While pharmacogenomic testing combined with clinical decision support has the potential to increase the safety and efficacy of medical treatments, the intake of multiple prescription drugs can – if not sufficiently addressed by decision support solutions – impair the effectiveness of such interventions by modulating the capacity of precisely those enzymes whose function pharmacogenomic tests try to predict. We quantified the potential extent of such drug-mediated mismatches between genotype-derived phenotypes and real phenotypes, commonly called “phenoconversion”, by screening claims data from 1,587,829 Austrian health insurance holders of the years 2006 and 2007 for concomitant prescriptions of drugs that can be dosed based on pharmacogenomics, and drugs that modulate enzyme activity. In total, 232,398 such prescription overlaps were detected, of which more than half (54.6%) could be attributed to co-prescriptions of moderate or strong modulators. Our results indicate that prescription drug-mediated phenoconversion is not uncommon, and should therefore be adequately reflected in decision support solutions by integrating algorithms to detect potential gene-drug-drug interactions.