Introduction: Pharmacovigilance signal prioritization is essential for efficient regulatory decision-making, yet Thailand lacks a standardized framework for this purpose, risking delayed or inconsistent responses to emerging drug safety signals and potentially compromising public health protection.

Aims: To develop and validate a signal prioritization system (SPS) for Thailand, adapted from the UK Medicines and Healthcare Products Regulatory Agency's (MHRA) Regulatory Pharmacovigilance Prioritization System.

Methods: The study was conducted in two phases. In Phase 1, the Thai SPS was developed through focus group discussions with key pharmacovigilance stakeholders. The developed SPS framework incorporated four weighted evaluation criteria: public health implications, regulatory obligations, strength of evidence, and public perception. Signals were classified into three priority tiers: top priority, increased priority, and standard priority. In Phase 2, the system was prospectively applied to drug–adverse event pairs identified from the Thai Vigibase, representing distinct signal categories: two confirmed signals (Andrographis paniculata–severe allergic reactions; COVID-19 vaccine [AstraZeneca]–chest pain), one monitored signal (dimenhydrinate–Stevens-Johnson syndrome/toxic epidermal necrolysis), and one refuted signal (denosumab–diabetes mellitus).

Results: The SPS demonstrated appropriate discrimination across signal categories. The AstraZeneca COVID-19 vaccine–chest pain pair was classified as top priority. Andrographis paniculata–severe allergic reactions and dimenhydrinate–Stevens-Johnson syndrome/toxic epidermal necrolysis were classified as increased priority, and denosumab–diabetes mellitus was classified as standard priority. Priority classifications aligned logically with signal confirmation status and expert opinions and were associated with defined operational response timeframes.

Conclusions: The SPS demonstrated preliminary feasibility in stratifying pharmacovigilance signals within Thailand's regulatory context, improving transparency and consistency in safety decision-making. Linking priority scores to structured risk management guidelines and defined response timeframes offers a scalable model for strengthening national pharmacovigilance systems in middle-income countries. These findings have implications for regulatory agencies seeking evidence-based frameworks for signal management prioritization.

Keywords: pharmacovigilance, signal prioritization, drug safety

Introduction:
Despite clinical concerns regarding GLP-1 receptor agonists and pancreatitis, evidence from traditional observational studies is inconsistent

Aims:
To estimate the absolute and relative within-person risk of incident acute pancreatitis across five classes of second-line antidiabetics.

Methods:
Using the Japan Medical Data Center (JMDC) Payer database (January 2005-February 2025), we characterised prescription trajectories for five second-line classes (GLP-1 receptor agonists, SGLT2 inhibitors, DPP-4 inhibitors, sulfonylureas, and thiazolidinediones) and calculated the 90-day absolute risk of acute pancreatitis following each prescription episode among adults (≥18 years) with diabetes. We subsequently conducted a multidrug self-controlled case series (SCCS) among individuals experiencing a first incident acute pancreatitis episode. Person-time was categorised into 60-day pre-risk, on-treatment, and off-treatment (baseline) periods, with additional split post-initiation windows evaluated. Age- and season-adjusted conditional Poisson models estimated incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Supplementary analyses assessed pancreatitis subtypes and a forearm-fracture negative control.

Results:
Among 671,118 initiators, DPP-4 and SGLT2 inhibitors were the most common index classes, with 51% of patients utilising two or more classes. The 90-day absolute risk was approximately 1.0-1.5 cases per 10,000 prescription episodes across all classes. The SCCS analysis included 2,401 individuals. On-treatment IRRs were not statistically significant across all classes (GLP-1: 1.00, 0.62-1.62; DPP-4: 1.13, 0.90-1.41; SGLT2: 1.11, 0.88-1.40; sulfonylurea: 1.17, 0.80-1.73; thiazolidinediones: 0.98, 0.56-1.73), with no risk elevation observed in the split windows. Conversely, pre-risk IRRs were significantly elevated for DPP-4 (2.44, 1.96-3.03), SGLT2 (2.99, 2.42-3.68), and sulfonylureas (1.95, 1.31-2.89), but not for GLP-1 or thiazolidinediones. The lack of association with forearm fractures further confirms the robustness of our findings.

Conclusions:
Absolute risk was low among initiators, and on-treatment pancreatitis risk was not observed in the SCCS. Pancreatitis risk is comparable across all five second-line anti-diabetic drugs.

Keywords: acute pancreatitis; self-controlled case series; second-line antidiabetics

Introduction: Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), also known as baboon syndrome, is a rare, benign, and self-limiting type IV hypersensitivity reaction. This is characterized by symmetrical erythema of intertriginous and flexural regions following systemic drug exposure.

Aim: This study aimed to evaluate potential safety signals associated with azole antifungals and SDRIFE using the FDA Adverse Event Reporting System (FAERS).

