Amiodarone hepatotoxicity: Prevalence and clinicopathologic correlations among 104 patients

The prevalence of apparent amiodarone‐related hepatic injury in 104 patients followed prospectively is compared to that reported in the literature. Asymptomatic elevation of serum aminotransferase levels was detected in approximately one‐fourth of the patients, a figure similar to the average of reported cases. The frequency of extrahepatic organ toxicity was increased in patients with elevated levels. Symptomatic “hepatitis” developed in 3% of this series and in less than 1% of cases in the litérature. Evidence of hepatic phospholipidosis and the development of pseudoalcoholic liver injury is most likely due to the biochemical effects of the drug and to possible metabolic idiosyncrasy, respectively. Serial blood enzyme measurements, as recommended by the manufacturer, may offer some protection against the development of more serious liver injury. However, levels of amiodarone may persist in various tissues for weeks to months following withdrawal, and stopping the drug does not guarantee the prompt reversal of any organ toxicity. Accordingly, the risks posed and benefits offered by amiodarone should be carefully weighed prior to discontinuing the drug, as the risk of sudden cardiac death may outweigh the hazards of ongoing hepatic, pulmonary or other toxicity.

[1]  H. Zimmerman,et al.  SERUM ENZYMES IN DISEASE: VII. SIGNIFICANCE OF ABNORMAL SERUM ENZYME LEVELS IN CARDIAC FAILURE , 1961, The American journal of the medical sciences.

[2]  S. Richman,et al.  Alterations in indices of liver function in congestive heart failure with particular reference to serum enzymes. , 1961, The American journal of medicine.

[3]  H. Zimmerman,et al.  Serum enzymes in disease. IX. Analysis of factors responsible for elevated values in infectious mononucleosis. , 1962, The American journal of medicine.

[4]  C. Heusghem,et al.  Long-term hepatic tolerance of amiodarone in the clinic. , 1969, European journal of pharmacology.

[5]  A. Vos,et al.  A peculiar cutaneous pigmentation from cordarone. , 1972, Dermatologica.

[6]  K. Nagashima,et al.  DRUG‐INDUCED GENERALIZED PHOSPHOLIPIDOSIS , 1972, Acta pathologica japonica.

[7]  M. Jonckheer,et al.  Hyperthyroidism as a possible complication of the treatment of ischemic heart disease with amiodarone. , 1973, Acta cardiologica.

[8]  R. Lüllmann-Rauch,et al.  Drug-induced phospholipidoses. II. Tissue distribution of the amphiphilic drug chlorphentermine. , 1975, CRC critical reviews in toxicology.

[9]  P. Nicod,et al.  Effect of amiodarone on serum triiodothyronine, reverse triiodothyronine, thyroxin, and thyrotropin. A drug influencing peripheral metabolism of thyroid hormones. , 1976, The Journal of clinical investigation.

[10]  S. R. Mills,et al.  Computed Tomography in the Diagnosis of Disorders of Excessive Iron Storage of the Liver , 1977, Journal of computer assisted tomography.

[11]  H. Zimmerman,et al.  Hepatotoxicity: The adverse effects of drugs and other chemicals on the liver , 1978 .

[12]  K. Kenyon,et al.  Amiodarone keratopathy: drug-induced lipid storage disease. , 1981, Archives of ophthalmology.

[13]  E. Prystowsky,et al.  Clinical efficacy and electrophysiology during long-term therapy for recurrent ventricular tachycardia or ventricular fibrillation. , 1981, The New England journal of medicine.

[14]  L. Horowitz,et al.  Amiodarone for control of sustained ventricular tachyarrhythmia: clinical and electrophysiologic effects in 51 patients. , 1982, The American journal of cardiology.

[15]  M. Josephson,et al.  Amiodarone pulmonary toxicity. , 1982, Annals of internal medicine.

[16]  E. Chew,et al.  Amiodarone-induced cornea verticillata. , 1982, Canadian journal of ophthalmology. Journal canadien d'ophtalmologie.

[17]  K. Bizière,et al.  Amiodaron neuropathy: further arguments for human drug-induced neurolipidosis. , 1982, European neurology.

[18]  J. Doppman,et al.  Computed Tomography of the Liver and Kidneys in Glycogen Storage Disease , 1982, Journal of computer assisted tomography.

[19]  V. Huckell,et al.  Diffuse alveolar damage syndrome associated with amiodarone therapy. , 1983, Canadian Medical Association journal.

[20]  W. Mckenna,et al.  Side effects and possible contraindications of amiodarone use. , 1983, American heart journal.

[21]  F. Morady,et al.  Long-term efficacy and toxicity of high-dose amiodarone therapy for ventricular tachycardia or ventricular fibrillation. , 1983, The American journal of cardiology.

[22]  P. Kudenchuk,et al.  Toxic and therapeutic effects of amiodarone in the treatment of cardiac arrhythmias. , 1983, Journal of the American College of Cardiology.

[23]  J. Alpert,et al.  Clinical Pharmacokinetics and Efficacy of Amiodarone for Refractory Tachyarrhythmias , 1983, Circulation.

[24]  R. Winkle,et al.  Amiodarone: clinical efficacy and toxicity in 96 patients with recurrent, drug-refractory arrhythmias. , 1983, Circulation.

[25]  J. Ruskin,et al.  Adverse reactions during treatment with amiodarone hydrochloride. , 1983, British medical journal.

[26]  P. Adams,et al.  High-performance liquid chromatographic measurement of amiodarone and desethylamiodarone in small tissue samples after enzymatic digestion. , 1983, Journal of clinical pathology.

