pirfenidone - risk of serious liver injury (advice on liver function testing)

Last edited 01/2022 and last reviewed 01/2022

Pirfenidone - risk of serious liver injury; updated advice on liver function testing

Pirfenidone (brand name Esbriet)

  • is an anti-fibrotic and anti-inflammatory agent indicated for the treatment of idiopathic pulmonary fibrosis
  • is known to commonly cause elevation of liver transaminases (ALT and AST), with associated concomitant increases in bilirubin in rare cases
  • a recent European review of safety data identified severe cases of drug-induced liver injury associated with pirfenidone reported post-marketing, including isolated cases with a fatal outcome. Reported events included hepatitis, liver injury, and liver failure
    • reports of serious liver injury are considered to be uncommon (may occur in between 1 in 100 and 1 in 1000 people who take pirfenidone) and the benefit-risk profile of pirfenidone in the approved indications remains favourable
    • aetiology is unclear
      • idiosyncratic reactions may underlie the occurrence of drug-induced liver injury following treatment with pirfenidone

Advice for healthcare professionals:

  • serious cases of drug-induced liver injury, including liver failure, have been reported in patients treated with pirfenidone; cases have been estimated to be of uncommon frequency but 2 reports worldwide had a fatal outcome
  • continue to monitor alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin levels before initiation, at monthly intervals during the first 6 months of treatment and every 3 months thereafter
  • advise patients to seek medical help immediately if they have signs and symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice
  • perform prompt clinical evaluation and measure liver function in patients who report symptoms that may indicate liver injury
  • in the event of significant elevation of liver enzymes or clinical signs and symptoms of liver injury, adjust the dose of pirfenidone or discontinue treatment (see table for new guidance)
  • monitor closely for signs of toxicity if pirfenidone is being used concomitantly with inhibitors of one or more other CYP isoenzymes involved in the metabolism of pirfenidone (see table)
  • report suspected adverse reactions associated with pirfenidone to the Yellow Card scheme


  1. Drug Safety Update volume 14, issue 4: November 2020: 2.