Seladelpar (Livdelzi®): A Comprehensive Monograph on a Novel PPARδ Agonist for the Treatment of Primary Biliary Cholangitis

Executive Summary

Seladelpar, marketed under the brand name Livdelzi®, is a first-in-class, orally administered, small-molecule drug representing a significant advancement in the treatment of primary biliary cholangitis (PBC). As a potent and highly selective agonist of the peroxisome proliferator-activated receptor delta (PPARδ), seladelpar offers a novel mechanism of action for a patient population with limited therapeutic options. In 2024, it received accelerated approval from the U.S. Food and Drug Administration (FDA) and a positive opinion for conditional marketing authorisation from the European Medicines Agency (EMA) for the treatment of PBC in adults who have an inadequate response to or are intolerant of the first-line therapy, ursodeoxycholic acid (UDCA).

The therapeutic efficacy of seladelpar is rooted in its ability to modulate critical metabolic and inflammatory pathways. By activating PPARδ, it potently inhibits bile acid synthesis through the downregulation of the rate-limiting enzyme CYP7A1, thereby reducing cholestatic liver injury. A key differentiating feature of seladelpar is its dual benefit: pivotal Phase 3 clinical trials have demonstrated not only a statistically significant improvement in biochemical markers of liver health, including a high rate of alkaline phosphatase (ALP) normalization, but also a significant reduction in moderate-to-severe pruritus (itching), a common and debilitating symptom of PBC. This unique clinical profile contrasts with other second-line therapies that may improve liver biochemistry but can exacerbate pruritus.

The robust clinical data and promising therapeutic profile culminated in the strategic acquisition of its developer, CymaBay Therapeutics, by Gilead Sciences for $4.3 billion. This transaction positions Livdelzi as a cornerstone asset within Gilead's extensive liver disease portfolio and signals strong commercial expectations. As a new entrant into the second-line PBC market, seladelpar is poised to shift the treatment paradigm, enabling a more holistic management approach that targets both disease progression and patient quality of life. Continued approval is contingent upon the verification of clinical benefit in ongoing long-term outcomes studies.

Drug Identity and Physicochemical Characteristics

Unambiguous identification of an active pharmaceutical ingredient is fundamental to its research, development, and clinical use. Seladelpar is a single R-configuration enantiomer, a structural characteristic that contributes to its specific pharmacological activity.[1] The drug is commercially formulated and administered as a lysine dihydrate salt to optimize its pharmaceutical properties.[3]

Nomenclature and Identifiers

Seladelpar is known by several names and is cataloged across numerous international chemical and pharmacological databases.

• Generic Name: Seladelpar [1]
• Brand Names:
• Livdelzi® (United States) [3]
• Lyvdelzi® (European Union; renamed from Seladelpar Gilead) [3]
• Developmental Codes: MBX-8025, RWJ-800025 [3]
• Salt Form: Seladelpar lysine dihydrate [3]

Chemical Structure and Formula

The chemical identity of seladelpar is defined by its specific molecular structure and composition.

• IUPAC Name: 2-propyl]sulfanyl-2-methylphenoxy]acetic acid [2]
• Molecular Formula (Free Acid): C21​H23​F3​O5​S [3]
• Molar Mass (Free Acid): 444.47 g·mol⁻¹ [3]
• Molecular Formula (Lysine Dihydrate Salt): C21​H23​F3​O5​S⋅C6​H14​N2​O2​⋅2H2​O [4]
• Molar Mass (Lysine Dihydrate Salt): 626.68 g·mol⁻¹ [4]
• Structural Representations (Free Acid):
• SMILES: CCO[C@H](COC1=CC=C(C=C1)C(F)(F)F)CSC2=CC(=C(C=C2)OCC(=O)O)C [3]
• InChI: InChI=1S/C21H23F3O5S/c1-3-27-17(11-28-16-6-4-15(5-7-16)21(22,23,24)13-30-18-8-9-19(14(2)10-18)29-12-20(25)26/h4-10,17H,3,11-13H2,1-2H3,(H,25,26)/t17-/m1/s1 [3]
• InChIKey: JWHYSEDOYMYMNM-QGZVFWFLSA-N [2]

Formulation and Presentation

Livdelzi is supplied for oral administration.

