Overview
11 DESCRIPTION LIVDELZI capsules contain seladelpar lysine, a peroxisome proliferator-activated receptor (PPAR)-delta (δ) agonist. Seladelpar is a single enantiomer of the R-configuration and is present as a lysine dihydrate salt. Seladelpar lysine dihydrate is a white to off-white powder with a molecular formula of C 21 H 23 F 3 O 5 S ∙C 6 H 14 N 2 O 2 ∙2H 2 O and a molecular weight of 626.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 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. 12.
Indications
- 1 INDICATIONS AND USAGE 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) [see Clinical Studies (14) ] . Improvement in survival or prevention of liver decompensation events have not been demonstrated.
Common Doses
- 10 mg
Dosage
2 DOSAGE AND ADMINISTRATION The recommended dosage of LIVDELZI is 10 mg orally once daily. Administer LIVDELZI with or without food. ( 2.1 ) 2.1 Recommended Dosage and Administration The recommended dosage of LIVDELZI is 10 mg orally once daily. Administer LIVDELZI with or without food [see Clinical Pharmacology (12.3) ] . 2.2 Administration Modification for Bile Acid Sequestrants Administer LIVDELZI at least 4 hours before or 4 hours after taking bile acid sequestrants, or at as great an interval as possible [see Drug Interactions (7.1) ] .
Contraindications
- 4 CONTRAINDICATIONS None. None.
Side Effects
- 6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in labeling: Fractures [see Warnings and Precautions (5.1) ] Liver Test Abnormalities [see Warnings and Precautions (5.2) ] Most common adverse reactions (reported in ≥5% and higher compared to placebo) are headache, abdominal pain, nausea, abdominal distension, and dizziness. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Gilead Sciences, Inc. at 1-800-GILEAD-5 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.
Interactions
- 7 DRUG INTERACTIONS Probenecid : Avoid concomitant use. ( 7.1 ) Strong CYP2C9 Inhibitors : Monitor for adverse effects. ( 7.1 ) Dual Moderate CYP2C9 and Moderate to Strong CYP3A4 Inhibitors : Monitor for adverse effects. ( 7.1 ) CYP2C9 Poor Metabolizers using Moderate to Strong CYP3A4 Inhibitors : Monitor for adverse effects. ( 7.1 ) Dual or Multiple Clinical Inhibitors of Drug Transporters OATP1B1, OATP1B3, and BCRP : Monitor for adverse effects. ( 7.1 ) Rifampin : Monitor biochemical response (e.g., ALP and bilirubin) when patients initiate rifampin. ( 7.