Rhythm Managed, Liver Damaged: Cholestatic Liver Injury From Mexiletine Use

Introduction: Mexiletine, a class 1B antiarrhythmic, is indicated for patients with life-threatening ventricular arrhythmias. Liver toxicity is rare, reported in 0.5% of cases and typically attributed to hypersensitivity-related hepatocellular injury. We report a rare case of cholestatic liver injury due to mexiletine.


Description: A 52-year-old man with morbid obesity and hypertension was admitted to the ICU with cardiogenic shock following an inferior STEMI requiring PCI and Impella 5.5® support. His course was complicated by ventricular fibrillation cardiac arrest and recurrent monomorphic ventricular tachycardia (VT) requiring defibrillation, cardioversions, amiodarone and lidocaine infusions. He was not eligible for VT ablation because of bilateral femoral artery injury from Impella removal and cardiac catheterization, requiring surgical repair.
He was transitioned to oral amiodarone but developed recurrent NSVT. Mexiletine 150 mg thrice daily was started, with amiodarone continued at 400 mg twice daily. Baseline liver function tests were ALT 39, AST 46, ALP 393, and Tbili 4.7. After 10 days, these peaked at AST 344, ALT 284, ALP 1033, Dbili 16.7, and Tbili 21.9. No signs of hypersensitivity such as fever, rash, eosinophilia, or atypical lymphocytosis were appreciated.
Evaluation of his cholestatic liver injury included right upper quadrant ultrasound showing no gallstones or common bile duct dilation, magnetic resonance cholangiopancreatography showing no ductal dilation or hepatic lesion, and CT revealing no biliary pathology. With persistent cholestatic liver injury in the absence of intrinsic or extrinsic biliary disease, mexiletine was discontinued due to suspected drug-induced liver injury.
Over the next 8 days, liver function tests improved to AST 22, ALT 35, ALP 286, Dbili 1.8, and Tbili 3.1. Liver function tests remained stable throughout the remaining 12 day hospitalization.


Discussion: Mexiletine has been linked to a low incidence of liver injury in clinical trials, which is mainly hepatocellular in nature and associated with hypersensitivity reactions. This case demonstrates that mexiletine may rarely be associated with cholestatic liver injury without evidence of hypersensitivity. Awareness of this pattern of liver injury should inform therapeutic use of mexiletine.