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Fundam Clin Pharmacol. 2018 Dec 21. doi: 10.1111/fcp.12435. [Epub ahead of print]

Rhabdomyolysis risk from the use of two-drug combination of antidyslipidemic drugs with antihypertensive and antidiabetic medications: a signal detection analysis.

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Department of Biostatistics, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.


Rhabdomyolysis is one of the most concerning complications of antidyslipidemic drugs. Most patients with dyslipidemia take multiple medications. Our objective was to explore which two-drug combinations lead to a higher risk of rhabdomyolysis. We analyzed data from the Japanese Adverse Drug Event Report (JADER) database between April 2004 and September 2017. The primary outcome was the report of rhabdomyolysis. We assessed the risk of rhabdomyolysis for the two-drug concomitant use of antidyslipidemic drugs (statin, fibrate, and ezetimibe) with antihypertensive and antidiabetic medications. The Norén and Gosho methods were used for detecting two-drug interactions. The JADER contained 468 292 records for patient characteristics, 2 973 172 drug information records, and 741 016 adverse reactions records. Rhabdomyolysis was reported in 5 017 patients. Concomitant use of pravastatin/fenofibrate, simvastatin/mefruside, fluvastatin/temocapril, bezafibrate/temocapril, bezafibrate/spironolactone, bezafibrate/metoprolol, bezafibrate/losartan, fluvastatin/mitiglinide, or fenofibrate/glibenclamide was detected as the signal of rhabdomyolysis in this analysis. Combination therapy with the drugs listed above has the potential of drug-drug interactions that could result in rhabdomyolysis in patients with dyslipidemia.


Japanese Adverse Drug Event Report ; Bayesian confidence propagation neural network method; drug interaction; reporting odds ratio; rhabdomyolysis; signal detection


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