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DOI: 10.1055/s-0036-1572009
Safety and tolerability of N-acetylcysteine (NAC) with pirfenidone in IPF: PANORAMA
Background: In Europe, NAC and pirfenidone are often combined in IPF clinical practice but the safety of this combination is unknown.
Method: In this randomised, double-blind, placebo (PBO)-controlled, phase 2 study, European patients on a stable dose of 1602 – 2403 mg/day pirfenidone were randomised to 24 weeks of NAC (1800 mg/day) or PBO. Adverse events (AEs) and functional parameters (spirometry, 6MWD, and SOBQ) were collected up to 28 days after end of treatment.
Results: 122 patients (98.4% White; 85.2% male; mean age 67.1 years) were randomised (NAC: 60; PBO: 62). Mean ± SD baseline % FVC and % DLCO were NAC: 68.8 ± 10.1 and 42.3 ± 10.2; PBO: 69.3 ± 11.1 and 42.2 ± 9.3 (FVC< 50% or DLCO < 35%: NAC: 28.3%; PBO: 29.0%). More patients had cardiac comorbidities in the NAC vs. PBO arm at baseline (31.7% vs. 17.7%, respectively).
AEs were reported by 76.7% (NAC) and 80.6% (PBO) of the patients; 5 patients discontinued due to AEs (NAC: 4; PBO: 1). Serious AEs (NAC: 3; PBO: 4) and deaths (NAC: 1; PBO: 3) were unrelated to treatment. Common AEs were balanced between arms except photosensitivity and upper abdominal pain (table). Cardiac AEs were reported by 3 patients (NAC: 1; PBO: 2). A potentially negative effect of NAC on FVC volume was observed.
n (%) |
NAC+pirfenidone (N = 60) |
PBO+pirfenidone (N = 62) |
Cough |
8 (13.3) |
7 (11.3) |
Photosensitivity |
8 (13.3) |
1 (1.6) |
Nasopharyngitis |
7 (11.7) |
7 (11.3) |
Diarrhoea |
6 (10.0) |
9 (14.5) |
Nausea |
4 (6.7) |
5 (8.1) |
Dyspnoea |
4 (6.7) |
4 (6.5) |
Bronchitis |
4 (6.7) |
3 (4.8) |
Upper abdominal pain |
4 (6.7) |
0 |
Conclusion: In PANORAMA, the combination of NAC and pirfenidone was generally well-tolerated.