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




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

KustantajaWiley

Julkaisuvuosi2026

Lehti: Basic and Clinical Pharmacology and Toxicology

Artikkelin numeroe70271

Vuosikerta139

Numero2

ISSN1742-7835

eISSN1742-7843

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

Julkaisun avoimuus kirjaamishetkelläAvoimesti saatavilla

Julkaisukanavan avoimuus Osittain avoin julkaisukanava

Verkko-osoitehttps://doi.org/10.1111/bcpt.70271

Rinnakkaistallenteen osoitehttps://research.utu.fi/converis/portal/detail/Publication/527059159

Rinnakkaistallenteen lisenssiCC BY NC

Rinnakkaistallennetun julkaisun versioKustantajan versio


Tiivistelmä

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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