Prevalence of clinically manifested drug interactions in hospitalized patients: A systematic review and meta-analysis.

Gonzaga de Andrade Santos, Tâmara Natasha; Mendonça da Cruz Macieira, Givalda; Cardoso Sodré Alves, Bárbara Manuella; Onozato, Thelma; Cunha Cardoso, Geovanna; Ferreira Nascimento, Mônica Thaís; Saquete Martins-Filho, Paulo Ricardo; Pereira de Lyra, Divaldo; Oliveira Filho, Alfredo Dias de

AIMS This review aims to determine the prevalence of clinically manifested drug-drug interactions (DDIs) in hospitalized patients. METHODS PubMed, Scopus, Embase, Web of Science, and Lilacs databases were used to identify articles published before June 2019 that met specific inclusion criteria. The search strategy was developed using both controlled and uncontrolled vocabulary related to the following domains: "drug interactions," "clinically relevant," and "hospital." In this review, we discuss original observational studies that detected DDIs in the hospital setting, studies that provided enough data to allow us to calculate the prevalence of clinically manifested DDIs, and studies that described the drugs prescribed or provided DDI adverse reaction reports, published in either English, Portuguese, or Spanish. RESULTS From the initial 5,999 articles identified, 10 met the inclusion criteria. The pooled prevalence of clinically manifested DDIs was 9.2% (CI 95% 4.0-19.7). The mean number of medications per patient reported in six studies ranged from 4.0 to 9.0, with an overall average of 5.47 ± 1.77 drugs per patient. The quality of the included studies was moderate. The main methods used to identify clinically manifested DDIs were evaluating medical records and ward visits (n = 7). Micromedex® (27.7%) and Lexi-Comp® (27.7%) online reference databases were commonly used to detect DDIs and none of the studies evaluated used more than one database for this purpose. CONCLUSIONS This systematic review showed that, despite the significant prevalence of potential DDIs reported in the literature, less than one in ten patients were exposed to a clinically manifested drug interaction. The use of causality tools to identify clinically manifested DDIs as well as clinical adoption of DDI lists based on actual adverse outcomes that can be identified through the implementation of real DDI notification systems is recommended to reduce the incidence of alert fatigue, enhance decision-making for DDI prevention or resolution, and, consequently, contribute to patient safety.