Skip to main content
SpringerLink
Log in

Amiodarone

Review of Pulmonary Effects and Toxicity

  • Review Article
  • Published:
Drug Safety Aims and scope Submit manuscript

Abstract

Amiodarone, a bi-iodinated benzofuran derivative, is, because of its high effectiveness, one of the most widely used antiarrhythmic agents. However, adverse effects, especially potentially fatal and non-reversible acute and chronic pulmonary toxicity, continue to be observed. This review provides an update of the epidemiology, pathophysiology, clinical presentation, treatment and outcome of amiodarone pulmonary effects and toxicity. Lung adverse effects occur in approximately 5% of treated patients. The development of lung complications appears to be associated with older age, duration of treatment and cumulative dosage, high levels of its desethyl metabolite, history of cardiothoracic surgery and/or use of high oxygen mixtures, use of iodinated contrast media, and probably pre-existing lung disease as well as co-existing respiratory infections. Amiodarone-related adverse pulmonary effects may develop as early as from the first few days of treatment to several years later. The onset of pulmonary toxicity may be either insidious or rapidly progressive. Cough, new chest infiltrates in imaging studies and reduced lung diffusing capacity in the appropriate clinical setting of amiodarone use, after the meticulous exclusion of infection, malignancy and pulmonary oedema, are the cardinal clinical and laboratory elements for diagnosis. Pulmonary involvement falls into two categories of different grades of clinical significance: (i) the ubiquitous ‘lipoid pneumonia’, the so-called ‘amiodarone effect’, which is usually asymptomatic; and (ii) the more appropriately named ‘amiodarone toxicity’, which includes several distinct clinical entities related to the differing patterns of lung inflammatory reaction, such as eosinophilic pneumonia, chronic organizing pneumonia, acute fibrinous organizing pneumonia, nodules or mass-like lesions, nonspecific interstitial pneumonia-like and idiopathic pulmonary fibrosis-like interstitial pneumonia, desqua-mative interstitial pneumonia, acute lung injury/acute respiratory distress syndrome (ARDS) and diffuse alveolar haemorrhage. Pleural/pericardial involvement may be observed. Three different and intertwined mechanisms of lung toxicity have been suggested: (i) a direct toxic effect; (ii) an immunemediated mechanism; and (iii) the angiotensin enzyme system activation. Mortality ranges from 9% for those who develop chronic pneumonia to 50% for those who develop ARDS. Discontinuation of the drug, control of risk factors and, in the more severe cases, corticosteroids may be of therapeutic value. Supportive measures for supervening ARDS in the intensive care setting may become necessary.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Dharmarajan TS, Shah AB, Dharmarajan L. Amiodarone-induced pulmonary toxicity: potentially fatal, recognize early during life! J Am Geriatr Soc 2008 Jul; 56(7): 1363–1

  2. Charlier R, Deltour G, Tondeur R. Recherche dans la serie des benzofurannes, VII: etude pharmacologique preliminaire du butyl-2 (diiodo 3’5’-beta-N-diethylaminoethoxy-4′benzoyl)-3 benzofurannes. Arch Int Pharma-codyn Ther 1962; 139: 255–62

    CAS  Google Scholar 

  3. Charlier R, Delaunois G, Bauthier J. Recherche dans la serie des benzofurannes, XL: propriete anti-arrhythmiques de l’amiodarone. Cardiologia 1969; 54: 83–9

    Article  PubMed  CAS  Google Scholar 

  4. Nademanee K, Singh BN, Stevenson WG, et al. Amiodarone and post-MI patients. Circulation 1993; 88: 764–8

    Article  PubMed  CAS  Google Scholar 

  5. Vassallo P, Trohman RG. Prescribing amiodarone: an evidence-based review of clinical indications. JAMA 2007; 298(11): 1312–22

    Article  PubMed  CAS  Google Scholar 

  6. Goldschlager N, Epstein AE, Naccarelli GV, et al. A practical guide for clinicians who treat patients with amiodarone: 2007. Heart Rhythm 2007; 4: 1250–9

    Article  PubMed  Google Scholar 

  7. Ernawati DK, Stafford L, Hughes JD. Amiodarone-induced pulmonary toxicity. Br J Clin Pharmacol 2008 July; 66(1): 82–7

    Article  PubMed  CAS  Google Scholar 

  8. Rotmensch HH, Liron M, Tupilski M, et al. Possible association of pneumonitis with amiodarone therapy [letter]. Am Heart J 1980; 100: 412–3

    Article  PubMed  CAS  Google Scholar 

  9. Ikäheimo K, Kettunen R, Mäntyjärvi M. Visual functions and adverse ocular effects in patients with amiodarone medication. Acta Ophthalmol Scand 2002; 80: 59–63

    Article  PubMed  Google Scholar 

  10. Tsang W, Houlden RL. Amiodarone-induced thyrotoxicosis: a review. Can J Cardiol 2009 Jul; 25(7): 421–4

    Article  PubMed  CAS  Google Scholar 

  11. Babatin M, Lee SS, Pollak PT. Amiodarone hepato-toxicity: review. Curr Vasc Pharmacol 2008 Jul; 6(3): 228–36

    Article  PubMed  CAS  Google Scholar 

  12. Dezile G, Roullier A, Arbeille-Brassart B. Interstitial pneumopathy in subjects treated with amiodarone [in French]. Presse Med 1983; 12: 2747–50

