Pharmacoepidemiology, Volume 4, Issue 1 (March 2025) – 6 articles

Background/Objectives: Direct oral anticoagulants (DOACs), when compared to the Vitamin K antagonist (VKA) warfarin, exhibit greater safety and effectiveness. However, DOACs may still have potential drug–drug interactions that result in major bleeding events. There is a paucity of studies on medications that have pharmacodynamic interactions with DOACs, such as selective serotonin reuptake inhibitors (SSRIs). This study evaluates the potential major bleeding risk associated with the concomitant use of SSRIs among nonvalvular atrial fibrillation (NVAF) patients who were receiving DOACs. Methods: Adult patients receiving DOACs with consecutive NVAF diagnoses were identified from the Penn State Health Electronic Health Records from 2013 to 2023. These patients were then checked for exposure (i.e., concomitant use of SSRIs). The outcome was time to the first occurrence of a major bleeding event, with a follow-up from the first DOAC prescription until a major bleeding event, death, or end of follow-up. This retrospective cohort study used a Cox cause-specific proportional hazard model to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) with inverse probability of treatment weighting to adjust for measurable confounding factors (e.g., demographics, comorbidities, comedications). Results: A total of 8657 NVAF patients who were receiving DOACs were identified. The mean age was 70.3 ± 11.95 years, and females comprised 39.8% of the study population. The baseline CHA2DS2-VASc score was 3.77 ± 1.76, and the HAS-BLED score was 2.98 ± 1.27. Among these patients, 2649 (30.6%) were co-prescribed with SSRIs. The unadjusted hazard ratio for SSRIs was 0.87 (95% CI: 0.76–0.99) and the adjusted hazard ratio was 0.68 (95% CI: 0.59–0.78). Conclusions: In patients with NVAF receiving DOACs, concomitant use of SSRIs was not associated with a higher risk of major bleeding. Full article

Background/Objectives: Despite an improved knowledgebase, effective intervention, and guidelines, many patients with depression do not receive adequate treatment and treatment discontinuation and non-response are common. It was intended to explore the challenges clinicians face while managing depression in their clinical practice and their suggestions for solutions. Methods: It was an online survey of 137 psychiatrists in 18 countries including both high and low economies, using a pre-designed questionnaire; with both quantitative and qualitative measures. Results: Antidepressant prescribing appeared close to the evidence-based guidelines. There was frequent use of other medications alongside antidepressants since treatment initiation. There were many challenges in managing depression, such as treatment non-response, resistance, and discontinuation; side effects, mostly sexual problems; inadequate psychological intervention; availability and affordability of treatment modalities; comorbidities, especially substance use and personality disorders; stigma; and lack of education and training. Suggested approaches for solutions included personalized treatment, quicker follow-up, psychoeducation, blending psychological intervention into routine clinical practice, improving continuity of care, and preventing treatment discontinuation. Support from governments for improving access, making interventions affordable, and providing socio-occupational support is essential. Training and development of professionals, public education providing information, and dealing with stigma are still relevant. Conclusions: The results indicated a need for reviewing current practices in managing depression, optimizing it with available resources, and preventing treatment discontinuation, and non-response. Making treatment available and affordable, public education fighting stigma to improve treatment acceptability, and research addressing gaps in interventions, especially for treatment resistance and psychotherapy are other approaches that may improve depression management. Full article

Background/Objectives: This systematic review aimed to identify a comprehensive list of potential opioid-related indicators from the published literature to assess prescribing safety in any setting. Methods: Studies that reported prescribing indicators from 1990 to 2019 were retrieved from a previously published systematic review. A subsequent search was conducted from seven electronic databases to identify additional studies from 2019 to June 2024. Potential opioid safety prescribing indicators were extracted from studies that reported prescribing indicators of non-injectable opioids prescribed to adults with concerns about the potential risk of harm. The retrieved indicators were split by each opioid, and duplicates were removed. The identified indicators were categorized by the type of problem, medication, patient condition/disease, and the risk of the indicators. Results: A total of 99 unique opioid-specific prescribing indicators were identified from 53 included articles. Overall, 42 (42%) opioid prescribing indicators focused on a specific class of opioids. Pethidine, tramadol, and fentanyl were the most frequently reported drugs (n = 22, 22%). The indicators account for six types of problems: medication inappropriate for the population (n = 20), omission (n = 8), inappropriate duration (n = 10), inadequate monitoring (n = 2), drug–disease interaction (n = 26), and drug–drug interaction (n = 33). Of all the indicators, older age (over 65) is the most common risk factor (n = 38, 39%). Central nervous system-related adverse effects are the risk of concern for the 28 (29%) indicators associated with drug–drug interactions. Furthermore, five of the six ’omission’ indicators are related to ’without using laxatives’. Conclusions: This review identified a comprehensive set of indicators for flagging patients at high risk of opioid-related harm, thereby supporting informed decision-making in optimizing opioid utilization. However, further research is essential to validate these indicators and evaluate their feasibility across diverse healthcare settings. Full article