• Dosage Form: 10 mg oral capsules.[5]
• Appearance: The capsules are described as opaque, hard gelatin, size 1, with a light gray opaque body and a dark blue opaque cap, printed with “CBAY” on the cap and “10” on the body.[11]

The key identifiers and physicochemical properties of seladelpar are consolidated in Table 1.

Table 1: Key Identifiers and Physicochemical Properties of Seladelpar

Property	Value	Source(s)
Generic Name	Seladelpar	1
Brand Name (US)	Livdelzi®	3
Drug Type	Small Molecule	1
IUPAC Name	2-propyl]sulfanyl-2-methylphenoxy]acetic acid	3
CAS Number (Free Acid)	851528-79-5	3
DrugBank ID	DB12390	1
PubChem CID	11236126	2
Molecular Formula (Free Acid)	C21​H23​F3​O5​S	2
Molar Mass (Free Acid)	444.47 g·mol⁻¹	3
Marketed Form	Lysine dihydrate salt	3

Pharmacological Profile: Mechanism of Action and Disposition

Seladelpar's clinical effects are a direct result of its specific molecular interactions and its behavior within the human body. Its profile is defined by its potent and selective pharmacodynamic activity and predictable pharmacokinetic properties.

Pharmacodynamics (Mechanism of Action)

Seladelpar is a potent and selective agonist of the Peroxisome Proliferator-Activated Receptor delta (PPARδ), a nuclear hormone receptor that plays a crucial role in regulating gene transcription.[3] PPARs exist as three isotypes (α, δ, and γ), each with distinct tissue distribution and target genes involved in energy homeostasis and metabolic function.[1] Seladelpar's therapeutic utility in PBC stems from its high affinity and selectivity for the PPARδ isotype.

Pharmacological studies have quantified this selectivity, demonstrating a half-maximal effective concentration (EC50​) of 2 nM for human PPARδ. The drug is over 750-fold more selective for PPARδ than for PPARα and over 2500-fold more selective than for PPARγ.[15] This high degree of selectivity is a critical pharmacological feature. Unlike less specific PPAR agonists, such as fibrates, which activate multiple isotypes, seladelpar's targeted action on PPARδ allows for precise engagement of pathways relevant to PBC pathology while minimizing off-target effects associated with PPARα or PPARγ activation. This "cleaner" mechanism is believed to be a primary driver of its favorable efficacy and safety profile at the approved therapeutic dose.

Upon activation, PPARδ forms a heterodimer with the retinoid X receptor (RXR) and binds to specific DNA sequences, thereby regulating the transcription of target genes in various liver cells, including hepatocytes, cholangiocytes, Kupffer cells, and stellate cells.[13] The downstream consequences of this gene regulation directly address the pathophysiology of PBC:

1. Bile Acid Homeostasis: The principal therapeutic effect of seladelpar is the potent inhibition of bile acid synthesis. In patients with PBC, the accumulation of toxic bile acids drives cholestatic liver injury.[1] Seladelpar activation of PPARδ leads to the transcriptional repression of the gene encoding cholesterol 7 alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in the classic pathway of bile acid synthesis.[13] By reducing the activity of this enzyme, seladelpar effectively decreases the total bile acid pool, alleviating the cholestatic burden on the liver.
2. Anti-inflammatory Effects and Pruritus Reduction: Chronic inflammation is a hallmark of PBC. Preclinical models have shown that PPARδ activation exerts anti-inflammatory effects.[13] This is clinically manifested in seladelpar's unique ability to significantly reduce pruritus, a debilitating symptom driven by both cholestasis and inflammatory mediators. Clinical data has directly linked seladelpar treatment to a reduction in circulating levels of interleukin-31 (IL-31), a cytokine strongly implicated in the sensation of itch.[3] This suggests that seladelpar's anti-pruritic action is not merely a secondary consequence of improved cholestasis but is also mediated by a direct immunomodulatory effect on pro-inflammatory and pro-pruritic pathways. This dual action on both the underlying cause (cholestasis) and a key symptom mediator (IL-31) likely explains its pronounced clinical benefit on pruritus.
3. Metabolic and Anti-fibrotic Potential: Preclinical studies have also indicated that seladelpar has favorable effects on lipid and glucose metabolism and may possess anti-fibrotic properties.[13] While not the primary basis for its approval in PBC, these additional activities could contribute to long-term benefits in modifying disease progression.