    PubMed  CAS  Google Scholar 

  13. Yamada Y, Shiga T, Matsuda N, et al. Incidence and predictors of pulmonary toxicity in Japanese patients receiving low-dose amiodarone. Circ J 2007; 71: 1610–6

    Article  PubMed  CAS  Google Scholar 

  14. Sunderji R, Kanji Z, Gin K. Pulmonary effects of low dose amiodarone: a review of the risks and recommendations for surveillance. Can J Cardiol 2000; 16: 1435–40

    PubMed  CAS  Google Scholar 

  15. Singh SN, Fisher SG, Singh BN, et al. Pulmonary effect of amiodarone in patients with heart failure. JACC 1997; 30: 514–7

    PubMed  CAS  Google Scholar 

  16. Labombarda F, Ou P, Stos B, et al. Acute amiodarone-induced pulmonary toxicity: an association of risk factors in a child operated by arterial switch operation. Congenit Heart Dis 2008; 3: 365–7

    Article  PubMed  Google Scholar 

  17. Singh SN, Fletcher RD, Fisher SG, et al. Amiodarone in patients with congestive heart failure and asymptomatic ventricular arrhythmia. N Engl J Med 1995; 333: 77–82

    Article  PubMed  CAS  Google Scholar 

  18. Dusman RE, Stanton MS, Miles WM, et al. Clinical features of amiodarone-induced pulmonary toxicity. Circulation 1990; 82: 51–9

    Article  PubMed  CAS  Google Scholar 

  19. Magro SA, Lawrence EC, Wheeler SH, et al. Amiodarone pulmonary toxicity: prospective evaluation of serial pulmonary function tests. J Am Coll Cardiol 1988; 12: 781–8

    Article  PubMed  CAS  Google Scholar 

  20. Weinberg BA, Miles WM, Klein LS, et al. Five-year follow-up of 589 patients treated with amiodarone. Am Heart J 1993; 125: 109–20

    Article  PubMed  CAS  Google Scholar 

  21. Gleadhill IC, Wise RA, Schonfeld SA, et al. Serial lung function testing in patients treated with amiodarone: a prospective study. Am J Med 1989; 86: 4–10

    Article  PubMed  CAS  Google Scholar 

  22. Ott MC, Khoor A, Leventhal JP, et al. Pulmonary toxicity in patients receiving low-dose amiodarone. Chest 2003; 123: 646–51

    Article  PubMed  Google Scholar 

  23. Ashrafian H, Davey P. Is amiodarone an underrecognized cause of acute respiratory failure in the ICU? Chest 2001; 120: 275–1

    Google Scholar 

  24. Polkey MI, Wilson POG, Rees PJ. Amiodarone pneumonitis: no safe dose. Respir Med 1995; 89: 233–5

    Article  PubMed  CAS  Google Scholar 

  25. Greenspon AJ, Kidwell GA, Hurley W, et al. Amiodarone-related postoperative adult respiratory distress syndrome. Circulation 1991 Nov; 84 (5 Suppl.): III407–15

    PubMed  CAS  Google Scholar 

  26. Van der Zeijden H, Znadstra DF. Amiodarone and the development of ARDS after lung surgery. Chest 1995; 107: 885–6

    Article  PubMed  Google Scholar 

  27. Van Mieghem W, Coolen L, Malysse I, et al. Amiodarone and the development of ARDS after lung surgery. Chest 1994; 105: 1642–5

    Article  PubMed  Google Scholar 

  28. Donaldson L, Grant IS, Naysmith MR, et al. Acute amiodarone-induced lung toxicity. Intensive Care Med 1998 Jun; 24(6): 626–30

    Article  PubMed  CAS  Google Scholar 

  29. Olshansky B, Sami M, Rubin A, et al. Use of amiodarone for atrial fibrillation in patients with preexisting pulmonary disease in the AFFIRM study. NHLBI AFFIRM investigators. Am J Cardiol 2005; 95: 404–5

    Article  PubMed  CAS  Google Scholar 

  30. Bargout R, Jankov A, Dincer E, et al. Amiodarone induces apoptosis of human and rat alveolar epithelial cells in vitro. Am J Physiol Lung Cell Mol Physiol 2000; 278: L1039–44

    PubMed  CAS  Google Scholar 

  31. Uhal BD, Wang R, Laukka J, et al. Inhibition of amiodarone-induced lung fibrosis but not alveolitis by angio-tensin system antagonists. Pharmacol Toxicol 2003; 92: 81–7

    Article  PubMed  CAS  Google Scholar 

  32. Uhal BD, Zhang H, Abdul-Hafez A, et al. Amiodarone induces angiotensinogen gene expression in lung alveolar epithelial cells through activation protein-1. Basic Clin Pharmacol Toxicol 2007; 100: 59–66

    Article  PubMed  CAS  Google Scholar 

  33. Nikaido A, Tada T, Nakamura K, et al. Clinical features of the effects of angiotensin system antagonists on amiodarone-induced pulmonary toxicity. Int J Cardiol 2010; 140: 328–35

    Article  PubMed  Google Scholar 

  34. Kosseifi SG, Halawa A, Bailey B, et al. Reduction of amiodarone pulmonary toxicity in patients treated with angiotensin-converting enzyme inhibitors and angiotensin receptor blocker. Ther Adv Respir Dis 2009; 3: 289–94

