Ludovica Vittoria Laino

Objective: We analysed adverse event reporting patterns associated with SSRIs using data from the European pharmacovigilance database, EudraVigilance. Methods: A descriptive analysis of individual case safety reports (ICSRs) was conducted between January 2020, 1st and December 2024, 31st. Disproportionality analysis were conducted for the two most frequently reported system organ classes (SOCs) and the three most frequently reported preferred terms (PTs). Results: During the study period, 21,665 ICSRs reporting at least one SSRI as suspected drug were retrieved. A total of 78,132 adverse events were identified, and sertraline ( N = 26,161; 33.5%) was the most reported SSRI. Most events were not serious, and the most reported criterion was Other Medically Important Condition ( N = 19,603; 25.1%). The most frequent outcome was “Unknown” ( N = 27,555). In the disproportionality analysis, for the SOC “Psychiatric Disorders”, escitalopram and fluvoxamine showed a higher disproportionate reporting (ROR 1.08; 95% CI 1.03–1.13; ROR 1.15; 95% CI 1.01–1.31, respectively). For the SOC “Nervous System Disorders”, paroxetine showed a higher disproportionate reporting (ROR 1.10; 95% CI 1.04–1.16). Headache higher disproportionate reporting with sertraline (ROR 1.17; 95% CI 1.04–1.30), while dizziness with escitalopram (ROR 1.42; 95% CI 1.25–1.61), and somnolence with fluvoxamine and paroxetine (ROR 1.86; 95% CI 1.27–2.72; ROR 1.58; 95% CI 1.33–1.89, respectively). Conclusions: SSRIs showed homogeneous adverse event reporting patterns, with relatively few differences in disproportional reporting between individual drugs. These results reinforce the importance of continuous pharmacovigilance monitoring.

Background: Teriparatide is approved for the treatment of osteoporosis and is generally well-tolerated. However, concerns remain about a possible association with osteosarcoma, a rare but aggressive bone malignancy. This pharmacovigilance study aims to evaluate the reporting frequency of osteosarcoma associated with teriparatide in the Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: Individual case safety reports (ICSRs) listing teriparatide as a suspected drug and osteosarcoma as an adverse event were extracted from the FAERS public dashboard up to 20 February 2025. Both descriptive and disproportionality analyses were performed. Results: A total of 112,798 ICSRs involving teriparatide were retrieved, of which 29 were reported. Most cases involved female patients (72.4%) and older patients (48.3%). Almost all reports (96.6%) were classified as serious, with death being the most common outcome (44.8%). Of the reports with information on concomitant medications, 31% included five or more medications, with vitamins being the most common. The disproportionality analysis showed a significantly higher reporting frequency of osteosarcoma with teriparatide compared to all other drugs (reporting odds ratio, ROR: 15.31; 95% CI: 10.53–22.26). This signal remained consistent when the analysis was restricted to reports submitted since 2006 (ROR: 15.88; 95% CI: 10.92–23.09). The information component (IC) analysis confirmed this finding (IC: 3.56; 95% CI: 2.95–4), and similar results were observed for the post-2006 subset (IC: 3.60; 95% CI: 2.99–4.05). However, the analysis compared to another osteoporosis drug (romosozumab) did not confirm any safety signal for teriparatide. Conclusions: This study highlights a disproportionate signal between teriparatide use and osteosarcoma when compared to all other drugs but not compared to romosozumab. Based on this and considering that previous evidence did not support an increased risk, further research is warranted to better understand this association.

Background: Hepatotoxicity induced by atomoxetine (ATX) and methylphenidate (MPH) when used to treat ADHD is a rare but potentially serious complication. This study aims to describe the hepatic adverse drug reactions (ADRs) reported for ATX and MPH by analysing data from the EudraVigilance database. Methods: Individual case safety reports (ICSRs) listing ATX and/or MPH as suspected drugs and reporting at least one adverse event (AE) within the ‘hepatobiliary disorders’ system organ class (SOC) were extracted for the period from 1 January 2012 to 20 May 2025. Descriptive and disproportionality analyses were then performed. Results: During the study period, 421 ICSRs reporting AEs classified under the “hepatobiliary disorders” SOC and involving ATX and/or MPH as suspected drugs were retrieved (ATX, N = 232; MPH, N = 181). Most cases involved adult (N = 261) and female (N = 222) patients. The majority of reports were classified as serious (N = 349). Overall, 375 AEs were identified. Drug-induced liver injury (DILI) was the most frequently reported AE (N = 103 ATX; N = 47 MPH), followed by hepatitis (N = 20 ATX; N = 9 MPH) and jaundice (N = 15 ATX; N = 20 MPH). The disproportionality analysis, based on a head-to-head comparison, showed a higher reporting frequency of hepatobiliary disorders for ATX compared to MPH (ROR 2.41 [95%CI 2.11–3.11]). Specifically, ATX was associated with significantly higher reporting frequencies than MPH for the AEs of DILI, hepatitis, and jaundice (6.42 [4.45–9.06]; 6.48 [2.95–14.24]; and 2.19 [1.12–4.27], respectively). Conclusions: This analysis, based on the EudraVigilance database, suggests that both drugs are associated with hepatobiliary adverse drug reactions, with a higher overall reporting frequency observed for ATX.

Acute myeloid leukemia (AML) is the most common acute leukemia in adults. Approximately 30% of patients present alterations in the FMS-like receptor tyrosine kinase 3 (FLT3) gene, which are associated with poor prognosis. FLT3 inhibitors – midostaurin (first-generation), gilteritinib and quizartinib (second-generation) – have been developed to block FLT3 activation. Given the need of optimizing treatment in FLT3-mutated AML, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to compare the safety profiles of FLT3 inhibitors. Following the PRISMA statement, we searched Embase, MEDLINE and Cochrane Library. The Cochrane Risk of Bias Tool for RCTs was used for quality assessment. Of 2132 references, seven RCTs, involving 2409 adult patients, met inclusion criteria: quizartinib and midostaurin in two trials each and gilteritinib in three. The most frequently reported adverse events (AEs) were classified under the System Organ Class (SOC) Blood and lymphatic system disorders ( N = 5474, 58.4% of them related to FLT3 inhibitors). The most frequently observed non-hematological AEs were gastrointestinal disorders, pyrexia, elevated ALT/AST and headache. FLT3 inhibitors are not associated with a significant increase in the risk of AEs compared to standard treatments. No meaningful differences in AE risk were observed among the three drugs. The only exception was an higher risk of ALT increased with gilteritinib (RR = 2.40, 95% CI: 1.16–4.95). Future studies should stratify safety outcomes by demographic and clinical characteristics and incorporate long-term follow-up for a more comprehensive safety assessment in clinical practice.