Pharmacokinetics (Absorption, Distribution, Metabolism, and Excretion)

The disposition of seladelpar in the body is characterized by rapid absorption, high protein binding, and extensive metabolism.

• Absorption: Following oral administration, seladelpar is rapidly absorbed, with a median time to reach peak plasma concentration (Tmax​) of approximately 1.5 hours.[1] The absorption is not significantly affected by food; administration with a high-fat meal did not produce clinically meaningful changes in its pharmacokinetic profile, which allows for convenient once-daily dosing with or without food.[1]
• Distribution: Seladelpar is extensively bound to plasma proteins, with a binding fraction greater than 99%.[2] This high degree of protein binding limits its distribution into tissues and has clinical implications, such as rendering hemodialysis an ineffective method for removal in the event of an overdose.[1]
• Metabolism: The drug undergoes extensive oxidative metabolism in the liver.[19] As detailed in the drug interactions section, cytochrome P450 enzymes, particularly CYP2C9, play a significant role in its clearance.[11]
• Excretion: The metabolites of seladelpar are primarily eliminated from the body via the urine.[19]

Clinical Efficacy in Primary Biliary Cholangitis

The approval of seladelpar was based on a robust clinical development program that demonstrated its efficacy in improving both biochemical markers of disease and patient-reported symptoms. The cornerstone of this evidence is the pivotal Phase 3 RESPONSE trial.

The Pivotal Phase 3 RESPONSE Trial (NCT04620733)

The RESPONSE trial was a global, multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of seladelpar in patients with PBC.[20] The study enrolled 193 adults who had an inadequate response to (defined by an ALP level ≥ 1.67 x ULN) or intolerance of UDCA.[20] Patients were randomized in a 2:1 ratio to receive either seladelpar 10 mg once daily or a matching placebo for 12 months. The vast majority of participants (93.8%) continued to receive standard-of-care background therapy with UDCA.[20]

Primary Endpoint: Biochemical Response

The primary endpoint was a composite measure of biochemical response at 12 months, defined as achieving all three of the following criteria:

1. Alkaline phosphatase (ALP) level less than 1.67 times the upper limit of normal (ULN).
2. A decrease in ALP of at least 15% from baseline.
3. A total bilirubin level within the normal range (≤ 1 x ULN).[20]

Treatment with seladelpar resulted in a highly statistically significant improvement in the primary endpoint. 61.7% of patients in the seladelpar group achieved a biochemical response, compared to only 20.0% in the placebo group. The difference of 41.7 percentage points (95% CI, 27.7 to 53.4; p<0.001) unequivocally demonstrated the drug's potent anti-cholestatic effect.[20]

Key Secondary Endpoints

The trial also met its key secondary endpoints, further substantiating the clinical benefits of seladelpar.

