Pharmacoepidemiology, Volume 2, Issue 4 (December 2023) – 7 articles

Prescription drug misuse is a global problem, especially in the United States (US). Clinician involvement is necessary in this crisis, and prescription drug monitoring programs (PDMPs) are a recommended tool for the prevention, recognition, and management of prescription opioid misuse. However, because of the plethora of differences between different PDMPs, research on their effects is mixed. Yet, despite varied evidence, policy on PDMP use is trending stricter and more comprehensive. We aimed to identify patterns in the research to inform clinicians and policy. Through a systematic review of four literature databases (CINAHL, Cochrane Database, Embase, and Medline/OVID), we found 56 experimental and quasi-experimental studies published between 2016 and 2023 evaluating PDMP effects on clinician behavior. To address study heterogeneity, we categorized studies by type of intervention and study outcome. The review suggests that more comprehensive PDMP legislation is associated with decreases in the number of opioid prescriptions overall and the number of risky prescriptions prescribed or dispensed. However, this review shows that much is still unknown, encourages improvements to PDMPs and policies, and suggests further research. Full article

Nirmatrelvir/ritonavir (PAXLOVID^TM, Pfizer) is an anti-infective inhibiting CYP3A4 indicated for the treatment of COVID-19 in adults at increased risk of severe COVID-19. As a newly approved product, PAXLOVID has limited safety information regarding rare events and serious adverse events (SAEs). This review describes the characterization of the real-world safety profile of products with similar pharmacological properties to PAXLOVID and aims to understand the impact of any drug interaction on the concomitantly prescribed products. A literature search of articles in PubMed published between 2018 and 2023 was conducted to assess the real-world frequency of safety outcomes of interest, specifically those meeting the criteria of serious adverse reaction. The review was restricted to observational, noninterventional studies and included CYP3A4 inhibitors prescribed for short-term treatment of infections in the outpatient setting. Twenty-one articles were included in the review. Most focused on a small, predefined list of safety outcomes and did not provide insight into the broader range of safety outcomes that might occur for the evaluated products with similar pharmacological properties to PAXLOVID or the impact of any interaction on the concomitant product. The findings highlight the challenges in obtaining proxy safety outcomes characteristics via a review of products with comparable pharmacological properties and underscore the need to have large, rapidly accessible data sources that can contribute to the safety profile of newly authorized products in the real world. Full article

Background: Medicines information (MI) is a specialist area of pharmacy that provides evidence-based answers to often complex medication queries, utilising resources such as textbooks and databases. With the advent of the COVID-19 pandemic, there was a need to change the way COVID-19-related queries were answered due to the rapid evolution of information on vaccination, treatment and prevention. Methods: Medicines information queries were retrospectively reviewed utilising the centre’s medicines information database from January 2020 through December 2022 using the COVID-19 keyword to retrieve relevant queries. Information was collected on the enquirer’s role, query category, time taken to complete the query, relevant keywords and references accessed. Keywords and references were analysed further to determine the types of queries asked and which references were helpful. Results: The centre received 214 COVID-19-related queries, predominantly in 2022. Most queries were from pharmacy staff (95.8%) and related to vaccination (n = 95, 44.4%) or treatment (n = 87, 40.7%). Government and specialist organisation websites were used most commonly as reference sources (24.6% and 16.5%, respectively) for their currency with COVID-19-specific resources (such as national guidelines, COVID-19 treatment interaction checkers) and textbooks/databases used less commonly. Conclusions: MI pharmacists have demonstrated their ability to obtain reliable COVID-19-related information, utilising and interpreting information from less traditional sources. Full article

Research Question and Objective: While the number of pharmacoepidemiological studies on stimulant-based ADHD medications has expanded rapidly in recent years, likely due to the stimulant shortage, few studies have analyzed non-stimulant ADHD medications from a pharmacoepidemiological perspective. Such research is important because a significant number of individuals with ADHD have medical or psychiatric conditions that preclude stimulant use. Furthermore, no studies, to our knowledge, have analyzed atomoxetine exchanges on the black market. In this report, we seek to fill both these gaps in the research by analyzing black market diversions of atomoxetine, a non-stimulant medication for ADHD. As ADHD medication diversion is a growing issue, we also hypothesize the pharmacoepidemiologic contributors to and implications of such diversion. Method: This study analyzed black market atomoxetine purchases entered on the web-based platform StreetRx between January 2015 and July 2019. Data included the generic drug name, dosage, purchase price, date, and location in the United States. The mean price per milligram was determined and a heatmap was generated. Results: The average price per milligram of 113 diverted atomoxetine submissions was USD 1.35 (±USD 2.76 SD) (Median = USD 0.05, Min = USD 0.01, Max = USD 20.00). The states with the most submissions included Michigan (11), Pennsylvania (9), Indiana (8), and Ohio (8). Conclusion: The cost per milligram of atomoxetine on the black market is over 50 times the cost per milligram of the generic prescribed form. Future qualitative studies should investigate reasons why individuals are motivated to purchase atomoxetine, a non-stimulant medication, on the black market (recreational vs. nootropic vs. other clinical uses). Full article

