Background/Objectives: Irinotecan is used in monotherapy or combined with other drugs for treating different cancer streams. SN-38, the active metabolite of irinotecan, is 70% inactivated by the uridine diphosphate (UDP) glucuronosyltransferase family 1 member A1 (UGT1A1) enzyme. The UGT1A1*6 (rs4148323) and *28 (rs3064744) alleles in the gene encoding the enzyme lead to decreased enzyme expression and increased severe irinotecan toxicity. Carrying one or two copies of these alleles results in a UGT1A1 intermediate or poor metabolizer status (IM, PM). The Food and Drug Administration (FDA)-approved drug labels and European Medicines Agency (EMA) European Public Assessment Report (EPAR) for irinotecan recommend dose adjustments based on UGT1A1 genotypes, but only for UGT1A1 PM patients. However, available pharmacogenetic (PGx) dosing guidelines for the UGT1A1–irinotecan interaction lack a consensus about considered genetic variants, genotype-translated phenotypes, and therapeutic recommendations. We aimed to describe evidence regarding the impact of the UGT1A1 genotype in irinotecan toxicity to inform irinotecan-dosing recommendations based on possible UGT1A1 genotypes. Methods: A systematic review was performed to find all the Phase I clinical trials looking for the maximum tolerated dose (MTD) or dose-limiting toxicities (DLTs) of irinotecan depending on the UGT1A1 genotype. Results: Toxicity-related events and the MTD of irinotecan differ among UGT1A1 normal metabolizers (NM), IM, and PM patients considering the UGT1A1*28 and/or *6 variants. Conclusions: Dose adjustments might also be recommended for UGT1A1 IM patients (*1/*28 or *1/*6 genotypes), with a 15% dose reduction considered.

Background/Objective: Multidrug-resistant (MDR) bacteria pose a significant threat to global health, especially in intensive care units (ICUs), where high antibiotic consumption drives antimicrobial resistance. Selective digestive decontamination (SDD) is a strategy designed to prevent nosocomial infections and colonization by MDR pathogens. This study aimed to evaluate the impact of implementing an SDD protocol on antibiotic consumption and colonization by carbapenemase-producing Enterobacterale (CPE) in a specific ICU setting. Methods: This quasi-experimental study was conducted in the ICU of a university hospital from June 2021 to June 2023. Patients were divided into two groups: pre-intervention (before SDD) and post-intervention (after SDD implementation). Data on antibiotic consumption (expressed as defined daily doses (DDDs) per 100 stays), nosocomial infections, colonization rates, and the incidence of MDR bacteria were collected. A statistical analysis was conducted to compare the pre- and post-intervention groups. Results: A total of 3266 patients were included, with 1532 in the pre-intervention group and 1734 in the post-intervention group. The implementation of the SDD protocol resulted in a significant reduction in total antibiotic consumption (p = 0.028), with notable decreases in carbapenem use (p < 0.01) and colonization by CPE (p = 0.0099). The incidence of nosocomial infections also decreased in the post-SDD group, although this reduction was not statistically significant. Conclusions: The implementation of the SDD protocol in this ICU setting significantly reduced antibiotic consumption and colonization by CPE. These findings suggest that SDD may be a valuable tool in managing antimicrobial resistance in critical care settings, without contributing to the development of MDR bacteria.

Background/Objectives: The clinical implementation of pharmacogenetics (PGx) remains limited, even for well-established drug–gene interactions. In addition to insufficient infrastructure and PGx education among healthcare professionals, there is currently no consensus regarding which genetic variants should be tested, the most appropriate testing approach (e.g., single-gene vs. multi-gene panels), or how to translate genotypes into actionable therapeutic recommendations. Methods: We describe the implementation of PGx in real daily clinical routine at a single institution to guide other centers. We analyze the drug–gene interactions and genetic variants included in our program based on allelic, genotypic, and phenotypic frequencies, resulting therapeutic recommendations. Linkage disequilibrium and haplotype analyses are also performed. Results and Conclusions: PGx testing was primarily requested by the oncology department. Not all variants included in typical panels had clinical utility in our setting. We do not recommend testing CYP2C19*17 prior to clopidogrel prescription, as it does not translate into a dosing recommendation. TPMT*3B may be considered just to confirm TPMT*3A due to its linkage with TPMT*3C. Similarly, we do not recommend the routine testing of CYP2C9*2 prior to siponimod prescription, as it does not inform therapeutic decisions according to the current drug label.

