• Cationic Amphiphilic Drug (CAD): it has both polar and non-polar constituents
    • Cationic amphiphilic drugs have a tendency to induce accumulation of phospholipids within tissues
  • Potent Inhibitor of Phospholipase A: leads to impaired phospholipid degaradation -> phospholipid accumulation in tissues
    • In about 50% of cases, alveolar macrophages and type II pneumocytes contain a markedly increased amount of phospholipid


  • PO:
  • IV:

Adverse Effects

Pulmonary Adverse Effects

Classical Amiodarone Pneumonitis (see Pneumonia, Interstitial Lung Disease-Etiology, and Cryptogenic Organizing Pneumonia)

  • Epidemiology
    • Occurs in 6% of amiodarone-treated patients
    • Most cases of pulmonary toxicity occur in men (but this may be due to increased prevalence of use in men)
    • Amiodarone lung toxicity may occur more readily in those with previously abnormal lung function and/or CXR
    • Dose-Relationship of Lung Toxicity
      • Most patients who develop lung toxicity have been taking the drug for at least a month (and some for a few years)
      • Most patients who develop lung toxicity are taking at least 400 mg/day (number of case reports of toxicity with doses of 200 mg/day): there are case reports of patients taking 200 mg/day for years with no toxicity until dose is increased to 400 mg/day
      • However, lung toxicity does not correlate with serum levels of amiodarone
  • Diagnosis
    • ABG: hypoxemia
    • PFT’s: restriction with decreased DLCO
    • Gallium Scan: positive in amiodarone pulmonary toxicity (due to inflammation), but negative in congestive heart failure
    • FOB: presence of foamy macrophages on BAL or TBB only confirms exposure to amiodarone, but does not indicate toxicity (importantly, absence of foamy macrophages rules out toxicity)
    • Open Lung Biopsy: may be necessary in some cases
      • BO: may be seen in cases with confluent lesions
      • BOOP: seen in some cases
      • Chronic Interstitial Pneumonia (with or without fibrosis)
      • Desquamative Interstitial Pneumonia (DIP)
      • Lymphocytic Interstitial Pneumonitis (LIP)
      • Phospholipidosis
        • Foamy macrophages: nonspecific finding (can be seen with use of chlorphentermine, neuroleptics, antidepressants, inhibitors of cholesterol synthesis as well as in lipid storage diseases, and a variety of other conditions in which the lung is injured such as ARDS and obstructive pneumonia) -> however, the absence of foamy macropahges eliminates the diagnosis
        • Type II pneumocytes with lamellar inclusions
      • Diffuse Alveolar Damage: some cases
      • Acute Necrotizing Pneumonia: some cases
      • Organizing Pneumonia (see Cryptogenic Organizing Pneumonia, [[Cryptogenic Organizing Pneumonia]]): some cases
      • Diffuse Alveolar Hemorrhage (see Diffuse Alveolar Hemorrhage, [[Diffuse Alveolar Hemorrhage]]): rare cases
    • CXR/Chest CT
      • Early in Course: interstitial, alveolar, or mixed alveolar-interstitial infiltrates
      • Focal or diffuse, asymmetric, upper lobe predominance (may mimic infiltrates of TB)
        • May be peripheral, mimicking the infiltrates of chronic eosinophilic pneumonia
        • Pleural effusion is uncommon
      • Later in Course: infiltrates progress and may coalesce with continued use
    • CBC: normal-mild leukocytosis with usually absent eosinophilia
      • However, some cases have eosinophilia, producing a pumonary infiltrates with eosinophilia-like picture
    • ESR: elevated (may decrease with drug withdrawal, supporting diagnosis of amiodarone lung toxicity)
    • ANA: negative
  • Clinical
    • Insidious Onset Presentation (80% of cases)
      • Insidious Onset of Dyspnea
      • Non-Productive Cough
      • Low-Grade Fever (without chills)
      • Pleuritic Chest Pain (10% of patients)
      • Crackles
      • Absence of Clubbing
    • Acute Pneumonia-Like Presentation (20% of cases)
  • Treatment
    • Withdrawal of amiodarone + corticosteroids (for at least 2-6+ months): most respond, but response is variable
    • Follow ESR: typically decreases with amiodarone withdrawal
  • Prognosis: fatal in 5-10% of cases

Hyperdense or Mass-Like Consolidation (see Lung Nodule or Mass and Cryptogenic Organizing Pneumonia)

