Diffuse lung diseases ascribed to drugs: a nationwide observational study over 37 years using the French Pharmacovigilance Database.

BACKGROUND

Drug-induced interstitial lung disease (DI-ILD) is a heterogeneous subgroup of interstitial lung disease (ILD). The number of molecules involved is increasing with time. Due to their low incidence, DI-ILDs may be detected only after a drug has been marketed, notably through adverse drug reaction (ADR) reports to pharmacovigilance centres. The aim of our study was to describe drug-induced diffuse lung disease cases notified to and recorded by the French Pharmacovigilance Database (FPVD), reported clinical pictures and the potentially causal drugs.

METHODS

This retrospective study included cases registered in the FPVD from 1 January 1985 to 1 April 2022 which had ADRs coded in MedDRA with a High-Level Group Term "Lower respiratory tract disorders (excluding obstruction and infection)" involving patients aged ≥18 years.

RESULTS

We analysed 7234 cases involving 13 059 suspect medications and 1112 specific molecules. Cases were categorised as serious in 96.7% and death ensued in 13.3%. Males accounted for 54.4% of the cases. Median (range) age was 69 (18-103) years. The most prevalent ADRs were "Interstitial lung disease" (51.0%), "Pulmonary oedema" (acute/non-acute) (15.6%) and "Pulmonary fibrosis" (10.5%). Anti-cancer drugs (31.2%) and cardiovascular drugs (29.1%) were the most prominent therapeutic classes involved, with amiodarone being the most commonly reported suspected drug (10.0%), followed by methotrexate (3.1%).

CONCLUSION

This study from a large nationwide dataset spanning 37 years is the largest known to date. Drug-induced diffuse lung diseases are serious with a potentially fatal outcome. Accurate diagnoses remain essential to identify the diseases properly and discontinue the culprit drug urgently.