Livdelzi

Drug overview for LIVDELZI (seladelpar lysine):

Generic name: SELADELPAR LYSINE (SEL-a-DEL-par)
Drug class: Peroxisome Proliferator-Activated Receptor (PPAR) Agonist
Therapeutic class: Hepatobiliary System Treatment Agents

Seladelpar lysine is a peroxisome proliferator-activated receptor (PPAR)-delta (delta) agonist.

No enhanced Uses information available for this drug.

DRUG IMAGES

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The following indications for LIVDELZI (seladelpar lysine) have been approved by the FDA:

Indications:
Primary biliary cholangitis

Professional Synonyms:
Hanot's cirrhosis
Primary biliary cirrhosis

Dosing information for LIVDELZI
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
LIVDELZI 10 MG CAPSULE	Maintenance	Adults take 1 capsule (10 mg) by oral route once daily

The following drug interaction information is available for LIVDELZI (seladelpar lysine):

Contraindicated
Severe
Moderate

There are 0 contraindications.

There are 1 severe interactions. These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.

Drug Interaction	Drug Names
Seladelpar/OAT3 Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Inhibitors of organic anion transporter 3 (OAT3) may inhibit the renal elimination of seladelpar.(1,2) CLINICAL EFFECTS: Concurrent use of organic anion transporter 3 (OAT3) inhibitors may result in an increase in both the therapeutic and toxic effects of seladelpar, such as hepatotoxicity.(1) Symptoms can include nausea, vomiting, jaundice, dark urine, abdominal pain, and unexplained fatigue. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of seladelpar states that concurrent administration of seladelpar with organic anion transporter 3 (OAT3) inhibitors should be avoided.(1) DISCUSSION: In a study in healthy subjects, concurrent administration of seladelpar (single 10 mg dose) with probenecid (500 mg) resulted in approximately a 2-fold increase in area-under-curve (AUC) and a 4.69-fold increase in concentration maximum (Cmax) of seladelpar.(1) OAT3 inhibitors linked to this monograph include: cabotegravir, leflunomide, nitisinone, probenecid, teriflunomide, and vadadustat.(1,2)	APRETUDE, ARAVA, AUBAGIO, CABENUVA, CABOTEGRAVIR ER (CABENUVA), HARLIKU, LEFLUNICLO, LEFLUNOMIDE, NITISINONE, NITYR, ORFADIN, PROBENECID, PROBENECID-COLCHICINE, TERIFLUNOMIDE, VAFSEO, VOCABRIA

Drug Interaction

Drug Names

Seladelpar/OAT3 Inhibitors

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Inhibitors of organic anion transporter 3 (OAT3) may inhibit the renal elimination of seladelpar.(1,2)

CLINICAL EFFECTS: Concurrent use of organic anion transporter 3 (OAT3) inhibitors may result in an increase in both the therapeutic and toxic effects of seladelpar, such as hepatotoxicity.(1) Symptoms can include nausea, vomiting, jaundice, dark urine, abdominal pain, and unexplained fatigue.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of seladelpar states that concurrent administration of seladelpar with organic anion transporter 3 (OAT3) inhibitors should be avoided.(1)

DISCUSSION: In a study in healthy subjects, concurrent administration of seladelpar (single 10 mg dose) with probenecid (500 mg) resulted in approximately a 2-fold increase in area-under-curve (AUC) and a 4.69-fold increase in concentration maximum (Cmax) of seladelpar.(1) OAT3 inhibitors linked to this monograph include: cabotegravir, leflunomide, nitisinone, probenecid, teriflunomide, and vadadustat.(1,2)

APRETUDE, ARAVA, AUBAGIO, CABENUVA, CABOTEGRAVIR ER (CABENUVA), HARLIKU, LEFLUNICLO, LEFLUNOMIDE, NITISINONE, NITYR, ORFADIN, PROBENECID, PROBENECID-COLCHICINE, TERIFLUNOMIDE, VAFSEO, VOCABRIA

There are 1 moderate interactions. The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.

