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Pirfenidone is primarily metabolized (70% to 80%) by CYP1A2, with a minor contribution from other CYP isoenzymes (including CYP2C9, 2C19, 2D6, and 2E1).
Concomitant administration of pirfenidone with fluvoxamine or other strong CYP1A2 inhibitors (e.g., enoxacin) is not recommended, as this will significantly increase pirfenidone exposure. Fluvoxamine or other strong CYP1A2 inhibitors should be discontinued prior to the initiation of pirfenidone and avoided during pirfenidone treatment. If fluvoxamine or other strong CYP1A2 inhibitors are the only available treatment options, a reduction in the pirfenidone dose is recommended. Adverse reactions should be monitored, and discontinuation of pirfenidone should be considered if necessary.
Concomitant administration of pirfenidone with ciprofloxacin (a moderate CYP1A2 inhibitor) will moderately increase pirfenidone exposure. If the use of ciprofloxacin at a dose of 750 mg twice daily cannot be avoided, a reduction in the pirfenidone dose is recommended. Close monitoring of patients is required when ciprofloxacin is used at a dose of 250 mg or 500 mg once daily.
Drugs or drug combinations that act as moderate or strong inhibitors of both CYP1A2 and one or more other CYP isoenzymes involved in pirfenidone metabolism (i.e., CYP2C9, 2C19, 2D6, and 2E1) should be discontinued prior to the initiation of pirfenidone and avoided during pirfenidone treatment.
Concomitant use of pirfenidone with CYP1A2 inducers may decrease pirfenidone exposure, which could result in loss of efficacy. Therefore, strong CYP1A2 inducers should be discontinued prior to the initiation of pirfenidone, and concomitant use of pirfenidone with strong CYP1A2 inducers should be avoided.
FDA，2023.02
