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

Adverse Reactions of Sladelpar

Common Adverse Reactions

Headache: Occurs in approximately 8% of patients.

Abdominal pain: Occurs in approximately 7% of patients.

Nausea: Occurs in approximately 6% of patients.

Abdominal distension: Occurs in approximately 6% of patients.

Dizziness: Occurs in approximately 5% of patients.

Serious Adverse Reactions

Hepatic Function Abnormalities

Clinical and laboratory liver assessments should be performed regularly before the initiation of treatment and during treatment.

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

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

Biliary Obstruction

Sladelpar should be avoided in patients with complete biliary obstruction.

If biliary obstruction is suspected (e.g., right upper quadrant pain, jaundice), treatment should be interrupted and appropriate clinical management should be initiated.

Precautions for Sladelpar

Contraindicated Populations and Hepatic Function Considerations

Contraindicated in patients with decompensated cirrhosis: Not recommended for patients with existing or developing decompensated cirrhosis (e.g., ascites, variceal bleeding, hepatic encephalopathy).

Hepatic function monitoring: For patients with cirrhosis, signs of decompensation should be monitored. Discontinuation of Sladelpar should be considered if patients progress to moderate or severe liver impairment (Child-Pugh Class B or C).

Drug Interactions

Avoid concomitant use: Co-administration with OAT3 inhibitors (e.g., probenecid) and strong CYP2C9 inhibitors should be avoided, as these drugs may increase the plasma concentration of Sladelpar.

Use with caution and monitor:

Rifampicin: May decrease the plasma concentration of Sladelpar and affect its efficacy. Biochemical indicators such as alkaline phosphatase and bilirubin should be monitored when starting co-administration.

Dual inhibitors: Close monitoring for adverse reactions is required when Sladelpar is used concomitantly with moderate CYP2C9 inhibitors combined with moderate-to-strong CYP3A4 inhibitors.

BCRP inhibitors: Drugs such as cyclosporine may increase Sladelpar exposure, requiring close monitoring.

CYP2C9 poor metabolizers: The risk of adverse reactions may increase when moderate-to-strong CYP3A4 inhibitors are used concomitantly; more frequent monitoring is needed.

Dosing interval: When used with bile acid sequestrants (e.g., certain lipid-lowering drugs), Sladelpar should be administered at least 4 hours before or after taking the sequestrant, or the interval should be extended as much as possible to avoid affecting absorption.