[27]  P. K. Lim,et al.  Neuropathy and fatal hepatitis in a patient receiving amiodarone. , 1984, British medical journal.

[28]  R. Miller,et al.  Dermal lipofuscinosis associated with amiodarone therapy. Report of a case. , 1984, Archives of dermatology.

[29]  K. Hostetler,et al.  Chloroquine treatment does not cause phospholipid storage by depleting rat liver lysosomes of acid phospholipase A. , 1984, Biochimica et biophysica acta.

[30]  S. Sherlock,et al.  Impaired oxidation of debrisoquine in patients with perhexiline liver injury. , 1984, Gut.

[31]  L. Horowitz,et al.  Steady-state serum amiodarone concentrations: relationships with antiarrhythmic efficacy and toxicity. , 1984, Annals of internal medicine.

[32]  P. Friedman,et al.  Pneumonitis after amiodarone therapy. , 1984, Radiology.

[33]  M. Shenasa,et al.  Abnormal abdominal computerized tomography with amiodarone therapy and clinical significance. , 1984, American heart journal.

[34]  F. Morady,et al.  Frequent neurologic toxicity associated with amiodarone therapy , 1984, Neurology.

[35]  P. Armstrong,et al.  Amiodarone hepatotoxicity simulating alcoholic liver disease. , 1984, The New England journal of medicine.

[36]  F E White,et al.  Long-term amiodarone therapy: a cause of increased hepatic attenuation on CT. , 1984, The British journal of radiology.

[37]  J. Joelson,et al.  Possible recurrence of amiodarone pulmonary toxicity following corticosteroid therapy. , 1984, Chest.

[38]  E. Downar,et al.  Amiodarone-associated phospholipidosis and fibrosis of the liver. Light, immunohistochemical, and electron microscopic studies. , 1984, Gastroenterology.

[39]  T. Sarna,et al.  Clinical and morphologic effects of amiodarone on the liver. , 1985, Gastroenterology.

[40]  P. Yagupsky,et al.  Fatal hepatic failure and encephalopathy associated with amiodarone therapy. , 1985, The Journal of pediatrics.

[41]  H. Goldberg,et al.  Increased hepatic density and phospholipidosis due to amiodarone. , 1985, AJR. American journal of roentgenology.

[42]  R. Fruncillo,et al.  Effect of phenobarbitone on the pharmacokinetics and tissue levels of amiodarone in the rat , 1985, The Journal of pharmacy and pharmacology.

[43]  D. Capron-Chivrac,et al.  [Acute hepatopathy caused by amiodarone. Study of a case and review of the literature]. , 1985, Gastroenterologie clinique et biologique.

[44]  B. Lown,et al.  Side effects and complications of amiodarone therapy. , 1985, American heart journal.

[45]  M. Nicholson,et al.  Value of hepatic computerized tomographic scanning during amiodarone therapy. , 1985, The American journal of cardiology.

[46]  K. Nademanee,et al.  Amiodarone, thyroid hormone indexes, and altered thyroid function: long-term serial effects in patients with cardiac arrhythmias. , 1986, The American journal of cardiology.

[47]  E. Downar,et al.  Amiodarone pulmonary toxicity: functional and ultrastructural evaluation. , 1986, Thorax.

[48]  J. Lupón-Rosés,et al.  Probable early acute hepatitis with parenteral amiodarone , 1986, Clinical cardiology.

[49]  K. Hostetler,et al.  Role of phospholipase A inhibition in amiodarone pulmonary toxicity in rats. , 1986, Biochimica et biophysica acta.

[50]  W. M. Smith,et al.  Long-term tolerance of amiodarone treatment for cardiac arrhythmias. , 1986, The American journal of cardiology.

[51]  M. Josephson,et al.  Amiodarone Hepatotoxicity: A Clinicopathologic Study of Five Patients , 1986 .

[52]  J. Rumessen Hepatotoxicity of amiodarone. , 2009, Acta medica Scandinavica.

[53]  R. Crapo,et al.  High incidence of clinical and subclinical toxicity associated with amiodarone treatment of refractory tachyarrhythmias. , 1986, The Canadian journal of cardiology.

[54]  D. Dhumeaux,et al.  Chronic liver disease after low daily doses of amiodarone. Report of three cases. , 1986, Journal of hepatology.

[55]  J. Porterfield,et al.  Amiodarone-associated pulmonary toxicity. A clinical and pathologic study of eleven cases. , 1987, American journal of clinical pathology.

[56]  J. Mason Drug therapy: amiodarone , 1987 .

[57]  L. Bertilsson,et al.  Extensive metabolizers of debrisoquine become poor metabolizers during quinidine treatment. , 1987, Pharmacology & toxicology.

[58]  M. Josephson,et al.  Relationship of steady-state serum concentrations of amiodarone and desethylamiodarone to therapeutic efficacy and adverse effects. , 1987, The American journal of medicine.

[59]  N. Shepherd,et al.  Granular cells as a marker of early amiodarone hepatotoxicity: a pathological and analytical study. , 1987, Journal of clinical pathology.

[60]  M. Pirovino,et al.  Amiodarone‐induced hepatic phospholipidosis: Correlation of morphological and biochemical findings in an animal model , 1988, Hepatology.

[61]  Gilinsky Nh,et al.  Fatal amiodarone hepatoxicity. , 1988 .

[62]  K. Hostetler,et al.  In vitro inhibition of lysosomal phospholipase A1 of rat lung by amiodarone and desethylamiodarone. , 1988, Biochimica et biophysica acta.

[63]  S Kacew,et al.  Amiodarone-induced phospholipidosis in rat alveolar macrophages. , 1988, The American review of respiratory disease.