Population-Level Incidence and Monitoring of Adverse Drug Reactions with Long-term Amiodarone Therapy

Introduction: 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 is lacking.Aims: The aim of this study was to assess laboratory monitoring of liver and thyroid function during amiodarone prescribing from 1989-2011 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: Utilising well-established record linkage database, a longitudinalretrospective analysis of 1413 patients on long-term amiodarone was carried out, analysing prescribing, biochemical and clinical data.Results: Forty-six per cent (46%), 28% and 21% of patients underwent liver, thyroid, and combined testing respectively in accordance with guideline recommendations. Thirteen per cent and 17% of patients did not have any ALT or TSH testing, respectively. During follow-up, 117 (9.5%) patients had an ALT 3xULN and 16% patients had an abnormal TSH, (n=125, <0.4mU/l and n=28, >10mU/l). One-hundredand 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<0.0005)Conclusion: In this population-based study, adherence to laboratory monitoringguidelines was sub-optimal. 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