Therapeutic Drug Monitoring of Amiodarone and Desethylamiodarone

Abstract

Amiodarone (AM) is used for the treatment of cardiac arrhythmias. European guidelines recommend amiodarone dosage 200-400 mg/day for long-term prevention of arrhythmias. Therapeutic drug monitoring (TDM) is a part of clinical practise in cardiology although the association between AM and DEA plasma concentrations/dose and clinical efficacy/toxicity is still unclear. Plasma concentrations of both AM and DEA ranging between 0.5-2.5 mg/L were most often observed in patients responded to AM therapy. We analyzed retrospectively trough levels of AM and DEA measured by high performance liquid chromatography method with UV detection in years 2013-2015. The dose of AM per kilogram of body weight needed to reach AM level of 1 mg/L was calculated and results were compared with real levels to evaluate compliance of patients. We compared also concentrations of AM and DEA in relation to recommended AM dosage and determined possible non-compliance by calculation of AM clearance. Amiodarone was prescribed on average dose 226 mg/day and 2.8 mg/kg/day. Measured concentrations ranged from 0.17 to 2.49 mg/L (median 0.67 mg/L) for AM and between 0.14-1.67 mg/L (median 0.62 mg/L) for DEA. Supposed therapeutic effective levels of 0.5 mg/L were not reached in 131 patients (30%) for AM and 178 patients (40%) for DEA. 159 patients (36%) of them were probably underdosed (especially with AM dose 100-200 mg/day) and 19 patients (4%) were likely non-compliant. Only 60% of patients reached supposed minimally therapeutic effective levels of AM or DEA, 36% of them was underdosed and 4% of patients was likely non-compliant. Therefore routine TDM of amiodarone including its active metabolite desethylamiodarone may help to achieve optimal dosage of amiodarone.