Pirfenidone (Esbriet)

Indications

CAPACITY 004 and 006 Trials (2011) [MEDLINE]
- Main Findings: pirfenidone reduced the decline in FVC
- Adverse Effects
  - Gastrointestinal Adverse Effects: nausea/vomiting, dyspepsia, anorexia
  - Other Adverse Effects: photosensitivity, rash, dizziness
ASCEND Trial (2014) [MEDLINE]
- Trial: randomized, multi-center, placebo-controlled phase 3 trial (n = 555), 52 week duration, pirfenidone dose: 2403 mg qday
- Main Findings
  - 47.9% decrease in patients who had at least a 10% decline in FVC or who died
  - 132.5% increase in patients with no decline in FVC
  - Improvement in progression-free survival
  - No change in all-cause mortality, death from IPF, or dyspnea scores
    - In pooled analysis with data from prior trials: decreased all-cause mortality and death from IPF
  - Decreased decline in 6-minute walk distance
- Adverse Effects
  - Gastrointestinal Adverse Effects: elevated LFT’s, nausea/vomiting, anorexia, weight loss, GERD, dyspepsia
  - Dermatologic Adverse Effects: rash
  - Other Adverse Effects: insomnia

Decrease in Fibroblast Proliferation and Synthesis of Fibrosis-Associated Proteins/Cytokines
Decrease in Transforming Growth Factor-Beta (TGF-Beta)-Induced Formation of Extracellular Matrix (Collagen)
Blocks Platelet-Derived Growth Factor-Induced Proliferative Effects

Hepatic: predominantly via CYP1A2 (to a lesser extent via CYP2C9, CYP2C19, CYP2D6, and CYP2E1)
- Elimination Half-Life: 3 hrs

PO Dosing
- Take with food
Hepatic Dose Adjustment
- Nt recommended for patients with liver disease
Renal Dose Adjustment
- Not recommended for patients with end-stage renal disease (or on hemodialsis)

Hepatic
- Child-Pugh Class A and B (Mild-Moderate Impairment): use with caution
- Child-Pugh Class C (Moderate Impairment): not recommended
Renal: use with caution
- CrCl <30 mL/min or End-Stage Renal Disease Requiring Hemodialysis: not recommended

Angioedema (see Angioedema, [[Angioedema]]): cases have been reported (occurs in <1% of cases)

Abdominal Pain (see Abdominal Pain, [[Abdominal Pain]]): occurs in 5-24% of cases
Anorexia (see Anorexia, [[Anorexia]]): occurs in 9-13% of cases
Diarrhea (see Diarrhea, [[Diarrhea]])
Dyspepsia (see Dyspepsia, [[Dyspepsia]])
Elevated Liver Function Tests (LFT’s) (see Drug-Induced Hepatotoxicity, [[Drug-Induced Hepatotoxicity]])
Gastroesophageal Reflux Disease (GERD) (see Gastroesophageal Reflux Disease, [[Gastroesophageal Reflux Disease]])
Nausea/Vomiting (see Nausea and Vomiting, [[Nausea and Vomiting]]): nausea occurs in 33-36% of cases
Weight Loss (se Weight Loss, [[Weight Loss]])

Pirfenidone inhibits PDGF isoforms in bleomycin hamster model of lung fibrosis at the translational level. Am J Physiol 1999;276:L311-L318
Effects of pirfenidone on transforming growth factor-beta gene expression at the transcriptional level in bleomycin hamster model of lung fibrosis. J Pharmacol Exp Ther 1999;291:367-373
Effects of pirfenidone on procollagen gene expression at the transcriptional level in bleomycin hamster model of lung fibrosis. J Pharmacol Exp Ther 1999;289:211-218
Combined corticosteroid and cyclophosphamide therapy does not alter survival in idiopathic pulmonary fibrosis. Chest 2004;125(6): 2169-2174 [MEDLINE]
CAPACITY 004 + 006 Trials: Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials. Lancet. 2011 May 21;377(9779):1760-9. doi: 10.1016/S0140-6736(11)60405-4. Epub 2011 May 13 [MEDLINE]
ASCEND Trial: A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2014 May 29;370(22):2083-92 [MEDLINE]