title: Population-level incidence and monitoring of adverse drug reactions with long-term amiodarone therapy.
abstract: BACKGROUND
  Amiodarone is associated with significant long-lasting adverse drug reactions (ADRs). Guidelines recommend laboratory monitoring during long-term use. However, data of compliance with laboratory monitoring are lacking.
  
  
  OBJECTIVE
  The aim of this study was to assess laboratory monitoring of liver and thyroid function during amiodarone prescribing from 1989 to 2011 in the Tayside, UK, population (approximately 400 000) in relation to National Guidelines recommending laboratory monitoring every 6 months. We also report the population-level incidence of abnormal liver and thyroid function in relation to total exposure of amiodarone.
  
  
  METHODS
  Utilizing well-established record-linkage database, a longitudinal retrospective analysis of 1413 patients on long-term amiodarone was carried out, analyzing prescribing, biochemical, and clinical data.
  
  
  RESULTS
  Forty-six percent (46%), 28%, and 21% of patients underwent liver, thyroid, and combined testing, respectively, in accordance with guideline recommendations. Thirteen percent and 17% of patients did not have any ALT or TSH testing, respectively. During follow-up, 117 (9.5%) patients had an ALT 3×ULN and 16% patients had an abnormal TSH, (n=125, <0.4 mU/L and n=28, >10 mU/L). One hundred and forty patients (10%) required thyroxine replacement therapy, and 40 (3%) required on hyperthyroid medication. Total amiodarone exposure increased the likelihood of abnormal biochemical testing 2.5-fold after 4 years therapy for liver and thyroid function (P<.0005).
  
  
  CONCLUSIONS
  In this population-based study, adherence to laboratory monitoring guidelines was suboptimal. There was a positive correlation with total amiodarone exposure and biochemical abnormalities and development of thyroid disease compared to the general population, highlighting the need for improvement and continued amiodarone monitoring.
authors.affiliation: College of Medical, Veterinary Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Stephen
authors.identifier: http://orcid.org/0000-0003-3076-7280
authors.initials: S
authors.lastname: Rankin
authors.affiliation: Division of Cardiovascular and Diabetes Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.
authors.forename: Douglas H
authors.initials: DH
authors.lastname: Elder
authors.affiliation: Department of Public Health, University of Dundee, Dundee, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Ogston
authors.affiliation: Division of Cardiovascular and Diabetes Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.
authors.forename: Jacob
authors.initials: J
authors.lastname: George
authors.affiliation: Division of Cardiovascular and Diabetes Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.
authors.forename: Chim C
authors.initials: CC
authors.lastname: Lang
authors.affiliation: Division of Cardiovascular and Diabetes Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Choy
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000638:Amiodarone / Q000008:administration & dosage / Q000009:adverse effects*; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis / Q000453:epidemiology*; D016208:Databases, Factual; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000592:standards*; D005260:Female; D019983:Guideline Adherence / Q000592:standards; D006801:Humans; D015994:Incidence; D008111:Liver Function Tests / Q000592:standards*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D017410:Practice Guidelines as Topic / Q000592:standards; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012307:Risk Factors; D012606:Scotland / Q000453:epidemiology; D013959:Thyroid Diseases / Q000139:chemically induced / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology*; D013960:Thyroid Function Tests / Q000592:standards*; D013997:Time Factors
chemical_list: D000889:Anti-Arrhythmia Agents; D000638:Amiodarone
keywords: Adverse drug reactions; Amiodarone; Hepatotoxicity; Monitoring; Prescribing; Thyroid disease