Drug Interaction Report

MONITOR: Concomitant use of aminolevulinate topical preparations with other known photosensitizing agents may enhance the phototoxic reaction to photodynamic therapy. These agents have each been individually associated with photosensitivity reactions and may have additive effects if administered concurrently. Medicinal products with known phototoxic or photoallergic potential include fluoroquinolones, phenothiazines, retinoids, sulfonamides, sulfonylureas, tetracyclines, thiazide diuretics, griseofulvin, and hypericin extracts (e.g., St John's Wort).

MANAGEMENT: Caution is advised and pharmacologic response to photodynamic therapy should be carefully monitored if concomitant use of other photosensitizing agents cannot be avoided. Patients should be advised to avoid exposure of treated areas to sunlight or bright indoor lights (e.g., examination lamps, operating room lamps, tanning beds, lights at close proximity) during the period between application of aminolevulinic acid or methyl aminolevulinate and photoactivation, and for 48 hours post-illumination. As sunscreen is not effective in protecting treated areas of skin, patients should be counseled to wear protective apparel, such as a wide-brimmed hat, long sleeve shirt, and gloves to protect themselves. Concomitant use with other topical medicinal products should be avoided. Some authorities recommend avoiding use of hypericin-containing products for 2 weeks prior to treatment with topical aminolevulinic acid.

ADJUST DOSING INTERVAL: Food significantly slows the rate but only modestly reduces the extent of absorption of pirfenidone. In healthy, older adult volunteers aged 50 to 66 years, administration of a single 801 mg oral dose of pirfenidone in the fed state resulted in an approximately 50% reduction in peak plasma concentration (Cmax) and a 15% to 20% reduction in systemic exposure (AUC) compared to administration in the fasted state. Median time to reach peak concentration (Tmax) increased from 0.5 hours to 3 hours with food. Less nausea and dizziness were observed in fed subjects compared to fasted subjects.

GENERALLY AVOID: Consumption of grapefruit juice is associated with inhibition of CYP450 1A2 and may increase the plasma concentrations of pirfenidone, which is primarily metabolized by the isoenzyme.

GENERALLY AVOID: Cigarette smoking may reduce pirfenidone exposure due to induction of CYP450 1A2, the isoenzyme primarily responsible for the metabolic clearance of pirfenidone. Following a single 801 mg oral dose of pirfenidone in 25 smokers and 25 healthy nonsmokers, the Cmax and AUC of pirfenidone in smokers were 68% and 46% of those in nonsmokers, respectively.

MANAGEMENT: Pirfenidone should be administered with food to reduce the likelihood of dizziness and gastrointestinal side effects such as nausea, diarrhea, dyspepsia, and vomiting. Patients who experience intolerance to therapy due to these adverse events should be reminded to take pirfenidone with food. If symptoms do not improve, or they worsen in severity, a dosage reduction or discontinuation of therapy may be warranted. Patients should be advised to avoid consumption of grapefruit and grapefruit juice during treatment with pirfenidone. Cigarette smoking should also be avoided during therapy to prevent reduced exposure to pirfenidone.