Elafibranor for Primary Biliary Cholangitis: Indication, Dosing, and Safety Overview

Indication​

Elafibranor is indicated for the treatment of primary biliary cholangitis (PBC) in adults. It may be used in combination with ursodeoxycholic acid (UDCA) in patients who have an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA.

Dosage and Administration​

The recommended dose is 80 mg taken orally once daily. Tablets should be swallowed whole with water. If a dose is missed, it should be skipped and the next dose taken at the scheduled time; doubling the dose is not permitted.

No dose adjustment is required for elderly patients (>65 years) or those with renal impairment. Use in children (<18 years) is not recommended due to lack of data. For patients with mild (Child‑Pugh A) or moderate (Child‑Pugh B) hepatic impairment, no dose adjustment is needed. Use in severe hepatic impairment (Child‑Pugh C) is not recommended because safety and efficacy have not been established.

Use in Special Populations​

Women of childbearing potential must use effective contraception during treatment and for at least 3 weeks after the last dose. Pregnancy must be excluded before starting therapy. If pregnancy occurs during treatment, the drug should be discontinued immediately. Animal studies have shown fetal loss, malformations, stillbirth, and perinatal mortality at clinically relevant exposures; therefore, Elafibranor is contraindicated during pregnancy.

It is unknown whether Elafibranor is excreted in human milk. Adverse effects on offspring were observed in animal studies. Breastfeeding should be avoided during treatment and for 3 weeks after the last dose.

Warnings and Precautions​

Elevations in liver enzymes (transaminases, bilirubin) may occur. Liver function should be assessed before treatment and monitored routinely during therapy. If symptoms such as jaundice, abdominal pain, nausea, vomiting, fatigue, anorexia, or dark urine appear, the cause should be investigated and temporary discontinuation considered.

Elafibranor may cause elevations in creatine phosphokinase (CPK). CPK levels should be measured before treatment and periodically thereafter. Particular caution is advised when used concomitantly with HMG‑CoA reductase inhibitors (statins); regular CPK monitoring is recommended. If unexplained muscle pain, soreness, or weakness occurs, the cause should be evaluated and dose interruption considered.

Based on animal data, Elafibranor carries a risk of teratogenicity and reduced fetal viability. It is contraindicated in women of childbearing potential who are not using effective contraception.

Each tablet contains less than 1 mmol (23 mg) of sodium, making it essentially “sodium‑free.”

Drug Interactions​

No specific drug interactions have been identified to date.

Adverse Reactions​

The most common adverse reactions (incidence >10% and higher than placebo) were abdominal pain (11.1% vs 5.7%), diarrhea (11.1% vs 9.4%), nausea (11.1% vs 5.7%), and vomiting (11.1% vs 1.9%). These events were generally mild to moderate in severity, occurred early in treatment, and resolved spontaneously within days to weeks without requiring dose adjustment or supportive care.

Headache occurred in 8.3% of patients (placebo 11.3%). Clinically significant CPK elevation leading to discontinuation occurred in 3.7% of patients (including two cases >5× ULN), all of which were mild to moderate and non‑serious. Mean CPK values at baseline and week 52 were within normal limits in both groups.

Contraindications​

Hypersensitivity to elafibranor or any of its excipients. Known or suspected pregnancy. Women of childbearing potential not using effective contraception.

Storage​

Store at room temperature; no refrigeration required. Keep out of reach of children. Dispose of unused medication according to local medical waste regulations; do not discard into sewage or household trash.