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Amiodarone-Induced Pulmonary Toxicity

Predisposing Factors, Clinical Symptoms and Treatment

  • Review Article
  • Pharmacoepidemiology
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Summary

Amiodarone is frequently used for the treatment of cardiac arrhythmias. Although the therapeutic efficacy of amiodarone has been established, its use is limited by its safety profile. Amiodarone-induced pulmonary toxicity is one of the most life-threatening complications of this therapy. It is a relatively rare adverse effect of amiodarone and is easily missed by any physician who is suddenly confronted with nonspecific pulmonary complaints during amiodarone treatment. There are several cumulative factors which may enhance the susceptibility of patients for amiodarone-induced pulmonary toxicity, such as advanced age and pre-existing pulmonary dysfunction. Several case studies and clinical trials of amiodarone have shown the possible occurrence of amiodarone-induced pulmonary toxicity during low dose and short-duration therapy. Therefore, the dose and duration of amiodarone treatment are not the only determinants of toxicity risk.

Amiodarone-induced pulmonary toxicity is characterised by various clinical manifestations such as coughing, dyspnoea, fever, bodyweight loss, respiration-related chest pain and bilateral lung infiltrates with no escavated nodules.

Once amiodarone-induced pulmonary toxicity has been diagnosed, therapeutic options are limited, but in most cases the disease is reversible, if diagnosed at an early stage.

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References

  1. Gosselink ATM, Crijns HJGM, Van Gelder IC, et al. Low dose amiodarone for maintenance of sinus rhythm after cardioversion of atrial fibrillation or flutter. JAMA 1992; 267: 3289–93

    Article  PubMed  CAS  Google Scholar 

  2. Doval HC, Nul DR, Grancelli HO, et al. Randomised trial of low dose-amiodarone in severe congestive heart failure. Lancet 1994; 344: 493–8

    Article  PubMed  CAS  Google Scholar 

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

    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. Julian DG. The amiodarone trials. Eur Heart J 1997; 18: 1361–63

    Article  PubMed  CAS  Google Scholar 

  6. Cairns JA, Connolly SJ, Roberts R, et al. Randomised trial of outcome after myocardial infarction in patients with frequent or repetitive ventricular premature depolarisations: CAMIAT. Lancet 1997; 349: 675–82

    Article  PubMed  CAS  Google Scholar 

  7. Sopher SM, Camm AJ. Adverse effects of amiodarone at low dose: plus ça change. J Am Coll Cardiol 1997; 30: 799–801

    Article  PubMed  CAS  Google Scholar 

  8. Julian DG, Camm AJ, Frangin G, et al. Randomised trial of effect of amiodarone on mortality in patients with left ventricular dysfunction after recent myocardial infarction: EMIAT. Lancet 1997; 349: 667–74

    Article  PubMed  CAS  Google Scholar 

  9. Vorperian VR, Havighurst TC, Miller S. Adverse effects of low dose amiodarone: a meta-analysis. J Am Coll Cardiol 1997; 30: 791–8

    Article  PubMed  CAS  Google Scholar 

  10. Epstein LM, Scheinman MM, Chin MC, et al. The use-dependent effects of acute and chronic amiodarone administration on His-Purkinje conduction and the interaction of beta-adrenergic stimulation. J Cardiovasc Electrophysiol 1991; 2: 156–67

    Article  Google Scholar 

  11. Rotmensch HH, et al. Possible association of pneumonitis with amiodarone therapy. Am Heart J 1980 Sep; 100(3): 412–3

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  13. Kennedy JI. Clinical aspects of amiodarone pulmonary toxicity. Clinics Chest Med 1990; 11: 119–29

    Google Scholar 

  14. Martin II WJ, Rosenow III EC. Amiodarone pulmonary toxicity: recognition and pathogenesis. Part II. Chest 1988; 93: 1242–8

    Article  PubMed  CAS  Google Scholar 

  15. Ohar JA, Jackson F, Dettenmeier PA, et al. Bronchoalveolar lavage cell count and differential are not reliable indicators of amiodarone-induced pneumonitis. Chest 1992; 102: 999–1004

    Article  PubMed  CAS  Google Scholar 

  16. Coudert B, Bailly F, Lombard JN. Amiodarone pneumonitis. Bronchoalveolar lavage findings in 15 patients and review of the literature. Chest 1992; 102: 1005–12

    Article  PubMed  CAS  Google Scholar 

  17. Pollak PT, Sharma AD, Carruthers SG. Relation of amiodarone hepatic and pulmonary toxicity to serum drug concentrations and superoxide dismutase activity. Am J Cardiol 1990; 65: 1185–91

