Incidence and Predictors of Pulmonary Toxicity in Japanese Patients Receiving Low-Dose Amiodarone

Abstract

Background Amiodarone-induced pulmonary toxicity (APT) is the most serious side-effect of amiodarone, and its detection and prevention are extremely important. This study was designed to evaluate the incidence and clinical risk factors of APT, and the utility of a pulmonary function test or serum KL-6 assay to predict pulmonary toxicity in Japanese patients receiving low-dose amiodarone. Methods and ResultsFive hundred consecutive patients receiving amiodarone were retrospectively evaluated. Mean follow-up period was 48 months and mean maintenance dose was 141 mg daily. Cumulative incidence of APT was 4.2%, 7.8%, and 10.6% at 1, 3, and 5 years, respectively. On multivariate analysis, age at the start (hazard ratio (HR) =1.48, 95% confidence interval (CI) 1.13 to 1.93) was a significant pretreatment risk factor. Age (HR =1.64, 95% CI 1.29 to 2.09), maintenance dose (HR =1.90, 95% CI 1.45 to 2.49) and plasma monodesethylamiodarone concentration (HR =1.30, 95%CI 1.08 to 1.58) were risk factors. Sensitivity and specificity in screening with measurement of percent predicted diffusion capacity of carbon monoxide, ≥15% individual decrease, were 68% and 69%, and for ≥20% individual decrease, were 59% and 74%, whereas those in screening with serum KL-6 assay, ≥500 U/ml, were 25% and 91%, respectively. Conclusions Even at low dose, amiodarone shows substantial pulmonary toxicity. Higher age and higher maintenance dose are risk factors. Further decreasing the maintenance dose of amiodarone should be considered in order to reduce the incidence of pulmonary toxicity, at least in Japanese patients. (Circ J 2007; 71: 1610 -1616

48-Year-Old Woman With Dyspnea, Cough, and Weight Loss

“…3 Higher daily doses are associated with a greater incidence of pulmonary toxicity but may occur in patients taking lower doses (Յ200 mg/d). [6][7][8] Amiodarone and its metabolite desethylamiodarone are cationic amphiphilics that accumulate in organs with high lipid content, including the lungs. 5 Both can be toxic to lung tissue even at therapeutic serum levels.…”

Long-Term Efficacy of Amiodarone Therapy for the Prevention of Recurrence of Paroxysmal Atrial Fibrillation Analysis Based on Patient Characteristics

“…34,35) The incidence of amiodarone-induced pulmonary toxicity was recently reported to be 2.1% per year in 500 Japanese patients on low maintenance doses of less than 200 mg daily, 36) which is not low compared with the 1.8% per year in a meta-analysis of 6,500 American and European patients in placebo-controlled amiodarone trials. 37) Other studies in small numbers of Japanese patients with atrial tachycardia found that 2.7-3.6% of patients receiving amiodarone developed pulmonary toxicity during mean follow-up periods of 30-36 months.…”

“…It is believed to be difficult to administer amiodarone to patients randomly as the first-choice drug for paroxysmal AF in routine practice in Japan because pulmonary toxic effects such as interstitial pneumonia occur at an incidence of about 2.1% yearly. 36) Secondly, recurrence of AF was diagnosed at the time of detection of AF on ECG. A study using ambulatory 24-hour monitoring reported that more than half of tachycardic episodes were not recognized by patients with paroxysmal AF who had obvious symptoms.…”

Amiodarone Induced Pulmonary Toxicity: A Fatal Case Report

“…AIPT increases 3-fold for every 10 years of age in patients aged >60 years compared to those aged <60 years. Patients receiving a daily dose greater than 400 mg/day are at higher risk compared to those receiving 200 mg/ day [10,11]. Moreover, a study among Japanese patients demonstrated that the incidence of AIPT increased from 4.2% to 7.8% and 10.6% with 1.3 years and 5 years use of amiodarone respectively, with a mean maintenance dose of 141 mg daily.…”