Drug Interactions between FemSeven Sequi Phase I and pirfenidone

Consumer information for this interaction is not currently available.

MONITOR: Coadministration with inhibitors of CYP450 1A2 may increase the plasma concentrations of pirfenidone, which is primarily (70% to 80%) metabolized by the isoenzyme. Other CYP450 isoenzymes also contribute to a minor extent, including CYP450 2C9, 2C19, 2D6, and 2E1. Concomitant inhibition of one or more of these isoenzymes in addition to CYP450 1A2 is expected to further increase the magnitude of interaction. In 27 healthy study subjects, administration of a single 801 mg dose of pirfenidone on day 6 of treatment with the moderate CYP450 1A2 inhibitor ciprofloxacin (750 mg twice daily) increased pirfenidone peak plasma concentration (Cmax) and systemic exposure (AUC) by 23% and 81%, respectively. In 25 healthy nonsmokers and 25 smokers who were administered a single dose of pirfenidone with the potent CYP450 1A2 inhibitor fluvoxamine (50 mg at bedtime for 3 days; 50 mg twice a day for 3 days; then 50 mg in the morning and 100 mg at bedtime for 4 days), pirfenidone AUC increased approximately 4-fold in nonsmoking subjects and 7-fold in smoking subjects. Fluvoxamine also inhibits CYP450 2C9, 2C19 and 2D6, although the extent to which these effects contribute to the interaction has not been established.

MANAGEMENT: Caution is advised when pirfenidone is used concomitantly with CYP450 1A2 inhibitors. Patients should be closely monitored for adverse reactions such as hepatotoxicity, photosensitivity, rash, nausea, diarrhea, vomiting and dyspepsia, and consideration be given to dosage reduction, brief interruption, or permanent discontinuation of pirfenidone if clinically necessary in accordance with the product labeling. Coadministration of pirfenidone with CYP450 1A2 inhibitors in addition to inhibitors of other CYP450 isoenzymes involved in the metabolism of pirfenidone should be avoided, including significant inhibitors of CYP450 2C9 (e.g., amiodarone, fluconazole, imatinib, gemfibrozil, miconazole), 2C19 (e.g., chloramphenicol, cimetidine, esomeprazole, fluconazole, lansoprazole, omeprazole), and/or 2D6 (e.g., bupropion, cinacalcet, fluoxetine, paroxetine, quinidine, terbinafine).