Background/Objectivses: Antibiotic consumption patterns in remote urban areas of the Amazon region are poorly understood. This study aimed to analyze antibiotic use in the adult population of Coari, a municipality in Amazonas, Brazil. Methods: A cross-sectional study was conducted between October and November 2021 in the urban area of Coari. 394 adults were interviewed using a structured questionnaire. Data on antibiotic use, sociodemographic factors, health service access, and self-reported illnesses were collected. Poisson regression was used to estimate prevalence ratios and identify factors associated with antibiotic use. Results: The prevalence of antibiotic use was 14.7% (n = 58). The most frequently used antibiotics were azithromycin (26.9%), cefalexin (20.9%), amoxicillin (19.4%), and ciprofloxacin (13.9%). Up to 34.5% of antibiotic use was conducted without a prescription, especially among adults aged 18 to 39 (59.1%). The main health problems that led to self-medication were COVID-19 (28.6%), urinary infection (14.3%), sore throat (37.5%), and intestinal infection (60.0%). Factors associated with antibiotic use included age 18 to 39 (adjusted PR = 3.73; CI = 1.37–10.09), having a family member hospitalized (adjusted PR = 2.61; CI = 1.39–4.89), having contracted COVID-19 (adjusted PR = 2.41; CI = 1.40–4.15), and frequency of visits by the community health agent to the home (adjusted PR = 0.35 CI = 0.15–0.81). Conclusions: The high use of broad-spectrum antibiotics (Watch), particularly azithromycin, for potentially inappropriate indications highlights the need to improve the management of antibiotic use in remote regions of Brazil. Community health agents, as key professionals between health services and the community, can play a key role in promoting the rational use of antibiotics and combating antimicrobial resistance in the Brazilian Amazon context. Full article

Background/Objectives: Functional dyspepsia is associated with abdominal pain and nausea, which leads to reduced quality of life, loss of productivity, and economic loss for patients. Itopride hydrochloride (itopride) stimulates the gastrointestinal smooth muscles, thereby promoting gastric emptying. It has been shown to significantly improve symptoms in patients with functional dyspepsia without severe side effects. Itopride has been available in Vietnam for many years; however, the cost-effectiveness of the drug has not been established. The aim of this study is to estimate the cost-effectiveness of itopride for the treatment of functional dyspepsia in Vietnam. Methods: A 3-stage Markov model with the following health states—controlled functional dyspepsia, uncontrolled functional dyspepsia, and dead—was developed. Functional dyspepsia was used to assess itopride over 10 years using 8-week cycles. A broader Vietnamese societal perspective was assumed for the analysis. Input was retrieved from the literature and through local clinical input from physicians in Vietnam. Output was reported as an incremental cost-effectiveness ratio (ICER) per quality-adjusted life years (QALY). A GDP/capita threshold (very cost-effective: 1 × GDP = Vietnamese Dong (VND) 64.1 M, cost-effective: 3 × GDP = VND 192.2 M) was used as recommended by the WHO in Vietnam. One-way and probabilistic sensitivity analyses were performed. Results: Itopride use resulted in an additional 0.28 QALYs at an extra cost of VND 11.2 M. This resulted in an ICER of VND 39.7 M per QALY, which is lower than the threshold of VND 192.2 M. One-way sensitivity analyses showed that the ICER was sensitive to varying the efficacy VND 31.8 M to VND 88.3 M), cost of itopride (ICER: VND 43.1 M to VND 56.5 M), and the health utility values (ICER: VND 45.2 M to VND 55.3 M). More than 80% of the simulations in the probabilistic sensitivity analysis were cost-effective at the 1 × GDP (VND 64.1 M) threshold, and 91.3% were cost-effective at the 3 × GDP (VND 192.2 M) threshold. Conclusion: This study shows that itopride hydrochloride is a very cost-effective treatment for functional dyspepsia in Vietnam, with the ICER (VND 39.7 M/QALY) being even lower than the 1 × GDP (VND 64.1 M) threshold. Full article

Background: Immuno-oncology has transformed cancer treatment, with immune checkpoint inhibitors (ICIs) like pembrolizumab playing a key role. While highly effective, these therapies can also cause immune-related adverse events. This study examines the incidence and characteristics of hepatobiliary adverse events (AEs) linked to pembrolizumab, using data from the FDA Adverse Event Reporting System (FAERS). Objective: To investigate the rates of hepatobiliary AEs linked to pembrolizumab, providing insights into the risks of liver and biliary system damage in patients prescribed pembrolizumab. Methods: This study utilized the FAERS database via OpenVigil 2.1. Adverse events (AEs) related to pembrolizumab were identified and compared to those associated with other drugs. Reporting odds ratios (RORs) were calculated to assess the likelihood of hepatobiliary AEs in pembrolizumab-treated patients. Results: In total, 594 hepatic AEs and 181 biliary AEs were identified. Significant hepatic AEs included elevated ALT (ROR 3.00, 95% CI: 2.685–3.351), hepatotoxicity (ROR 6.436, 95% CI: 5.72–7.242), and hepatic cytolysis (ROR 15.721, 95% CI: 13.854–17.84). Immune-mediated hepatitis exhibited the highest ROR of 346.716 (95% CI: 303.568–395.997). For biliary AEs, cholangitis (ROR 19.597, 95% CI: 16.852–22.791) and sclerosing cholangitis (ROR 24.735, 95% CI: 19.888–30.763) were the most prominent. Conclusions: Pembrolizumab is associated with a significant risk of hepatobiliary adverse events, particularly immune-mediated hepatitis and cholangitis. The elevated RORs for these conditions highlight the importance of close monitoring and managing liver and biliary functions in patients undergoing pembrolizumab checkpoint blockade. These findings emphasize the need for personalized treatment strategies to mitigate risks and optimize outcomes in cancer immunotherapy, especially for those with preexisting hepatobiliary conditions. Full article