There is a special interest in the implementation of pharmacogenetics in clinical practice, although there are some barriers that are preventing this integration. A large part of these pharmacogenetic tests are focused on drugs used in oncology and psychiatry fields and for antiviral drugs. However, the scientific evidence is also high for other drugs used in other medical areas, for example, in cardiology. In this article, we discuss the evidence and guidelines currently available on pharmacogenetics for clopidogrel, warfarin, acenocoumarol, and simvastatin and its implementation in daily clinical practice.

Azathioprine is commonly used as an immunosuppressive antimetabolite in the treatment of acute lymphoblastic leukemia, autoimmune disorders (such as Crohn's disease and rheumatoid arthritis), and in patients receiving organ transplants. Thiopurine-S-methyltransferase (TPMT) is a cytoplasmic trans-methylase catalyzing the S-methylation of thiopurines. The active metabolites obtained from thiopurines are hydrolyzed into inactive forms by the Nudix hydrolase 15 (NUDT15). The TPMT*2 (defined by rs1800462), *3A (defined by rs1800460 and rs1142345), *3B (defined by rs1800460), *3C (defined by rs1142345), *6 (defined by rs75543815), and NUDT15 rs116855232 genetic variant have been associated, with the highest level of evidence, with the response to azathioprine, and, the approved drug label for azathioprine and main pharmacogenetic dosing guidelines recommend starting with reduced initial doses in TPMT intermediate metabolizer (IM) patients and considering an alternative treatment in TPMT poor metabolizer (PM) patients. This study aims to assess the clinical impact of azathioprine dose tailoring based on TPMT genotyping studying the azathioprine toxicity and efficacy, treatment starts, and dose adjustments during follow-up, comparing TPMT IM/PM and normal metabolizer (NM) patients. It also studied the association of NUDT15 rs116855232 with response to azathioprine in patients receiving a tailored treatment based on TPMT and characterized the TMPT and NUDT15 studied variants in our population. Results show that azathioprine dose reduction in TPMT IM patients (TPMT*1/*2, *1/*3A, or *1/*3C genotypes) is related to lower toxicity events compared to TPMT NM (TPMT *1/*1 genotype), and lower azathioprine dose adjustments during follow-up without showing differences in the efficacy. The results support the hypothesis of existing other genetic variants affecting azathioprine toxicity.

Polypoidal choroidal vasculopathy (PCV) is usually regarded as a subtype of choroidal neovascularization (CNV) that is secondary to age-related macular degeneration (AMD) characterized by choroidal vessel branching, ending in polypoidal lesions. Despite their close association, PCV and neovascular AMD have shown differences, especially regarding patients’ treatment response. Currently, antivascular endothelial growth factor (anti-VEGF) drugs, such as ranibizumab, bevacizumab and aflibercept, have demonstrated their efficacy in CNV patients. However, in PCV, anti-VEGF treatments have shown inconclusive results. Many genetic polymorphisms have been associated with a variable response in exudative/wet AMD patients. Thus, the aim of this study is to explore the genetic variants affecting anti-VEGF drug response in PCV patients. In this regard, we performed a systematic review and meta-analysis. We found four variants (CFH I62V, CFH Y402H, ARMS2 A69S, and HTRA1-62A/G) that have been significantly related to response. Among them, the ARMS2 A69S variant is assessed in our meta-analysis. In conclusion, in order to implement anti-VEGF pharmacogenetics in clinical routines, further studies should be performed, distinguishing physio-pathogenic circumstances between PCV and exudative AMD and the combined effect on treatment response of different genetic variants.

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.

A severe form of myopia defined as pathologic/high myopia is the main cause of visual impairment and one of the most frequent causes of blindness worldwide. It is characterized by at least 6 diopters or axial length (AL) of eyeball > 26 mm and choroidal neovascularization (CNV) in 5 to 10% of cases. Ranibizumab is a humanized recombinant monoclonal antibody fragment targeted against human vascular endothelial growth factor A (VEGF-A) used in the treatment of CNV. It acts by preventing VEGF-A from interacting with its receptors (VEGFR-1 and -2) encoded by the FLT1 and KDR genes. Several studies found that the KDR and FLT1 genotypes may represent predictive determinants of efficacy in ranibizumab-treated neovascular age-related macular degeneration (nAMD) patients. We performed a retrospective study to evaluate the association of single nucleotide polymorphisms (SNPs) in VEGFR coding genes with the response rate to ranibizumab in patients with high myopia and CNV. In the association study of genotypes in FLT1 with the response to ranibizumab, we found a significant association between two FLT1 variants (rs9582036, rs7993418) with ranibizumab efficacy at the 12-month follow-up. About the KDR gene, we found that two KDR variants (rs2305948, rs2071559) are associated with best-corrected visual acuity (BCVA) improvement and KDR (rs2239702) is associated with lower rates of BCVA worsening considering a 12-month follow-up period.