Real world co-prescribing contraindicated drugs with fluconazole and itraconazole.

PURPOSE: This study aimed to investigate co-prescribing of contraindicated drugs with fluconazole and itraconazole using real-world nationwide data. METHODS: This retrospective cross-sectional study was performed using claims data collected by the Health Insurance Review and Assessment Service (HIRA) of Korea during 2019-2020. To determine the drugs that should be avoided in patients taking fluconazole or itraconazole, Lexicomp® and Micromedex® were used. The co-prescribed medications, co-prescription rates, and potential clinical consequences of the contraindicated drug-drug interactions (DDIs) were investigated. RESULTS: Of the 197 118 prescriptions of fluconazole, 2847 co-prescriptions with drugs classified as contraindicated DDI by either Micromedex® or Lexicomp® were identified. Further, of the 74 618 prescriptions of itraconazole, 984 co-prescriptions with contraindicated DDI were identified. Solifenacin (34.9%), clarithromycin (18.1%), alfuzosin (15.1%), and donepezil (10.4%) were frequently found in the co-prescriptions of fluconazole, whereas tamsulosin (40.4%), solifenacin (21.3%), rupatadine (17.8%), and fluconazole (8.8%) were frequently found in the co-prescriptions of itraconazole. In 1105 and 95 co-prescriptions of fluconazole and itraconazole, accounting for 31.3% of all co-prescriptions, potential DDIs were associated with a risk of corrected QT interval (QTc) prolongation. Of the total 3831 co-prescriptions, 2959 (77.2%) and 785 (20.5%) were classified as contraindicated DDI by Micromedex® alone and by Lexicomp® alone, respectively, whereas 87 (2.3%) were classified as contraindicated DDI by both Micromedex® and Lexicomp®. CONCLUSIONS: Many co-prescriptions were associated with the risk of DDI-related QTc prolongation, warranting the attention of healthcare providers. Narrowing the discrepancy between databases that provide information on DDIs is required for optimized medicine usage and patient safety.

Frequencies of Combined Dysfunction of Cytochromes P450 2C9, 2C19, and 2D6 in an Italian Cohort: Suggestions for a More Appropriate Medication Prescribing Process.

Improper drug prescription is a main cause of both drug-related harms (inefficacy and toxicity) and ineffective spending and waste of the healthcare system's resources. Nowadays, strategies to support an improved, informed prescription process may benefit from the adequate use of pharmacogenomic testing. Using next-generation sequencing, we analyzed the genomic profile for three major cytochromes P450 (CYP2C9, CYP2C19, CYP2D6) and studied the frequencies of dysfunctional isozymes (e.g., poor, intermediate, or rapid/ultra-rapid metabolizers) in a cohort of 298 Italian subjects. We found just 14.8% of subjects with a fully normal set of cytochromes, whereas 26.5% of subjects had combined cytochrome dysfunction (more than one isozyme involved). As improper drug prescription is more frequent, and more burdening, in polytreated patients, since drug-drug interactions also cause patient harm, we discuss the potential benefits of a more comprehensive PGX testing approach to support informed drug selection in such patients.

The impact of a restricted pregabalin prescription policy on drug utilization: An observational multicenter study.

Background: The Saudi Food and Drug Authority (SFDA) classified pregabalin as a controlled substance in 2018; however, whether this policy change has affected pregabalin use is unclear. This study examined the trends in pregabalin prescriptions before and after the SFDA restriction. In addition, the co-prescription of controlled analgesics and the use of pregabalin for approved indications were also evaluated. Method: A cross-sectional study was conducted on outpatient pregabalin prescriptions from three healthcare centers in Saudi Arabia. Interrupted time series analysis was used to assess changes over time in pregabalin prescriptions and the number of patients receiving pregabalin. June 2016 to June 2017 was identified as the pre-restriction period, and July 2018 to July 2019 as the post-restriction period. Results: In this study, 77,760 pregabalin prescriptions were identified. There were 9,076 patients on pregabalin in the pre-restriction period with 16,875 prescriptions, compared with 7,123 patients and 19,484 prescriptions post-restriction. The total number of pregabalin users decreased by 21.5% post-restriction, and prescriptions increased by 15.5%. There was no significant change in the monthly trends in pregabalin prescriptions before and after the restriction. However, the of tramadol and acetaminophen/codeine prescriptions in patients who were using pregabalin increased in the post-restriction period by 21% and 16.1%, respectively. Conclusion: Pregabalin use was reduced after the SFDA-enforced prescription restriction was implemented. This was accompanied by increased narcotics use in the post-implementation phase.