    Article  PubMed  Google Scholar 

  35. Adams PC, Holt DW, Storey GC, et al. Amiodarone and its desethyl metabolite: tissue distribution and morphologic changes during long-term therapy. Circulation 1985; 72: 1064–75

    Article  PubMed  CAS  Google Scholar 

  36. Lapinsky SE, Mullen JB, Balter MS. Rapid pulmonary phospholipid accumulation induced by intravenous amiodarone. Can J Cardiol 1993; 9: 322–24

    PubMed  CAS  Google Scholar 

  37. Haffajee CI, Love JC, Canada AT, et al. Clinical pharm-acokinetics and efficacy of amiodarone for refractory tachyarrhythmias. Circulation 1983; 67: 1347–55

    Article  PubMed  CAS  Google Scholar 

  38. Kaushik S, Hussain A, Clarke P, et al. Acute pulmonary toxicity after low-dose amiodarone therapy. Ann Thorac Surg 2001;72: 1760–1

    Article  PubMed  CAS  Google Scholar 

  39. Kharabsheh S, Abendroth CS, Kozak M. Fatal pulmonary toxicity occurring within two weeks of initiation of amiodarone. Am J Cardiol 2002; 89: 896–8

    Article  PubMed  Google Scholar 

  40. Halliwell WH. Cationic amphiphilic drug-induced phos-pholipidosis. Toxicol Pathol 1997; 25(1): 53–60

    Article  PubMed  CAS  Google Scholar 

  41. Hostetler KY, Reasor MJ, Walker RE, et al. Role of phospholipase A inhibition in amiodarone pulmonary toxicity in rats. Biochim Biophys Acta 1986; 875: 400–5

    Article  PubMed  CAS  Google Scholar 

  42. Anderson N, Borlak J. Drug-induced phospholipidosis. FEBS Lett 2006; 580: 5533–40

    Article  PubMed  CAS  Google Scholar 

  43. Chung MJ, Lee KS, Franquet T, et al. Metabolic lung disease: imaging and histopathologic findings. Eur J Radiol 2005; (54): 233–45

  44. Bedrossian C, Warren C, Ohar J, et al. Amiodarone pulmonary toxicity: cytopathology, ultrastructure, and immunocytochemistry. Ann Dign Pathol 1997; (1): 47–56

  45. Kennedy JI, Myers JL, Plumb VJ, et al. Amiodarone pulmonary toxicity: clinical, radiologic, and pathologic correlations. Arch Intern Med 1987; 147: 50–5

    Article  PubMed  CAS  Google Scholar 

  46. Minchin RF, Ho PC, Boyd MR. Reductive metabolism of nitrofurantoin by rat lung and liver in vitro. Biochem Pharmacol 1986; 35: 575–80

    Article  PubMed  CAS  Google Scholar 

  47. Fantone JC, Phan SH. Oxygen metabolite detoxifying enzyme levels in bleomycin-induced fibrotic lungs. Free Radic Biol Med 1988; 4: 399–402

    Article  PubMed  CAS  Google Scholar 

  48. Venkatesan N, Punithavathi V, Chandrakasan G. Curcumin protects bleomycin-induced lung injury in rats. Life Sci 1997; 61: L51–8

    Article  Google Scholar 

  49. Myers JL, Kennedy JI, Plumb VJ. Amiodarone lung: pathologic findings in clinically toxic patients. Hum Pathol 1987 Apr; 18(4): 349–54

    Article  PubMed  CAS  Google Scholar 

  50. Baritussio A, Marzini S, Agostini M, et al. Amiodarone inhibits lung degradation of SP-A and perturbs the distribution of lysosomal enzymes. Am J Physiol Lung Cell Mol Physiol 2001; 281: L1189–99

    PubMed  CAS  Google Scholar 

  51. Reasor MJ, Kacew S. An evaluation of possible mechanisms underlying amiodarone-induced pulmonary toxicity. Proc Soc Exp Biol Med 1996 Sep; 212(4): 297–304

    PubMed  CAS  Google Scholar 

  52. Massey TE, Leeder RG, Rafeiro E, et al. Mechanisms in the pathogenesis of amiodarone-induced pulmonary toxicity. Can J Physiol Pharmacol 1995 Dec; 73(12): 1675–85

    Article  PubMed  CAS  Google Scholar 

  53. Otsuka M, Takahashi H, Shiratori M, et al. Reduction of bleomycin induced lung fibrosis by candesartan cilexetil, an angiotensin II type 1 receptor antagonist. Thorax 2004; 59: 31–8

    Article  PubMed  CAS  Google Scholar 

  54. Lopez AD, Avasarala S, Grewwal S, et al. Differential role of the Fas/Fas ligant apoptotic pathway in inflammation and lung fibrosis associated with reovirus 1/L induced bronchiolitis obliterans organizing pneumonia and acute respiratory distress syndrome. J Immunol 2009; 183: 8244–57

    Article  PubMed  CAS  Google Scholar 

  55. Selman M, Pardo A. The epithelial/fibroblastic pathway in the pathogenesis of idiopathic pulmonary fibrosis. Am J Respir Cell Mol Biol 2003; 29: S93–7

    PubMed  CAS  Google Scholar 

  56. Kuruma T, Maruyama T, Hiramatsu S, et al. Relationship between amiodarone-induced subclinical lung toxicity and Th1/Th2 balance. Int J Cardiol 2009 May 15; 134(2): 224–30

