Seladelpar is a novel peroxisome proliferator-activated receptor delta (PPAR-δ) agonist indicated for the treatment of adult patients with primary biliary cholangitis (PBC) who have an inadequate response to ursodeoxycholic acid (UDCA) or are intolerant to UDCA.

What are the Precautions for Using Seladelpar?

Applicable Populations and Usage Restrictions

Seladelpar is mainly used in combination with UDCA for adult PBC patients with an inadequate response to UDCA, or as monotherapy for patients intolerant to UDCA.

It is not recommended for patients with existing or progressive decompensated cirrhosis (e.g., those with ascites, variceal bleeding, or hepatic encephalopathy).

Discontinuation of Seladelpar should be considered if patients progress to moderate or severe hepatic insufficiency (Child-Pugh Class B or C) during treatment.

Hepatic Function Abnormalities

Seladelpar has been shown to cause significant elevation of serum transaminases when administered at high doses (5 to 20 times the recommended dosage).

Regular clinical and laboratory liver assessments must be performed prior to the initiation of treatment and during the treatment course.

Treatment should be immediately interrupted if liver function test parameters (ALT, AST, total bilirubin, alkaline phosphatase) deteriorate, or if clinical signs of hepatitis develop (e.g., jaundice, right upper quadrant pain, eosinophilia).

Permanent discontinuation of the drug should be considered if hepatic function deteriorates again after reinitiating treatment.

Drug Interactions

Avoid concomitant use: Co-administration with organic anion transporter 3 (OAT3) inhibitors (e.g., probenecid) or strong CYP2C9 inhibitors should be avoided, as these drugs can significantly increase the plasma concentration of Seladelpar.

Use with caution and monitor: Co-administration with rifampicin (an enzyme inducer) may reduce the efficacy of Seladelpar; biochemical indicators such as alkaline phosphatase (ALP) and bilirubin should be monitored.

Close monitoring for adverse reactions is required when Seladelpar is used in combination with moderate CYP2C9 inhibitors plus moderate-to-strong CYP3A4 inhibitors, or with breast cancer resistance protein (BCRP) inhibitors (e.g., cyclosporine).

For CYP2C9 poor metabolizers (individuals with reduced metabolic capacity due to genetic variations), concomitant use with moderate-to-strong CYP3A4 inhibitors will further increase drug exposure, and more frequent monitoring for adverse reactions is necessary.

Medication Monitoring for Seladelpar

Laboratory Tests

Complete liver function panel: Including ALT, AST, alkaline phosphatase (ALP), and total bilirubin (TB).

Renal function assessment: Measure serum creatinine and calculate the estimated glomerular filtration rate (eGFR).

Bone health assessment: Consider bone mineral density testing based on the patient’s individual risk profile.

Regular Monitoring During Treatment

Liver function: Monitor ALT, AST, ALP, and TB regularly after the start of treatment (e.g., once a month, with the interval appropriately extended after the condition stabilizes).

Renal function: Monitor serum creatinine and eGFR on a regular basis.

Fracture signs: Inform patients of the risk of fractures and advise them to promptly report any new-onset pain, limited mobility, or suspected fractures. Assess bone health regularly in accordance with clinical guidelines.

Adverse reaction monitoring: Pay attention to the most common adverse reactions (e.g., headache, abdominal pain, nausea, abdominal distension, dizziness) and manage them in a timely manner. Meanwhile, be alert to less common reactions such as rash, alopecia, and anemia.