Utilisation of drugs with pharmacogenetic recommendations in children in Switzerland

The Pharmacogenomics Journal ARTICLE www.nature.com/tpj OPEN Utilisation of drugs with pharmacogenetic recommendations in children in Switzerland Nina L. Wittwer 1,2, Christoph R. Meier1,2,3, Carola A. Huber4, Romy Tilen5,6, Canan Yilmaz1, Henriette E. Meyer zu Schwabedissen5, ✉ Samuel Allemann 7,8 and Cornelia Schneider1,2,8 1234567890();,: © The Author(s) 2025 Pharmacogenetics (PGx) is increasingly implemented in the adult population, but its potential in children remains uncertain. The aim of this study was to investigate PGx drug utilization in children in Switzerland, using Helsana claims data between 2017 and 2021. We identified 82 drugs with paediatric guideline annotations associated with variants in 24 genes from the Pharmacogenomics Knowledgebase. Of 159 172 children continuously insured, 66.1% claimed at least one PGx drug during the study period. The three PGx drugs with the highest user numbers were systemically administered ibuprofen (59.1%), ondansetron (8.3%), and locally administered fluorouracil (7.5%). Over 96% of all potential drug-gene interactions were caused by seven genes (CYP2C9, CYP2D6, DPYD, CYP2C19, MT-RNR1, CACNA1S, and RYR1). The high number of children claiming PGx drugs in Switzerland implies that a significant number of children could benefit from PGx testing. The Pharmacogenomics Journal (2025)25:19 ; https://doi.org/10.1038/s41397-025-00378-x INTRODUCTION Drug-gene-interactions (DGIs) refer to situations where a genetic variant and a drug interact, resulting in an altered drug response [1–3]. Individual genetic factors affecting pharmacodynamics or pharmacokinetics in DGIs can lead to variability in drug exposure and /or response resulting in treatment failure or toxicity [1, 2]. Pharmacogenomics aims to enhance an individuals’ drug response through a personalised, and therefore safer and more effective therapy [4]. Children are a vulnerable patient group and frequently affected by adverse drug reactions [5]. In adults, pharmacogenetic (PGx) testing has been demonstrated to reduce the number of adverse drug reactions, which is associated with fewer hospital admissions due to adverse drug reactions and with improved treatment responses [6–10], but these results cannot easily be transferred to children. Children represent a heterogeneous group ranging from preterm new-borns to adolescents. In the postnatal phase, both age and genotype affect enzyme expression and activity [11]. Moreover, ontogenesis influences the activity of drugmetabolizing enzymes and transporters [12]. Of particular significance in this context are individuals below the age of two years, as ontogenetic variability is most pronounced in this age group [12]. The implementation of PGx for children has proceeded slower than anticipated and is still limited [13, 14]. PGx dosing guidelines applicable for children by the Clinical Pharmacogenetics Implementation Consortium (CPIC) [15, 16], the Dutch Pharmacogenetics Working Group (DPWG) [17, 18], and the Canadian Pharmacogenomics Network for Drug Safety (CPNDS) [19, 20] are available on the Pharmacogenomics Knowledgebase (PharmGKB, www.pharmgkb.org) [21]. These guidelines shall facilitate the implementation of PGx in clinical practice by helping paediatricians and pharmacists to interpret PGx findings. The majority of existing PGx studies in children focus on the hospital setting and /or specific medical conditions such as mental illnesses, sickle cell anaemia, or children with burns and surgery [22–27]. To assess the benefit of PGx testing in children, it is crucial to understand the utilisation of PGx drugs in paediatrics. To date, most studies examining the prevalence of PGx drugs in children have been conducted in the United States of America (USA) and Canada [23, 28–32]. Currently, there is insufficient research on the frequency of PGx prescriptions in paediatrics in Europe [33]. Therefore, the aim of this study was to analyse the utilisation of PGx drugs in children and adolescents in Switzerland. The objectives were to assess the prevalence of PGx drug prescriptions, to identify the most frequently used PGx drugs, and thereby to determine the most relevant PGx genes in different age groups. MATERIALS AND METHODS Data source We used claims data from one of the largest Swiss health insurance providers (Helsana Group), which covers approximately 1.2 million people (15% of the Swiss population) annually across all 26 cantons with basic health insurance. The Helsana database is representative of the Swiss population. This database has previously been used for several drug safety 1 Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland. 2Hospital Pharmacy, University Hospital Basel, Basel, Switzerland. 3Boston Collaborative Drug Surveillance Program, Lexington, MA, USA. 4Department of Health Sciences, Helsana Group, Zürich, Switzerland. 5Biopharmacy, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland. 6University Children’s Hospital Zurich, Department of Infectious Diseases and Hospital Epidemiology, Zürich, Switzerland. 7Pharmaceutical Care, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland. 8These authors contributed equally: Samuel Allemann, Cornelia Schneider. ✉email: Received: 15 May 2024 Revised: 27 March 2025 Accepted: 24 June 2025 N.L. Wittwer et al. 2 Table 1. PGx drugs with corresponding genes. Gene Gene name Drug ABCG2 ATP binding cassette subfamily G member 2 Allopurinol, rosuvastatin CACNA1S Calcium voltage-gated channel subunit alpha1 S Desflurane, enflurane, halothane, isoflurane, methoxyflurane, sevoflurane, succinylcholine CFTR Cystic fibrosis transmembrane conductance regulator Ivacaftor CYP2B6 Cytochrome P450 2B6 Efavirenz, sertraline CYP2C19 Cytochrome P450 2C19 Amitriptyline, citalopram, clomipramine, clopidogrel, dexlansoprazole, doxepin, escitalopram, imipramine, lansoprazole, omeprazole, pantoprazole, sertraline, trimipramine, voriconazole CYP2C9 Cytochrome P450 2C9 Acenocoumarol, celecoxib, flurbiprofen, fluvastatin, fosphenytoin, ibuprofen, lornoxicam, meloxicam, phenytoin, piroxicam, tenoxicam, warfarin CYP2D6 Cytochrome P450 2D6 Amitriptyline, atomoxetine, clomipramine, codeine, desipramine, doxepin, fluvoxamine, hydrocodone, imipramine, nortriptyline, ondansetron, paroxetine, pimozide, risperidone, tramadol, trimipramine, tropisetron, venlafaxine, vortioxetine CYP3A4 Cytochrome P450 3A4 Tacrolimus CYP3A5 Cytochrome P450 3A5 Tacrolimus CYP4F2 Cytochrome P450 4F2 Warfarin DPYD Dihydropyrimidine dehydrogenase Capecitabine, fluorouracil G6PD Glucose-6-phosphate dehydrogenase Dapsone, methylene blue, nitrofurantoin, pegloticase, primaquine, rasburicase, tafenoquine HLA-A Human leukocyte antigen A Carbamazepine HLA-B Human leukocyte antigen B Abacavir, allopurinol, carbamazepine, fosphenytoin, pheny (...truncated)