• Alkaline Phosphatase (ALP) Normalization: A key secondary endpoint was the proportion of patients achieving a normal ALP level (≤ 1 x ULN) at 12 months. This is an increasingly important therapeutic goal, as evidence suggests that ALP normalization is associated with the best long-term outcomes. In the RESPONSE trial, 25.0% of patients treated with seladelpar achieved ALP normalization, a remarkable result compared to 0% of patients in the placebo group (p<0.001).[20]
• Pruritus Reduction: A critical differentiator for seladelpar is its effect on pruritus. The trial assessed the change in itch severity from baseline to 6 months using the pruritus Numerical Rating Scale (NRS), an 11-point scale from 0 (no itch) to 10 (worst itch imaginable). Among patients with moderate-to-severe pruritus at baseline (NRS ≥ 4), those receiving seladelpar experienced a significantly greater reduction in their itch scores. The least-squares mean change from baseline was -3.2 points for the seladelpar group versus -1.7 points for the placebo group (least-squares mean difference, -1.5; 95% CI, -2.5 to -0.5; p=0.005).[6] This improvement was rapid, with benefits seen as early as one month, and was sustained through the 12-month study period.[6]

The strong performance of seladelpar on both biochemical and symptomatic endpoints marks a pivotal development in PBC management. Historically, therapies have forced a trade-off; for instance, the first approved second-line agent, obeticholic acid, improves ALP but is known to worsen pruritus.[27] Seladelpar is the first agent to demonstrate a statistically significant and clinically meaningful benefit on both fronts. This dual efficacy empowers clinicians and patients to pursue a more holistic treatment goal that encompasses not only the slowing of disease progression as measured by surrogate biochemical markers but also the significant improvement of a highly burdensome, quality-of-life-impairing symptom. This potential to redefine the objectives of PBC therapy is a major implication of the RESPONSE trial findings.

Table 2: Summary of Key Efficacy Endpoints from the Phase 3 RESPONSE Trial at 12 Months

Efficacy Endpoint	Seladelpar 10 mg (N=128)	Placebo (N=65)	Treatment Difference (95% CI)	p-value
Primary Composite Biochemical Response	61.7%	20.0%	41.7% (27.7 to 53.4)	<0.001
ALP Normalization	25.0%	0%	25.0% (18.3 to 33.2)	<0.001
Pruritus NRS Change from Baseline (at Month 6)	-3.2	-1.7	-1.5 (-2.5 to -0.5)	0.005

Long-Term Efficacy and Confirmatory Trials

Evidence for the durability of seladelpar's effects comes from the ASSURE open-label extension study, which enrolled patients from previous trials.

• ASSURE Open-Label Extension Study: Interim results from ASSURE demonstrated that the benefits of seladelpar are sustained and may even deepen over time. Among patients from legacy studies who completed 24 months of treatment, 70% met the composite biochemical response endpoint, and 42% achieved ALP normalization.[22] The improvement in pruritus was also durable, with a mean NRS reduction of 3.1 points maintained at 24 months.[28]
• AFFIRM Confirmatory Outcomes Trial (NCT06051617): Seladelpar's approval by the FDA was granted under an accelerated pathway, which is based on the drug's effect on a surrogate endpoint (ALP reduction) that is considered reasonably likely to predict clinical benefit. To convert this to a full approval, a confirmatory trial demonstrating a direct benefit on clinical outcomes is required.[23] The ongoing AFFIRM trial is a randomized, placebo-controlled study designed to fulfill this requirement. It will evaluate the effect of seladelpar on a composite endpoint of clinical outcomes, including mortality, liver transplant, and liver decompensation events (e.g., variceal bleeding, ascites), in patients with PBC and compensated cirrhosis.[30] The trial is expected to be completed in 2030, and its results will be critical for establishing the long-term, disease-modifying impact of seladelpar.[29]

Safety, Tolerability, and Risk Management

A comprehensive evaluation of a drug's safety profile is essential for its clinical application. The safety of seladelpar at the approved 10 mg daily dose has been well-characterized in its clinical development program, particularly in the pivotal RESPONSE trial.

