Rhabdomyolysis during concomitant ticagrelor and rosuvastatin - a breast cancer resistance protein -mediated drug interaction?

Minna Lehtisalo, Wilma Kiander, Anne M Filppula, Feng Deng, Heidi Kidron, Mari Korhonen, Johanna Sinkko, Kimmo Koivula, Mikko Niemi

Research output: Contribution to journalArticleScientificpeer-review

5 Citations (Scopus)
29 Downloads (Pure)

Abstract

We present 3 patients diagnosed with rhabdomyolysis 1–6 months after the initiation of concomitant rosuvastatin and ticagrelor medication. A literature review and Food and Drug Administration adverse event reporting system revealed >40 reports of rhabdomyolysis during concomitant ticagrelor and rosuvastatin, including 3 with a fatal outcome. We show that ticagrelor inhibits breast cancer resistance protein-, organic anion transporting polypeptide (OATP) 1B1-, 1B3- and 2B1-mediated transport of rosuvastatin in vitro with half-maximal unbound inhibitory concentrations of 0.36, 4.13, 7.5 and 3.26 μM, respectively. A static drug interaction model predicted that ticagrelor may inhibit intestinal breast cancer resistance protein and thus increase rosuvastatin plasma exposure 2.1-fold, whereas the OATP-mediated hepatic uptake of rosuvastatin should not be inhibited due to relatively low portal ticagrelor concentrations. Taken together, concomitant use of ticagrelor with rosuvastatin may increase the systemic exposure to rosuvastatin and the risk of rosuvastatin-induced rhabdomyolysis. Further studies are warranted to investigate the potential pharmacokinetic interaction between ticagrelor and rosuvastatin in humans.

Original languageEnglish
Pages (from-to)2309-2315
Number of pages7
JournalBritish Journal of Clinical Pharmacology
Volume89
Issue number7
DOIs
Publication statusPublished - Jul 2023
MoE publication typeA1 Journal article-refereed

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