Elafibranor is a peroxisome proliferator-activated receptor (PPAR) agonist. In 2024, it was approved in the United States for the treatment of primary biliary cholangitis (PBC).

What are the side effects of Elafibranor?

Common Side Effects

Metabolism-related: Weight gain (23%), weight loss (5%)

Digestive system: Diarrhea (11%), abdominal pain (11%), nausea (11%), vomiting (11%), constipation (8%), gastroesophageal reflux disease (6%), dry mouth (5%)

Musculoskeletal system: Arthralgia (8%), muscle injury (7%), fracture (6%)

Skin reactions: Rash (5%)

Serious Side Effects Requiring Vigilance for Elafibranor

Muscle Injury and Rhabdomyolysis

Risk manifestations: Myalgia (4%), elevated creatine kinase (CPK) (4%). One patient with baseline cirrhosis who was also using statins developed rhabdomyolysis accompanied by acute kidney injury.

Countermeasures: Evaluate symptoms of myalgia/myopathy before medication administration, and regularly monitor CPK levels during treatment. If new or worsening muscle pain occurs, discontinue the medication immediately.

Fetal Toxicity

Animal data: Administration of elafibranor to pregnant rats can cause fetal death, weight loss, and blue-black discoloration of the tail.

Contraindication: Elafibranor is contraindicated in pregnant women. Women of childbearing age must confirm a negative pregnancy test before using the medication, and adopt effective contraceptive measures (non-hormonal or barrier methods) during treatment and for 3 weeks after discontinuing the medication.

Allergic Reactions

Manifestations: Rash, pruritus, facial swelling, etc., which mostly occur 2-30 days after medication administration.

Management: Severe reactions require permanent discontinuation of the medication; mild to moderate reactions require interruption of treatment and anti-allergic management.

Precautions for Elafibranor Administration

Contraindications

Contraindicated in patients allergic to the active ingredient or excipients.

Not recommended for patients with decompensated cirrhosis (e.g., ascites, variceal bleeding, hepatic encephalopathy).

Medication Use in Special Populations

Hepatic impairment: No dose adjustment is required for patients with Child-Pugh Class A hepatic impairment; for patients with Child-Pugh Class B/C hepatic impairment, signs of decompensation should be monitored, and the medication should be discontinued if necessary.

Lactation: Breastfeeding is prohibited during treatment and for 3 weeks after the last dose.

Elderly patients (≥75 years old): Enhanced monitoring of adverse reactions is required.

Drug Interactions

Statins: Concurrent use increases the risk of myopathy, so close monitoring of muscle symptoms is necessary.

Rifampicin: May reduce the efficacy of elafibranor, so monitoring of alkaline phosphatase (ALP)/bilirubin levels is required.

Hormonal contraceptives: May reduce contraceptive efficacy; it is recommended to switch to non-hormonal contraception or add a barrier method.