Drug interactions of Elafibranor

1. Effects of Elafibranor on Other Drugs

Hormonal Contraceptives

Clinical Impact: Elafibranor is a weak CYP3A4 inducer [see Clinical Pharmacology (12.3)]. Concomitant administration of elafibranor with hormonal contraceptives (e.g., birth control pills, skin patches, implants) may decrease the systemic exposure of progestogens and ethinyl estradiol (CYP3A4 substrates), which could result in contraceptive failure and/or increased breakthrough bleeding.

Interventions: During elafibranor treatment and for at least 3 weeks after the last dose, patients using hormonal contraceptives should switch to an effective non-hormonal contraceptive method or add a barrier contraceptive method to their hormonal contraception.

HMG-CoA Reductase Inhibitors (Statins)

Clinical Impact: Elevated creatine phosphokinase (CPK) levels and/or myalgia have occurred in patients receiving elafibranor monotherapy. Concomitant use of elafibranor with HMG-CoA reductase inhibitors (statins) that carry a risk of myalgia may increase the risk of myopathy, though the mechanism has not been fully elucidated.

Interventions: Monitor for signs and symptoms of muscle injury. Consider regular assessments (clinical examination, CPK measurement) during treatment. If new or worsening muscle pain or myopathy occurs, interrupt elafibranor treatment.

2. Effects of Other Drugs on Elafibranor

Rifampin

Clinical Impact: Concomitant administration of elafibranor with rifampin (a metabolic enzyme inducer) may decrease the systemic exposure of elafibranor and its active metabolite by increasing metabolism, which could lead to delayed or suboptimal biochemical response.

Interventions: When a patient starts taking rifampin during elafibranor treatment, monitor for biochemical response (e.g., alkaline phosphatase [ALP] and bilirubin levels).

Bile Acid Sequestrants

Clinical Impact: Bile acid sequestrants may interfere with the effects of elafibranor by reducing its absorption and systemic exposure, which could decrease the efficacy of elafibranor.

Interventions: Administer elafibranor at least 4 hours before or at least 4 hours after taking bile acid sequestrants, or allow for the longest possible interval between administrations if feasible.

FDA，2024.06