elafibranor (Iqirvo)

Indications

• treatment of primary biliary cholangitis combination with ursodeoxycholic acid
  • monotherapy in patients unable to tolerate ursodeoxycholic acid

Contraindications

• pregnancy
• not recommended in patients who have or develop decompensated cirrhosis

Dosage

• 80 mg PO QD with or without food
• 80 mg Oral Tablet
• no specific geriatric dosing recommended
• no dosage adjustment for renal failure

Adverse effects

• myalgia, myopathy, rhabdomyolysis
• increased risk of fractures
• fetal toxicity
• > 5%
  • weight gain/ weight loss, diarrhea, abdominal pain, nausea/vomiting, arthralgia, constipation, GERD, dry mouth, rash

Drug interactions

• weak CYP3A4 inducer

Mechanism of action

• peroxisome proliferator-activated receptor agonist (PPAR agonist)
  • elafibranor & its active metabolite activate PPAR-alpha, PPAR-gamma, & PPAR-delta
  • reduces serum alkaline phosphatase
  • signaling pathway for PPAR-delta includes FGF21-dependent downregulation of CYP7A1, the key enzyme for synthesis of bile acids from cholesterol

* improvement in survival or prevention of liver failure has not been demonstrated

More general terms

• receptor agonist
• gastrointestinal agent

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=9864881
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=9904854
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=75988815