Drug Interaction Report

GENERALLY AVOID: Patients exposed to photosensitizing agents at the same time as or in the 30 to 90 days following treatment with porfimer may be at an increased risk of a photosensitivity reaction (e.g., erythema, swelling, pruritus, burning sensations, feeling hot, and/or blisters). These agents have each been individually associated with photosensitivity reactions and may have additive effects if used together. Medicinal products with known phototoxic or photoallergic potential include, but are not limited to, hypericin-containing products (e.g., St. John's Wort), griseofulvin, thiazide diuretics, sulfonylureas, phenothiazines, sulfonamides, quinolones, and tetracyclines. Photosensitivity with porfimer is due to residual drug being present in the skin. Porfimer is cleared from a variety of tissues over 40 to 72 hours after treatment, but organs of the reticuloendothelial system (e.g., liver, spleen), skin and the tumor itself retain the drug for a longer period. Patients treated with porfimer will be photosensitive for at least 30 days and possibly up to 90 days or more for patients with hepatic or severe renal dysfunction. In clinical studies of porfimer, photosensitivity reactions occurred in approximately 20% of cancer patients and 69% of high-grade dysplasia in Barrett's esophagus patients.

MANAGEMENT: Use of photosensitizing agents should be avoided for at least 30 days and maybe up to 90 days or longer after porfimer treatment depending on the patient's hepatic function, renal function, and/or ability to tolerate exposure to sunlight. Following treatment with porfimer, patients should follow measures outlined in the product labeling for light and sun exposure. It is important to counsel patients to expose their skin to ambient indoor light as it is not only safe but will help eliminate porfimer through the skin by a process called "photobleaching." Before exposing skin or eyes to direct sunlight or bright indoor light (e.g., examination lamps, dental lamps, operating room lamps, floodlights, halogen lamps, unshaded light bulbs at close proximity, etc.), patients should test for residual photosensitivity as described in porfimer's product labeling.

GENERALLY AVOID: Theoretically, grapefruit and grapefruit juice may increase the plasma concentrations of hydroxychloroquine or chloroquine and the risk of toxicities such as QT interval prolongation and ventricular arrhythmias. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruit. Following coadministration with cimetidine, a weak to moderate CYP450 3A4 inhibitor, a 2-fold increase in chloroquine exposure occurred. Since chloroquine and hydroxychloroquine have similar structures and metabolic elimination pathways, a similar interaction may be observed with hydroxychloroquine. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.

ADJUST DOSING INTERVAL: Administration with food or milk may reduce the incidence of hydroxychloroquine-related gastrointestinal adverse effects.

MANAGEMENT: Although clinical data are lacking, it may be advisable to avoid the consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract during hydroxychloroquine or chloroquine therapy. Hydroxychloroquine should be administered with food or milk to reduce the occurrence of gastrointestinal upset.