Multimorbidity and chronic co-prescription networks and potential interactions in adult patients with epilepsy: MorbiNet study.

OBJECTIVE: We constructed epilepsy multimorbidity networks to study associations with chronic conditions, and co-prescriptions and drug-disease networks to assess potential interactions. We conducted a population-based study in Catalonia, Spain, with electronic files of 3,135,948 adult patients with multimorbidity, 32,625 of them with epilepsy (active diagnosis any time during 2006-2017). We constructed epilepsy comorbidity networks using logistic regression models from odds ratio estimates adjusted by age, sex, and comorbidities with R software and generated trajectories to study the progression of epilepsy. We constructed drug-disease and co-prescription networks using mixed models with repeated measures adjusting by age, sex, and period with chronic prescription invoiced data. Comorbidity more frequently preceding epilepsy included cerebrovascular accident (OR: 3.59), congenital anomalies (2.18), and multiple sclerosis (1.33); and following epilepsy: dementia (1.91), personality disorder (1.59), alcohol abuse (1.22), and Parkinson (1.21). Mental retardation (13.08), neurological cancer (8.49), benign neoplasm (4.69), infections (3.14), and psychosis (1.58) might precede or not epilepsy. A common progression was to schizophrenia, dementia, and other neurological diseases (mainly cerebral palsy and other degenerative diseases of nervous system). Co-prescription associations with major-moderate potential interactions were 54% for carbamazepine, 61% phenytoin, 53% phenobarbital, and 32% valproate. Major potential interactions were with antipsychotic, anxiolytic, opioid, cardiovascular, and other anti-seizure medications (ASMs). The most frequent comorbidities of epilepsy were congenital, cerebrovascular, and neurological and psychiatric conditions. High comorbidity and co-prescription with potential interactions can increase the complexity of care of patients with epilepsy.

Co-prescription of gabapentinoids and opioids among adults with and without osteoarthritis in the United Kingdom between 1995 and 2017.

OBJECTIVES: To produce national and regional estimates and trends for gabapentinoid-opioid co-prescribing rates in patients with OA, both in absolute terms and relative to matched controls without OA. METHODS: Using the UK Clinical Practice Research Datalink database we first constructed age-sex-practice-date 1:1 matched cohorts of patients aged ≥40 years with and without a new diagnosis of OA between 1995-2017 and estimated the relative incidence of a first gabapentinoid prescription. Incident gabapentinoid users in both cohorts were followed to estimate and compare the event rate of gabapentinoid-opioid co-prescription (prescription from both classes within the same 28-day window). RESULTS: The incidence of first gabapentinoid prescription was 3-fold higher in patients with OA than in matched controls [n = 215 357; incidence rate ratio (IRR) 2.93; 95% CI: 2.87, 3.00]. Among incident gabapentinoid users with OA (n = 27 374, median follow-up 3.9 years) the event rate of gabapentinoid-opioid co-prescription was 4.03 (4.02-4.05) per person-year. The rate was higher in OA patients classed as long-term gabapentinoid users (6.24; 6.22-6.26). These rates were significantly higher than in incident gabapentinoid users without OA [adjusted-IRR: 1.29 (1.28-1.30)]. This elevated risk was observed across age, sex, geographic regions, and calendar years, when restricted to strong opioids and to long-term gabapentinoid users, and when co-prescription was defined as within 14 days and same-day prescribing. CONCLUSIONS: Patients with OA not only have a higher risk of being prescribed a gabapentinoid but, once prescribed a gabapentinoid, are also at greater risk of opioid co-prescription. Strict restriction of gabapentinoid-opioid co-prescription, and improved access to, and uptake of, effective non-pharmacological and surgical alternatives for OA are required.

Correlates of Benzodiazepine Use and Adverse Outcomes Among Patients with Chronic Pain Prescribed Long-term Opioid Therapy.

