Drug Interaction Report

MONITOR: Concomitant use of verteporfin with other known photosensitizing agents may increase the risk of photosensitivity reactions. Examples of 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 will become photosensitive, so they should avoid exposure of unprotected skin, eyes, or other body organs to direct sunlight, bright indoor lights (e.g., tanning salons, bright halogen lights, high power lighting in a surgery operating room), and even prolonged exposure from light-emitting medical devices (e.g., pulse oximeter) for 5 days following the infusion of verteporfin. Patients should be counseled to protect their skin and eyes by wearing protective clothing and dark sunglasses if they must go outdoors in daylight during this time, as UV sunscreens are not effective in protecting against photosensitivity reactions. If emergency surgery is necessary within 48 hours of the verteporfin infusion, as much of the patient's internal tissue as possible should be protected from intense light. Patients should be encouraged to expose their skin to ambient indoor light as it is safe and will help eliminate verteporfin through the skin by a process called "photobleaching."

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.