Precautions for Using Pirfenidone

The safety of pirfenidone has been evaluated in more than 1,400 subjects, of whom over 170 received pirfenidone treatment for more than 5 years in clinical trials.

Precautions for Using Pirfenidone

Elevated Liver Enzymes and Drug-Induced Liver Injury (DILI)

Drug-induced liver injury has been observed during pirfenidone treatment. During post-marketing surveillance, both non-severe and severe cases of DILI have been reported, including cases of severe liver injury leading to death. The incidence of elevated ALT and/or AST ≥3 times the upper limit of normal (ULN) was higher in patients receiving pirfenidone (3.7%) compared with those in the placebo group (0.8%). Elevations of ALT and AST ≥3 times the ULN can be reversed by dose adjustment or discontinuation of treatment.

Liver function tests (ALT, AST, and bilirubin) should be performed prior to initiating pirfenidone treatment, once monthly for the first 6 months after treatment initiation, every 3 months thereafter, and as clinically indicated. For patients reporting symptoms suggestive of liver injury (including fatigue, anorexia, right upper quadrant discomfort, dark urine, or jaundice), liver function tests should be performed immediately. Dose adjustment or treatment interruption may be required for elevated liver enzymes.

Photosensitivity or Rashes

The incidence of photosensitivity reactions was higher in patients receiving pirfenidone (9%) compared with those in the placebo group (1%). Patients should avoid or minimize exposure to sunlight and fluorescent lights, regularly use sunscreen (SPF 50 or higher), wear clothing that protects against sun exposure, and avoid concomitant use of medications that may cause photosensitivity. Dose reduction or treatment discontinuation may be required.

Severe Cutaneous Adverse Reactions (SCARs)

During post-marketing surveillance, severe cutaneous adverse reactions have been reported with the use of pirfenidone, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS). If signs or symptoms of SCARs occur, pirfenidone treatment should be interrupted until the cause of the reaction is determined. Consultation with a dermatologist is recommended. Pirfenidone should be permanently discontinued if SCARs are confirmed.

Gastrointestinal Disorders

Patients receiving pirfenidone had higher incidences of nausea, diarrhea, dyspepsia, vomiting, gastroesophageal reflux disease, and abdominal pain. Among patients taking pirfenidone daily, 18.5% required dose reduction or treatment interruption due to gastrointestinal events, compared with 5.8% in the placebo group; 2.2% of daily pirfenidone users discontinued treatment due to gastrointestinal events, versus 1.0% in the placebo group. The most common (>2%) gastrointestinal events leading to dose reduction or treatment interruption were nausea, diarrhea, vomiting, and dyspepsia. Dose adjustment may be required.

Managing Side Effects of Pirfenidone

1.Some patients may experience side effects when taking pirfenidone. Be sure to discuss any potential side effects that may arise with them so that you can help manage these reactions.

2.Inform patients that some side effects may diminish over time.

3.In clinical studies of pirfenidone, some side effects occur shortly after treatment initiation and/or diminish over time:

4.Photosensitivity: In clinical studies, most such reactions occurred within the first 6 months of treatment. Photosensitivity developed in 9% of patients taking pirfenidone (versus 1% of patients not taking pirfenidone).

5.Gastrointestinal discomfort: These issues most commonly occur early in treatment—primarily within the first 3 months—and diminish over time. 2.2% of patients had to discontinue pirfenidone due to gastrointestinal discomfort (versus 1% of patients not taking pirfenidone).