  • Epidemiology: uncommon
  • Diagnosis
    • CXR/Chest CT
      • Confluent infiltrate or nodule or mass: may cavitate
      • Chest CT is useful: amiodarone is iodinated and infiltrate will appear denser than surrounding soft tissue in the chest wall
  • Pathology: cryptogenic organizing pneumonia
  • Treatment/Prognosis: withdraw amiodarone -> complete resolution may take 2-12 months

Acute Lung Injury-ARDS (see Acute Lung Injury-ARDS)

  • Epidemiology: uncommon -> occurs in post-operative setting, 18-72 hrs after surgery
  • Physiology: may be related to high FIO2 administration during and/or after the procedure

Diffuse Alveolar Hemorrhage (see Diffuse Alveolar Hemorrhage)

  • Epidemiology: rare (only a few reported cases of amiodarone-associated diffuse alveolar hemorrhage)
  • Physiology: diffuse alveolar damage
  • Pathology: bland alveolar hemorrhage (absence of pulmonary capillaritis)

Pleural Effusion (see Pleural Effusion-Exudate)

  • Diagnosis: exudative (PMN, macrophage, or lymphocyte-predominant)

Cardiac Adverse Effects

  • Bradycardia (see Bradycardia)
  • Conduction Disturbances
  • Hypotension (see Hypotension)
  • Negative Inotropy
  • Postural Hypotension due to Dysautonomia
  • Potential for Alteration of Metabolism of Other Drugs
    • Digoxin
    • Coumadin
    • Phenytoin
    • Procainamide
    • Quinidine
  • Proarrhythmic Effects
  • QT Prolongation/Torsade (see Torsade): definite association with torsade

Gastrointestinal Adverse Effects

Hematologic Adverse Effects

  • Bone Marrow Suppression

Hepatic Adverse Effects

  • Asymptomatic Abnormal Liver Function Tests (LFT’s): appears to be associated with serum amiodarone levels
  • Granulomatous Hepatitis
  • Hepatic Nodules

Neuromuscular Adverse Effects

  • Extrapyramidal Manifestations
  • Peripheral Neuropathy (see Peripheral Neuropathy): appears to be associated with serum amiodarone levels
  • Postural Hypotension due to Dysautonomia
  • Proximal Muscle Weakness
  • Sleep Disturbances: vivid dreams, nightmares, and sleeplessness

Ocular Adverse Effects

  • Corneal Microdeposits: 100% of cases
  • Halo Vision

Thyroid Adverse Effects

Skin Adverse Effects

  • Bluish Discoloration of Skin
  • Photodermatitis


  • Amiodarone. N Engl J Med 1987. 316; 455-466 [MEDLINE]
  • Atypical pulmonary and neurologic complications of amiodarone in the same patient. Report of a case and review of the literature. Arch Intern Med 1987. 1471805-1809 [MEDLINE]
  • Amiodarone pulmonary toxicity presenting as a solitary lung mass. Chest 1988. 93425-427 [MEDLINE]
  • Amiodarone‐induced pulmonary mass. Ann Thorac Surg 1989. 47918-919 [MEDLINE]
  • Amiodarone pulmonary toxicity: CT findings in symptomatic patients. Radiology. 1990 Oct;177(1):121-5 [MEDLINE]
  • Comparison of the Bayesian approach and a simple algorithm for assessment of adverse drug events. Clin Pharmacol Ther 1995. 58692-698 [MEDLINE]
  • Multivesiculated macrophages: their implication in fine‐needle aspiration cytology of lung mass lesions. Diagn Cytopathol 1998. 1998-101 [MEDLINE]
  • Pulmonary mass and multiple lung nodules mimicking a lung neoplasm as amiodarone‐induced pulmonary toxicity. Eur J Intern Med 2001. 12372-376 [MEDLINE]
  • Pulmonary nodules with the CT halo sign. Respiration 2002 [MEDLINE]
  • Exogenous lipoid pneumonia with unusual CT pattern and FDG positron emission tomography scan findings. Eur Radiol 2002. 12(suppl 3)S171-S173.S173 [MEDLINE]
  • Lung masses in a 70‐year‐old man. Chest 2005. 1271433-1436 [MEDLINE]
  • Amiodarone toxicity presenting as pulmonary mass and peripheral neuropathy: the continuing diagnostic challenge. Postgrad Med J. 2006 January; 82(963): 73-75 [MEDLINE]