Overall Safety Profile and Common Adverse Events

In the 12-month RESPONSE trial, seladelpar was generally well-tolerated. The overall incidence of adverse events was comparable between the seladelpar and placebo groups (86.7% vs. 84.6%, respectively). Importantly, the rate of serious adverse events was also similar between the two arms (7.0% vs. 6.2%), and investigators reported no treatment-related serious adverse events.[20]

The most frequently reported adverse reactions that occurred in at least 5% of patients taking Livdelzi and at a higher rate than placebo are summarized in Table 3. These were generally mild to moderate in severity.

Table 3: Incidence of Common Adverse Reactions (≥5% and >Placebo) in the RESPONSE Trial

Adverse Reaction	Livdelzi 10 mg (N=128)	Placebo (N=65)
Headache	8%	3%
Abdominal pain	7%	2%
Nausea	6%	5%
Abdominal distension	6%	3%
Dizziness	5%	2%
Source: 12

Warnings and Precautions

The prescribing information for Livdelzi includes specific warnings and precautions for clinicians to consider.

• Liver Test Abnormalities: The history of seladelpar's development provides important context for this warning. Initial dose-finding studies that explored significantly higher doses (50 mg and 200 mg daily) were associated with dose-related, transient elevations in serum transaminases (ALT and AST).[2] This finding prompted a temporary halt and re-evaluation of the development program. However, this history should not be viewed as a persistent liability but rather as evidence of a rigorous and successful dose-optimization process. Subsequent development focused on the 10 mg dose, which, in the large Phase 3 RESPONSE trial, did not demonstrate a pattern of transaminase elevations and had a rate of discontinuation due to liver test abnormalities that was comparable to placebo.[2] This narrative demonstrates that a safe and effective therapeutic window was successfully identified. Nonetheless, the official label recommends obtaining baseline liver assessments prior to starting therapy and monitoring them during treatment as clinically indicated.[12]
• Fractures: An increased risk of bone fractures has been identified as a potential adverse event associated with seladelpar treatment.[32] Clinicians are advised to consider this risk in patients, particularly those with other risk factors for fracture, and to monitor bone health according to current standards of care.[12]
• Biliary Obstruction: The use of Livdelzi is not recommended in patients with complete biliary obstruction. If obstruction is suspected during treatment, the drug should be interrupted, and the patient should be managed as clinically indicated.[12]

Clinically Significant Drug-Drug Interactions

Seladelpar's metabolism and transport are mediated by pathways that are susceptible to interactions with other medications. Careful management is required to avoid altered drug exposure and potential adverse effects. The key interactions are summarized in Table 4.

Table 4: Key Drug-Drug Interactions and Management Strategies

Interacting Agent/Class	Examples	Effect on Seladelpar	Clinical Recommendation	Source(s)
OAT3 Inhibitors	Probenecid	Significantly increased exposure	Avoid concomitant use	11
Strong CYP2C9 Inhibitors	Fluconazole	Significantly increased exposure	Avoid concomitant use	11
BCRP Inhibitors	Cyclosporine, Rosuvastatin	Increased exposure	Monitor closely for adverse effects	5
Potent Inducers (e.g., of CYP enzymes)	Rifampin	Decreased exposure and potential loss of efficacy	Monitor biochemical response (ALP, bilirubin)	5
Bile Acid Sequestrants	Cholestyramine, Colestipol, Colesevelam	Decreased absorption	Administer Livdelzi at least 4 hours before or 4 hours after the sequestrant	11

Regulatory and Commercial Landscape

The journey of seladelpar from an investigational compound to an approved therapy has been marked by significant regulatory milestones and a major strategic corporate acquisition, reflecting high confidence in its clinical and commercial potential.

Global Regulatory Trajectory

Seladelpar has successfully navigated the regulatory pathways in the world's two largest pharmaceutical markets, receiving special designations that underscore its potential to address an unmet medical need.

