A SUSPECT COMBINATION: TICAGRELOR AND ROSUVASTATIN CAUSING RHABDOMYOLYSIS
Andrea Huang1,2, Sneha Amin1,2, Mitchum Bower2,3, Alison Stephen2, Sanjeev Baweja2, Venkat Manickavasagam2, William James2, Victoria Sasongko2 1Renal Department, Liverpool Hospital, Liverpool, New South Wales, Australia2Renal Department, Lismore Base Hospital, Lismore, New South Wales, Australia3Prince of Wales Hospital, Randwick, New South Wales, Australia
Abstract
Background
The interaction between Ticagrelor and Atorvastatin/Simvastatin is established via inhibition of Cytochrome-P450 (CYP3A4) leading to higher serum statin levels.1 This increases the risk of drug-mediated rhabdomyolysis and acute kidney injury. In contrast, Rosuvastatin is primarily metabolised through the 2C9 enzyme and the interaction with Ticagrelor is not as clearly defined.1,2,4 We present a case of a drug interaction resulting in acute kidney injury.
Case report
A 74-year-old man was admitted with six days of worsening myalgias and dark urine. Admission investigations revealed a creatine kinase of 45,989units/L and creatinine of 736umol/L (baseline creatinine 95umol/L), consistent with acute kidney injury secondary to rhabdomyolysis. The patient had been admitted one month prior with a ST-elevation myocardial infarct where he had been discharged on Aspirin and Ticagrelor in addition to his long term Rosuvastatin 40mg daily and Ezetimibe. Due to concerns of drug interaction, Ticagrelor was changed to Clopidogrel and Rosuvastatin was ceased. Renal function gradually improved without dialysis to 158umol/L six weeks after discharge. HMG-COA reductase antibodies returned negative. He was subsequently commenced on PCSK-9 inhibitor as a cholesterol lowering agent in the outpatient setting.
Conclusions
The interaction between rosuvastatin and ticagrelor is likely multifactorial and cannot be solely attributed to P450 inhibition. Ticagrelor can independently cause an acute kidney injury via an unknown mechanism; this can thereby lead to higher levels of renally-excreted Rosuvastatin thus potentiating the risk of rhabdomyolysis.1,3,4 Whilst the interaction between Rosuvastatin and Ticagrelor is less clear than other statins and is likely, it is necessary to be aware of potential drug interactions leading to severe adverse reactions especially in light of its increasing Ticagrelor popularity after the PLATO trial.2,5
Biography
Dr Andrea Huang is a current second year Renal Advanced Trainee in the Central-Southwest-Regional network. She graduated from University of Sydney in 2017 and trained at both Nepean Blue Mountains LHD and Southwestern Sydney LHD.