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Precision medicine is complex, even for decisions about single drugs for single diseases, as it requires expert consideration of multiple measurable factors that affect pharmacokinetics and pharmacodynamics, and many patient-specific variables. Given the increasing number of patients with multiple conditions and medications, there is a need to apply lessons learned from precision medicine in monotherapy and single disease management to optimise polypharmacy. However, precision medicine for optimisation of polypharmacy is particularly challenging because of the vast number of interacting factors that influence drug use and response. In this narrative review, we aim to provide and apply the latest research findings to achieve precision medicine in the context of polypharmacy. Specifically, this review aims to (1) summarise challenges in achieving precision medicine specific to polypharmacy; (2) synthesise the current approaches to precision medicine in polypharmacy; (3) provide a summary of the literature in the field of prediction of unknown drug\u2013drug interactions (DDI) and (4) propose a novel approach to provide precision medicine for patients with polypharmacy. For our proposed model to be implemented in routine clinical practice, a comprehensive intervention bundle needs to be integrated into the electronic medical record using bioinformatic approaches on a wide range of data to predict the effects of polypharmacy regimens on an individual. In addition, clinicians need to be trained to interpret the results of data from sources including pharmacogenomic testing, DDI prediction and physiological-pharmacokinetic-pharmacodynamic modelling to inform their medication reviews. Future studies are needed to evaluate the efficacy of this model and to test generalisability so that it can be implemented at scale, aiming to improve outcomes in people with polypharmacy.<\/jats:p>","DOI":"10.1017\/pcm.2023.10","type":"journal-article","created":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T03:41:47Z","timestamp":1678419707000},"source":"Crossref","is-referenced-by-count":17,"title":["Polypharmacy and precision medicine"],"prefix":"10.1017","volume":"1","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7876-6004","authenticated-orcid":false,"given":"Kenji","family":"Fujita","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7123-9583","authenticated-orcid":false,"given":"Nashwa","family":"Masnoon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6896-6376","authenticated-orcid":false,"given":"John","family":"Mach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0927-7295","authenticated-orcid":false,"given":"Lisa Kouladjian","family":"O\u2019Donnell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5970-1501","authenticated-orcid":false,"given":"Sarah N.","family":"Hilmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2023,3,10]]},"reference":[{"key":"S2752614323000108_r92","unstructured":"Medbase (2015a) RENBASE - Drug Dosing in Renal Failure. 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