Summary of pirfenidone-related adverse event (AE) management strategies
| Pirfenidone-related AEs | Prevention | Management |
| General | Slower titration schedule | Dose reductions Dose interruptions |
| Gastrointestinal | Taking pirfenidone with a substantial meal, specifically the full dose at the end of a meal or spreading out during a meal | Dose reductions/interruptions with a slow titration back to full dose Reduce the morning dose if nausea is experienced at that time of day Proton-pump inhibitors |
| Skin | Continuous skin protection with clothing and broad-spectrum SPF 50 sunscreen Avoid use of other medications associated with phototoxicity | With severe phototoxicity, treat with steroids or silver sulfadiazine Dose reductions for a rash followed by discontinuation if the rash persists and a slow titration back to full dose Discontinuation if an allergic reaction to pirfenidone occurs |
| Liver | Perform AST, ALT and bilirubin tests before pirfenidone initiation Monitor at monthly intervals for the first 6 months and then every 3 months thereafter | If AST and ALT elevations (>3× to ≤5× ULN) occur without symptoms or hyperbilirubinaemia, the dose may be reduced or interrupted until values return to normal If AST and ALT elevations (>3× to ≤5× ULN) are accompanied by hyperbilirubinaemia, permanently discontinue pirfenidone If patients exhibit >5× ULN, permanently discontinue pirfenidone |
| Important considerations with drug–drug interactions | For strong CYP1A2 inhibitors, such as fluvoxamine and enoxacin, pirfenidone should be reduced to 267 mg three times daily (801 mg·day−1) For moderate CYP1A2 inhibitors, such as ciprofloxacin at a dosage of 750 mg twice daily, pirfenidone should be reduced to 534 mg three times daily (1602 mg·day−1) |
SPF: sun protection factor; AST: aspartate transaminase; ALT: alanine transaminase; ULN: upper limit of normal; CYP1A2: cytochrome P450 1A2.