[A Case of Statin-Associated Muscle Symptoms (SAMS) Due to Drug-Drug Interaction between Statin and Pazopanib].

Abstract

A woman in her 60s underwent a left nephrectomy in 2007 after being diagnosed with left renal cell carcinoma. In 2020, computed tomography (CT) revealed pancreatic metastasis, and subsequently axitinib therapy was initiated. However, axitinib therapy was discontinued due to hand-foot syndrome and nivolumab therapy was initiated in 2021. Follow-up CT scans indicated the progression of pancreatic and lymph node metastases, prompting the initiation of pazopanib therapy. Twelve days after the initiation of pazopanib therapy, she was admitted to our department with complaints of fever, fatigue, and skin rash. She was hospitalized with suspected drug eruption, drug-induced liver injury, and infection. Her symptoms improved with discontinuation of pazopanib, and antibiotic treatment; however, on the 8ᵗʰ day of hospitalization, she experienced lower limb weakness. On the 16ᵗʰ day, blood tests revealed markedly elevated creatine kinase (CK) levels (26, 565 IU/l). Short tau inversion recovery (STIR) magnetic resonance imaging (MRI) revealed high signal intensity in the hamstring and adductor muscles, leading to the diagnosis of myositis. Consequently, pitavastatin treatment was discontinued. CK levels decreased promptly after the discontinuation of statin treatment, and limb weakness improved as well. Pitavastatin is transported from the blood into the liver via organic anion-transporting polypeptide 1B1 (OATP1B1) located on the hepatocyte surface. Previous reports have indicated that tyrosine kinase inhibitors, such as pazopanib, can inactivate OATP1B1, leading to an increase in the plasma concentration of statins. In the present case, myositis was considered to have resulted from a drug-drug interaction between pitavastatin and pazopanib.