Rhabdomyolysis induced by darolutamide and rosuvastatin

Abstract

Introduction: Darolutamide is a second-generation nonsteroidal androgen receptor antagonist approved for treatment of castrate-resistant, nonmetastatic prostate cancer and metastatic hormone-sensitive prostate cancer. Case report: A mid-70s man with castration-resistant prostate cancer was initiated on darolutamide. Due to impaired renal function and a history of poor tolerance to previous chemotherapy, the patient was started at 300 mg per day with a plan to titrate to the recommended renal-adjusted dose. He was admitted to the hospital for complaints of lower extremity weakness during week 11 of treatment. Physical examination and imaging did not indicate any significant pathology from cancer or other medical conditions causing his symptoms. The pharmacist identified and reported a significant drug interaction between darolutamide and rosuvastatin. Management & Outcome: The suggested change was rosuvastatin discontinuation. Limiting the rosuvastatin dose to 5 mg is recommended during concomitant use with darolutamide. Since the patient had been receiving rosuvastatin 40 mg daily, he was potentially receiving five times the maximum dose. Considering the patient's complaints of myalgia and a marked elevation in creatine phosphokinase, his condition confirmed the diagnosis of rosuvastatin-darolutamide-induced rhabdomyolysis. Clinical symptoms improved and creatinine phosphokinase (CPK) elevation subsided following rosuvastatin cessation. Discussion: Darolutamide inhibition of breast cancer resistance protein (BCRP), organic anion-transporting polypeptides (OATP), and other protein transporters impacts clearance of substrate drugs to varying extents. Clinical relevance of inhibition depends on the extent to which affected proteins and transporters contribute to the clearance of the substrate. Rosuvastatin's significant reliance on BCRP for active efflux leads to an elevated risk of statin-associated muscle symptoms when co-administered with darolutamide.