Indications
Pharmacology
- 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
Administration
Adverse Effects
Pulmonary Adverse Effects
- 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
- 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
- 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
- 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)
- 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
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
Skin Adverse Effects
- Bluish Discoloration of Skin
- Photodermatitis
References
- 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]