Drug Interaction Report

ADDITIONAL CONTRACEPTION RECOMMENDED: Coadministration with elafibranor may decrease the plasma concentrations and efficacy of hormonal contraceptives. The proposed mechanism is elafibranor-mediated induction of CYP450 3A4, the isoenzyme primarily responsible for the metabolic clearance of hormonal contraceptives. Coadministration of elafibranor (80 mg at steady state) with the CYP450 3A4 substrate simvastatin (20 mg single dose) decreased the peak plasma concentration (Cmax) and systemic exposure (AUC) of simvastatin's active metabolite (simvastatin beta-hydroxyacid) by 26% and 32%, respectively. In addition, elafibranor can cause fetal harm when administered to pregnant women.

MANAGEMENT: Women using hormonal contraceptives (including oral, injectable, transdermal, and implantable forms) should be advised of the risk of breakthrough bleeding and unintended pregnancy during coadministration with elafibranor. Because use of elafibranor may cause embryo-fetal harm, it is particularly important that patients not become pregnant during treatment. Therefore, hormonal contraceptives should not be used as the sole method of birth control in women of childbearing potential treated with elafibranor. Female patients of reproductive potential should use a highly effective, non-hormonal method of contraception during treatment and for at least 3 weeks after treatment. Input from a gynecologist or similar expert on adequate contraception, including emergency contraception, should be sought as needed. Intrauterine systems are unlikely to be significantly affected because of their local action.