What is the time to onset of pulmonary fibrosis with amiodarone (antiarrhythmic medication)?

From the Guidelines

Amiodarone-induced pulmonary fibrosis typically develops after months to years of treatment, with most cases occurring after 6-12 months of therapy. The time to onset of pulmonary fibrosis with amiodarone is a critical consideration in the management of patients taking this antiarrhythmic medication. According to the guidelines for use and monitoring of amiodarone 1, regular monitoring with pulmonary function tests and chest imaging is recommended for early detection, especially during the first year of treatment.

Key Considerations

• The risk of developing pulmonary fibrosis is dose-dependent, with an estimated incidence of 5-15% of patients taking amiodarone long-term.
• Patients with pre-existing lung disease, those receiving oxygen therapy, or those undergoing pulmonary angiography or surgery have increased susceptibility.
• The mechanism involves direct cytotoxicity to lung cells, phospholipidosis (accumulation of phospholipids in tissues), immune-mediated inflammation, and oxidative damage from the high iodine content of amiodarone.

Monitoring Recommendations

• Complete history and physical examination with special attention to heart failure, arrhythmia, and concomitant medications at baseline and regularly thereafter.
• Heart rate surveillance and thyroid studies at regular intervals.
• Liver transaminase levels and digoxin level (if taking digoxin) should be monitored closely.
• Chest radiograph and pulmonary function tests, including diffusing capacity of lung for carbon monoxide, should be performed at baseline and if any suspected pulmonary toxicity occurs. However, it is essential to note that pulmonary toxicity can occasionally occur within the first few weeks of treatment or even years after discontinuation due to amiodarone's extremely long half-life (approximately 58 days) and its tendency to accumulate in lung tissue 1.

From the Research

Time to Onset of Pulmonary Fibrosis with Amiodarone

• The time to onset of pulmonary fibrosis with amiodarone can vary, but most cases of amiodarone-induced lung injury develop during the first 2 years of treatment 2.
• A case study reported a patient who developed amiodarone-induced pulmonary fibrosis after 5 years of treatment with a daily dose of 200 mg/day 3.
• Another case report described a patient who developed amiodarone-induced pulmonary toxicity after 3 months of treatment with a dose of 400 mg orally twice daily 4.
• A study suggested that the cumulative dose of amiodarone may be a risk factor for pulmonary toxicity, with a cumulative dose of >150 gr associated with an increased risk 5.
• An early study reported 5 cases of pulmonary fibrosis associated with amiodarone use, with the time to onset ranging from 1 to 6 years 6.

Risk Factors and Diagnosis

• Advanced age and pre-existing pulmonary dysfunction may enhance susceptibility to pulmonary toxicity 3.
• The diagnosis of amiodarone-induced pulmonary toxicity is often made by exclusion, and pulmonary evaluation with chest X-ray and pulmonary function testing is recommended when amiodarone is started 2.
• A documented decline in the diffusing capacity of greater than 20% is useful in suggesting the need for closer monitoring or for further diagnostic testing 2.
• High-resolution computed tomography (HRCT) may be used to diagnose amiodarone-induced pulmonary toxicity, with findings including ground-glass opacities and nodules in both lungs 4, 5.

Treatment and Prognosis

• Treatment of amiodarone-induced pulmonary toxicity consists primarily of stopping amiodarone, and corticosteroid therapy can be life-saving for severe cases 2, 4, 5.
• The prognosis of amiodarone lung disease is generally favorable, but pulmonary toxicity may initially progress despite drug discontinuation and may recur after steroid withdrawal 2.