Novel Chemotherapy Combination Leading to Novel Problems: A Case Report on Sulfonylurea Toxicity Secondary to Hepatic Impairment

Introduction: Hepatic impairment can make dosing medications a challenge. This is especially pertinent when patients are using insulin secretagogues such as sulfonylureas to control their diabetes. Sulfonylureas are metabolized via the CYP2C9 hepatic pathway and impaired clearance can lead to increased drug levels and hypoglycemia. We present a case of sulfonylurea toxicity in the setting of hepatic impairment secondary to a clinical trial of chemotherapy which resolved upon the chemotherapy's discontinuation. Case Description/Methods: A 66 y/o male with a medical history of type 2 diabetes mellitus (on glimepiride 4 mg BID, semaglutide 0.25 mg qweekly) and renal cell carcinoma (RCC) (stage 4) presented via EMS for an episode of encephalopathy and hypoglycemia. The patient was enrolled in a clinical trial of axitinib and pembrolizumab combination therapy for his RCC. On presentation the patient's mentation was altered, he was pale and diaphoretic, but his pulse, blood pressure, and respiratory rate were normal. Glucose on the scene was 26. Initial laboratory studies in the ED were remarkable for AST 200, ALT 436, and eGFR of 78. Of note, chart review showed previously normal AST/ALT/glucose. Patient was given dextrose by EMS and started on dextrose 10% in the ED. Imaging showed no structural issue to explain his encephalopathy. Despite infusion of dextrose the patient required continued boluses of D50 due to hypoglycemia for the first 24 hours of hospitalization. He was started on octreotide once sulfonylurea toxicity was suspected. His AST/ALT returned to normal limits after his chemotherapy was held and he then remained euglycemic on oral intake and SSI alone. He was discharged for close follow up and further treatment discussion with his oncologist. Discussion: Chemotherapy regimens have multiple adverse reactions including hepatotoxicity. It is important for providers to consider how this may affect the metabolism of medications. Sulfonylureas have a narrow therapeutic window and can easily cause hypoglycemia. This patient had been tolerating his anti-hyperglycemic regimen for months without incident. Weeks after starting a clinical trial with combination axitinib and pembrolizumab for his RCC he developed hypoglycemia and acute liver injury with increasing AST/ALT. He responded well to management with octreotide and dextrose infusions. Literature review did not yield a previously described link between this novel chemotherapy regimen for RCC and hypoglycemia secondary to reduced sulfonylurea metabolism.