These Highlights Do Not Include All The Information Needed To Use Livdelzi Safely And Effectively. See Full Prescribing Information For Livdelzi.

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)].

Storage and Handling

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) [see USP Controlled Room Temperature].

Dispense only in original container to protect from light.

PBC patients who received 5-times the recommended dosage or 20-times the recommended dosage of LIVDELZI experienced an increase in liver transaminases, muscle pain, and/or elevations in creatine phosphokinase, which resolved upon LIVDELZI discontinuation [see Warnings and Precautions (5.2)].

There is no specific treatment for overdose with LIVDELZI. General supportive care of the patient is indicated, as appropriate. If indicated, elimination of unabsorbed drug should be achieved by emesis or gastric lavage; usual precautions should be observed to maintain the airway. Because seladelpar is highly bound to plasma proteins, hemodialysis should not be considered.

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.

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 C₂₁H₂₃F₃O₅S ∙C₆H₁₄N₂O₂ ∙2H₂O and a molecular weight of 626.7 g/mol. Its solubility in water is pH dependent. It is slightly soluble at low pH and very soluble at high pH. The chemical name for seladelpar lysine dihydrate is 2-[4-[[(2R)-2-ethoxy-3-[4-(trifluoromethyl)phenoxy]propyl]thio]-2-methylphenoxy]acetic acid, lysine dihydrate, and the chemical structure is:

LIVDELZI (seladelpar) capsules are supplied in a 10 mg strength for oral administration. Each capsule contains 14.1 mg of seladelpar lysine and the following inactive ingredients: butylated hydroxytoluene, colloidal silicon dioxide, croscarmellose sodium, magnesium stearate, mannitol, microcrystalline cellulose, and hard gelatin shells.

The light gray opaque (body)/dark blue opaque (cap) capsule shells contain gelatin, titanium dioxide, black iron oxide, yellow iron oxide, red iron oxide and the colorant FD&C Blue #2.

The safety and effectiveness of LIVDELZI in pediatric patients have not been established.

Of the 128 LIVDELZI-treated patients in Trial 1, 29 (23%) patients were 65 years of age and older and 2 (2%) were 75 years of age and older. No overall differences in safety or effectiveness were observed between patients 65 to 75 years of age and younger adult patients. No dosage adjustment for patients 65 years of age and older is necessary.

Clinical studies of LIVDELZI did not include sufficient numbers of patients 75 years of age and older to determine whether they respond differently from younger adult patients. Because of limited clinical experience with LIVDELZI in patients older than 75 years old, closer monitoring of adverse events in patients older than 75 years is recommended [see Clinical Pharmacology (12.3)].

The efficacy of LIVDELZI was evaluated in Trial 1 (NCT04620733), a 12-month, randomized, double-blind, placebo-controlled trial. The trial included 193 adult patients with PBC with an inadequate response or intolerance to UDCA. Patients were included in the trial if their ALP was greater than or equal to 1.67-times the ULN and total bilirubin (TB) was less than or equal to 2-times the ULN. Patients were excluded from the trial if they had other chronic liver diseases, clinically important hepatic decompensation including portal hypertension with complications, or cirrhosis with complications (e.g., Model for End Stage Liver Disease [MELD] score of 12 or greater, known esophageal varices or history of variceal bleeds, history of hepatorenal syndrome).

Patients were randomized to receive LIVDELZI 10 mg (N=128) or placebo (N=65) once daily for 12 months. LIVDELZI or placebo was administered in combination with UDCA in 181 (94%) patients during the trial, or as a monotherapy in 12 (6%) patients who were unable to tolerate UDCA.

None.

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)]

• 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)

The recommended dosage in patients with mild, moderate, or severe renal impairment is the same as in patients with normal renal function. Patients with end-stage renal disease on dialysis have not been studied [see Clinical Pharmacology (12.3)].

Following a single dose administration, seladelpar systemic exposure increased dose-proportionally from 2 mg (0.2 times the recommended dosage) to 15 mg (1.5 times the recommended dosage) and greater than dose proportionally at higher doses. For a dose increase from 10 mg to 200 mg (20 times the recommended dosage), mean C_max and mean AUC for seladelpar increased 70-fold and 27-fold, respectively.