• United States (FDA): On August 14, 2024, the U.S. FDA granted Accelerated Approval for Livdelzi for the treatment of PBC.[3] This approval was based on the surrogate endpoint of ALP reduction demonstrated in the RESPONSE trial. The FDA had previously granted the application several key designations that facilitated its development and review, including Breakthrough Therapy Designation, Orphan Drug Designation, and Priority Review.[22] The New Drug Application (NDA) was approved without the need for an advisory committee meeting, signaling the agency's confidence in the robustness of the data package.[22] Full approval is contingent upon the successful completion of the AFFIRM confirmatory outcomes trial.[23]
• European Union (EMA): Following a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) in December 2024, the European Commission granted a Conditional Marketing Authorisation for Lyvdelzi in February 2025.[3] Similar to the FDA's accelerated approval, this authorization is based on data that fulfills an unmet medical need, with the requirement to provide more comprehensive long-term data post-authorization.[7] In Europe, seladelpar also benefited from PRIME (PRIority MEdicines) status and Orphan Drug Designation.[7]
• Other Regions: Regulatory submissions have also been made to other major health authorities, including the UK's Medicines and Healthcare products Regulatory Agency (MHRA).[23]

Corporate Development and Strategic Acquisition

The development of seladelpar was spearheaded by CymaBay Therapeutics, which licensed the compound (then known as MBX-8025) from Janssen Pharmaceutica NV.[3] CymaBay successfully advanced the drug through a comprehensive clinical program, culminating in the positive Phase 3 RESPONSE trial.

In a move that highlighted the perceived value of seladelpar, Gilead Sciences announced its acquisition of CymaBay Therapeutics in February 2024, a transaction valued at $4.3 billion that was completed in March 2024.[39] The timing of this acquisition was highly strategic. Gilead announced the deal on the same day that the FDA accepted CymaBay's NDA for Priority Review, a point at which the clinical data was mature and positive, and the regulatory path to approval was clear and significantly de-risked.[35]

This was not a speculative investment in early-stage science but a calculated acquisition of a near-market, potential best-in-disease asset. The high valuation for a company whose primary asset was seladelpar reflects immense confidence in the drug's potential to become a market leader and a major revenue driver. For Gilead, the acquisition was a perfect strategic fit, adding a highly promising therapy to its well-established liver disease franchise and allowing it to leverage its formidable global commercialization and regulatory infrastructure to ensure a successful launch.[35]

Therapeutic Positioning and Comparative Analysis

Seladelpar enters a therapeutic landscape for PBC that has been long-dominated by a single first-line agent, with limited and imperfect second-line options. Its unique clinical profile positions it to significantly alter the existing treatment algorithm.

Role in PBC Treatment Guidelines

According to established clinical practice guidelines from the American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL), the management of PBC follows a stepwise approach:

• First-Line Therapy: UDCA is the universal, evidence-based first-line therapy for all patients diagnosed with PBC.[41]
• Second-Line Therapy: Approximately 40% of patients exhibit an inadequate biochemical response to UDCA after one year of treatment, placing them at higher risk for disease progression.[42] For these patients, guidelines recommend the consideration of second-line therapy in addition to UDCA.[42] Livdelzi is specifically indicated for this patient population, providing a new, on-label, evidence-based option.[3]

Comparative Analysis with Other Second-Line Therapies

Seladelpar's primary competitors in the second-line setting are obeticholic acid (OCA) and off-label fibrates.

• vs. Obeticholic Acid (OCA): OCA, a farnesoid X receptor (FXR) agonist, was the first approved second-line therapy for PBC. While it effectively reduces ALP levels, its utility is significantly limited by its primary side effect: dose-dependent pruritus, which can be severe and often leads to treatment discontinuation.[27] This creates a major clinical dilemma, particularly for patients who already suffer from itch. Seladelpar offers a clear and compelling advantage. Not only does it improve biochemical markers, but it also provides significant relief from pruritus.[20] This fundamental difference in the side effect profile positions seladelpar as a superior option for the majority of PBC patients who experience pruritus.
• vs. Fibrates (Bezafibrate, Fenofibrate): Fibrates are pan-PPAR agonists that are used off-label in some regions for PBC. They have been shown to improve liver biochemistry, and some evidence suggests they may be more effective than OCA at reducing ALP and may also have some anti-pruritic effects.[18] However, their use is limited by several factors. As off-label therapies, they lack the robust, indication-specific Phase 3 data and formal regulatory approval that seladelpar possesses.[18] Their mechanism is less specific, and they carry known risks of myalgia and renal dysfunction.[18] Seladelpar provides a more targeted, evidence-based, and on-label alternative.

