Comedication with interacting drugs predisposes amiodarone users in cardiac and surgical intensive care units to acute liver injury: A retrospective analysis

Risk factors and underlying mechanisms for liver injury associated with amiodarone remain elusive. This study aimed to investigate the drug-related covariates for acute liver injury by amiodarone—an intriguing compound of high lipophilicity, with a long half-life and notable efficacy. The medical, pharmacy, and laboratory records of new amiodarone users admitted to the cardiac or surgical intensive care units of a medical center were examined retrospectively. A Cox regression model with time-varying dose-related variables of amiodarone was utilized to estimate the hazard ratio (HR) of amiodarone-associated liver injury while adjusting for concomitant therapy and relevant covariates. Of the 131 eligible patients among 6,572 amiodarone users (46,402 prescriptions), 6 were identified as amiodarone-associated liver injury cases. In comparison to controls (n = 125), this liver injury cohort (n = 6) had significantly higher numbers of amiodarone-interacting (2.7 ± 2.0 vs 0.9 ± 0.9 drugs, P = .02) and hepatotoxic (3.8 ± 0.8 vs 2.5 ± 1.7 drugs, P = .03) comedications. The number of comedications with amiodarone-interacting potential (HR 2.07, 95% confidence interval [CI] 1.02−4.22, P = .04) and amiodarone cumulative doses standardized by body surface area (HR 6.82, 95% CI 1.72–27.04, P = .01) were independent risk factors for liver injury associated with amiodarone. Drug-related (amiodarone cumulative dose, interacting drugs) factors were significant predictors of amiodarone-associated acute liver injury. A prudent evaluation of each medication profile is warranted to attain precision medicine at the level of patient care, especially for those treated by medications with complex physicochemical and pharmacokinetic properties, such as amiodarone.