OBJECTIVE: To examine the correlates and odds of receiving overlapping benzodiazepine and opioid prescriptions and whether co-prescription was associated with greater odds of falling or visiting the emergency department. DESIGN: Cross-sectional study. SETTING: A large private integrated health system and a Veterans Health Administration integrated health system. SUBJECTS: Five hundred seventeen adults with musculoskeletal pain and current prescriptions for long-term opioid therapy. METHODS: A multivariate logistic regression model examined correlates of having overlapping benzodiazepine and opioid prescriptions in the year before enrollment in the cross-sectional study. Negative binomial models analyzed the number of falls in the past three months and past-year emergency department visits. In addition to propensity score adjustment, models controlled for demographic characteristics, psychiatric diagnoses, medications, overall comorbidity score, and opioid morphine equivalent dose. RESULTS: Twenty-five percent (N = 127) of participants had co-occurring benzodiazepine and opioid prescriptions in the prior year. Odds of receiving a benzodiazepine prescription were significantly higher among patients with the following psychiatric diagnoses: anxiety disorder (adjusted odds ratio [AOR] = 4.71, 95% confidence interval [CI] = 2.67-8.32, P < 0.001), post-traumatic stress disorder (AOR = 2.24, 95% CI = 1.14-4.38, P = 0.019), and bipolar disorder (AOR = 3.82, 95% CI = 1.49-9.81, P = 0.005). Past-year overlapping benzodiazepine and opioid prescriptions were associated with adverse outcomes, including a greater number of falls (risk ratio [RR] = 3.27, 95% CI = 1.77-6.02, P = 0.001) and emergency department visits (RR = 1.66, 95% CI = 1.08-2.53, P = 0.0194). CONCLUSIONS: Among patients with chronic pain prescribed long-term opioid therapy, one-quarter of patients had co-occurring prescriptions for benzodiazepines, and dual use was associated with increased odds of falls and emergency department visits.

Acceptability of Naloxone Co-Prescription Among Primary Care Providers Treating Patients on Long-Term Opioid Therapy for Pain.

BACKGROUND: Naloxone co-prescription is recommended for patients on long-term opioids for pain, yet there are few data on the practice. OBJECTIVE: To explore naloxone co-prescribing acceptability among primary care providers for patients on long-term opioids. DESIGN: We surveyed providers at six safety-net primary care clinics in San Francisco that had initiated naloxone co-prescribing. Providers were encouraged to offer naloxone to patients on long-term opioids or otherwise at risk of witnessing or experiencing an overdose. Surveys were administered electronically 4 to 11 months after co-prescribing began. KEY RESULTS: One hundred eleven providers (69 %) responded to the survey, among whom 41.4 % were residents; 40.5 % practiced internal medicine and 55.0 % practiced family medicine. Most (79.3 %) prescribed naloxone, to a mean of 7.7 patients; 99.1 % were likely to prescribe naloxone in the future. Providers reported they were likely to prescribe naloxone to most patients, including those on low doses, defined as <20 morphine equivalent mg daily (59.8 %), ≥65 years old (83.9 %), with no overdose history (80.7 %), and with no substance use disorder (73.6 %). Most providers felt that prescribing naloxone did not affect their opioid prescribing, 22.5 % felt that they might prescribe fewer opioids, and 3.6 % felt that they might prescribe more. Concerns about providing naloxone were largely administrative, relating to time and pharmacy or payer logistics. Internists (incidence rate ratio [IRR] = 0.49, 95 % CI = 0.26-0.93, p = 0.029), those licensed for 5-20 years (IRR = 2.10, 95 % CI = 1.35-3.25, p = 0.001), and those with more patients prescribed long-term opioids (IRR = 1.10, 95 % CI = 1.05-1.14, p <0.001) were independently more likely to prescribe a greater number of naloxone compared to participants without these exposures. CONCLUSIONS: Naloxone co-prescription is considered acceptable among primary care providers. Barriers such as time and dispensing logistics may be alleviated by novel naloxone formulations intended for laypersons recently approved by the U.S. Food and Drug Administration.

Trends in Stimulant and Sedative/Hypnotic Dispensing: An Exploratory Study.

