Elafibranor is a peroxisome proliferator-activated receptor (PPAR) agonist. Approved in the United States in 2024 for the treatment of primary biliary cholangitis (PBC), it is indicated for use in combination with ursodeoxycholic acid (UDCA) in adult patients who have an inadequate response to UDCA, or as monotherapy in patients who are intolerant to UDCA.

How to Use Elafibranor

Dosage Regimen

Standard Dosage: The recommended dose is 80 mg orally once daily, which can be taken with food or on an empty stomach.

Pretreatment Assessment: Before initiating treatment, it is necessary to assess for symptoms of muscle pain or myopathy, and confirm that women of childbearing potential are not pregnant.

Precautions for Concomitant Use

Bile Acid Sequestrants: If concurrent use with bile acid sequestrants (e.g., cholestyramine) is required, the administration of elafibranor and the sequestrant should be separated by at least 4 hours to reduce the risk of drug-drug interactions.

Dosage Adjustment of Elafibranor

Management of Adverse Reactions

Muscle Toxicity: If new or worsening muscle pain, myopathy, or rhabdomyolysis (accompanied by elevated creatine phosphokinase [CPK]) occurs, treatment must be discontinued.

Liver Injury: During treatment, liver function (including alanine transaminase [ALT], aspartate transaminase [AST], and bilirubin) should be monitored regularly. If liver function indicators deteriorate or symptoms of hepatitis (such as jaundice, right upper abdominal pain) appear, medication should be suspended.

Allergic Reactions: Severe allergic reactions require permanent discontinuation of the drug; for mild to moderate allergic reactions, the drug can be suspended and symptomatic treatment administered.

Adjustment for Drug-Drug Interactions

Statins: When used concomitantly with statins, close monitoring for muscle symptoms is necessary, and treatment should be discontinued if needed.

Rifampicin: Rifampicin may decrease the plasma concentration of elafibranor, so it is necessary to monitor alkaline phosphatase (ALP) and bilirubin levels.

Use of Elafibranor in Special Populations

Patients with Hepatic or Renal Impairment

Hepatic Impairment: No dosage adjustment is required for patients with mild hepatic impairment (Child-Pugh Class A); elafibranor is contraindicated in patients with moderate to severe hepatic impairment (Child-Pugh Class B/C) or decompensated cirrhosis.

Renal Impairment: No dosage adjustment is needed for patients with mild to severe renal impairment (estimated glomerular filtration rate [eGFR] ≥ 15 mL/min). Data on the use of elafibranor in patients with end-stage renal disease (eGFR < 15 mL/min) are limited, so caution is advised.

Pregnancy and Lactation

Pregnancy: Animal studies have shown fetal toxicity (e.g., fetal death, developmental delay), so elafibranor is contraindicated in pregnant women. Before starting treatment, it is necessary to confirm that the patient is not pregnant, and effective contraceptive measures (non-hormonal or barrier methods) should be used during treatment.

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

Elderly and Pediatric Patients

Elderly Patients (≥ 65 Years Old): No dosage adjustment is required, but enhanced monitoring for adverse reactions is recommended in patients aged 75 years and older.

Pediatric Patients: The efficacy of elafibranor in pediatric patients under 18 years of age has not been established, and its use is contraindicated in this population.