SELADELPAR LYSINE Drug Interactions: What You Need to Know

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

Sequestrants : Administer at least 4 hours before or 4 hours after taking a bile acid sequestrant, or at as great an interval as possible. ( 7.1 )

7.1 Effect of Other Drugs on LIVDELZI Table 2 includes clinically significant drug interactions affecting LIVDELZI.

Table

2: Clinically Significant Interactions Affecting LIVDELZI Concomitant Drug or Class Potential Effect on Seladelpar Exposure ↑ = Increase, ↓ = Decrease.

Clinical Intervention

Probenecid ↑ seladelpar Avoid concomitant administration of LIVDELZI with probenecid. Strong CYP2C9 Inhibitors ↑ seladelpar Monitor patients for adverse effects during concomitant use of LIVDELZI with strong CYP2C9 inhibitors.

Dual

Moderate CYP2C9 and Moderate or Strong CYP3A4 Inhibitors (e.g., fluconazole) ↑ seladelpar Monitor patients for adverse effects during concomitant use of LIVDELZI with drugs that are dual moderate CYP2C9 and moderate or strong CYP3A4 inhibitors. CYP2C9 Poor Metabolizers Using Moderate or Strong CYP3A4 Inhibitors ↑ seladelpar Monitor patients who are CYP2C9 poor metabolizers for adverse effects during concomitant use of LIVDELZI with moderate or strong CYP3A4 inhibitor. Dual or Multiple Clinical Inhibitors of Drug Transporters OATP1B1, OATP1B3, and BCRP (e.g, cyclosporine) ↑ seladelpar Monitor patients for adverse effects during concomitant use of LIVDELZI with dual or multiple clinical inhibitors of drug transporters OATP1B1, OATP1B3, and BCRP. Rifampin ↓ seladelpar Concomitant use of LIVDELZI with rifampin, an inducer of metabolizing enzymes, may result in delayed or suboptimal LIVDELZI biochemical response. Monitor the biochemical response (e.g., ALP and bilirubin) when patients initiate rifampin during LIVDELZI treatment.

Bile Acid

Sequestrants ↓ seladelpar Bile acid sequestrants may interfere with the action of LIVDELZI by reducing its absorption and systemic exposure, which may reduce LIVDELZI efficacy. Administer LIVDELZI at least 4 hours before or 4 hours after taking a bile acid sequestrant, or at as great an interval as possible [see Dosage and Administration (2.2) ] .

None. None.

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 <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> . 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 <span class="opacity-50 text-xs">[see Overdosage (10) ]</span> . 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.