Lung toxicity related to trimethoprim/sulfamethoxazole: pharmacovigilance data review.

Summary

Global pharmacovigilance signals implicate trimethoprim/sulfamethoxazole in multiple severe lung toxicities, including ARDS and acute lung injury, with a 26% fatality among reported cases. Disproportionality analyses show elevated reporting odds for ARDS (2.9), acute lung injury (7.5), eosinophilic pneumonia (4.1), and diffuse alveolar damage (3.7).

Key Findings

• 755 TMP/SMX-related lung toxicity cases in VigiBase with 26.1% fatal outcomes; 17 cases in the French database.
• Significantly elevated reporting odds: ARDS 2.9, acute lung injury 7.5, eosinophilic pneumonia 4.1, diffuse alveolar damage 3.7 (all with 95% CIs excluding 1).
• Interstitial lung disease was the most frequent pattern (30.5%).

Clinical Implications

Maintain high suspicion for drug-induced lung injury (e.g., ARDS, ALI, eosinophilic pneumonia) in patients on TMP/SMX; prompt drug withdrawal and early diagnostic workup may reduce severe outcomes. Patient counseling on respiratory symptoms is warranted.

Limitations

• Spontaneous reporting subject to underreporting and reporting bias; incidence rates cannot be derived.
• Causality cannot be established; limited clinical detail and confounding by indication possible.

Future Directions

Prospective pharmacoepidemiologic studies to estimate incidence and risk factors; mechanistic studies to elucidate pathogenesis; decision-support alerts to flag risk in EHRs.