28 Utilization of pharmacogenetic medications at a German pediatric University Hospital

Introduction Pharmacogenetic (PGx) guided drug therapy is a promising approach for improving drug response and safety. The implementation of PGx information into clinical routine is currently ongoing in adult medicine, but still limited in pediatrics. Thus, we aimed to analyze the impact of PGx on the prescription of medications used in the real-world setting of a German Children's University hospital. Methodology A retrospective database analysis was performed using routine medication data from patients on general pediatric wards between 2014 and 2019. The database included 25,339 admissions of 16,289 patients. Of these, we analyzed the 17,543 admissions of 11,611 patients who received medication during hospital stays (i) to elucidate the frequency of PGx relevant drugs and (ii) to identify underlying PGx target genes. For the analyses we considered all currently listed 74 drugs with a pediatric guideline annotation on PharmGKB.org website. An age-stratified ranking list for clinically relevant PGx medications has been established. Results 37.9% (n = 4,401) of all hospitalized patients with medication (n = 11,611) received at least one PGx drug. Only 35 of the 74 PGx drugs with pediatric recommendations were used, resulting in 5,633 exposures to PGx drugs. The most commonly administered PGx drugs were ibuprofen (3,407/5,633, 60.5%), omeprazole (797/5,633, 14.1%), tobramycin (409/5,633, 7.3%), tramadol (198/5,633, 3.5%) and ondansetron (174/5,633, 3.1%). There were no age dependent differences regarding drug exposure except for aminoglycosides which were more often used in neonates, infants and toddlers. The analysis of PGx recommendations related to pharmacogenes resulted in 17 genes relevant for our study population. Here, CYP2C9, CYP2C19, CYP2D6, MT-RNR1, and HLA-B*15:02 are the top candidates. Conclusion Similar to adults, a high proportion of children and adolescents are treated with at least one PGx drug at our pediatric center, for which PGx guidelines recommend genetic testing preemptively. Based on our prescription data a total of 17 PGx genes should be considered for testing in clinical routine. In addition to PGx, developmental aspects of pharmacotargets need to be addressed in more detail to refine the implementation of PGx into pediatric medicine.