Amiodarone pulmonary toxicity. Clinical, radiologic, and pathologic correlations

Kennedy, John I.; Myers, Jeffrey L.; Plumb, Vance J.; Fulmer, Jack D.

doi:10.1001/archinte.147.1.50

Cited by 63 publications

(66 citation statements)

References 28 publications

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“…Although widely used, it is known to have significant adverse side effects on various organs, such as the liver, neuromuscular system, thyroid, cornea, skin, and lungs (for a review see Connolly, 1999). Although several organ systems can be affected, pulmonary complications are perhaps the most deleterious and occur in approximately 10% of patients, usually after 2 or more months of treatment (Kennedy et al, 1987), and clinically significant lung damage seems to require a very high total dose of amiodarone (as much as 200 g; Dusman et al, 1990). Nonetheless, acute presentations can occur within weeks of initiating treatment (Ashrafian and Davey, 2001;Lardinois et al, 2002), and the problem of adverse effects is a limiting factor for long-term utilization of amiodarone.…”

Section: Discussionmentioning

confidence: 99%

Synthesis and Antifungal Activity of Derivatives of 2- and 3-Benzofurancarboxylic Acids

Hejchman

Ostrowska

Maciejewska

et al. 2012

J Pharmacol Exp Ther

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Section: Discussionmentioning

confidence: 99%

Synthesis and Antifungal Activity of Derivatives of 2- and 3-Benzofurancarboxylic Acids

Hejchman

Ostrowska

Maciejewska

et al. 2012

J Pharmacol Exp Ther

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“…18,19) In the lung tissue or bronchoalveolar lavage (BAL) of IP patients administered AMD, many inflammatory cells such as monocytes, macrophages, and polynuclear cells are recognized.…”

Section: )mentioning

confidence: 99%

Obesity Is Associated With the Development of Interstitial Pneumonia Under Long-Term Administration of Amiodarone in Refractory Atrial Fibrillation Patients

et al. 2016

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SummaryAlthough oral amiodarone (AMD) has been used for the management of atrial fibrillation (AF), serious complications such as interstitial pneumonia (IP) occur very occasionally. We evaluated which factors were associated with the development of IP under the long-term administration of AMD in patients with refractory AF. This study included 122 consecutive patients (65.8 ± 11.4 years, mean body mass index [BMI] of 23.2 ± 4.3 kg/m 2 ) who orally received AMD to inhibit AF between January 2004 and December 2013. Administration of AMD was begun at 400 mg daily as a loading dose, and was continued at a dosage of 50-400 mg daily after the initial loading phase, determined by the control of the arrhythmias and occurrence of side-effects. The clinical factors were compared between the patients with and without adverse effects, especially IP.During an average follow-up period of 49.2 ± 28.2 months, 53 patients (43.4%) were determined to have converted and maintained sinus rhythm. In contrast, adverse effects were detected in 46 patients (37.7%) with AMD. IP occurred in 8 patients (6.6%), thyrotoxicosis in 35 (28.7%), and others in 5 (4.1%). Four (50.0%) out of 8 patients complicated with IP had obesity (BMI > 27 kg/m 2 ). Among the clinical factors, only obesity was significantly associated with the development of IP (P = 0.026).In patients with refractory AF, AMD had an antiarrhythmic effect with long-term administration, but greater adverse effects were also observed. Obesity was the most significant factor associated with the development of IP. ( Further, AMD has many pharmacological effects in addition to its potassium channel blocker effect, such as calcium channel blocker, sodium channel blocker, and sympathetic inhibitory actions. It also has a high distribution in fatty tissue and a long half-life. Mono-desethylamiodarone, a metabolite of AMD (M-AMD), also possesses pharmacological activity equivalent to that of AMD. Oral AMD is effective for refractory atrial fibrillation (AF).1-5) Although serious lung injury such as interstitial pneumonia (IP) occasionally occurs (10%), the mortality rate is 2%. 2,6) In recent years, the administration of AMD has increased in AF patients, and serious complications such as interstitial pneumonia (IP) occasionally occur. Therefore, we evaluated which factors were associated with the development of IP under long-term administration of AMD in patients with refractory AF. MethodsStudy population: Among 294 consecutive patients who were orally administered AMD between January 2004 and December 2013 at our institute, 122 (41.5%) with AF were included in this retrospectively study. The patients had either a paroxysmal or persistent pattern of AF. The clinical characteristics of the patients are outlined in Table I. AF therapy and amiodarone: After defining the anticoagulation therapy, a rate control or rhythm control strategy was chosen as the AF management. The clinical decision to use a rhythm or rate control strategy needed to consider several factors, including the degree of ...

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“…23 The common histological findings of APT are alveolar damage and foamy intra-alveolar macrophages. 24 Lung cell injury has been suggested to be mediated by changes in proteins, lipids and several lysosomal enzymes, 23,25 regulation of apoptosis, 26 etc. It was recently suggested that metabolites containing the diethylaminoethoxy group, such as monodesethylamiodarone, have a crucial role in toxicity for alveolar macrophages.…”

Section: Circulation Journal Vol71 October 2007mentioning

confidence: 99%

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

Yamada

Shiga

Matsuda

et al. 2007

Circ J

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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

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Amiodarone pulmonary toxicity. Clinical, radiologic, and pathologic correlations

Cited by 63 publications

References 28 publications

Synthesis and Antifungal Activity of Derivatives of 2- and 3-Benzofurancarboxylic Acids

Synthesis and Antifungal Activity of Derivatives of 2- and 3-Benzofurancarboxylic Acids

Obesity Is Associated With the Development of Interstitial Pneumonia Under Long-Term Administration of Amiodarone in Refractory Atrial Fibrillation Patients

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

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