SELADELPAR CAP,ORAL

Clinical Criteria Summary

Decompensated cirrhosis (e.g., Child-Pugh Class B or C) or a prior decompensation event, including hepatorenal syndrome, MELD ≥ 12, hepatocellular carcinoma, hepatic encephalopathy, international normalized ratio (INR) > 1.3, platelet count < 150 x 103/microL
Compensated cirrhosis with evidence of portal hypertension (e.g., ascites, gastroesophageal varices, persistent thrombocytopenia)
Complete biliary obstruction
Severely advanced primary biliary cholangitis (PBC) defined as total bilirubin greater than upper limit of normal (ULN) and albumin less than the lower limit of normal
Alanine aminotransferase (ALT and/or aspartate aminotransferase (AST) > 3 times ULN
Other chronic liver conditions, such as primary sclerosing cholangitis, autoimmune hepatitis, metabolic dysfunction-associated steatohepatitis (MASH), and alpha-1 antitrypsin deficiency
Concomitant OAT3 inhibitors or strong CYP2C9 inhibitors

Prescribed and monitored by a VA or VA Community Care hepatologist or locally designated expert in PBC
Documented diagnosis of PBC without cirrhosis or PBC with compensated cirrhosis and no evidence of portal hypertension
Tried ursodiol monotherapy (unless medically inadvisable) and had intolerance or inadequate response after 12 months (stable dose for at least 3 months at 13–15 mg/kg/day)
Tried elafibranor (unless medically inadvisable) and had intolerance or inadequate response after 13 weeks

For patients who are pregnant or plan to become pregnant: Counseling provided on potential risks vs benefits of treatment
For patients who are lactating / providing breastmilk to an infant or plan to do so: Counseling provided on potential risks vs benefits of treatment

Treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults who have an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA.
Accelerated approval based on reduction of alkaline phosphatase (ALP); improvement in survival or prevention of liver decompensation events has not been demonstrated. Continued approval contingent upon verification and description of clinical benefit in confirmatory trials.

Pretreatment: Clinical and laboratory liver assessments (ALT, AST, total bilirubin, alkaline phosphatase).
Monitoring during therapy: Clinical and laboratory liver assessments as per routine patient care.

Complete biliary obstruction.
Concomitant OAT3 inhibitors (e.g., probenecid, rifampicin).
Concomitant strong CYP2C9 inhibitors (e.g., fluconazole, fluoxetine, ticlopidine).
Decompensated cirrhosis (e.g., ascites, variceal bleeding, hepatic encephalopathy).

Consider discontinuing therapy for: Worsening of liver tests; Progression to moderate or severe (Child-Pugh B or C) hepatic impairment.
Interrupt therapy for: Worsening of liver tests or development of clinical hepatitis (e.g., jaundice, right upper quadrant pain, eosinophilia); Suspected biliary obstruction.
Other warnings/precautions include bone fractures and liver test abnormalities (observed at higher than recommended doses [50 mg and 200 mg daily]).

Pregnancy: Insufficient human data; animal studies showed reduction of fetal growth and pre-weaning survival without malformations or adverse embryofetal survival. No clinical recommendations provided.
Lactation: Insufficient human data; weigh benefits vs risks.
Geriatric (≥65 years): No overall differences in safety or effectiveness compared to younger adults; no dosage adjustment necessary.
Renal Impairment: No dosage adjustment for mild, moderate, or severe renal impairment; not studied in patients with end-stage renal disease on dialysis.
Hepatic Impairment: Mild (Child-Pugh A) requires no dosage adjustment; moderate or severe (Child-Pugh B or C) requires consideration of discontinuing therapy.

Second-line therapy after UDCA.
An adequate trial of UDCA is defined as ≥ 1 year at 13–15 mg/kg/d, with ≥ 3 months at a stable dosage.