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Liver function tests should be performed before initiating pirfenidone treatment.
The recommended daily maintenance dose of pirfenidone is 801 mg three times a day, totaling 2403 mg per day. The dose should be taken with meals at the same time each day.
After starting treatment, the dosage should be gradually escalated over 14 days to the full daily dose of 2403 mg, as specified below:
Days 1–7: 267 mg three times a day (801 mg per day)
Days 8–14: 534 mg three times a day (1602 mg per day)
From Day 15 onwards: 801 mg three times a day (2403 mg per day)
Doses exceeding 2403 mg per day are not recommended for any patient. Patients should not take a double dose to make up for a missed one. The daily dosage should not be administered more than three times.
If a patient misses pirfenidone doses for 14 days or longer, treatment should be restarted using the initial 2-week dose escalation schedule until the full maintenance dose is reached. For treatment interruptions of less than 14 days, the dose prior to interruption may be resumed.
If a patient develops significant adverse reactions (e.g., gastrointestinal reactions, photosensitivity reactions or rash, severe cutaneous adverse reactions [SCAR]), temporary dose reduction or treatment interruption of pirfenidone should be considered to allow symptom resolution. If SCAR is confirmed, pirfenidone should be permanently discontinued.
Dosage Adjustment for Elevated Liver Enzymes
Dose adjustment or treatment interruption may also be required if elevations in liver enzymes and bilirubin occur.
For elevated liver enzymes, adjust the dosage as follows:
If a patient develops ALT and/or AST levels > 3× but ≤ 5× the upper limit of normal (ULN) without symptoms or hyperbilirubinemia after initiating pirfenidone: Discontinue confounding medications, rule out other causes, and monitor the patient closely. Repeat liver function tests as clinically indicated.
The full daily dose may be continued if clinically appropriate, or the dose may be reduced or treatment interrupted (e.g., until liver function tests return to the normal range), followed by gradual escalation back to the full dose based on tolerability.
If a patient develops ALT and/or AST levels > 3× but ≤ 5× ULN accompanied by symptoms or hyperbilirubinemia: Permanently discontinue pirfenidone; the patient should not be rechallenged with pirfenidone.
If a patient develops ALT and/or AST levels > 5× ULN: Permanently discontinue pirfenidone; the patient should not be rechallenged with pirfenidone.
Strong CYP1A2 Inhibitors (e.g., fluvoxamine, enoxacin)
Reduce the pirfenidone dose to 267 mg three times a day (801 mg per day).
Moderate CYP1A2 Inhibitors (e.g., ciprofloxacin)
When ciprofloxacin is administered at a dose of 750 mg twice daily, reduce the pirfenidone dose to 534 mg three times a day (1602 mg per day).
FDA，2023.02
