Safety and tolerability of acetylcysteine and pirfenidone combination therapy in idiopathic pulmonary fibrosis: a randomised, double-blind, placebo-controlled, phase 2 trial

Pirfenidone safety and adverse event management in idiopathic pulmonary fibrosis

“…In PANORAMA, a randomised, double-blind, placebo-controlled phase II European study that assessed the safety and tolerability of oral N-acetylcysteine (NAC) combined with pirfenidone in patients with IPF (n=60, pirfenidone plus NAC), the addition of NAC did not significantly affect the safety profile of pirfenidone; however, an increased incidence of photosensitivity in the pirfenidone plus NAC versus pirfenidone plus placebo group was observed (13% versus 2%), which could not be explained by additional analyses [25]. The most frequent other TEAEs in the pirfenidone plus NAC group were cough (13%), nasopharyngitis (12%), diarrhoea (10%), nausea (7%), dyspnoea (7%) and bronchitis (7%).…”

“…The most frequent other TEAEs in the pirfenidone plus NAC group were cough (13%), nasopharyngitis (12%), diarrhoea (10%), nausea (7%), dyspnoea (7%) and bronchitis (7%). In the group using additional NAC, a more rapid disease progression (as measured by FVC) was observed and the authors conclude that addition of NAC to pirfenidone is unlikely to be beneficial in IPF function [25].…”

Trends in diagnosis and management of idiopathic pulmonary fibrosis in Canada

“…The frequent use of both N-acetylcysteine and pirfenidone by our respondents may be influenced by the perceived safety of NAC and clinical trial data on pirfenidone published subsequent to the 2011 statement. 13 (Note: this survey was conducted prior to the publication of trials of NAC monotherapy and pirfenidone 4,14 and a recent study suggesting harm with the combination of NAC and pirfenidone 15 .) The 2011 Statement makes strong recommendations against several pharmacologic therapies including the use of prednisone monotherapy.…”

Pharmacotherapy for idiopathic pulmonary fibrosis: current landscape and future potential

“…The 2015 guidelines gave a "conditional" recommendation against its use, which implied the potential benefit of NAC may occur in a minority of patients with IPF [3]. In a subsequent report of the results from the PANORAMA trial [16], which was designed to determine the safety of combined therapy with pirfenidone plus NAC, exploratory analyses from the data gathered suggested no therapeutic potential associated with NAC. Other post hoc studies have suggested potential therapeutic effects with NAC monotherapy in a subgroup of patients with genotypes for TOLLIP, and indicate a need for further clinical trials in a precise subgroup of patients with IPF stratified by specific genotypes for treatment with NAC using a pharmacogenomic approach [17].…”