OBJECTIVE: To investigate patterns and trends of co-prescriptions of stimulants and sedatives within the last 6 years at a tertiary care center. METHOD: Patients 18 years of age and older who were dispensed at least one stimulant prescription from an institutional pharmacy between 1/1/2015 and 7/1/2021 were included. Prescription data for any co-prescribed sedative/hypnotic were collected. RESULTS: Both the number of stimulant dispenses and the number of patients with stimulant dispenses increased significantly with yearly incidence rate ratios of 1.115 (95% CI [1.110, 1.119]) and 1.090 (95% CI [1.084, 1.096]), respectively. The number of patients with a stimulant dispensed who also had a benzodiazepine or "Z-drug" sedative-hypnotic dispensed at any point in the search timeframe increased significantly with incidence rate ratios of 1.077 and 1.092, respectively. The number of stimulant dispenses, number of patients with stimulant dispenses, and number of patients with a stimulant dispensed who also had both a benzodiazepine and Z-drug dispensed at any point in the search timeframe increased significantly more in Non-White than in White patients. CONCLUSIONS: The results confirm previous findings of increases in dispensing of stimulants over the past 6 years and report increased polypharmacy of stimulants and sedative-hypnotics.

Drug Utilization Study of Gastroprotective Agents in Medicine and Surgery Wards of a Tertiary Care Teaching Hospital.

Introduction Drug utilization research (DUR) is "the marketing, distribution, prescription, and use of drugs in a society, with special emphasis on the resulting medical, social, and economic consequences" as per the definition of the World Health Organization (WHO). The ultimate goal of DUR is to evaluate whether the drug treatment is rational or not. Various gastroprotective agents are available today, such as proton pump inhibitors, antacids, and histamine 2A receptor antagonists (H2RAs). Proton pump inhibitors block the gastric H+/K+-adenosine triphosphatase (ATPase) via covalent binding to cysteine residues of the proton pump to inhibit gastric acid secretion. Antacids are compounds containing different combinations, such as calcium carbonate, sodium bicarbonate, aluminum, and magnesium hydroxide. Histamine 2A receptor antagonists (H2RAs) decrease gastric acid secretion by reversibly binding to histamine H2 receptors located on gastric parietal cells, thereby inhibiting the binding and action of the endogenous ligand histamine. A recent literature review has shown that inappropriate use of gastroprotective agents has increased the risk for adverse drug reactions (ADRs) and drug interactions. Methods A total of 200 inpatient prescriptions were analyzed. The extent of prescribing, dosing information given, and cost incurred on the use of gastroprotective agents in both surgery and medicine inpatient departments was assessed. Prescriptions were also analyzed using WHO core indicators and for drug-drug interactions. Results Proton pump inhibitors were prescribed to 112 male patients and 88 female patients. The most common diagnosis was diseases of the digestive system with 54 (27.5%) cases, followed by diseases of the respiratory tract with 48 (24%) cases. Out of 200 patients, 51 comorbidities were reported from 40 patients. Among all prescriptions, injection of pantoprazole was the most common route of administration (181 (90.5%)), followed by tablets of pantoprazole (19 (9.5%)). The most common dose prescribed of pantoprazole was 40 mg in 191 (95.5%) patients in both departments. The frequency of therapy was also most commonly prescribed twice daily (BD) in 146 (73%) patients. Potential drug interaction was most commonly found with aspirin in 32 (16%) patients. The total cost incurred on proton pump inhibitor therapy of the medicine and surgery departments was 20,637.4 Indian Rupees (INR). Of this, the cost for patients admitted in the medicine ward was 11,656.12 INR and in the surgery department was 8,981.28 INR. Conclusion Gastroprotective agents are a group of drugs that are used to protect the stomach and the gastrointestinal tract (GIT) from acid-related injury. Our study found that proton pump inhibitors were the most commonly prescribed gastroprotective agents among inpatient prescriptions, with pantoprazole being the most frequently used. The most common diagnosis among patients was diseases of the digestive system, and most of the prescriptions were for injection administration at a dose of 40 mg twice daily. These findings suggest that there may be opportunities for improvement in the rational use of gastroprotective agents to reduce the risk of adverse drug reactions and interactions and lower healthcare costs. Overall, the study highlights the need for healthcare providers to be aware of the appropriate use of gastroprotective agents to minimize irrational prescriptions and reduce polypharmacy.

Co prescription of anti-acid therapy reduces the bioavailability of mycophenolate mofetil in systemic sclerosis patients: A crossover trial.