Following once daily dosing, seladelpar steady-state was achieved by day 4 and AUC increase was less than 30%. In PBC patients, median (CV) C_max and AUC for seladelpar was 90.5 (42.5%) ng/mL and 817 (44%) ng*h/mL, respectively at steady state following once daily dosing of 10 mg.

CYP2C9 activity is decreased in individuals with genetic variants such as CYP2C9*2 and CYP2C9*3. Compared to CYP2C9 normal metabolizers (*1/*1, n=84) after a single dose of seladelpar 1 mg to 15 mg, dose-normalized AUC_0–inf was 48% higher in CYP2C9 poor metabolizers (*2/*3, n=2) and 24% higher in CYP2C9 intermediate metabolizers (*1/*2, *1/*8, *1/*3, *2/*2, n=28). Dose-normalized C_max was similar for CYP2C9 normal, intermediate, and poor metabolizers. Seladelpar pharmacokinetics was not evaluated in patients who are CYP2C9 poor metabolizers with two no function alleles (e.g., *3/*3). CYP2C9 poor metabolizers may have increased AUC when seladelpar is used concomitantly with a moderate to strong CYP3A4 inhibitor [see Drug Interactions (7.1), Use in Specific Populations (8.8)].

The prevalence of CYP2C9 poor metabolizers is approximately 2 to 3% in White populations, 0.5 to 4% in Asian populations, and <1% in African American populations. Additional decreased or nonfunctional alleles (e.g., *5, *6, *11) are more prevalent in African American populations.

No dosage adjustment is recommended for PBC patients with mild hepatic impairment (Child-Pugh A) [see Clinical Pharmacology (12.3)].

The safety and efficacy of LIVDELZI in patients with decompensated cirrhosis have not been established. Use of LIVDELZI is not recommended in patients who have or develop decompensated cirrhosis (e.g., ascites, variceal bleeding, hepatic encephalopathy).

Monitor patients with cirrhosis for evidence of decompensation. Consider discontinuing LIVDELZI if the patient progresses to moderate or severe hepatic impairment (Child-Pugh B or C).

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).

Avoid use of LIVDELZI in patients with complete biliary obstruction. If biliary obstruction is suspected, interrupt LIVDELZI and treat as clinically indicated.

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.

• 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)

The recommended dosage of LIVDELZI is 10 mg orally once daily. Administer LIVDELZI with or without food. (2.1)

Capsules: 10 mg, opaque, hard gelatin capsules, size 1, with light gray opaque body and a dark blue opaque cap, printed with "CBAY" on the cap and "10" on the body.

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.

Monitor CYP2C9 poor metabolizers who receive a concomitant moderate to strong CYP3A4 inhibitor more frequently for adverse reactions.

Seladelpar is a CYP2C9 and CYP3A4 substrate. Increased seladelpar AUC is expected in patients who are CYP2C9 poor metabolizers with concomitant use of a moderate to strong CYP3A4 inhibitor [see Drug Interactions (7.1), Clinical Pharmacology (12.5)].

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In Trial 1, 193 patients were randomized to receive either LIVDELZI 10 mg (N=128) or placebo (N=65) once daily for 12 months [see Clinical Studies (14)]. LIVDELZI or placebo was administered in combination with UDCA in 94% of patients and as monotherapy in 6% of patients who were unable to tolerate UDCA.

Hepatic Impairment: Monitor patients with cirrhosis for evidence of decompensation. Consider discontinuation if patient progresses to moderate or severe hepatic impairment (Child-Pugh B or C). (8.7)

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Table 2 includes clinically significant drug interactions affecting LIVDELZI.

The recommended dosage of LIVDELZI is 10 mg orally once daily. Administer LIVDELZI with or without food [see Clinical Pharmacology (12.3)].

In a 2-year study in CD-1 mice, seladelpar produced an increased incidence of lens cataracts at 5 mg/kg/day in both sexes (6-times and 19-times the recommended dose in male and female mice, respectively, based on AUC). In a 2-year study in Sprague-Dawley rats, seladelpar produced an increased incidence of cornea inflammation at 10 mg/kg/day (14-times the recommended dose based on AUC) and cornea mineralization at 30 mg/kg/day (79-times the recommended dose based on AUC), with both effects observed in males only. The incidence of cornea inflammation was not increased in male rats at 3 mg/kg/day (5-times the recommended dose based on AUC).

NDC 61958-3301-1

Livdelzi^®

seladelpar

10 mg

For Oral Use Only

30 capsules

Rx only

GILEAD

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)].