Methods: A retrospective pharmacovigilance study was conducted using FAERS data from the fourth quarter of 2003 to the third quarter of 2025. Data were extracted using OpenVigil 2.1, and SDRIFE cases were identified using Preferred Terms from the Medical Dictionary for Regulatory Activities (MedDRA). Disproportionality analysis was performed using the reporting odds ratio (ROR) with 95% confidence intervals (CI). Subgroup analyses based on age, sex, and individual azole agents were also conducted. A signal was considered significant when the lower limit of the 95% CI exceeded 1 and at least 5 cases were reported.

Results: A total of 72 azole-associated SDRIFE reports were identified. The overall ROR was 22.801 (95% CI: 17.827–29.162), indicating a strong association between azole antifungals and SDRIFE. Most cases occurred in adults aged 18–55 years (n=49), and females accounted for the majority of reports (n=42). Itraconazole demonstrated the strongest signal (ROR: 162.937; 95% CI: 120.530–220.264) with 46 cases, followed by clotrimazole, fluconazole, posaconazole, and voriconazole. No SDRIFE reports were identified for ketoconazole, miconazole, oteseconazole, efinaconazole, or oxiconazole.

Conclusion: This study identified a potential association between azole antifungals and SDRIFE, with itraconazole showing the strongest disproportionality signal. Further epidemiological and clinical investigations are needed to confirm these findings and explore underlying mechanisms.

Keywords: Azole antifungals; SDRIFE; pharmacovigilance.

Introduction: Chemotherapy for breast cancer is associated with a high burden of adverse drug reactions (ADRs), yet ADR reporting in Indian oncology settings remains inadequate due to limited pharmacovigilance awareness. Active surveillance is essential to identify ADR patterns and high-risk populations for timely intervention.
Objective: To evaluate drug prescription patterns, and determine the nature, frequency, severity, and predictors of ADRs in breast cancer patients receiving chemotherapy across tertiary care hospitals.
Methods: A hospital-based longitudinal cohort study was conducted (January 2023–August 2024) at three tertiary care centers in Karnataka, India: JSS Hospital and Narayana Multispecialty Hospital, Mysuru, and M.S. Ramaiah Medical College, Bengaluru. A total of 385 female patients with histologically confirmed breast cancer were enrolled. ADRs were assessed using the WHO-UMC causality scale and Naranjo algorithm and classified by severity, preventability, and predictability. Predictors were analyzed using odds ratios. Data was analyzed using JMP® 18.
Results: The predominant age group was >51 years (48.83%). Doxorubicin + cyclophosphamide was the most prescribed regimen (62.1%). A total of 2,066 ADRs were documented; fatigue (63.64%), alopecia, and gastrointestinal disturbances were most prevalent. Most ADRs were mild-to-moderate and a significant proportion was preventable. Advanced age, higher BMI, comorbidities, and advanced cancer stage were significant predictors of ADR occurrence.
Conclusion: This multicenter pharmacovigilance study demonstrates a substantial ADR burden in breast cancer chemotherapy, with fatigue as the leading adverse event. Active monitoring revealed a high proportion of preventable ADRs, underscoring the need for individualized risk assessment and strengthened pharmacovigilance reporting to PvPI in oncology practice.
Keywords: Pharmacovigilance; adverse drug reactions; breast cancer; chemotherapy; WHO-UMC; Naranjo algorithm; PvPI; ADR predictors.

Introduction: Methotrexate (MTX), an antimetabolite that inhibits dihydrofolate reductase, is a key component of therapy for pediatric leukemia and lymphoma. However, MTX-associated adverse events (AEs) may compromise treatment outcomes. Integrating pharmacovigilance and pharmacogenomic evidence may improve understanding of toxicity susceptibility and support precision medicine approaches.

Aims: To characterize MTX-associated AEs in pediatric oncology patients and integrate pharmacogenomic evidence to identify potential genetic determinants of toxicity.

Methods: MTX-related AEs reports in children aged 1–18 years with hematolymphoid malignancies were retrieved from the FDA Adverse Event Reporting System (FAERS) via OpenVigil 2.1(Q4 2004–Q3 2025). Reports with a frequency >3 were included. Signal detection was performed using reporting odds ratio (ROR), proportional reporting ratio (PRR), and chi-square (χ²) statistics. Signals were considered significant when ROR >1, PRR ≥2, and χ² >4. Pharmacogenomic annotations relevant to pediatric MTX therapy were extracted from curated pharmacogenomic databases and mapped to identified toxicity signals.

Results: A total of 3,820 MTX-associated AEs were identified. Reports were more frequent in males (51.9%) and in children aged 1–10 years (59.7%). The United States (16.3%) and Canada (13.9%) contributed the highest number of reports. Among 672 unique preferred terms, 508 significant safety signals were detected. Neurological (9.9%) and gastrointestinal/mucosal (8.7%) disorders were the most frequent AE categories, while febrile neutropenia (n=839) and neurotoxicity (n=374) were the most reported AEs. Pneumonia (PRR=224.17) and increased drug level (PRR=192.15) showed the strongest disproportionality signals. Pharmacogenomic evaluation shows variants in SLCO1B1 (rs10841753), MTHFR (rs1801131), ABCB1 (rs1045642), and TYMS (rs45445694), along with genes involved in MTX transport and folate metabolism, as potential contributors to variability in toxicity risk.

