BACKGROUND: Well-established side effects of trimethoprim/sulfamethoxazole include cutaneous and liver toxicity, hypersensitivity syndrome and blood dyscrasias. Trimethoprim/sulfamethoxazole has also been associated with severe lung toxicity (LT) but reports are scarce. METHODS: We investigated pharmacovigilance data and reviewed spontaneous reports of trimethoprim/sulfamethoxazole-related LT recorded in the French national pharmacovigilance database (FPVD) and the WHO global database of adverse events (VigiBase®) up to 31 December 2023. We performed disproportionality analysis to detect a possible pharmacovigilance signal. RESULTS: A total of 755 patients with trimethoprim/sulfamethoxazole-related LT were reported in VigiBase®, 17 of which were from the FPVD. In VigiBase®, interstitial lung disease was the most frequent LT pattern (30.5%). A fatal outcome was reported in 197 patients (26.1%). Significant reporting ORs were observed for the following trimethoprim/sulfamethoxazole-related LT patterns: interstitial lung disease 1.5 (95% CI: 1.3-1.7)
acute respiratory distress syndrome 2.9 (95% CI: 2.5-3.5)
eosinophilic pneumonia 4.1 (95% CI: 3.2-5.2)
diffuse alveolar damage 3.7 (95% CI: 2.6-5.3)
organizing pneumonia 2.1 (95% CI: 1.4-3.1)
pulmonary toxicity 1.9 (95% CI: 1.3-2.9)
acute lung injury 7.5 (95% CI: 4.9-11.6) and hypersensitivity pneumonitis 2.7 (95% CI: 1.7-4.2). CONCLUSIONS: We highlight statistically significant disproportionality for several trimethoprim/sulfamethoxazole-related LT patterns, which constitutes a pharmacovigilance signal. Trimethoprim/sulfamethoxazole-related LT is rare, but may be critical and even life-threatening. Physicians should be aware of potential trimethoprim/sulfamethoxazole-related LT and should inform their patients, since early intervention could prevent severe outcome.