Causality assessment · Causality: well established

Amiodarone and Pulmonary fibrosis (interstitial lung disease): is the FAERS signal real?

n=395 co-reports · PRR 39.7 · ROR 41.1

A written Bradford Hill assessment of one drug–event pair. The grade is a judgement about the signal, not a statement that this drug causes this event in any one person; FAERS counts are reports, not rates.

Causality: well established

Amiodarone ↔ Pulmonary fibrosis (interstitial lung disease)

n=395 co-reports · PRR 39.7 · ROR 41.1 Interstitial lung disease (related term): n=271 · PRR 10.6

Amiodarone is a highly lipophilic antiarrhythmic that accumulates in tissue, and its best-known serious long-term toxicity is pulmonary — pneumonitis that can progress to irreversible fibrosis. Because it is used long-term and its tissue burden is cumulative, guidelines and the prescribing information recommend periodic chest imaging and pulmonary-function monitoring for patients on the drug. The reaction is idiosyncratic in timing but clearly exposure-related, and the same iodine-rich, tissue-sequestering pharmacology produces the drug's other signature effects — thyroid dysfunction (both hyper- and hypothyroidism), corneal microdeposits, and hepatotoxicity. The comparatively modest FAERS counts relative to its lethality reflect aggressive monitoring and the fact that amiodarone use has declined as safer antiarrhythmics and ablation have expanded.

Regulatory basis: amiodarone prescribing information (pulmonary toxicity, thyroid, hepatic, ocular monitoring). Established literature on amiodarone-induced pulmonary toxicity.

Bradford Hill viewpoint	Status	Note
Temporality (necessary)	met	Pneumonitis typically emerges after months of cumulative exposure
Strength	met	PRR 40 for pulmonary fibrosis, one of the largest on the page despite modest counts
Consistency	met	Replicated across decades of case series and the prescribing information
Specificity	partial	Also causes thyroid, corneal, and hepatic toxicity — not lung-specific
Biological gradient	met	Risk tracks with cumulative dose/duration
Plausibility	met	Lipophilic tissue accumulation and an iodine-rich molecule drive direct pneumocyte toxicity
Coherence	met	Coheres with the broader amiodarone organ-toxicity profile
Experiment	partial	Drug discontinuation improves outcomes; no randomized exposure-removal trial
Analogy	met	Analogous to other drug-induced interstitial lung disease (e.g. nitrofurantoin, methotrexate)

This page's own qualitative read, not an automated/citation-gated assessment.

✗ Searched; the trial that surfaced was not evidence either way. The top results-posting amiodarone study (a rate- vs rhythm-control atrial-fibrillation trial, NCT02132767) captured only a single “pulmonary embolism” term in one arm — an unrelated vascular event, not drug-induced lung fibrosis. Amiodarone's pulmonary toxicity develops over months to years, far beyond the follow-up window of typical registered trials, which is why it was characterized through long-term cohort and case data instead.