database and their association with the risk of prescription drug overdose death. SUMMARY: Maine PMP records of individuals who died of prescription overdose deaths between 2006 and 2010 were selected (n = 690). For each subject, an age, gender, and residence matched cohort of PMP users in a 50: 1 ratio was identified (n = 34,500). Key Messages: Prescription opioids contributed to 480 of 690 prescription deaths, many co-ingestions were noted, and OR for overdose death increased with milligram of morphine equivalent (MME)/day >100. The majority who were prescribed MME >100 per day received a prescription within 90 days of overdose matching the toxicology cause of death. CONCLUSIONS: Medication profiles available through state PMP can identify dosing of prescriptions associated with drug overdose death.

Assessment of manual blood pressure and heart rate measurement skills of pharmacy students: a follow-up investigation.

OBJECTIVES: To evaluate the impact of a laboratory course on the manual blood pressure (BP) and heart rate (HR) measurement skills of pharmacy students. METHODS: After 1 lecture and 1 laboratory session on vital sign technique, pharmacy students enrolled in a patient assessment laboratory course were randomly paired with a classmate and manually measured the classmate's BP and HR. Within 2 minutes, the BP and HR were measured by an Omron 711-AC automatic monitor. The same assessment procedures with manual and automatic measurements were repeated near the end of the laboratory course. Student skills were also evaluated through direct observation by faculty members. RESULTS: Student and machine measurements of systolic blood pressure (SBP), diastolic blood pressure (DBP), and HR significantly correlated at the final assessment (r = 0.92, 0.83, and 0.91 respectively; p < 0.001 for each. The proportion of student and device values agreeing to within 5 units (mmHg and beats-per-minute) at baseline versus at the final assessment significantly improved from 38% to 67% for SBP, 51% to 77% for DBP, and 52% to 79% for HR (p < 0.001 for each). The percentage of students correctly performing all 13 AHA endorsed steps for BP measurement improved significantly from 4.6% to 75.6% (p < 0.001). CONCLUSIONS: Significant improvement and the attainment of competency in manual vital signs measurement were demonstrated by pharmacy students after 11 weeks of skill rehearsal in a laboratory course.

Evaluation of pharmacy students' blood pressure and heart rate measurement skills after completion of a patient assessment course.

OBJECTIVES: To evaluate pharmacy students' skills at measuring brachial artery blood pressure and radial heart rate at the completion of a patient assessment course in the second-professional year of a doctor of pharmacy (PharmD) program. METHODS: Students enrolled in a required patient assessment laboratory course (n = 83) participated in this study. Each student was randomly matched with a classmate and manually measured the classmate's blood pressure by auscultation of the brachial artery and heart rate by palpation of the radial pulse. RESULTS: The student-device absolute disagreement was 6.5 +/- 4.8 mmHg for systolic blood pressure (SBP), 6.2 +/- 4.5 mmHg for diastolic blood pressure (DBP), and 5.3 +/- 4.0 beats per minute (BPM) for heart rate. Student and machine measurements of SBP, DBP, and HR significantly correlated. CONCLUSIONS: Pharmacy students in the second-professional year of a PharmD program demonstrated competence in but not mastery of manual blood pressure and heart rate measurement. These skills need further refinement during third- and fourth-professional year APPEs.