Background/Objectives: Sacituzumab govitecan (SG) releases SN-38, the same active metabolite as irinotecan, thereby sharing key metabolic pathways and toxicity mechanisms. The clearance of SN-38 is strongly influenced by UGT1A1 polymorphisms, particularly the UGT1A1*28 allele. While UGT1A1*28 genotyping routinely guides irinotecan dosing, no such recommendations exist for SG. This study describes the relationship between UGT1A1*28 and severe SG-related toxicity in real-world practice, identifying early safety signals and exploring the clinical and economic impact. Methods: This retrospective observational study (2021–2025) included patients with metastatic breast cancer treated with SG and patients with advanced gastrointestinal malignancies treated with irinotecan at a tertiary hospital. In the SG cohort, genotyping followed grade ≥3 toxicity; in the irinotecan cohort, it was performed prospectively. Toxicity (Common Terminology Criteria for Adverse Events version 5.0) and healthcare costs related to hospitalizations were estimated using official institutional tariffs. Results: All nine SG patients with severe toxicity (100%) carried the UGT1A1*28 allele. In the irinotecan cohort (n = 74), which was managed with genotype-guided dosing, severe toxicity and hospitalization were less frequent. SG was associated with higher mean costs per treated patient (€2817.01 vs. €1233.63), driven by toxicity-related admissions (33.3% vs. 10.8%). Genotyping costs (€10.51) were negligible compared to daily hospitalization expenses (up to €1984.90). Conclusions: Severe SG-related toxicity reveals a consistent UGT1A1*28-associated vulnerability. Given the drug’s recent approval in Spain, these data represent an urgent real-world safety signal. The marked disparity between low genotyping costs and high hospitalization expenses supports implementing preventive UGT1A1 testing to optimize the safety and sustainability of sacituzumab govitecan therapy.

Fluoropyrimidines (FPs) are commonly prescribed in many cancer streams. The EMA and FDA-approved drug labels for FPs recommend genotyping the DPYD*2A (rs3918290), *13 (rs55886062), *HapB3 (rs56038477), alleles, and DPYD rs67376798 before treatment starts. We implemented the DPYD genotyping in our daily clinical routine, but we still found patients showing severe adverse drug events (ADEs) to FPs. We studied among these patients the DPYD rs1801265, rs17376848, rs1801159, rs1801160, rs1801158, and rs2297595 as explanatory candidates of the interindividual differences for FP-related toxicities, examining the association with the response to FPs . We also studied the impact of DPYD testing for FP dose tailoring in our clinical practice and characterized the DPYD gene in our population. We found a total acceptance among physicians of therapeutic recommendations translated from the DPYD test, and this dose tailoring does not affect the treatment efficacy. We also found that the DPYD*4 (defined by rs1801158) allele is associated with a higher risk of ADEs (severity grade ≥ 3) in both the univariate (O.R. = 5.66; 95% C.I. = 1.35–23.67; p = 0.014) and multivariate analyses (O.R. = 5.73; 95% C.I. = 1.41–28.77; p = 0.019) among FP-treated patients based on the DPYD genotype. This makes it a candidate variant for implementation in clinical practice.

Fluoropyrimidines (FPs) are commonly prescribed in many cancer streams. The DPYD*2A (rs3918290), *13 (rs55886062), *HapB3 (rs56038477), alleles, and DPYD rs67376798, had shown the highest level of evidence about their association with FPs response. The EMA and FDA-approved drug labels for FPs, recommend genotyping these variants before treatment starts. We implemented the DPYD genotyping in our daily clinical routine, but we still find patients showing severe adverse drug events (ADEs) to FPs. We studied among these patients the association with the response to FPs of DPYD rs1801265, rs17376848, rs1801159, rs1801160, rs1801158, and rs2297595; as explanatory candidates of the interindividual differences for the FP-related toxicities. We also studied the impact of DPYD*2A, *13, *HapB3, and rs67376798 genotype for FP dose tailoring in our clinical practice and characterized the DPYD gene in our population. We found that FP dose lowering based on DPYD genotype does not affect the treatment efficacy. Also, the DPYD*4 (defined by rs1801158) allele was associated with a higher risk of ADEs (severity grade ≥ 3) in both the univariate (O.R.= 5.66; 95% C.I.= 1.35 – 23.67; p= 0.014) and multivariate analyses (O.R.= 5.73; 95% C.I.= 1.41 – 28.77; p= 0.019). This makes it a candidate variant for implementation in clinical practice.