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)].

Storage and Handling

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) [see USP Controlled Room Temperature].

Dispense only in original container to protect from light.

PBC patients who received 5-times the recommended dosage or 20-times the recommended dosage of LIVDELZI experienced an increase in liver transaminases, muscle pain, and/or elevations in creatine phosphokinase, which resolved upon LIVDELZI discontinuation [see Warnings and Precautions (5.2)].

There is no specific treatment for overdose with LIVDELZI. General supportive care of the patient is indicated, as appropriate. If indicated, elimination of unabsorbed drug should be achieved by emesis or gastric lavage; usual precautions should be observed to maintain the airway. Because seladelpar is highly bound to plasma proteins, hemodialysis should not be considered.

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.

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 C₂₁H₂₃F₃O₅S ∙C₆H₁₄N₂O₂ ∙2H₂O and a molecular weight of 626.7 g/mol. Its solubility in water is pH dependent. It is slightly soluble at low pH and very soluble at high pH. The chemical name for seladelpar lysine dihydrate is 2-[4-[[(2R)-2-ethoxy-3-[4-(trifluoromethyl)phenoxy]propyl]thio]-2-methylphenoxy]acetic acid, lysine dihydrate, and the chemical structure is:

LIVDELZI (seladelpar) capsules are supplied in a 10 mg strength for oral administration. Each capsule contains 14.1 mg of seladelpar lysine and the following inactive ingredients: butylated hydroxytoluene, colloidal silicon dioxide, croscarmellose sodium, magnesium stearate, mannitol, microcrystalline cellulose, and hard gelatin shells.

The light gray opaque (body)/dark blue opaque (cap) capsule shells contain gelatin, titanium dioxide, black iron oxide, yellow iron oxide, red iron oxide and the colorant FD&C Blue #2.

The safety and effectiveness of LIVDELZI in pediatric patients have not been established.

Of the 128 LIVDELZI-treated patients in Trial 1, 29 (23%) patients were 65 years of age and older and 2 (2%) were 75 years of age and older. No overall differences in safety or effectiveness were observed between patients 65 to 75 years of age and younger adult patients. No dosage adjustment for patients 65 years of age and older is necessary.

Clinical studies of LIVDELZI did not include sufficient numbers of patients 75 years of age and older to determine whether they respond differently from younger adult patients. Because of limited clinical experience with LIVDELZI in patients older than 75 years old, closer monitoring of adverse events in patients older than 75 years is recommended [see Clinical Pharmacology (12.3)].

The efficacy of LIVDELZI was evaluated in Trial 1 (NCT04620733), a 12-month, randomized, double-blind, placebo-controlled trial. The trial included 193 adult patients with PBC with an inadequate response or intolerance to UDCA. Patients were included in the trial if their ALP was greater than or equal to 1.67-times the ULN and total bilirubin (TB) was less than or equal to 2-times the ULN. Patients were excluded from the trial if they had other chronic liver diseases, clinically important hepatic decompensation including portal hypertension with complications, or cirrhosis with complications (e.g., Model for End Stage Liver Disease [MELD] score of 12 or greater, known esophageal varices or history of variceal bleeds, history of hepatorenal syndrome).

Patients were randomized to receive LIVDELZI 10 mg (N=128) or placebo (N=65) once daily for 12 months. LIVDELZI or placebo was administered in combination with UDCA in 181 (94%) patients during the trial, or as a monotherapy in 12 (6%) patients who were unable to tolerate UDCA.

None.

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)]

• 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)

The recommended dosage in patients with mild, moderate, or severe renal impairment is the same as in patients with normal renal function. Patients with end-stage renal disease on dialysis have not been studied [see Clinical Pharmacology (12.3)].

Following a single dose administration, seladelpar systemic exposure increased dose-proportionally from 2 mg (0.2 times the recommended dosage) to 15 mg (1.5 times the recommended dosage) and greater than dose proportionally at higher doses. For a dose increase from 10 mg to 200 mg (20 times the recommended dosage), mean C_max and mean AUC for seladelpar increased 70-fold and 27-fold, respectively.

Following once daily dosing, seladelpar steady-state was achieved by day 4 and AUC increase was less than 30%. In PBC patients, median (CV) C_max and AUC for seladelpar was 90.5 (42.5%) ng/mL and 817 (44%) ng*h/mL, respectively at steady state following once daily dosing of 10 mg.

