Seladelpar

LIVDELZI is indicated for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults who have had an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA. This indication is approved under accelerated approval based on a reduction of alkaline phosphatase (ALP). Improvement in survival or prevention of liver decompensation events have not been demonstrated. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). LIVDELZI is a peroxisome proliferator-activated receptor (PPAR)-delta agonist indicated for the 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.

Seladelpar is a peroxisome proliferator-activated receptor (PPAR)-delta (δ) agonist. However, the mechanism by which seladelpar exerts its therapeutic effects in patients with PBC is not well understood. Pharmacological activity that is potentially relevant to therapeutic effects includes inhibition of bile acid synthesis through activation of PPARδ, which is a nuclear receptor expressed in most tissues, including the liver. Published studies show that PPARδ activation by seladelpar reduces bile acid synthesis through Fibroblast Growth Factor 21 (FGF21)-dependent downregulation of CYP7A1, the key enzyme for the synthesis of bile acids from cholesterol.

The recommended dosage of LIVDELZI is 10 mg orally once daily. Administer LIVDELZI with or without food. Recommended Dosage and Administration The recommended dosage of LIVDELZI is 10 mg orally once daily.

None. None.

Fractures: Consider the risk of fracture in patients treated with LIVDELZI. Monitor bone health according to current standards of care. Liver Test Abnormalities: Obtain baseline clinical and laboratory liver assessments prior to starting LIVDELZI and monitor during treatment. Interrupt or discontinue LIVDELZI if the liver tests worsen. Biliary Obstruction: Avoid use in patients with complete biliary obstruction. If biliary obstruction is suspected, interrupt LIVDELZI and treat as clinically indicated.

The following clinically significant adverse reactions are described elsewhere in labeling: Fractures Liver Test Abnormalities Most common adverse reactions (reported in ≥5% and higher compared to placebo) are headache, abdominal pain, nausea, abdominal distension, and dizziness.

Probenecid: Avoid concomitant use. Strong CYP2C9 Inhibitors: Monitor for adverse effects. Dual Moderate CYP2C9 and Moderate to Strong CYP3A4 Inhibitors: Monitor for adverse effects. CYP2C9 Poor Metabolizers using Moderate to Strong CYP3A4 Inhibitors: Monitor for adverse effects. Dual or Multiple Clinical Inhibitors of Drug Transporters OATP1B1, OATP1B3, and BCRP: Monitor for adverse effects. Rifampin: Monitor biochemical response (e.g., ALP and bilirubin) when patients initiate rifampin. Bile Acid Sequestrants: Administer at least 4 hours before or 4 hours after taking a bile acid sequestrant, or at as great an interval as possible.

Store at 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F) [s ee USP Controlled Room Temperature]. Dispense only in original container to protect from light.