OBJECTIVE: Mycophenolate mofetil (MMF) is an effective treatment option for interstitial lung disease (ILD) in systemic sclerosis (SSc). Many patients require co-administration of proton pump inhibitors (PPI) or H2 receptor blockers (HRB) because of various gastrointestinal (GI) manifestations in SSc. Co-treatment with PPI or HRB have shown to reduce serum drug levels in post-transplant patients. We wanted to see if there is a similar phenomenon for Mycophenolate in SSc. METHODS: Twenty SSc patients, who were on a stable dose of MMF (1.5-3 g) underwent a sequential cross over study with MMF alone in the first month, followed by co-treatment with Ranitidine and then Esomeprazole in the second and third month respectively. Estimation of 12-hour area under curve (AUC) of Mycophenolic Acid (MPA) levels and total GI score were calculated at the end of each month and compared between the treatment arms. [Trial registration: CTRI/2020/06/025,939] RESULTS: Co-administration of esomeprazole was associated with 32.7% (mean difference = 22.28 µg h ml-1) reduction in mean AUC MPA, whereas ranitidine caused a reduction of 21.97% (mean difference = 14.93 µg h ml-1) in MPA AUC when compared to MMF without anti-acid therapies. The addition of ranitidine or esomeprazole resulted in significant reduction in the total GI score. CONCLUSION: Co-administration of PPI or HRB can significantly reduce the bioavailability of MMF in patients with SSc. To avoid therapeutic failure of MMF drug level monitoring is essential when these agents are co-prescribed with MMF.

Five-year incidence of substance use and mental health diagnoses following exposure to opioids or opioids with benzodiazepines during an emergency department encounter for traumatic injury.

BACKGROUND: Benzodiazepines and opioids are used alone or in conjunction in certain care settings, but each have the potential for misuse. OBJECTIVE: This longitudinal observational study evaluated substance use and mental health outcomes associated with providing opioids with or without benzodiazepine to treat traumatic injury in the emergency department (ED) setting. METHODS: We analyzed a limited dataset obtained through the IBM Watson Health Explorys. Matched cohorts were defined for: 1) patients treated with opioids during the ED encounter (ED-Opioid) vs. neither opioid or benzodiazepine treatment (No medication) (n = 5372); 2) patients treated with opioids and benzodiazepines during the ED encounter (ED-Opioid+Benzodiazepines) vs. No Medication (n = 2454); and 3) ED-Opioid+Benzodiazepines vs. ED-Opioid (n = 2454). Patients consisted of adults with an emergency department encounter in the MetroHealth System (Cleveland, Ohio) with a chief complaint of traumatic injury and medical records for five years following the encounter. Control patients for each cohort were matched to the exposure patients on demographics, body mass index, and residential zip code median income. Outcomes were five-year incidence rates for alcohol, substance use, depression, and anxiety-related diagnoses. RESULTS: Our results indicate that, although receiving opioids during the ED visit predicted a relatively lower likelihood of subsequent substance use and mental health diagnoses, the brief co-use of benzodiazepines was strongly associated with poorer outcomes. CONCLUSIONS: Even brief exposure to co-prescribed opioids and benzodiazepines during emergency traumatic injury care may be associated with negative substance use and mental health consequences in the years following the event.

New means, new measures: assessing prescription drug-seeking indicators over 10 years of the opioid epidemic.

BACKGROUND AND AIMS: Prescription drug-seeking (PDS) from multiple prescribers is a primary means of obtaining prescription opioids; however, PDS behavior has probably evolved in response to policy shifts, and there is little agreement about how to operationalize it. We systematically compared the performance of traditional and novel PDS indicators. DESIGN: Longitudinal study using a de-identified commercial claims database. SETTING: United States, 2009-18. PARTICIPANTS: A total of 318 million provider visits from 21.5 million opioid-prescribed patients. MEASUREMENTS: We applied binary classification and generalized linear models to compare predictive accuracy and average marginal effect size predicting future opioid use disorder (OUD), overdose and high morphine milligram equivalents (MME). We compared traditional indicators of PDS to a network centrality measure, PageRank, that reflects the prominence of patients in a co-prescribing network. Analyses used the same data and adjusted for patient demographics, region, SES, diagnoses and health services. FINDINGS: The predictive accuracy of a widely used traditional measure (N + unique doctors and N + unique pharmacies in 90 days) on OUD, overdose and MME decreased between 2009 and 2018, and performed no better than chance (50% accuracy) after 2015. Binarized PageRank measures however exhibited higher predictive accuracy than the traditional binary measures throughout 2009-2018. Continuous indicators of PDS performed better than binary thresholds, with days of Rx performing best overall with 77-93% predictive accuracy. For example, days of Rx had the highest average marginal effects on overdose and OUD: a 1 standard deviation increase in days of Rx was associated with a 6-8% [confidence intervals (CIs) = 0.058-0.061 and 0.078-0.082] increase in the probability of overdose and a 4-5% (CIs = 0.038-0.043 and 0.047-0.053) increase in the probability of OUD. PageRank performed nearly as well or better than traditional indicators of PDS, with predictive performance increasing after 2016. CONCLUSIONS: In the United States, network-based measures appear to have increasing promise for identifying prescription opioid drug-seeking behavior, while indicators based on quantity of providers or pharmacies appear to have decreasing utility.