    Article  PubMed  Google Scholar 

  57. Reinhart PG, Gairola CG. Amiodarone-induced pulmonary toxicity in Fischer rats: release of tumor necrosis factor alpha and transforming growth factor beta by pulmonary alveolar macrophages. J Toxicol Environ Health 1997; 52: 353–65

    PubMed  CAS  Google Scholar 

  58. Argyriou M, Hountis P, Antonopoulos N, et al. Acute fatal post-CABG low dose amiodarone lung toxicity. Asian Cardiovasc Thorac Ann 2007 Dec; 15(6): e66–8

    PubMed  Google Scholar 

  59. Skroubis G, Galiatsou E, Metafratzi Z, et al. Amiodarone-induced acute lung toxicity in an ICU setting. Acta An-aesthesiol Scand 2005 Apr; 49(4): 569–71

    Article  CAS  Google Scholar 

  60. Charles PE, Doise JM, Quenot JP, et al. Amiodarone-related acute respiratory distress syndrome following sudden withdrawal of steroids. Respiration 2006; 73: 248–9

    PubMed  Google Scholar 

  61. Wood DL, Osborn MJ, Rooke J, et al. Amiodarone pulmonary toxicity: report of two cases associated with rapidly progressive fatal respiratory distress syndrome after pulmonary angiography. Mayo Clin Proc 1985; 60: 601–3

    Article  PubMed  CAS  Google Scholar 

  62. Behnia M. Association of alveolar hemorrhage with amiodarone: role of bronchoscopy. Tanaffos 2008; 7(2): 75–8

    Google Scholar 

  63. Pollak PT. Clinical organ toxicity of antiarrhythmic compounds: ocular and pulmonary manifestations. Am J Cardiol 1999; 84: 37–45

    Article  Google Scholar 

  64. Camus P, Martin WJ, Rosenow EC. Amiodarone pulmonary toxicity. Clin Chest Med 2004; 25(1): 65–75

    Article  PubMed  Google Scholar 

  65. Fraire AE, Guntupalli KK, Greenberg SD, et al. Amiodarone pulmonary toxicity: a multidisciplinary review of current status. South Med J 1993; 86(1): 67–77

    Article  PubMed  CAS  Google Scholar 

  66. Thiyagarajan T, Mahajan V, Katragadda S, et al. Amiodarone induced acute interstitial pneumonitis. BMJ Case Reports. Epub 2009 Mar 6

  67. Goldstein I, Topilsky M, Segev D, et al. Very early onset of acute amiodarone pulmonary toxicity presenting with hemoptysis. Chest 1997 May; 111(5): 1446–7

    Article  PubMed  CAS  Google Scholar 

  68. Iskandar SB, Abi-Salem B, Keith RL, et al. Amiodarone-induced alveolar hemorrhage. South Med J 2006; 99: 383–7

    Article  PubMed  Google Scholar 

  69. Papiris SA, Manali ED, Kalomenidis I, et al. Bench-to-bedside review: pulmonary-renal syndromes — an update for the intensivist. Crit Care 2007; 11(3): 213

    Article  PubMed  Google Scholar 

  70. Gutierez R, del Pozo J, Carrión C, et al. Vasculitis associated with amiodarone treatment [letter]. Ann Pharmacother 1994; 28(4): 537

    Google Scholar 

  71. Scharf C, Oechslin EN, Salomon F, et al. Clinical picture: amiodarone-induced pulmonary mass and cutaneous vasculitis. Lancet 2001; 358(9298): 2045

    Article  PubMed  CAS  Google Scholar 

  72. Dootson G, Byatt C. Amiodarone-induced vasculitis and a review of the cutaneous side-effects of amiodarone. Clin Exp Dermatol 1994; 19: 422–4

    Article  PubMed  CAS  Google Scholar 

  73. Stafford L. Hypersensitivity reaction to amiodarone in a patient with a previous reaction to an iodinated radiocontrast agent. Ann Pharmacother 2007 Jul; 41(7): 1310–4

    Article  PubMed  CAS  Google Scholar 

  74. Junge B, Popp W, Ruehm S, et al. Fire eater’s risk: lipoid pneumonia following aspiration of a liquid hydrocarbon mixture. Pneumologie 2002; 56(9): 547–9

    Article  PubMed  CAS  Google Scholar 

  75. Spickard III A, Hirschmann JV. Exogenous lipoid pneumonia. Arch Intern Med 1994; 154: 686–92

    Article  PubMed  Google Scholar 

  76. Katzenstein A-LA. Katzenstein and Askin’s surgical pathology of nonneoplastic lung disease: major problems in pathology. 4th ed. Philadelphia (PA): WB Saunders, 2006

    Google Scholar 

  77. Barta Z, Szabo GG, Bruckner G, et al. Endogenous lipoid pneumonia associated with undifferentiated connective tissue disease (UCTD). Med Sci Monit 2001; 7: 134–6

    PubMed  CAS  Google Scholar 

  78. Nicholson AG, Wells AU, Hooper J, et al. Successful treatment of endogenous lipoid pneumonia due to Niemann-Pick type b disease with whole-lung lavage. Am J Respir Crit Care Med 2002; 165: 128–31