    Article  PubMed  CAS  Google Scholar 

  18. Rothmensch HH, Belhassen B, Swanson B, et al. Steady-state serum amiodarone concentrations: relationship with anti-arrhythmic efficacy and toxicity. Ann Intern Med 1984; 101: 462–9

    Google Scholar 

  19. 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 

  20. Ulrik CS, Backer V, Aldershville J, et al. Serial pulmonary function tests in patients treated with low dose amiodarone. Am Heart J 1992; 123: 1550–4

    Article  PubMed  CAS  Google Scholar 

  21. Roca J, Heras M, Rodriguez-Roisin R, et al. Pulmonary complications after long term amiodarone treatment. Thorax 1992; 47: 372–6

    Article  PubMed  CAS  Google Scholar 

  22. Mason JW. Toxicity of amiodarone. Circulation 1985; 72 Suppl. 3: 272

    Google Scholar 

  23. Jessurun GAJ, Hoogenberg K, Crijns HJGM. Bronchiolitis obliterans organising pneumonia during low dose amiodarone therapy. Clin Cardiol 1997; 20: 300–2

    Article  PubMed  CAS  Google Scholar 

  24. Singh SN, Fletcher RD, Fisher SG. Pulmonary effects of amiodarone in patients with heart failure [abstract]. Circulation 1995; 92 Suppl. 1: 195

    Google Scholar 

  25. 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 

  26. Costabel U, Guzman J. BOOP: what is old, what is new? Eur Respir J 1991; 4: 771–3

    PubMed  CAS  Google Scholar 

  27. Izumi T. Proceeding of the international congress on bronchiolitis obliterans organising pneumonia. Chest 1992; 102 Suppl.: 1S–50S

    Article  Google Scholar 

  28. Heipel J, Dawdy J, George CFP, et al. Bronchiolitis obliterans secondary to amiodarone. Can J Hosp Pharm 1993; 46: 275–7

    Google Scholar 

  29. Camus P, Lombard J, Perrichon M, et al. Bronchiolitis obliterans organizing pneumonia in patients taking acebutolol and amiodarone. Thorax 1989; 44: 711–9

    Article  PubMed  CAS  Google Scholar 

  30. Tisdale JE, Follin SL, Ordelova A. Risk factors for the development of specific noncardiovascular adverse effects associated with amiodarone. J Clin Pharmacol 1995; 35: 351–6

    PubMed  CAS  Google Scholar 

  31. 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 

  32. Goldstein I, Topilsky M, Segev D. Very early onset of acute amiodarone pulmonary toxicity presenting with hemoptysis. Chest 1997; 111: 1446–7

    Article  PubMed  CAS  Google Scholar 

  33. Van der Zeyden H, Zandstra D, van Hengstum M. Low dose amiodarone pulmonary toxicity in a patient with a history of pneumonectomy. Intensive Care Med 1992; 18: 422–3

    Article  PubMed  Google Scholar 

  34. Herndon JC, Cook AO, Ramsay MAE. Postoperative unilateral pulmonary edema: possible amiodarone pulmonary toxicity. Anesthesiology 1992; 76: 308–12

    Article  PubMed  CAS  Google Scholar 

  35. Balser JR. The rational use of intravenous amiodarone in the perioperative period. Anesthesiology 1997; 86: 974–87

    Article  PubMed  CAS  Google Scholar 

  36. Sats AK, Stoelting RK, Gibbs PS. Intraoperative pulmonary edema in a patient being treated with amiodarone. Anesth Analg 1991; 73: 821–3

    Google Scholar 

  37. Malden ES, Tartar VM, Gutierrez FR. Acute fatality following pulmonary angiography in a patient on an amiodarone regimen — a case report. Angiology 1993; 44: 152–5

    Article  PubMed  CAS  Google Scholar 

  38. Dunn M, Glassroth J. Pulmonary complications of amiodarone toxicity. Prog Cardiovasc Dis 1989; 31: 447–53

    Article  PubMed  CAS  Google Scholar 

  39. 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 

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Authors and Affiliations

  1. Department of Cardiology, University Hospital Groningen, Thoraxcentre, Hanzeplein 1, 9700 RB, Groningen, The Netherlands

    Gillian A. J. Jessurun & Harry J. G. M. Crijns

  2. Department of Pulmonary Diseases, Medical Centre Alkmaar, Alkmaar, The Netherlands

    Wim G. Boersma

Authors
  1. Gillian A. J. Jessurun
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  2. Wim G. Boersma
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  3. Harry J. G. M. Crijns
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Jessurun, G.A.J., Boersma, W.G. & Crijns, H.J.G.M. Amiodarone-Induced Pulmonary Toxicity. Drug-Safety 18, 339–344 (1998). https://doi.org/10.2165/00002018-199818050-00003

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