A large-scale database study for the prescription status of a new voltage-gated Ca2+ channel α2δ ligand, mirogabalin, in Japan.

BACKGROUND: A new voltage-gated Ca2+ channel α2δ ligand, mirogabalin, was first approved for treating peripheral neuropathic pain in Japan in 2019. This is the first report on the prescription status of mirogabalin using a large-scale prescription database. RESEARCH DESIGN AND METHODS: The authors analyzed the prescription data of 12,924 patients prescribed mirogabalin between 1 June and 31 August 2020. The endpoints were the number of patients prescribed, prescription days, prescription doses, dose changes, co-prescription patterns, medication possession ratio (MPR), and treatment discontinuation rates (TDRs). RESULTS: Mirogabalin was newly prescribed to 7,914 patients in the 3-month study period. Most patients were prescribed mirogabalin at about 10 mg/day during the study period, and 30.9% of patients were prescribed ≥ 20 mg/day on Day 90 after the first prescription. The most frequently prescribed concomitant drug was celecoxib. The MPR (80 to 110%) was 86.2%, indicating good treatment adherence. The cumulative TDRs during ≤ 7 Days, Days 31-60, and 61-90 were 14.0%, 70.0%, and 77.9%, respectively. CONCLUSIONS: Mirogabalin was prescribed to a considerable number of patients. These results may be useful for optimizing mirogabalin use for patients with peripheral neuropathic pain in daily clinical practice. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000042592.

Legal requirements and recommendations to prescribe naloxone.

BACKGROUND: The continued toll of opioid-related overdoses has motivated efforts to expand availability of naloxone to persons at high risk of overdose, with 2016 federal guidance encouraging clinicians to co-prescribe naloxone to patients with increased overdose risk. Some states have pursued analogous or stricter legal requirements that could more heavily influence prescriber behavior. METHODS: We conducted a systematic legal review of state laws that mandate or recommend that healthcare providers prescribe naloxone to patients with indicators for opioid overdose risk. We coded relevant statutes and regulations for: applicable populations, patient criteria, educational requirements, and exemptions. RESULTS: As of September 2019, 17 states had enacted naloxone co-prescribing laws, the earliest of which was implemented by Louisiana in January 2016. If patient overdose risk criteria are met, over half of these states mandate that providers prescribe naloxone (7 states, 41.1 %) or offer a naloxone prescription (2 states, 11.8 %); the remainder encourage prescribers to consider prescribing naloxone (8 states). Most states (58.8 %) define patient overdose risk based on opioid dosages prescribed, although the threshold varies substantially; other common overdose risk criteria include concomitant opioid and benzodiazepine prescriptions and patient history of substance use disorder or mental illness. CONCLUSIONS: A growing minority of states has adopted a naloxone prescribing law, although these policies remain less prevalent than other naloxone access laws. By targeting higher-risk patients during clinical encounters, naloxone prescribing requirements could increase naloxone prescribed, destigmatize naloxone use, and reduce overdose harms. Further investigation into policy effectiveness, unintended consequences, and appropriate parameters is warranted.

Correlates of opioid and benzodiazepine co-prescription among people living with HIV in British Columbia, Canada: A population-level cohort study.