    PubMed  Google Scholar 

  79. Chiang IC, Lin YT, Liu GC, et al. Exogenous lipoid pneumonia: serial chest plain roentgenography and high-resolution computerized tomography findings. Kaoh-siung J Med Sci 2003; 19(12): 593–8

    Article  Google Scholar 

  80. Baron SE, Haramati LB, Rivera VT. Radiological and clinical findings in acute and chronic exogenous lipoid pneumonia. J Thorac Imaging 2003; 18(4): 217–24

    Article  PubMed  Google Scholar 

  81. Rossi SE, Erasmus JJ, Volpacchio M, et al. “Crazy-paving” pattern at thin-section CT of the lungs: radiologic-pathologic overview. Radiographics 2003; 23(6): 1509–19

    Article  PubMed  Google Scholar 

  82. Carrilon Y, Tixier E, Revel D, et al. MR diagnosis of lipoid pneumonia. J Comput Assist Tomogr 1988; 12: 876–7

    Article  Google Scholar 

  83. Papiris SA, Maniati MA, Manoussakis MN, et al. Ortho-deoxia in amiodarone-induced acute reversible pulmonary damage. Chest 1994 Mar; 105(3): 965–6

    Article  PubMed  CAS  Google Scholar 

  84. Martin II WJ, Rosenow III EC. Amiodarone pulmonary toxicity: recognition and pathogenesis. Part I. Chest 1988; 93: 1067–75

    Article  PubMed  Google Scholar 

  85. Polverosi R, Zanellato E, Doroldi C. Thoracic radiography and high resolution computerized tomography in the diagnosis of pulmonary disorders caused by amiodarone. Radiol Med 1996; 92: 58–62

    PubMed  CAS  Google Scholar 

  86. Cottin V, Cordier JF. Eosinophilic pneumonias. Allergy 2005; 60: 841–57

    Article  PubMed  CAS  Google Scholar 

  87. Milbrandt EB, Byron W, Davis B. Progressive infiltrates and eosinophilia with multiple possible causes. Chest 2000; 118: 230–4

    Article  PubMed  CAS  Google Scholar 

  88. Camus P, Fanton A, Bonniaud P, et al. Interstitial lung disease induced by drugs and radiation. Respiration 2004; 71: 301–26

    Article  PubMed  Google Scholar 

  89. Coudert B, Bailly F, Lombard JN, et al. Amiodarone pneumonitis: bronchoalveolar lavage findings in 15 patients and review of the literature. Chest 1992; 102: 105–12

    Article  Google Scholar 

  90. Epler GR. Bronchiolitis obliterans organizing pneumonia. Arch Intern Med 2001; 161: 158–64

    Article  PubMed  CAS  Google Scholar 

  91. Oymak FS, Dermirbas HM, Mavili E, et al. Brochiolitis obliterans organizing pneumonia: clinical and roentgen-ological features in 26 patients. Respiration 2005; 72: 254–62

    Article  PubMed  Google Scholar 

  92. Malhorta A, Muse VV, Mark EJ. Case records of the Massachusetts General Hospital: weekly clinico-pathological exercises. Case 12–2008. An 82-year old man with dyspnea and pulmonary abnormalities. N Engl J Med 2003; 348: 1574–85

    Article  Google Scholar 

  93. Antón Aranda E, Alkiza Basanñz R, Laplaza Jiménez Y. Bronchiolitis obliterans organizing pneumonia secondary to amiodarone treatment. Neth J Med 1998; 53: 109–12

    Article  PubMed  Google Scholar 

  94. Jessurum GA, Hoogenberg K, Crinjs HJ. Bronchiolitis obliterans organizing pneumonia during low dose amiodarone therapy. Clin Cardiol 1997; 20: 300–2

    Article  Google Scholar 

  95. Epler GR. Drug-induced bronchiolitis obliterans organizing pneumonia. Clin Chest Med 2004; 25: 89–94

    Article  PubMed  Google Scholar 

  96. Valle JM, Alvarez D, Antúnez J, et al. Bronchiolitis obliterans organizing pneumonia secondary to amiodarone: a rare aetiology. Eur Respir J 1995; 8: 470–1

    Article  PubMed  CAS  Google Scholar 

  97. Camus P, Lombard JN, Perrichon M, et al. Bronchiolitis obliterans organizing pneumonia in patients taking ace-butolol or amiodarone. Thorax 1989; 44: 711–5

    Article  PubMed  CAS  Google Scholar 

  98. Conte SC, Pagan V, Murer B. Bronchiolitis obliterans organizing pneumonia secondary to amiodarone: clinical, radiological and histological pattern. Monaldi Arch Chest Dis 1997; 52: 24–6

    PubMed  CAS  Google Scholar 

  99. Oren S, Turkot S, Golzman B, et al. Amiodarone induced bronchiolitis obliterans organizing pneumonia. Respir Med 1996; 90: 167–9

    Article  PubMed  CAS  Google Scholar 

  100. Rakita L, Sobol SM, Mostow N, et al. Amiodarone pulmonary toxicity. Am Heart J 1983; 106 (4 Pt 2): 906–16

    Article  PubMed  CAS  Google Scholar 

  101. American Thoracic Society/European Respiratory Society. International multidisciplinary consensus classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med 2002; 165: 277–304

