Drug Interaction Report

ADDITIONAL CONTRACEPTION RECOMMENDED: Coadministration with lesinurad may decrease the plasma concentrations of contraceptive hormones and reduce their effectiveness. The interaction has not been evaluated in pharmacokinetic studies. However, lesinurad is a weak inducer of CYP450 3A4, the isoenzyme responsible for the metabolic clearance of contraceptive hormones. Lesinurad has been shown to induce the metabolism of other CYP450 3A4 substrates in interaction studies.

MANAGEMENT: Hormonal contraceptives, including oral, injectable, transdermal, and implantable forms, may not be reliable when used with lesinurad. Female patients of reproductive potential receiving hormonal contraceptives should practice additional methods of contraception during treatment with lesinurad.

Coadministration with grapefruit juice may increase the bioavailability of oral estrogens. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits. In a small, randomized, crossover study, the administration of ethinyl estradiol with grapefruit juice (compared to herbal tea) increased peak plasma drug concentration (Cmax) by 37% and area under the concentration-time curve (AUC) by 28%. Based on these findings, grapefruit juice is unlikely to affect the overall safety profile of ethinyl estradiol. However, as with other drug interactions involving grapefruit juice, the pharmacokinetic alterations are subject to a high degree of interpatient variability. Also, the effect on other estrogens has not been studied.