Livdelzi

Clinical summary

Indications and usage 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. 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. 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). ( 1 ) Limitations of Use Use of LIVDELZI is not recommended in patients who have or develop decompensated cirrhosis (e.g., ascites, variceal bleeding, hepatic encephalopathy). ( 8.7 ) Limitations of Use Use of LIVDELZI is not recommended in patients who have or develop decompensated cirrhosis (e.g., ascites, variceal bleeding, hepatic encephalopathy) [see Use in Specific Populations (8.7) ] . Dosage and administration 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) ] . Warnings and cautions 5 WARNINGS AND PRECAUTIONS Fractures : Consider the risk of fracture in patients treated with LIVDELZI. Monitor bone health according to current standards of care. ( 5.1 ) 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. ( 5.2 ) Biliary Obstruction : Avoid use in patients with complete biliary obstruction. If biliary obstruction is suspected, interrupt LIVDELZI and treat as clinically indicated. ( 5.3 ) 5.1 Fractures Fractures occurred in 4% of LIVDELZI-treated patients compared to no placebo-treated patients [see Adverse Reactions (6.1) ] . Consider the risk of fracture in the care of patients treated with LIVDELZI and monitor bone health according to current standards of care. 5.2 Liver Test Abnormalities LIVDELZI has been associated with dose-related increases in serum transaminase (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) levels greater than 3-times upper limit of normal (ULN) in PBC patients receiving 50 mg once daily (5-times higher than the recommended dosage) and 200 mg (20-times higher than the recommended dosage) once daily. Transaminase levels returned to pretreatment levels upon LIVDELZI discontinuation. LIVDELZI 10 mg once daily did not show a similar pattern for increases in transaminase levels [see Overdosage (10) ] . Obtain baseline clinical and laboratory assessments at treatment initiation with LIVDELZI and monitor thereafter according to routine patient management. Interrupt LIVDELZI treatment if the liver tests (ALT, AST, total bilirubin [TB], and/or alkaline phosphatase [ALP]) worsen, or the patient develops signs and symptoms consistent with clinical hepatitis (e.g., jaundice, right upper quadrant pain, eosinophilia). Consider permanent discontinuation if liver tests worsen after restarting LIVDELZI. 5.3 Biliary Obstruction Avoid use of LIVDELZI in patients with complete biliary obstruction. If biliary obstruction is suspected, interrupt LIVDELZI and treat as clinically indicated. Drug 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. ( 7.1 ) Bile Acid Se