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

Abstract

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 468292 records for patient characteristics, 2973172 drug information records, and 741016 adverse reactions records. Rhabdomyolysis was reported in 5017 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.