Nancy Mayer, DO1, Matthew Sutherland, DO1, Dhaval Patel, DO2 1Riverside Medical Center, Bourbonnais, IL; 2Digestive Disease Consultants, Kankakee, IL Introduction: Dofetilide, a class III antiarrhythmic agent, is generally regarded as having minimal hepatotoxicity compared to other drugs in its class, specifically amiodarone. In this report, we describe an exceedingly rare case of suspected drug-induced liver injury (DILI) from dofetilide.
Case Description/
Methods: A 52-year-old man with early persistent arial fibrillation, recently started on dofetilide, presented with one day of jaundice and scleral icterus. He reported dark urine, acholic stools, and generalized yellowing of his skin and eyes. Liver chemistry revealed a mixed hepatocellular–cholestatic injury pattern with elevated transaminases and cholestatic indices (total bilirubin 4.1 mg/dL, alkaline phosphatase 194 U/L, aspartate aminotransferase 61 U/L, alanine aminotransferase 189 U/L). He denied herbal or supplement use, recent travel, blood transfusions, intravenous drug use, or a family history of liver disease; alcohol intake was infrequent and limited. Comprehensive evaluation, including viral (HAV, HBV, HCV, CMV, EBV, HSV), metabolic (hemochromatosis, Wilson disease), autoimmune (ANA, ASMA, AMA), and toxic (acetaminophen, alcohol) panels, was unrevealing. MRCP showed biliary sludge without cholelithiasis or ductal dilation. Dofetilide was discontinued, after which liver enzymes improved. Given the temporal relationship to dofetilide initiation five days earlier, drug-induced liver injury was suspected. Discussion: Only four other cases of dofetilide-associated DILI have been reported. Proposed mechanisms of hepatotoxicity include reactive metabolite formation via CYP450 metabolism, bile salt export pump inhibition causing cholestasis, or idiosyncratic immune responses where the drug or metabolite acts as a hapten, triggering T-cell–mediated liver injury. Clinical trial data cited in the LiverTox database indicate that approximately 15% of patients on dofetilide experienced liver enzyme elevations. The incidence was similar to placebo groups, suggesting a potential but limited hepatotoxic effect. This is supported by manufacturer data showing hepatic adverse events such as “liver damage” occur in ≤2% of patients and numerically more frequently with Tikosyn than with placebo. In our patient, the Roussel Uclaf Causality Assessment Method (RUCAM) yielded a score of 7, signifying a probable link between the drug and the observed liver injury. This case adds to limited literature and underscores the need for baseline and early post-initiation liver-function monitoring when prescribing dofetilide.
Disclosures: Nancy Mayer indicated no relevant financial relationships. Matthew Sutherland indicated no relevant financial relationships. Dhaval Patel indicated no relevant financial relationships.
Nancy Mayer, DO1, Matthew Sutherland, DO1, Dhaval Patel, DO2. P3937 - The High Cost of Rhythm Control: A Rare Case of Dofetilide-Induced Liver Injury, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.