CYP2C9 activity is decreased in individuals with genetic variants such as CYP2C9*2 and CYP2C9*3. Compared to CYP2C9 normal metabolizers (*1/*1, n=84) after a single dose of seladelpar 1 mg to 15 mg, dose-normalized AUC_0–inf was 48% higher in CYP2C9 poor metabolizers (*2/*3, n=2) and 24% higher in CYP2C9 intermediate metabolizers (*1/*2, *1/*8, *1/*3, *2/*2, n=28). Dose-normalized C_max was similar for CYP2C9 normal, intermediate, and poor metabolizers. Seladelpar pharmacokinetics was not evaluated in patients who are CYP2C9 poor metabolizers with two no function alleles (e.g., *3/*3). CYP2C9 poor metabolizers may have increased AUC when seladelpar is used concomitantly with a moderate to strong CYP3A4 inhibitor [see Drug Interactions (7.1), Use in Specific Populations (8.8)].

The prevalence of CYP2C9 poor metabolizers is approximately 2 to 3% in White populations, 0.5 to 4% in Asian populations, and <1% in African American populations. Additional decreased or nonfunctional alleles (e.g., *5, *6, *11) are more prevalent in African American populations.

No dosage adjustment is recommended for PBC patients with mild hepatic impairment (Child-Pugh A) [see Clinical Pharmacology (12.3)].

The safety and efficacy of LIVDELZI in patients with decompensated cirrhosis have not been established. Use of LIVDELZI is not recommended in patients who have or develop decompensated cirrhosis (e.g., ascites, variceal bleeding, hepatic encephalopathy).

Monitor patients with cirrhosis for evidence of decompensation. Consider discontinuing LIVDELZI if the patient progresses to moderate or severe hepatic impairment (Child-Pugh B or C).

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).

Avoid use of LIVDELZI in patients with complete biliary obstruction. If biliary obstruction is suspected, interrupt LIVDELZI and treat as clinically indicated.

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.

• 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)

The recommended dosage of LIVDELZI is 10 mg orally once daily. Administer LIVDELZI with or without food. (2.1)

Capsules: 10 mg, opaque, hard gelatin capsules, size 1, with light gray opaque body and a dark blue opaque cap, printed with "CBAY" on the cap and "10" on the body.

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.

Monitor CYP2C9 poor metabolizers who receive a concomitant moderate to strong CYP3A4 inhibitor more frequently for adverse reactions.

Seladelpar is a CYP2C9 and CYP3A4 substrate. Increased seladelpar AUC is expected in patients who are CYP2C9 poor metabolizers with concomitant use of a moderate to strong CYP3A4 inhibitor [see Drug Interactions (7.1), Clinical Pharmacology (12.5)].

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In Trial 1, 193 patients were randomized to receive either LIVDELZI 10 mg (N=128) or placebo (N=65) once daily for 12 months [see Clinical Studies (14)]. LIVDELZI or placebo was administered in combination with UDCA in 94% of patients and as monotherapy in 6% of patients who were unable to tolerate UDCA.

Hepatic Impairment: Monitor patients with cirrhosis for evidence of decompensation. Consider discontinuation if patient progresses to moderate or severe hepatic impairment (Child-Pugh B or C). (8.7)

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Table 2 includes clinically significant drug interactions affecting LIVDELZI.

The recommended dosage of LIVDELZI is 10 mg orally once daily. Administer LIVDELZI with or without food [see Clinical Pharmacology (12.3)].

In a 2-year study in CD-1 mice, seladelpar produced an increased incidence of lens cataracts at 5 mg/kg/day in both sexes (6-times and 19-times the recommended dose in male and female mice, respectively, based on AUC). In a 2-year study in Sprague-Dawley rats, seladelpar produced an increased incidence of cornea inflammation at 10 mg/kg/day (14-times the recommended dose based on AUC) and cornea mineralization at 30 mg/kg/day (79-times the recommended dose based on AUC), with both effects observed in males only. The incidence of cornea inflammation was not increased in male rats at 3 mg/kg/day (5-times the recommended dose based on AUC).

NDC 61958-3301-1

Livdelzi^®

seladelpar

10 mg

For Oral Use Only

30 capsules

Rx only

GILEAD

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)].