S3656 Capecitabine-induced Acute Hepatic Encephalopathy

Abstract

Introduction: Capecitabine is a prodrug metabolized in the liver to fluorouracil, which is a pyrimidine analog that inhibits DNA synthesis, making it useful in treating a variety of malignancies including the neuroendocrine type 1.Common side effects include fatigue, nausea, vomiting, palmar-plantar erythrodysesthesia, and dermatitis. Common lab abnormalities that follow capecitabine initiation include pancytopenia, anemia, transaminitis, and hyperbilirubinemia. Encephalopathy, dysarthria, ataxia, confusion, and mood changes have been reported in less than 5% of patients using this medication. Case Description/Methods: A 62-year-old male with a history of pancreatic cancer with metastasis to the liver, who presented to the emergency department with altered mentation a week ago. Symptoms included worsening fatigue, confusion, progressed to inability to perform activities of daily life. Of note, the he started on capecitabine as part of his chemotherapy regimen three days prior to the onset of new symptoms. Home medications included amlodipine, chlorthalidone, metoprolol succinate, octreotide weekly injection, and ondansetron as needed for nausea. Physical exam was significant for disorientation to time, asterixis, and slight dysarthria in addition to hepatomegaly, which is of chronic nature. Lab values were consistent with mild transaminitis as ALT and AST were 44 IU/L and 52 IU/L, respectively. Ammonia level was 139 mcmol/L. Urea nitrogen was 23 mg/dL and creatinine was 1.56 mg/dL which is at patient’s baseline. Acute hepatitis panel was negative and abdominal ultrasound showed innumerable metastatic lesions, seen on a previous MRI of the liver, but was not consistent with cirrhotic changes. Patient was admitted and started on lactulose for hepatic encephalopathy, which was thought to be drug-induced, due to capecitabine. Discussion: Hyperammonemia has not been reported in the literature as a side effect of capecitabine. Treatment does not differ from hepatic encephalopathy caused by cirrhosis. Patients are monitored clinically for resolution of symptoms and may require discontinuation of the medication to prevent recurrent episodes. Our patient was improving after the second day of lactulose and holding the offending agent. Hyperammonemia has not been reported in patients taking capecitabine. The purpose of this report is to alert practitioners of such complications as prompt recognition of encephalopathy and appropriate treatment is key to improve symptoms and alter a patient's chemotherapy if needed.