    Google Scholar 

  102. Wolkove N, Baltzan M. Amiodarone pulmonary toxicity. Can Respir J 2009; 16(2): 43–8

    PubMed  CAS  Google Scholar 

  103. Lim KK, Radford DJ. Amiodarone pneumonitis diagnosed by gallium-67 scintigraphy. Heart Lung Circ 2002; 11: 59–62

    Article  PubMed  Google Scholar 

  104. Beasly MB, Franks TJ, Galvin JK, et al. Acute fibrinous organizing pneumonia: a histological pattern of lung injury and possible variant of diffuse alveolar damage. Arch Pathol Lab Med 2002; 126: 1064–70

    Google Scholar 

  105. Jarand J, Lee A, Leigh R. Amiodaronoma: an unusual form of amiodarone-induced pulmonary toxicity. CMAJ 2007; 176(10): 1411–3

    Article  PubMed  Google Scholar 

  106. Ruangchira-Urai R, Colby TV, Klein J, et al. Nodular amiodarone lung disease. Am J Surg Pathol 2008; 32: 1654–60

    Article  PubMed  Google Scholar 

  107. Arnon R, Raz I, Chajek-Shaul T, et al. Amiodarone pulmonary toxicity presenting as a solitary lung mass. Chest 1988; 93: 425–7

    Article  PubMed  CAS  Google Scholar 

  108. Inampudi P, Gross BH, Tankanow LB. Lung masses in a 70 year old man. Chest 2005; 127: 1433–6

    Article  PubMed  Google Scholar 

  109. Schechter CJ, O’Neill G, Schweppe I, et al. Asymptomatic cavitary pneumonitis due to amiodarone pulmonary toxicity. Tex Heart Inst J 1985; 12: 371–5

    PubMed  CAS  Google Scholar 

  110. Rodriguez Garcia JL, Garcia Nieto JC, Ballesta F, et al. Pulmonary mass and multiple lung nodules mimicking a lung neoplasm as amiodarone induced pulmonary toxicity. Eur J Intern Med 2001; 12: 372–6

    Article  PubMed  Google Scholar 

  111. Sheikhzadeh A, Schäfer U, Schnabel A. Drug-induced lupus erythematosus by amiodarone. Arch Intern Med 2002 Apr 8; 162(7): 834–6

    Article  PubMed  Google Scholar 

  112. Gonzalez-Rothi RJ, Hannan SE, Hood CI, et al. Amiodarone pulmonary toxicity presenting as bilateral exudative pleural effusions. Chest 1987; 92: 179–82

    Article  PubMed  CAS  Google Scholar 

  113. Carmichael LC, Newman JH. Lymphocytic pleural exu-date in a patient receiving amiodarone. Br J Clin Pract 1996; 50(4): 228–30

    PubMed  CAS  Google Scholar 

  114. Morelock SY, Sahn SA. Drugs and the pleura. Chest 1999; 116: 212–21

    Article  PubMed  CAS  Google Scholar 

  115. Stein B, Zaatari GS, Pine JR. Amiodarone pulmonary toxicity: clinical, cytologic and ultrastructural findings. Acta Cytol 1987; 31(3): 357–61

    PubMed  CAS  Google Scholar 

  116. Akoun G, Gauthier-Rahman S, Milleron BJ. Amiodarone-induced hypersensitivity pneumonitis: evidence of an immunological cell-mediated mechanism. Chest 1984; 85: 133–5

    Article  PubMed  CAS  Google Scholar 

  117. Vernhet H, Bousquet C, Durand G, et al. Reversible amiodarone-induced lung disease: HRCT findings. Eur Radiol 2001; 11(9): 1697–703

    Article  PubMed  CAS  Google Scholar 

  118. Clarke B, Ward DE, Honey M. Pneumonitis with pleural and pericardial effusion and neuropathy during amiodarone therapy. Int J Cardiol 1985; 8: 81–8

    Article  PubMed  CAS  Google Scholar 

  119. Susano R, Caminal L, Ramos D, et al. Amiodarone induced lupus. Letter Ann Rheum Dis 1999; 58: 655–6

    Article  CAS  Google Scholar 

  120. Zimetbaum P. Amiodarone for atrial fibrillation. N Engl J Med 2007; 356: 935–41

    Article  PubMed  CAS  Google Scholar 

  121. Endoh Y, Hanai R, Uto K, et al. Diagnostic accuracy of KL-6 as a marker of amiodarone-induced pulmonary toxicity. Pace 2000; 23: 2010–3

    PubMed  CAS  Google Scholar 

  122. Bandoh S, Fujita J, Ohtsuki Y, et al. Sequential changes of KL-6 in sera of patients with interstitial pneumonia associated with polymyositis/dermatomyositis. Ann Rheum Dis 2000; 59(4): 257–62

    Article  PubMed  CAS  Google Scholar 

  123. Kobayashi J, Kitamura S. Serum KL-6 for the evaluation of active pneumonitis in pulmonary sarcoidosis. Chest 1996; 109: 1276–82

    Article  PubMed  CAS  Google Scholar 

  124. Standertskjöld-Nordenstam CG, Wandtke JC, Hood WB, et al. Amiodarone pulmonary toxicity: chest radiography and CT in asymptomatic patients. Chest 1985; 88: 143–5

    Article  PubMed  Google Scholar 

  125. Rossi SE, Erasmus JJ, McAdams HP, et al. Pulmonary drug toxicity: radiologic and pathologic manifestations. Radiographics 2000; 20: 1245–59

