Pharmacoepidemiology, Volume 4, Issue 4 (December 2025) – 4 articles

Herbal medicinal products are increasingly used alongside conventional medicines, raising the risk of potential interactions such as pharmacodynamic drug–herb interactions (PD-DHIs) that can cause serious adverse drug reactions (ADRs). This review aims to present available pharmacological, clinical and pharmacoepidemiological literature regarding potential DHIs associated with serotonin syndrome or cardiac arrhythmias. Furthermore, it assesses the current evidence using the Oxford Centre for Evidence-Based Medicine (CEBM) 2009 framework. Serotonin syndrome most often results from combining serotonergic herbs (e.g., St. John’s wort) with antidepressants like serotonin reuptake inhibitors (SSRIs), as supported by repeated case reports and mechanistic plausibility (CEBM Level 3, Grade C). Other herbs such as black cohosh, ginseng, Syrian rue, turmeric, rhodiola, ashwagandha, and L-tryptophan/5-HTP have been linked to serotonin syndrome when used with SSRIs, serotonin-norepinephrine reuptake inhibitors (SNRIs), or monoamine oxidase inhibitors (MAOIs), but evidence is limited (Levels 4–5, Grade D). For cardiac arrhythmias, PD-DHIs arise when herbs interact with drugs that alter cardiac electrophysiology—such as QT-prolonging agents, psychotropics, antiarrhythmics or digoxin—thereby amplifying arrhythmogenic risk. Ephedra with sympathomimetics is strongly associated with arrhythmias (Level 2–3, Grade B). Licorice may potentiate digoxin and QT-prolonging drugs via hypokalemia (Level 4, Grade C). Other related PD-DHIs include aconite with antiarrhythmics, bitter orange or caffeine with QT-prolonging psychotropics, yohimbine with cardiovascular agents, and aloe or senna with digoxin. Overall, the evidence for PD-DHIs varies from moderate to weak but large-scale pharmacoepidemiological data is scarce. Future approaches, including artificial intelligence with explainable machine learning and network pharmacology, may integrate mechanistic, clinical, and real-world data to improve early detection or prediction of PD-DHIs. However, several specific challenges must be addressed. Therefore, it is crucial for healthcare providers in both clinical and community settings to increase their awareness of these interactions and ADRs to ensure the safe use of herbal remedies alongside conventional therapies. Full article

Immunocompromised outpatients, including people living with HIV/AIDS (PLWH), diabetes, cancer, and organ transplant recipients, are at high risk of antimicrobial resistance (AMR) due to their weakened immune systems and use of immunosuppressive therapies. The high prevalence of prophylactic and therapeutic antibiotic use in this vulnerable population, coupled with frequent contact with healthcare facilities and limited outpatient antimicrobial resistance surveillance systems, contributes to the increase in antimicrobial resistance. The majority of available data pertains to inpatients, and there is a lack of comprehensive outpatient information on pathogen distribution, resistance patterns, and diagnostic challenges. Moreover, nonspecific clinical presentations, diminished inflammatory responses, and limitations of traditional diagnostic methods complicate infection diagnosis in this population. Increasing resistance surveillance, developing rapid diagnostic tools, and implementing accurate and personalized approaches are key strategies to reduce the burden of disease, mortality, and healthcare costs in the immunocompromised outpatient population. This study was designed as a narrative review based on a comprehensive search of major databases and guidelines. It aims to examine the available evidence and address the challenges associated with AMR in immunocompromised outpatients. Full article

Background: Adherence to tyrosine kinase inhibitors (TKIs), the first-line treatment for renal cell carcinoma (RCC), is critical to ensure intended treatment outcomes. However, 75% of patients with RCC have persistency gaps (>7 days) within the first 90 days after initiating TKIs. This study explored factors affecting TKI adherence in RCC patients to inform future interventions. Methods: A retrospective cohort study was conducted at a specialist oncology hospital in Northwest England from October 2020 to October 2022 on patients with RCC treated with TKIs. TKI prescriptions and persistence gaps (>7 days) were identified from electronic dispensing records. Factors associated with persistence gaps were retrieved by reviewing patients’ clinical records. We used descriptive statistics to summarise the results and Kaplan–Meier analysis to assess the probability and the time to the first gap, stratified by adverse drug effect (ADE)-related and non-ADE-related gaps. Results: Among 165 included patients, 611 persistence gaps were identified. ADEs accounted for 59% (n = 464) of 787 recorded factors, with diarrhoea being the most frequent ADE (9.5%). Patients holding leftover TKIs were the primary (15.1%) non-ADE factor for persistency gaps. At least one gap was observed with 82% of patients (n = 135); 19% had ≥5 ADE-related gaps, and 25% had ≥5 non-ADE-related gaps. ADE-related gaps typically occurred within the first three months (50%), while non-ADE-related gaps were not time-dependent. Conclusions: ADEs, including diarrhoea and pain-related reactions, were the most frequently reported issues affecting TKI persistency in patients with RCC. These ADEs are likely to impact patients’ quality of life and adherence. Future qualitative research is warranted to explore patients’ care needs and additional factors such as health literacy and self-efficacy. Full article

Background: While adverse drug events (ADEs) are a major public health concern, data on the occurrence of lethal or fatal ADEs in Japan are limited. Therefore, this study aimed to elucidate the characteristics and reporting trends of lethal or fatal ADEs by analyzing the Japanese Adverse Drug Event Report (JADER), a pharmacovigilance database. Methods: Of the individual ADE reports registered in the JADER database between April 2004 and March 2024 (fiscal year (FY) 2004–2023), all data involving individuals aged ≥ 20 years with complete data on sex and age were included in this analysis. Descriptive statistics were used to summarize the results. Results: The number of ADE cases registered in the JADER database increased approximately 2.3-fold from 21,824 in FY 2004 to 50,520 in FY 2023. Lethal or fatal ADE cases increased throughout the study period. In particular, the reporting rate of fatal ADEs reported in JADER appears to have increased in recent years. Lethal or fatal ADEs were reported more frequently among men and individuals aged ≥ 70 years. The recent increase in the reported rates of lethal or fatal ADEs may be largely influenced by the increased number of ADE reports associated with antineoplastic agents. The increase in the number of reports on immune checkpoint inhibitors is particularly notable. Conclusions: This study provides new insights into demographic and drug-related characteristics, as well as time trends associated with lethal or fatal ADEs in Japan. Further studies are needed to confirm these findings. Full article