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 are lacking. Aims: 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). Conclusion: 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