Amiodarone Toxicity with Cumulative Doses To the Editor: The article titled “Manifestations of Lung Toxicity: Amiodarone-induced Bronchiolitis Obliterans Organizing Pneumonia” (BOOP; July/August 2006) raised awareness about a serious complication of a commonly used antiarrhythmic agent. Several published case reports have described incidents of amiodarone-induced BOOP. Little is known, however, about the pathophysiologic processes involved in, or the factors predisposing patients taking amiodarone to, BOOP.1
The authors noted that BOOP toxicity could occur even with low doses of amiodarone, but they also should have highlighted that the cumulative total dose is more relevant than the daily dose in causing pulmonary toxicity.2 This suggests that amiodarone has a direct toxic effect on the lung.3
Amiodarone-induced BOOP presents with cough, dyspnea, and pleuritic chest pain, making it difficult for physicians to clinically differentiate this diagnosis from other diagnoses, such as heart failure, pulmonary embolism, or pneumonia.4 Patients with amiodarone-induced BOOP may, therefore, be misdiagnosed or go undiagnosed. The fact that open-lung biopsy is usually needed to confirm the link between amiodarone and lung toxicity further contributes to the difficulty in diagnosing this problem. Although the diagnosis may be difficult to make, empiric therapy may be worthwhile, given the favorable prognosis with therapy.
Marshaleen Henriques-Forsythe, MD Morehouse School of Medicine Atlanta, Ga
1. Ott MC, Khoor A, Leventhal JP, et al. Pulmonary toxicity in patients receiving low-dose amiodarone. Chest. 2003; 123:646-651.
2. Valle JM, Alvarez D, Antunez J, et al. Bronchiolitis obliterans organizing pneumonia secondary to amiodarone: a rare aetiology. Eur Respir J. 1995; 8:470-471.
3. Martin WJ II, Rosenow EC III. Amiodarone pulmonary toxicity. Recognition and pathogenesis (part 2). Chest. 1988; 93:1242-1248.
The Author Replies: Dr Henriques-Forsythe’s comments on our article are appreciated. We agree that pulmonary toxicity usually occurs several months to several years after the initiation of amiodarone therapy and is more likely to occur with a high maintenance dosage (>400 mg/day). This does suggest a direct toxic effect of amiodarone on the lungs. However, the reference Dr Henriques-Forsythe cites as evidence1 also states that the relationship between pulmonary toxicity and amiodarone dosages and blood levels is variable, suggesting a role for an indirect inflammatory or immune process within the lung.1
Although the likelihood of pulmonary toxicity may be reduced in patients taking smaller daily doses, or within 2 to 3 weeks of starting amiodarone therapy with low cumulative doses, toxicity can still occur, albeit infrequently.2,3
Sanjay Sarin, MD Geisinger Medical Center Danville, Pa
1. Martin WJ II, Rosenow EC III. Amiodarone pulmonary toxicity. Recognition and pathogenesis (part 2). Chest. 1988; 93:1242-1248.
2. Kharabsheh S, Abendroth CS, Kozak M. Fatal pulmonary toxicity occurring within two weeks of initiation of amiodarone. Am J Cardiol. 2002; 89:896-898.
3. Polkey MI, Wilson PO, Rees PJ. Amiodarone pneumonitis: no safe dose. Respir Med. 1995; 89:233-235.
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