BACKGROUND: Co-prescribing benzodiazepines and opioids is relatively contraindicated due to the possible overdose risk. However, people living with HIV (PLWH) may have concurrent psychiatric and/or chronic pain diagnoses that may lead to the use of opioids and/or benzodiazepines for symptomatic treatment. Consequently, some PLWH may be at-risk for the health harms associated with the co-prescribing of these medications. Given this, the objectives of this study were to first examine the prevalence of opioids and benzodiazepines co-prescribing, and second, to characterize patient factors associated with the co-prescribing of opioids and benzodiazepines among PLWH in British Columbia (BC), Canada. METHODS: Using data derived from a longitudinal BC cohort, we used bivariable and multivariable generalized estimating equation models to establish the prevalence of a benzodiazepine and opioid co-prescription and determine factors associated with this practice. RESULTS: Between 1996 and 2015, 14 484 PLWH were included in the study and were followed for the entire study period. At baseline, 548 people (4%) were co-prescribed opioids and benzodiazepines, 6593 (46%) were prescribed opioids only, 2887 (20%) were prescribed benzodiazepines only, and 4456 (31%) were prescribed neither medication. A total of 3835 (27%) participants were prescribed both medications at least once during the study period. Factors positively associated with concurrent opioid and benzodiazepine prescribing included: depression/mood disorder [adjusted odds ratio (AOR) = 1.32; 95% confidence interval (CI) = 1.22-1.43] and anxiety disorder (AOR = 1.45; 95% CI = 1.27-1.66), whereas female sex (AOR = 0.76; 95% CI = 0.64-0.91) and substance use disorder (SUD) (AOR = 0.82; 95% CI = 0.74-0.90) were negatively associated with the outcome. CONCLUSION: Our findings indicate that co-prescription of opioids and benzodiazepines was seen at some point during study follow-up in over a quarter of PLWH. Given the known risks associated with this prescribing practice, future research can focus on the outcomes of co-prescribing among this patient population and the development of strategies to reduce the co-prescribing of opioids and benzodiazepines.

Recent prescription status of oral analgesics in Japan in real-world clinical settings: retrospective study using a large-scale prescription database.

Background: Information on prescriptions of oral analgesics for the treatment of pain is beneficial. However, there have been few reports on the prescription status of oral analgesics from a nation-wide, large-scale prescription database in Japan. Research design and methods: The authors analyzed the prescription data of 2,042,302 patients prescribed oral analgesics in 2017. The numbers/proportions of patients prescribed oral analgesics, adherence with approved doses, co-prescription patterns, dose changes, drug adherence, and treatment-discontinuation rates were evaluated. Results: Loxoprofen was prescribed to 32.5% of the patients, followed by celecoxib, prescribed to 16.0% of patients. Acetaminophen and pregabalin were prescribed to 10.5% and 9.4% of patients, respectively. Many analgesics were prescribed at lower doses than the approved doses. The most frequently used concomitant medication was pregabalin. For duloxetine and pregabalin, high proportions of patients were prescribed these drugs for > 90 days. Conclusions: Loxoprofen was the most prescribed of the non-steroidal anti-inflammatory drugs in Japan. The information obtained provides an overview of prescribed oral analgesics in Japan and could be useful for potential research into prescribed oral analgesics in the future.

New approaches to pharmacosurveillance for monitoring prescription frequency, diversity, and co-prescription in a large sentinel network of companion animal veterinary practices in the United Kingdom, 2014-2016.