We studied the role of adherence to antihypertensive drug therapy (AHT) in blood pressure (BP) control in a type 2 diabetes (T2D) population treated in secondary care in the DIAbetes and LifEstyle Cohort Twente-1 (DIALECT-1). In addition, intensification of AHT was assessed. Adherence was determined by using the medication possession ratio (MPR), calculated with pharmacy dispensing data for a period of two years following baseline. Adherence was defined as an MPR ≥ 80%. The proportion of adherent patients was compared between patients who had BP-on target (BP-OT) and BP-not on target (BP-NOT). Of the 385 patients included, 56% achieved their BP target. The proportion of adherent patients did not differ between BP-OT and BP-NOT (96% vs. 96%; p = 0.91). Intensification of AHT, including ‘increase in dosage’ and ‘start of a new drug’, was assessed in the two years following baseline. In only 37% of patients with uncontrolled BP during follow-up was AHT intensified. To conclude, adherence to AHT was high and there does not seem to be a relationship between adherence and BP control. There is an opportunity to improve AHT in patients who do not reach their BP target. Full article

Overuse and misuse of antibiotics have led to the emergence of antibiotic-resistant bacteria and pose a significant threat due to adverse drug reactions, increased healthcare costs, and poor patient outcomes. Antibiotic stewardship programs, including antibiotic de-escalation, aim to optimize antibiotic use and to reduce the development of antibiotic resistance. This systematic review and meta-analysis aim to fill the gap by analyzing the current literature on the implications of antibiotic de-escalation in patients on antibiotic use, duration of hospital stay, mortality, and cost; to update clinical practice recommendations for the proper use of antibiotics; and to offer insightful information about the efficacy of antibiotic de-escalation. Based on the PRISMA 2020 recommendations, a comprehensive literature search was conducted using electronic databases and reference lists of identified studies. Eligible studies were published in English, conducted in humans, and evaluated the impact of antibiotic de-escalation on antibiotic consumption, length of hospitalization, mortality, or cost in hospitalized adult patients. Data were extracted using a standardized form, and the quality of included studies was assessed using the Newcastle–Ottawa Scale. The data from 25 studies were pooled and analyzed using the Revman-5 software, and statistical heterogeneity was evaluated using a chi-square test and I2 statistics. Among the total studies, seven studies were conducted in pediatric patients and the remaining studies were conducted in adults. The studies showed a wide range of de-escalation rates, with most studies reporting a rate above 50%. In some studies, de-escalation was associated with a decrease in antimicrobial utilization and mean length of stay, but the impact on overall cost was mixed. Our pooled analysis for mortality reported that a significant difference was observed between the de-escalation group and the non-de-escalation group in a random effect model (RR = 0.67, 95% CI 0.52–0.86, p = 0.001). The results suggest that de-escalation therapy can be applied in different healthcare settings and patient populations. However, the de-escalation rate varied depending on the study population and definition of de-escalation. Despite this variation, the results of this systematic review support the importance of de-escalation as a strategy to optimize antibiotic therapy and to reduce the development of subsequent antibiotic resistance. Further studies are needed to evaluate the impact of de-escalation on patient outcomes and to standardize the definition of de-escalation to allow for better comparison of studies. Full article

Vancomycin is not appreciably passaged via the colonic membrane to the gastrointestinal (GI) tract in persons with an intact gut epithelium due to its large chemical structure. However; hospitalized patients with diarrhea often have a disrupted GI tract. The aim of this study was to determine the frequency of detectable vancomycin concentrations in the stool of patients with antibiotic-associated diarrhea receiving IV vancomycin. This was a multicenter cohort study of hospitalized patients with stool samples collected for Clostridioides difficile testing. Leftover stool samples were collected from patients who had received at least 3 days of IV vancomycin. Fecal vancomycin was quantified by high-performance liquid chromatography. The study cohort included 33 unique patients, majority female (54.5%) aged 60 years (range 23–84). Eighteen of thirty-three patients (54.5%) tested positive for C. difficile toxins. The average duration of systemic vancomycin administration prior to stool collection was 3.5 (range 2–15) days. Three of 33 (9%) stool samples had a detectable vancomycin concentration (range 1.2–13.2 mcg/mL). These concentrations may promote the development of vancomycin-resistant Enterococcus or van mutations in C. difficile, leading to vancomycin resistance. Further studies on implications are warranted. Full article