    PubMed  CAS  Google Scholar 

  126. Siniakowicz RM, Narula D, Suster B, et al. Diagnosis of amiodarone pulmonary toxicity with high-resolution computerized tomographic scan. J Cardiovasc Electro-physiol 2001; 12: 431–6

    Article  CAS  Google Scholar 

  127. Kuhlman JE, Teigen C, Ren H, et al. Amiodarone pulmonary toxicity: CT findings in symptomatic patients. Radiology 1990; 177: 121–5

    PubMed  CAS  Google Scholar 

  128. Mason JW. Amiodarone pulmonary toxicity and Professor Hounsfield. J Cardiovasc Electrophysiol 2001; 12: 437–8

    Article  PubMed  CAS  Google Scholar 

  129. Nicholson AA, Hayward C. The value of computed tomography in the diagnosis of amiodarone-induced pulmonary toxicity. Clin Radiol 1989; 40: 564–7

    Article  PubMed  CAS  Google Scholar 

  130. Marchiori E, Franquet T, Gasparetto TD, et al. Consolidation with diffuse or focal high attenuation: computed tomography findings. J Thorac Imaging 2008; 23: 298–304

    Article  PubMed  Google Scholar 

  131. Hoteit MA, Sanchez W. A bright liver. Clin Gastroenterol Hepatol 2008; 6: xxii

    Article  PubMed  Google Scholar 

  132. Nicholson AA, Caplin JL, Steventon DM. Measurement of tissue-bond amiodarone and its metabolites by computed tomography. Clin Radiol 1994; 49: 14–8

    Article  PubMed  CAS  Google Scholar 

  133. Markos J, Veronese ME, Nicholson MR, et al. Value of hepatic computerized tomographing scanning during amiodarone therapy. Am J Cardiol 1985; 56: 89–92

    Article  PubMed  CAS  Google Scholar 

  134. Van-Rooij WJ, Vandermeer SC, Van Royen EA, et al. Pulmonary gallium-67 uptake in amiodarone pneumonitis. J Nucl Med 1984; 25: 211–3

    PubMed  CAS  Google Scholar 

  135. Moinuddin M, Rockett J. Gallium scintigraphy in the detection of amiodarone lung toxicity. AJR Am J Roent-genol 1986; 147(3): 607–9

    CAS  Google Scholar 

  136. Zhu YY, Botvinick E, Dae M, et al. Gallium lung scintigraphy in amiodarone pulmonary toxicity. Chest 1988; 93: 1126–31

    Article  PubMed  CAS  Google Scholar 

  137. Foresti V, Carini L, Lovagnini-Scher CA, et al. Amiodarone lung toxicity: role of pulmonary function tests. Int J Clin Pharmacol Res 1987; 7(5): 373–80

    PubMed  CAS  Google Scholar 

  138. Costabel U, Guzman J, Bonella F, et al. Bronchoalveolar lavage in other interstitial lung diseases. Semin Respir Crit Care Med 2007; 28: 514–24

    Article  PubMed  Google Scholar 

  139. Israël-Biet D, Venet A, Caubarrère I, et al. Bronchoalveolar lavage in amiodarone pneumonitis: cellular abnormalities and their relevance to pathogenesis. Chest 1987; 91: 214–21

    Article  PubMed  Google Scholar 

  140. Karpel JP, Ligenza C, Aldrich T, et al. Amiodarone-induced interstitial lung disease: evidence for sensitized T lymphocytes [abstract]. Am Rev Respir Dis 1988; 137: S347

    Google Scholar 

  141. Akoun G, Milleron BJ, Badaro DM, et al. Pleural T-lymphocyte subsets in amiodarone-associated pleuro-pneumonitis. Chest 1989; 95: 506–7

    Article  Google Scholar 

  142. Wilson BP, Jaworski AJ, Donner ME, et al. Amiodarone induced pulmonary toxicity in the rat. Lung 1989; 167: 301–11

    Article  PubMed  CAS  Google Scholar 

  143. Nagata N, Suematsu R, Yoshii C, et al. Characterization of amiodarone pneumonitis as related to inflammatory cells and surfactant apoprotein. Chest 1997; 112: 1068–74

    Article  PubMed  CAS  Google Scholar 

  144. Mermolja M, Rott T, Debeljak A. Cytology of bronch-oalveolar lavage in some rare pulmonary disorders: pulmonary alveolar proteinosis and amiodarone pulmonary toxicity. Cytopathology 1994; 5: 9–16

    Article  PubMed  CAS  Google Scholar 

  145. Xaubet A, Roca J, Rodriguez-Roisin R, et al. Bronch-oalveolar lavage cellular analysis and gallium lung scan in the assessment of patients with amiodarone-induced pneumonitis. Respiration 1987; 52: 272–80

    Article  PubMed  CAS  Google Scholar 

  146. Pozzi E, Sada E, Luisetti M, et al. Interstitial pneumopathy and low-dose amiodarone. Eur J Respir Dis 1984; 65: 620–2

    PubMed  CAS  Google Scholar 

  147. Nalos PC, Kass RM, Gang ES, et al. Life-threatening postoperative pulmonary complications in patients with previous amiodarone pulmonary toxicity undergoing cardiothoracic operations. J Thorac Cardiovasc Surg 1987; 93: 904–12

