Comprehensive assessment of the long-term safety of pirfenidone in patients with idiopathic pulmonary fibrosis

Respirology. 2014 Jul;19(5):740-7. doi: 10.1111/resp.12297. Epub 2014 May 18.


Background and objective: Pirfenidone is an oral antifibrotic agent that is approved in several countries for the treatment of idiopathic pulmonary fibrosis (IPF). We performed a comprehensive analysis of safety across four clinical trials evaluating pirfenidone in patients with IPF.

Methods: All patients receiving pirfenidone 2403 mg/day in the Phase 3 CAPACITY studies (Studies 004 and 006) and all patients receiving at least one dose of pirfenidone in one of two ongoing open-label studies in patients with IPF (Studies 002 and 012) were selected for inclusion. Safety outcomes were evaluated from baseline until 28 days after the last dose of study drug.

Results: A total of 789 patients were included in the analysis. The median duration of exposure to pirfenidone was 2.6 years (range, 1 week-7.7 years), and the cumulative total exposure was 2059 person exposure years (PEY). Gastrointestinal and skin-related events were the most commonly reported adverse events; these were almost always mild to moderate in severity, and rarely led to treatment discontinuation. Elevations (>3× upper limit of normal) in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) occurred in 21/789 (2.7%) patients; the adjusted incidence of AST/ALT elevations was 1.7 per 100 PEY.

Conclusions: This comprehensive analysis of safety in a large cohort of IPF patients receiving pirfenidone for a total of 2059 PEY demonstrates that long-term treatment with pirfenidone is safe and generally well tolerated.

Keywords: adverse event; idiopathic pulmonary fibrosis; pirfenidone; safety; treatment.

Publication types

  • Evaluation Study
  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alanine Transaminase / blood
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Aspartate Aminotransferases / blood
  • Biomarkers / blood
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Idiopathic Pulmonary Fibrosis / drug therapy*
  • Male
  • Middle Aged
  • Pyridones / adverse effects*
  • Pyridones / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Time Factors


  • Anti-Inflammatory Agents, Non-Steroidal
  • Biomarkers
  • Pyridones
  • pirfenidone
  • Aspartate Aminotransferases
  • Alanine Transaminase