Seladelpar is a peroxisome proliferator-activated receptor (PPAR)-δ agonist. It is indicated for combination therapy with ursodeoxycholic acid (UDCA) in adult patients who have an inadequate response to UDCA, or as monotherapy in patients who are intolerant to UDCA.

Precautions for Seladelpar Administration

Administration in Special Populations

Patients with renal impairment: No dose adjustment is required for patients with mild to severe renal impairment. However, data on patients with end-stage renal disease (ESRD) are limited, so cautious use is recommended.

Elderly patients: No dose adjustment is needed for patients aged 65 years and older. However, clinical experience with patients aged over 75 years is limited, and enhanced monitoring for adverse reactions is advised.

Pregnancy and lactation: Women of childbearing age should use effective contraceptive measures during treatment and for at least 5 months after the last dose. Lactating women should discontinue breastfeeding.

Dosage Regimen

The recommended dose is 10 mg of seladelpar capsules taken orally once daily, which can be administered with or without food.

The capsules are opaque hard gelatin capsules with a specification of 10 mg, featuring an opaque light gray body and an opaque dark blue cap.

Hepatic Dysfunction

Seladelpar may cause elevations in serum transaminases.

Baseline clinical and laboratory liver assessments should be obtained before treatment, and regular monitoring should be conducted during treatment.

If hepatic function deteriorates or clinical symptoms of hepatitis occur, consideration should be given to interrupting or permanently discontinuing treatment.

Drug Interactions

Special attention should be paid to interactions with OAT3 inhibitors, strong CYP2C9 inhibitors, rifampicin, dual moderate CYP2C9 and moderate-to-strong CYP3A4 inhibitors, BCRP inhibitors, and bile acid sequestrants.

Seladelpar and bile acid sequestrants should be administered at an interval of at least 4 hours.

Treatment Monitoring for Seladelpar

Routine Monitoring Items

Baseline assessment: Includes a comprehensive medical history, physical examination, liver function tests (ALT, AST, total bilirubin), thyroid function tests, renal function tests (creatinine, eGFR), and complete blood count.

Monitoring during treatment: Clinical symptoms and signs should be evaluated every 3–4 weeks, and liver function, renal function, and thyroid function should be rechecked regularly. Special attention should be paid to monitoring changes in ALP levels, as this is a key indicator for assessing therapeutic efficacy.

Adverse Reaction Monitoring

Common adverse reactions: Include headache (8%), abdominal pain (7%), nausea (6%), abdominal distension (6%), and dizziness (5%). Most are mild to moderate and usually do not require treatment discontinuation.

Laboratory abnormalities: Attention should be paid to eGFR decrease (10% of patients experience a decrease of ≥25%), hemoglobin reduction (37%), lymphopenia (32%), AST elevation (30%), ALT elevation (26%), and hyponatremia (24%).

Monitoring for serious adverse reactions: Be alert to immune-mediated adverse reactions such as pneumonia, colitis, hepatitis, endocrinopathies, nephritis, and myocarditis. Relevant symptoms should be promptly evaluated and managed.

Patient Education and Follow-Up

Inform patients to take the medication strictly as prescribed by the doctor and not to adjust the dose on their own. Emphasize the requirement for an interval when using seladelpar with bile acid sequestrants. Remind patients to report any new symptoms or worsening of existing symptoms.

Advise patients to maintain adequate fluid intake and pay attention to personal hygiene to reduce the risk of infection. Recommend regular self-examination for changes in the skin and mucous membranes.

For patients with poor CYP2C9 metabolism who are co-administered with moderate-to-strong CYP3A4 inhibitors, the frequency of adverse reaction monitoring should be increased.