ORIGINAL RESEARCH article
Front. Drug Saf. Regul.
Sec. Respiratory Drug Safety
A Real-World Disproportionality Analysis of Roflumilast Using the US Food and Drug Administration adverse event reporting system Data
Provisionally accepted
- Shanghai Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Introduction: Roflumilast, a selective phosphodiesterase-4 inhibitor, is prescribed to reduce exacerbations in severe COPD, but its real-world safety profile remains insufficiently characterized. Methods: We conducted a retrospective pharmacovigilance study using the FDA Adverse Event Reporting System (FAERS). Reports from 2004–2025Q1 listing roflumilast as the primary suspect were extracted, deduplicated, and analyzed. Disproportionality analysis employed four algorithms— Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). Safety signals were defined by established thresholds. Time-to-onset and Weibull modeling were applied to assess temporal patterns. Results: A total of 3,140 reports were identified, primarily involving older COPD patients. The median time-to-onset was 4 days (IQR 0–34), with 72% occurring within 30 days. Thirty Preferred Terms met signal criteria. Frequent signals included diarrhoea, weight decreased, nausea, dyspnoea, insomnia, and headache. Psychiatric events such as depression and suicidal ideation were notable. The strongest disproportionality was observed for gastroduodenal ulcer (ROR 47.1) and COPD (ROR 25.7). System Organ Class enrichment was most evident in gastrointestinal, psychiatric, and respiratory disorders. Discussion/Conclusion: This real-world analysis confirms roflumilast's established adverse effects (gastrointestinal upset, weight loss, insomnia) and highlights concerning psychiatric signals. Most events occurred early, underscoring the need for close monitoring during treatment initiation. The use of multiple disproportionality methods enhances signal detection robustness and supports ongoing pharmacovigilance in clinical practice.
Keywords: Roflumilast, adverse drug reactions, Pharmacovigilance, FDA adverse event reporting system (FAERS), Real-world evidence
Received: 13 Oct 2025; Accepted: 25 Nov 2025.
Copyright: © 2025 Huang, Ma, Wang, Gu and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Baiqing Huang
Shaorui Gu
Xisheng Wang
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.