The introduction of seladelpar fundamentally changes the clinical decision-making process for second-line PBC therapy. Previously, the choice was often a compromise between the on-label efficacy of OCA and its pruritus liability, or the off-label use of fibrates with a less robust evidence base. Now, the patient's symptom profile becomes a central determinant of therapy. For the up to 70% of PBC patients who experience pruritus, seladelpar emerges as the logical choice, as it is the only agent proven to address both the underlying cholestasis and this burdensome symptom simultaneously.[43] This ability to segment the market based on symptomology gives seladelpar a distinct and powerful therapeutic niche.

Prescribing Information and Clinical Application

This section provides a summary of essential information for the safe and effective clinical use of Livdelzi (seladelpar).

Approved Indication

Livdelzi is a PPARδ 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.[11]

This indication is approved under an accelerated pathway based on a reduction in alkaline phosphatase. Improvement in survival or prevention of liver decompensation events has not yet been demonstrated. Continued approval may be contingent upon verification of clinical benefit in a confirmatory trial.[12]

• Limitations of Use: The use of Livdelzi is not recommended in patients who have or develop decompensated cirrhosis (e.g., Child-Pugh Class B or C), which may be characterized by ascites, variceal bleeding, or hepatic encephalopathy.[12]

Dosage and Administration

• Recommended Dosage: The recommended dosage is 10 mg taken orally once daily.[12]
• Administration: Livdelzi can be taken with or without food.[12]
• Bile Acid Sequestrants: If a patient is also taking a bile acid sequestrant (e.g., cholestyramine), Livdelzi should be administered at least 4 hours before or 4 hours after the sequestrant to avoid impaired absorption.[11]

Monitoring and Safety Considerations

• Baseline and Ongoing Monitoring: Clinicians should obtain baseline clinical and laboratory liver assessments (ALT, AST, total bilirubin, and ALP) prior to initiating Livdelzi and monitor these parameters during treatment as part of routine patient care.[12] Treatment should be interrupted or discontinued if liver tests worsen significantly or if signs of clinical hepatitis develop.[12]
• Hepatic Impairment: Patients with compensated cirrhosis (Child-Pugh A) should be closely monitored for any evidence of liver decompensation. Discontinuation of Livdelzi should be considered if a patient's liver function progresses to moderate or severe impairment (Child-Pugh B or C).[11]

Use in Specific Populations

• Pregnancy: There is insufficient data on the use of Livdelzi in pregnant women to assess drug-associated risks. A pregnancy safety study has been established to collect prospective data on maternal and fetal outcomes for women exposed to seladelpar during pregnancy. Healthcare providers are encouraged to report pregnancies by calling 1-800-445-3235.[29]
• Lactation: It is not known whether seladelpar or its metabolites are present in human milk or what effects they may have on the breastfed infant or on milk production. The clinical need for the drug should be weighed against the potential risks to the infant.[11]

Patient Counseling

Patients should be counseled on several key aspects of their treatment with Livdelzi:

• The importance of taking the medication once daily as prescribed.
• The most common side effects, including headache, abdominal pain, nausea, and dizziness.[33]
• The potential risk of bone fractures and the need to report any new fractures or significant pain.[33]
• The importance of immediately reporting any signs or symptoms of worsening liver disease, such as jaundice, abdominal swelling, black or bloody stools, or mental changes like confusion.[6]
• The necessity of separating the administration of Livdelzi from any bile acid sequestrants by at least 4 hours.[33]

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