Risk of Drug-Induced Liver Injury associated with the use of Esbriet®

In collaboration with the South African Health Products Regulatory Authority (SAHPRA), Roche Products (Pty) Ltd would like to inform you of the risk of drug-induced liver injury (DILI) associ- ated with use of Esbriet® (pirfenidone):

The Professional Information (PI) and Patient Information Leaflet (PIL) will be updated in line with this new safety information.

Background on the safety concern

Esbriet (pirfenidone) is an anti-fibrotic and anti-inflammatory medicine indicated for the treatment of idiopathic pulmonary fibrosis (IPF).

Recently, serious hepatic adverse events including cases with fatal outcome have been repor- ted in IPF patients treated with pirfenidone. Although the aetiology is unclear, idiosyncratic re- actions may underlie DILI following treatment with pirfenidone. During clinical development, an increased cumulative incidence of hepatic treatment-emergent adverse events was observed in patients treated with pirfenidone (9,5 %) vs. placebo (4,3 %), the majority of which were laboratory abnormalities.

An overview of the available data from clinical trials, post-marketing data and literature showed that the majority of the reported hepatic events occurred within the first months of treatment with pirfenidone.

Advice to healthcare professionals:

  • Hepatic transaminases and bilirubin levels should be investigated before treatment initiation, subsequently at monthly intervals for the first 6 months and then every 3 months thereafter.
  • Prompt clinical evaluation and liver function tests should be performed in patients with symptoms that may indicate DILI such as fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice.
  • If a patient exhibits aminotransferase elevation >3 to <5 x ULN accompanied by hyperbilirubinaemia or clinical signs or symptoms indicative of liver injury, or aminotransferase elevation to ≥5 x ULN, Esbriet® should be permanently discontinued.

Healthcare professionals are urged to report any adverse drug reactions (ADRs) or product quality issues associated with the use of Esbriet® (pirfenidone) to Roche Products (Pty) Ltd, or to SAHPRA via the eReporting link available on the SAHPRA website (www.sahpra.org.za).

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