Table 3.
Strategy for the prevention and management of adverse events related to antifibrotic therapy.
| Pirfenidone | Nintedanib | ||||
|---|---|---|---|---|---|
| Type of AE | Gastrointestinal | Cutaneous | Hepatic | Gastrointestinal | Hepatic |
| AE prevention | Take pirfenidone with plenty of food. Titration for 4 weeks instead of 2. |
Avoid exposure to sunlight or intense artificial light. Applications of complete protection cream every 2 h. Use of sunglasses and protective clothing. Avoid use of phototoxic drugs. |
Monitor liver bio-chemistry (ALT, AST and bilirubin) at baseline, monthly for 6 months and then every 3 months. | Take nintedanib with food. | Monitor liver biochemistry (ALT, AST, bilirubin) at baseline, monthly for the first 3 months and then periodically. |
| AE treatment | Prokinetics and proton pump inhibitors. | Steroids or sulphadiazine if severe phototoxicity. | Antidiarrheal (loperamide). Antiemetics. Proper hydration. |
||
| Dose reduction | Reduce doses to 1–2 capsules 2–3 times daily. Make the reduction at the time point in which the AE is most pronounced. | Reduce dose to 1 capsule every 8 h for one week. | If AST and ALT are increased (>3 to 5× ULN) or there are symptoms or hyperbilirubinemia, reduce doses until values recovery. | Reduce to 100 mg/12 h if persistent diarrhoea. | If AST/ALT are increased (>3 to 5× ULN) reduce dosage until values recovery. Then, re-scale doses up to max tolerated. |
| Dose interruption | If AE persists, temporarily discontinue therapy until symptom resolution. | Discontinue doses for 14 days if rash persists and subsequently re-escalate. Do not re-escalate if the rash does not subside. |
Permanently discontinue if the elevations of AST and ALT are accompanied by symptoms of hyperbilirubinemia or if the elevations are >5× ULN. | Stop doses if severe diarrhoea for one week. Discontinue permanently if there is no improvement. |
Permanently stop doses if elevations are accompanied by severe symptoms of liver damage. |
Abbreviations: AE: adverse events; ALT: alanine amino-transferase; AST: aspartate amino transferase; max.: maximum; ULN: upper limit of normality.