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

Yunn Fang Ho, Hsin Ying Chou, Jan Show Chu, Ping Ing Lee

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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] 1.024.22, 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.

Original languageEnglish
Article numbere12301
JournalMedicine (United States)
Volume97
Issue number37
DOIs
Publication statusPublished - Sep 1 2018

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Chemical and Drug Induced Liver Injury
Polypharmacy
Amiodarone
Anti-Arrhythmia Agents
Critical Care
Drug-Related Side Effects and Adverse Reactions
Drug Interactions
Proportional Hazards Models
Intensive Care Units
Young Adult
Retrospective Studies
Regression Analysis
Liver
Wounds and Injuries
Pharmaceutical Preparations
Confidence Intervals
Precision Medicine
Body Surface Area

Keywords

  • Adverse drug reaction
  • Drug-induced liver injury
  • Intensive care unit
  • Risk factor

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Comedication with interacting drugs predisposes amiodarone users in cardiac and surgical intensive care units to acute liver injury : A retrospective analysis. / Ho, Yunn Fang; Chou, Hsin Ying; Chu, Jan Show; Lee, Ping Ing.

In: Medicine (United States), Vol. 97, No. 37, e12301, 01.09.2018.

Research output: Contribution to journalArticle

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abstract = "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] 1.024.22, 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.",
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