Pharmaceutical agents (PAs) are commonly prescribed in companion animal practice in the United Kingdom. However, little is known about PA prescription on a population-level, particularly with respect to PAs authorised for human use alone prescribed via the veterinary cascade; this raises important questions regarding the efficacy and safety of PAs prescribed to companion animals. This study explored new approaches for describing PA prescription, diversity and co-prescription in dogs, cats and rabbits utilising electronic health records (EHRs) from a sentinel network of 457 companion animal-treating veterinary sites throughout the UK over a 2-year period (2014-2016). A novel text mining-based identification and classification methodology was utilised to semi-automatically map practitioner-defined product descriptions recorded in 918,333 EHRs from 413,870 dogs encompassing 1,242,270 prescriptions; 352,730 EHRs from 200,541 cats encompassing 491,554 prescriptions, and 22,526 EHRS from 13,398 rabbits encompassing 18,490 prescriptions respectively. PA prescription as a percentage of booked consultations was 65.4% (95% confidence interval, CI, 64.6-66.3) in dogs; in cats it was 69.1% (95% CI, 67.9-70.2) and in rabbits, 56.3% (95% CI, 54.7-57.8). Vaccines were the most commonly prescribed PAs in all three species, with antibiotics, antimycotics, and parasiticides also commonly prescribed. PA prescription utilising products authorised for human use only (hence, 'human-authorised') comprised 5.1% (95% CI, 4.7-5.5) of total canine prescription events; in cats it was 2.8% (95% CI, 2.6-3.0), and in rabbits, 7.8% (95% CI, 6.5-9.0). The most commonly prescribed human-authorised PA in dogs was metronidazole (antibiotic); in cats and rabbits it was ranitidine (H2 histamine receptor antagonist). Using a new approach utilising the Simpson's Diversity Index (an ecological measure of relative animal, plant etc. species abundance), we identified differences in prescription based on presenting complaint and species, with rabbits generally exposed to a less diverse range of PAs than dogs or cats, potentially reflecting the paucity of authorised PAs for use in rabbits. Finally, through a novel application of network analysis, we demonstrated the existence of three major co-prescription groups (preventive health; treatment of disease, and euthanasia); a trend commonly observed in practice. This study represents the first time PA prescription has been described across all pharmaceutical families in a large population of companion animals, encompassing PAs authorised for both veterinary and human-only use. These data form a baseline against which future studies could be compared, and provides some useful tools for understanding PA comparative efficacy and risks when prescribed in the varied setting of clinical practice.

Co-prescription of opioids with benzodiazepine and other co-medications among opioid users: differential in opioid doses.

PURPOSE: This study investigated the patterns of opioid co-prescription with benzodiazepine and other concomitant medications among opioid users. Opioid dose in each type of co-prescription was also examined. PATIENTS AND METHODS: This cross-sectional study was conducted among opioid users receiving concomitant medications at an outpatient tertiary hospital setting in Malaysia. Opioid prescriptions (morphine, fentanyl, oxycodone, dihydrocodeine and tramadol) that were co-prescribed with other medications (opioid + benzodiazepines, opioid + antidepressants, opioid + anticonvulsants, opioid + antipsychotics and opioid + hypnotics) dispensed from January 2013 to December 2014 were identified. The number of patients, number of co-prescriptions and the individual mean opioid daily dose in each type of co-prescription were calculated. RESULTS: A total of 276 patients receiving 1059 co-prescription opioids with benzodiazepine and other co-medications were identified during the study period. Of these, 12.3% of patients received co-prescriptions of opioid + benzodiazepine, 19.3% received opioid + anticonvulsant, 6.3% received opioid + antidepressant and 10.9% received other co-prescriptions, including antipsychotics and hypnotics. The individual mean opioid dose was <100 mg/d of morphine equivalents in all types of co-prescriptions, and the dose ranged from 31 to 66 mg/d in the co-prescriptions of opioid + benzodiazepine. CONCLUSION: Among the opioid users receiving concomitant medications, the co-prescriptions of opioid with benzodiazepine were prescribed to 12.3% of patients, and the individual opioid dose in this co-prescription was moderate. Other co-medications were also commonly used, and their opioid doses were within the recommended dose. Future studies are warranted to evaluate the adverse effect and clinical outcomes of the co-medications particularly in long-term opioid users with chronic non-cancer pain.

Integrated cardiovascular safety: multifaceted considerations in drug development and therapeutic use.

INTRODUCTION: Cardiovascular safety has become a central component of contemporary drug development and therapeutic use since noncardiovascular drugs can exert cardiovascular harms. Appropriate preapproval investigations and monitoring during clinical practice are therefore advantageous. Areas covered: Integrated cardiovascular safety is a broad field of investigation. This review focuses on three areas of assessment specifically chosen to exemplify advances and challenges in this field: the cardiotoxicity of oncologic agents, off-target blood pressure (BP) increases to noncardiovascular drugs, and the cardiovascular safety of new antidiabetic drugs for type 2 diabetes (T2D). Expert opinion: Good progress has been made in the field of Cardio-oncology in the last decade, and endeavors to include discipline-specific training in medical curricula are particularly encouraging. Less formalized progress has been made with regard to addressing off-target BP increases. In the third domain discussed, recent developments suggest that the focus of attention may shift from cardiovascular safety to cardiovascular benefit in light of a recent decision by the US FDA: in December 2016 it approved a new indication for empagliflozin to reduce the risk of cardiovascular death in adult patients with T2D and established cardiovascular disease.