    PubMed  CAS  Google Scholar 

  148. Darey P. Is amiodarone an underrecognized cause of acute respiratory failure in the ICU? Chest 2001; 120: 275–82

    Article  Google Scholar 

  149. Rosenbaum MB, Chiale PA, Halpern MS, et al. Clinical efficacy of amiodarone as an antiarrhythmic agent. Am J Cardiol 1976; 38: 934–44

    Article  PubMed  CAS  Google Scholar 

  150. Homoud MK. Review: amiodarone reduces risk for sudden death but not all-cause mortality in cardiomyopathy. ACP Journal Club. Ann Intern Med 2009; 151: JC4–13

    PubMed  Google Scholar 

  151. Esinger W, Schleiffer T, Leinberger H, et al. Steroid-refractory amiodarone-induced pulmonary fibrosis: clinical features and morphology after an amiodarone-free interval of 3 months. Dtsch Med Wochenschr 1988; 113: 1638–41

    Article  PubMed  CAS  Google Scholar 

  152. Parra O, Ruiz J, Ojanguren I, et al. Amiodarone toxicity: recurrence of interstitial pneumonitis after withdrawal of the drug. Eur Respir J 1989; 2: 905–7

    PubMed  CAS  Google Scholar 

  153. Chendrasekhar A, Barke RA, Druck P. Recurrent amiodarone pulmonary toxicity. South Med J 1996; 89: 85–6

    Article  PubMed  CAS  Google Scholar 

  154. Zaher C, Hamer A, Peter T, et al. Low-dose steroid therapy for prophylaxis of amiodarone-induced pulmonary infiltrates [letter]. N Engl J Med 1983; 308: 779

    Article  PubMed  CAS  Google Scholar 

  155. Cox G, Johnson J, Kinnear WJ, et al. Amiodarone and the lung: wide variations in clinical practice. Respir Med 2000; 94: 1130–1

    Article  PubMed  CAS  Google Scholar 

  156. Card JW, Racz WJ, Brien JF. Attenuation of amiodarone-induced pulmonary fibrosis by vitamin E is associated with suppression of transforming growth factor-beta1 gene expression but not prevention of mitochondrial dysfunction. J Pharmacol Exp Ther 2003; 304(1): 277–83

    Article  PubMed  CAS  Google Scholar 

  157. Card JW, Leeder RG, Racz WJ, et al. Effects of dietary vitamin E supplementation on pulmonary morphology and collagen deposition in amiodarone- and vehicle-treated hamsters. Toxicology 1999; 133: 75–84

    Article  PubMed  CAS  Google Scholar 

  158. Darmanata JI, Van Zandwijk N, Düren DR, et al. Amiodarone pneumonitis: three further cases with a review of published reports. Thorax 1984; 39: 57–64

    Article  PubMed  CAS  Google Scholar 

  159. Riley SA, William SE, Cooke NJ. Alveolitis after treatment with amiodarone. BMJ 1982; 284: 161–2

    Article  PubMed  CAS  Google Scholar 

  160. Nicolet-Chatelain G, Prevost MC, Escamilla R, et al. Amiodarone induced pulmonary toxicity: immuno-allergologic tests and bronchoalveolar lavage phospho-lipid content. Chest 1991; 99: 363–9

    Article  PubMed  CAS  Google Scholar 

  161. Hughes M, Binning A. Intravenous amiodarone in intensive care: time for reappraisal? Intensive Care Med 2000; 26: 1730–

    Google Scholar 

  162. Ohar JA, Jackson Jr F, Redd RM, et al. Usefulness of serial pulmonary function testing as an indicator of amiodarone toxicity. Am J Cardiol 1989; 64: 1322–6

    Article  PubMed  CAS  Google Scholar 

  163. Marchlinski FE, Gansler TS, Waxman HL, et al. Amiodarone pulmonary toxicity. Ann Intern Med 1982; 97(6): 839–45

    PubMed  CAS  Google Scholar 

  164. Kudenchuk PJ, Pierson DJ, Greene HL, et al. Prospective evaluation of amiodarone pulmonary toxicity. Chest 1984; 86: 541–8

    Article  PubMed  CAS  Google Scholar 

  165. Poll LW, May P, Koch JA, et al. HRCT findings of amiodarone pulmonary toxicity: clinical and radiologic regression. J Cardiovasc Pharmacol Ther 2001; 6: 307–11

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Mr Spyros Vlachos for assistance with the preparation of the figure section. No sources of funding were used in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.

Author information

Authors and Affiliations

  1. 2nd Pulmonary Department, ‘Attikon’ University Hospital, National and Kapodistrian University of Athens, Athens Medical School, 1 Rimini Street, 12462, Haidari, Greece

    Spyros A. Papiris (Associate Professor of Medicine and Head), Christina Triantafillidou, Likurgos Kolilekas, Despoina Markoulaki & Effrosyni D. Manali

Authors
  1. Spyros A. Papiris
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christina Triantafillidou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Likurgos Kolilekas
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Despoina Markoulaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Effrosyni D. Manali
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Spyros A. Papiris.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Papiris, S.A., Triantafillidou, C., Kolilekas, L. et al. Amiodarone. Drug-Safety 33, 539–558 (2010). https://doi.org/10.2165/11532320-000000000-00000

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/11532320-000000000-00000

Keywords

Search

Navigation