Oncology Drug Dosing in Gilbert Syndrome Associated with UGT1A1: A Summary of the Literature

Gilbert's Syndrome (GS) is a hereditary condition that affects approximately 10% of the population. It is characterized by intermittent, unconjugated hyperbilirubinemia in the absence of hepatocellular damage and hemolysis. Although GS is often described as a benign laboratory finding, it may alter drug metabolism by decreasing the ability to conjugate drugs. Genetic polymorphisms, specifically the UGT1A1*28 allele, may reduce glucuronidation by 30%, which severely impacts the ability to metabolize certain medications. Antineoplastic agents used in oncologic settings have toxic side effects, and alterations in metabolism may result in severe or even life-threatening toxicities. Many of the drug monographs provided by manufacturers contain dose adjustment parameters for hepatic function, utilizing serum bilirubin as a surrogate marker. However, in patients with GS, hepatic function remains normal in the setting of hyperbilirubinemia, and there is scant literature to provide guidance on empiric dosage adjustment. In this review, we conducted a literature search of routinely used oncology medications and assessed the need for empiric dose adjustments in the setting of GS.