engleski

Pharmacogenomics - a promising tool for elderly patients on polytherapy

Polypharmacy is highly prevalent in elderly patients and is associated with drug-drug interactions, adverse drug reactions (ADRs), more frequent hospital admissions and higher health- care costs. A pharmacogenomic approach enables personalized medication regimens based on individual genetic variations predominantly of ADME genes, involved in the pharmacokinetics of medicinal products. The majority of current pharmacogenomic decision support tools provide assessment only of single drug- gene interactions without taking into account complex drug-drug and drug-drug-gene interactions which are prevalent in polypharmacy and can result in ADRs or insufficient drug efficacy. Implementation of pharmacogenetic testing into the clinic is ongoing in Croatia for 20 years. Genotyping of metabolic enzymes of phase I (CYPs, DPD), phase II (TPMT, UGTs, NAT2), ABC, SLC transporters, and drug targets, represents a valuable tool for analysing the causal relationship between drug intake and dose related ADRs especially in elderly polymedicated patients. The availability of genomic testing has grown, but its clinical application is still insufficient. The objective was to develop comprehensive pharmacogenomic decision support for medication risk assessment in elderly polymedicated patients that simultaneously accounts for multiple drug and gene effects. To study the possible genetic associations with ADRs, School of Medicine University of Zagreb, University Hospital Centre Zagreb, and Croatian Agency for Medicinal Products & Medical Devices (HALMED) have piloted a project to collect DNA and phenotype data of ADR cases using international standardized phenotypic criteria. Patients with ADRs (N=860) and controls were genotyped for pharmacogenes. Univariate and multivariate prediction of ADRs were carried by means of binary logistic regression in order to identify novel associations or validate findings in cohorts of patients with well- defined phenotypes. We developed a comprehensive knowledge repository of actionable pharmacogenes at the University Hospital Centre Zagreb. HALMED developed a method for informing physicians or pharmacists and their patients about a possible pharmacogenetic involvement in the ADR pathogenesis. An anonymized copy of the test results has been used for the interpretation of possible signals. Several publications from this project have been published, depending on the medication in question (warfarin, statins, clopidogrel, methotrexate, AEDs, psychotropic drugs). Pharmacogenomic knowledge repository is an excellent genesis for pharmacogenomic testing implementation in clinical practice and pharmacogenetic counselling after a reported ADR. By using a pharmacogenomics approach, individualized strategies in medication can improve drug safety and efficacy in the elderly patient population with polypharmacy.

adverse drug reactions ; polypharmacy ; elderly patients

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