Conclusions: Integration of FAERS-derived safety signals with pharmacogenomic evidence identified clinically relevant MTX toxicities and potential genetic determinants of susceptibility in pediatric leukemia and lymphoma. Findings support future risk-stratified monitoring and precision-guided MTX therapy.

Keywords: Pediatrics, Methotrexate-toxicity, Pharmacovigilance,

Introduction: Alpelisib, a selective phosphatidylinositol-3-kinase (PI3K) alpha inhibitor for PIK3CA-mutated metastatic breast cancer, is frequently associated with hyperglycemia. However, diabetic ketoacidosis (DKA) remains a rare but potentially life-threatening adverse event, and real-world evidence describing its clinical characteristics and severity remains limited.

Aims: To evaluate the pharmacovigilance safety signal and clinical outcomes of alpelisib-associated DKA utilizing the FDA Adverse Event Reporting System (FAERS) and published case reports.

Methods: A pharmacovigilance study was conducted using FAERS reports through May 2026 coded with the MedDRA preferred term “diabetic ketoacidosis.” Reporting odds ratios (RORs) were calculated to assess disproportionality, and serious clinical outcomes were evaluated. PubMed and Embase were systematically searched through May 2026 for published alpelisib-associated DKA cases.

Results: A total of 139 alpelisib-associated DKA reports were identified in FAERS, demonstrating a significant disproportionality signal (ROR 22.33, 95% confidence interval [CI] 18.87-26.41). Compared with pooled PI3K/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway-targeted agents, alpelisib remained associated with disproportionate DKA reporting (ROR 6.76, 95% CI 5.35-8.54). Among these reported cases, 79.1% resulted in hospitalization, 16.5% were life-threatening, and 9.4% resulted in death. The systematic review identified 24 published cases (median age: 65.5 years; range: 45-84). Only 25.0% of patients had pre-existing diabetes, while 33.3% had prediabetes. Median time to DKA onset was 28 days (range 7-180 days), with 54.2% occurring within 30 days of treatment initiation. One-third of patients required intensive care unit admission. Rechallenge was attempted in 37.5% of cases, with recurrent hyperglycemia occurring in 88.9%.

Conclusions: Alpelisib is associated with a clinically significant DKA safety signal and substantial morbidity. DKA frequently develops during the first month of therapy and can strike patients without established diabetes. Early pharmacist-led glucose monitoring and patient education may facilitate prompt recognition and management.

Keywords: alpelisib; diabetic ketoacidosis; FAERS

Background: Existing gabapentinoid surveillance focuses on fatalities, while non-fatal harms are poorly characterised. In hospital data, this is due to a lack of substance-specific International Classification of Diseases (ICD) codes. Free-text entries in hospital records may provide a more sensitive method for detecting gabapentinoid poisonings and co-ingestions.

Objectives: To examine 15-year trends in emergency department (ED) presentations for gabapentinoid poisoning in Victoria, Australia, and to describe patient characteristics, intent, and patterns of co-ingestion.

Methods: Gabapentinoid-related poisonings were identified using a free-text search of the ‘Description of Event’ field, supplemented by relevant ICD-10 codes. Two reviewers verified cases to exclude non-poisoning mentions. Quarterly presentation rates per 100,000 population were calculated, and trends were assessed by age, sex, medication type, intent, and co-ingested substances, including alcohol.

Results: We identified 1,207 presentations involving gabapentinoid poisoning from 2009/10 to 2023/24 financial year. Rates increased from 0.1 per 100,000 in 2009/10 to 2.2 in 2020/21, before stabilising in the following years. Presentations were most common among adults aged 25-44 years (45.5%), and females accounted for 56% of cases. Nearly half of presentations were recorded as intentional (49.5%), particularly among females and those aged under 65 years. Co-ingestion with opioids (22.1%) or benzodiazepines (25.0%) was frequent, although 36.2% of presentations involved gabapentinoids alone. Among gabapentinoid-alone presentations, almost one-third (29.7%) were unintentional, and most presentations in adults aged ≥65 years were unintentional (59.7%).

Conclusions: This is the first Australian study to use free-text descriptions to identify non-fatal gabapentinoid poisoning in the ED setting. ED presentations involving gabapentinoid poisoning increased substantially in Victoria over the past decade, broadly paralleling prescribing trends. A substantial proportion of poisonings involved gabapentinoids alone, underscoring the need to reassess the perceived safety profile of gabapentinoids and to strengthen prescribing vigilance.