A1 Refereed original research article in a scientific journal

Using Pharmacovigilance Data for Signal Detection of Drug Interactions for Rosuvastatin;




AuthorsLevomäki, Ronja; Hirvensalo, Päivi; Tornio, Aleksi; Filppula, Anne M.

PublisherWiley

Publication year2026

Journal: Basic and Clinical Pharmacology and Toxicology

Article numbere70271

Volume139

Issue2

ISSN1742-7835

eISSN1742-7843

DOIhttps://doi.org/10.1111/bcpt.70271

Publication's open availability at the time of reportingOpen Access

Publication channel's open availability Partially Open Access publication channel

Web address https://doi.org/10.1111/bcpt.70271

Self-archived copy’s web addresshttps://research.utu.fi/converis/portal/detail/Publication/527059159

Self-archived copy's licenceCC BY NC

Self-archived copy's versionPublisher`s PDF


Abstract

The 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitor rosuvastatin is a substrate of breast cancer resistance protein (BCRP). BCRP inhibition increases rosuvastatin plasma concentrations and may result in concentration-dependent muscle toxicity, at worst rhabdomyolysis. We investigated if concomitant use of rosuvastatin and drugs identified as in vitro BCRP inhibitors shows an increased number of rhabdomyolysis events based on pharmacovigilance data. From reports in the US Food and Drug Administration Adverse Event Reporting System for patients using rosuvastatin, we formed interaction (rosuvastatin with inhibitor) and non-interaction (rosuvastatin without inhibitor) groups for 71 BCRP inhibitors. These groups were further divided into subgroups with or without rhabdomyolysis. For each inhibitor, we calculated reporting odds ratio (ROR) and 95% confidence intervals (CIs). We identified 9777 individual rosuvastatin-related reports during 2013–2023, including 815 rhabdomyolysis reports. Of the 71 inhibitors, 19 had enough reports for analysis. Significantly increased RORs were obtained for the clinical BCRP inhibitors febuxostat (ROR 2.47, 95% CI 1.38–4.43) and ticagrelor (ROR 4.15, 95% CI 3.32–5.20). Amiodarone, erlotinib and rifampicin showed significantly increased RORs. Our findings support known interactions involving febuxostat and ticagrelor and suggest that also other BCRP inhibitors may increase the risk of rosuvastatin-induced rhabdomyolysis.


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Last updated on 25/08/2026 10:45:17 AM