Drug Interaction	Drug Names
Seladelpar/Bile Acid Sequestrants SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Bile acid sequestrants may bind to seladelpar in the gut, resulting in decreased absorption of seladelpar.(1) CLINICAL EFFECTS: Coadministration of bile acid sequestrants with seladelpar may result in reduced efficacy of seladelpar.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of seladelpar states to administer bile acid sequestrants (cholestyramine, colesevelam, and colestipol) at least 4 hours before or 4 hours after administration of seladelpar, or at as great an interval as possible.(1) DISCUSSION: Bile acid sequestrants are known to bind to drugs when given concurrently. Administration with seladelpar may result in decreased systemic absorption.(1)	CHOLESTYRAMINE, CHOLESTYRAMINE LIGHT, CHOLESTYRAMINE RESIN, COLESEVELAM HCL, COLESTID, COLESTIPOL HCL, PREVALITE, QUESTRAN, QUESTRAN LIGHT, WELCHOL

Drug Interaction

Drug Names

Seladelpar/Bile Acid Sequestrants

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Bile acid sequestrants may bind to seladelpar in the gut, resulting in decreased absorption of seladelpar.(1)

CLINICAL EFFECTS: Coadministration of bile acid sequestrants with seladelpar may result in reduced efficacy of seladelpar.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer of seladelpar states to administer bile acid sequestrants (cholestyramine, colesevelam, and colestipol) at least 4 hours before or 4 hours after administration of seladelpar, or at as great an interval as possible.(1)

DISCUSSION: Bile acid sequestrants are known to bind to drugs when given concurrently. Administration with seladelpar may result in decreased systemic absorption.(1)

CHOLESTYRAMINE, CHOLESTYRAMINE LIGHT, CHOLESTYRAMINE RESIN, COLESEVELAM HCL, COLESTID, COLESTIPOL HCL, PREVALITE, QUESTRAN, QUESTRAN LIGHT, WELCHOL

Contraindication List
Hepatic failure

The following adverse reaction information is available for LIVDELZI (seladelpar lysine):

Overview
Severe
Less Severe

Adverse reaction overview.

The most common adverse reactions (reported in >=5% of patients and higher compared to placebo) with seladelpar in clinical studies were headache, abdominal pain, nausea, abdominal distension, and dizziness.

There are 0 severe adverse reactions.

There are 13 less severe adverse reactions.

More Frequent	Less Frequent
Abdominal distension Abnormal hepatic function tests Acute abdominal pain Dizziness Headache disorder Nausea	Alopecia Anemia Cough Dyspepsia Fracture Kidney disease with reduction in glomerular filtration rate (GFr) Skin rash

Rare/Very Rare
None.

The following precautions are available for LIVDELZI (seladelpar lysine):

Pediatric
Pregnant
Lactation
Geriatric

Safety and efficacy of seladelpar have not been established in pediatric patients <18 years of age.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None

Human data regarding seladelpar use during pregnancy are inadequate to inform a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal studies, no malformations or effects on embryofetal survival occurred in pregnant rats or rabbits following seladelpar treatment exposures up to 176-times and 49-times the recommended dose, respectively. Reduction of fetal growth associated with maternal toxicity occurred in pregnant rabbits at 49-times the recommended dose, but not at 3-times the recommended dose.

In a study in pregnant rats during organogenesis through lactation, postnatal growth and pre-weaning survival of offspring was reduced at 115-times the recommended dose, but not at 16-times the recommended dose. Pregnancies in seladelpar-treated patients should be reported to Gilead Sciences, Inc. at 1-800-445-3235.

It is not known whether seladelpar is distributed into human milk. Effects of the drug on breastfed infants or milk production are also not known. Consider the developmental and health benefits of breastfeeding along with the mother's clinical need for seladelpar and any potential adverse effects on the breastfed infant from the drug or the underlying maternal condition.

In the RESPONSE trial, 23% of patients were >=65 years of age and 2% of patients were >=75 years of age. No differences in safety or efficacy were observed between older patients between 65 and 75 years of age and younger patients, and no dosage adjustments are recommended. Due to limited clinical experience with patients >=75 years of age, close monitoring of adverse events is recommended.