Background/Objectives: Fluoropyrimidines are widely used chemotherapeutic agents in various solid tumors. Germline variants in the DPYD gene, which encodes the enzyme dihydropyrimidine dehydrogenase (DPD), are known to impair drug metabolism and increase the risk of severe toxicity. This umbrella review aims to synthesize the current evidence from systematic reviews on the association between DPYD variants and fluoropyrimidine-induced toxicity. Methods: A comprehensive search was conducted in PubMed, Web of Science, Scopus, and the Cochrane Library from inception to 2023, including gray literature. Systematic reviews assessing fluoropyrimidine toxicity in oncologic patients with DPYD variants were included. Study quality was assessed using the AMSTAR-2 tool. Registration number in PROSPERO: CRD42023401226. Results: Two independent investigators performed the study selection, quality assessment, and data collection. Eight systematic reviews met the inclusion criteria. Methodological confidence was rated as critically low in six, low in one, and medium in another one. The reviews included 125 primary studies, most of them focused on four key DPYD variants (DPYD2*A, DPYD*13, c.2846A>T, and HapB3), all of which showed consistent associations with an increased risk of severe toxicity. Rare variants such as DPYD*4, *5, and *6 were also examined, though evidence remains limited. Pharmacogenetics-guided dosing of fluoropyrimidines significantly reduced toxicity rates in several studies. The integration of DPYD genotyping with phenotyping approaches faces limitations; these tests should complement rather than replace genotyping information. Conclusions: This umbrella review confirms the clinical relevance of DPYD genotyping to predict and mitigate fluoropyrimidine toxicity. Incorporating genotyping into clinical practice, potentially alongside phenotyping and therapeutic drug monitoring, may enhance patient safety and treatment efficacy.

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Objective To determine the pharmaceutical interventions in patients eligible for phase I cancer clinical trials, focusing specifically on exclusion criteria related to medication or relevant interactions. Method Descriptive, observational study conducted at a comprehensive cancer centre. Patients undergoing screening for phase I clinical trials (March 2019–December 2022) were included. The pharmacist reviewed concomitant medication and provided a recommendation. Results The concomitant medication of 512 patients eligible to participate in 84 phase I clinical trials was analysed. In 230 (44.9%) patients, the clinical trial treatment included oral medication. The median number of concomitant medications was 5 (IQR 3–8) per patient. A total of 280 pharmaceutical interventions were performed in 140 (27.3%) patients: 240 (85.7%) were due to interactions in 124 (24.2%) patients, and 40 (14.3%) were due to exclusion criteria in 34 (6.6%) patients. Interactions and exclusion criteria were detected in 18 (3.5%) patients. The main groups of drugs involved were 68 (24.3%) antacids and antiulcer drugs, 28 (10.0%) antidepressants and 26 (9.3%) opioids. Acceptance analysis of the recommendation was applicable in 215 cases; in 208 (96.7%), the pharmaceutical intervention was accepted. Differences were identified for exclusion criteria (7 vs 27) and interactions (37 vs 87) between parenteral and oral clinical trial medication (p<0.001). Conclusion The pharmacist’s review of concomitant medication during the screening period in phase I clinical trials enables the detection of prohibited medication or relevant interactions, potentially avoiding screening failures and increasing the efficacy and safety of treatments.

Eosinophilic Granulomatosis with Polyangiitis (EGPA) is a systemic vasculitis classified among the antineutrophil cytoplasmic antibody (ANCA) associated vasculitides. Eosinophils play a key role in its pathogenesis, with interleukin-5 (IL-5) being the most potent stimulator of their proliferation and activation. In recent years, treatment strategies have evolved with the introduction of biological agents targeting IL-5 or its receptor. This review summarizes the current evidence on the efficacy and safety of anti-IL-5 therapies, focusing on mepolizumab and benralizumab. A bibliographic search was conducted in PubMed, Web of Science, and Scopus, including studies of adults diagnosed with EGPA treated with anti-IL-5 therapies. The search was limited to articles published in the last 10 years in English or Spanish. Available data consistently show that these agents reduce corticosteroid requirements, lower eosinophil counts, and improve disease control. Regarding mepolizumab, real-world studies indicated that both 100 mg and 300 mg doses are equally effective, while the influence of ANCA status on treatment response remains controversial. Otorhinolaryngologic relapses have also been reported. Benralizumab 30 mg every 4 weeks showed remission rates comparable to mepolizumab, although further research is needed to determine the optimal dosing regimen. Overall, anti-L-5 therapies represent an effective and safe option for EGPA. Future research should focus on larger, multicenter trials to clarify the pathophysiology of the disease and facilitate the identification of predictive biomarkers, leading for personalized therapeutic strategies.

Human albumin solution (HAS) is a plasma-derived product used for a wide variety of clinical indications, although only some of these are supported by solid scientific evidence. Objectives The primary aim of this study was to analyze the level of evidence supporting the clinical indications for which HAS is used at a secondary care hospital. Secondary objectives were to evaluate dosing appropriateness and perform a subanalysis of the internal medicine department. Methods Retrospective, observational, multidisciplinary study of adults who received at least one dose of HAS during 2019. We analyzed sociodemographic, clinical, laboratory, and pharmacotherapy variables. The indications for which HAS was used were classified into the four evidence-based categories established by the American Society for Apheresis: high priority (category I), reasonable evidence (II), weak evidence (III), and treatment not recommended (IV). Clinical guideline recommendations were used to evaluate dosing appropriateness. Results The study population comprised 142 patients (41% women), mean (SD) age of 66 (14) years. The main admission diagnoses were decompensated cirrhosis (32%) and septic shock (31%). In total, 223 courses of HAS were prescribed. The main indications were treatment of anasarca and hypoalbuminemia (32%), prevention of paracentesis-induced circulatory dysfunction after large-volume paracentesis (17%), resuscitation in septic shock (13%), and treatment of protein malnutrition (9%). Just 26% of hospital-wide indications were supported by strong evidence (category I); 13% category II, 8% category III, and 53% category IV. In the internal medicine department, 36% of indications were in category I, 16% in category III, 48% in category IV. An appropriate dosing regimen was used in just four category I indications. Conclusions A large proportion of HAS indications at our hospital are supported by weak evidence. Training to promote the rational use of HAS is needed. Protocols and local clinical guidelines could help standardize and optimize its use.