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