Maralixibat (Monograph)

Brand name: Livmarli
Drug class: Cholelitholytic Agents

Medically reviewed by Drugs.com on May 10, 2025. Written by ASHP.

Introduction

Ileal bile acid transporter (IBAT) inhibitor.

Uses for Maralixibat

Cholestatic Pruritus in Alagille Syndrome

Treatment of cholestatic pruritus associated with Alagille syndrome in patients ≥3 months of age. Designated an orphan drug by FDA for use in this condition.

Alagille syndrome is an autosomal dominant, multisystem disorder caused by various mutations affecting the Notch signaling pathway. The syndrome, which is usually diagnosed in infancy, mainly affects the liver and is associated with significant cholestasis. Patients often suffer from intractable pruritus. Some drugs have been used for symptomatic treatment (e.g., ursodiol, cholestyramine, rifampin, colesevelam, antihistamines). Maralixibat may provide an additional option.

Cholestatic Pruritus in Progressive Familial Intrahepatic Cholestasis

Treatment of cholestatic pruritus associated with progressive familial intrahepatic cholestasis in patients ≥12 months of age. Designated an orphan drug by FDA for use in this condition. Not recommended for use in subgroup of progressive familial intrahepatic cholestasis type 2 patients with specific ABCB11 variants resulting in non-functional or complete absence of bile salt export pump (BSEP) protein.

Progressive familial intrahepatic cholestasis is a rare, autosomal recessive liver disorder that typically presents during infancy or early childhood. Severe pruritus is a characteristic clinical manifestation of progressive familial intrahepatic cholestasis type 1 and 2 disease. Some therapies have been used for symptomatic treatment (e.g., ursodiol, cholestyramine, rifampin) with limited efficacy. Maralixibat may provide an additional therapeutic option.

Maralixibat Dosage and Administration

General

Pretreatment Screening

• Assess baseline liver function (e.g., ALT, AST, total bilirubin, direct bilirubin, INR).

• Obtain fat-soluble vitamin (e.g., vitamins A, D, E, and K [measured using INR levels]) serum levels at baseline; initiate vitamin supplementation if a deficiency is diagnosed.

Patient Monitoring

• Monitor for the development of liver-related adverse reactions during therapy.

• Monitor liver function (e.g., ALT, AST, total bilirubin, direct bilirubin, INR) frequently during the initial 6-8 months of therapy, and as clinically indicated thereafter.

• Monitor for fat-soluble vitamin deficiency (e.g., vitamins A, D, E, and K [measured using INR levels]) during therapy; initiate vitamin supplementation if a deficiency is diagnosed.

• Monitor for the development of adverse GI effects during treatment.

• Monitor patients for signs of propylene glycol toxicity.

Administration

Oral Administration

Administer orally as a solution. Use the 9.5 mg per mL solution for treatment of Alagille syndrome and the 19 mg per mL solution for treatment of progressive familial intrahepatic cholestasis. Do not substitute the two strengths of maralixibat for one another.

Carefully calculate maralixibat dose volume. Maralixibat solution contains propylene glycol (364.5 mg/mL); use particular caution in patients <5 years of age.

Administer oral solution 30 minutes before a meal using provided calibrated measuring device (0.5 mL, 1 mL, or 3 mL oral dispenser).

If once daily dose is missed, take the missed dose as soon as possible within 12 hours of the time it is usually taken, and then resume normal dosing schedule. If the dose is missed by >12 hours, skip the missed dose and take next dose at regularly scheduled time.

If twice daily dose is missed, take the missed dose as soon as possible within 6 hours of the time it is usually taken, and then resume normal dosing schedule. If the dose is missed by >6 hours, skip the missed dose and take next dose at regularly scheduled time.

Administer maralixibat at least 4 hours before or after administration of bile acid sequestrants.

Dosage

Available as maralixibat chloride; dosage expressed in terms of maralixibat.

Pediatric Patients

Cholestatic Pruritus in Alagille Syndrome

Oral

Age ≥3 months: Initially, 190 mcg/kg once daily in the morning for one week, then increase dosage to 380 mcg/kg once daily, as tolerated.

For patients who weigh ≥70 kg, the maximum daily dose volume is 3 mL or 28.5 mg per day.

Use oral solution containing 9.5 mg of maralixibat per mL for treatment of cholestatic pruritus in Alagille syndrome. Individual dose volumes by patient weight are described in Table 1.

Cholestatic Pruritus in Progressive Familial Intrahepatic Cholestasis

Oral

Age ≥12 months: Initially, 285 mcg/kg once daily in the morning. Then increase dose to 285 mcg/kg twice daily, 428 mcg/kg twice daily, and then 570 mcg/kg twice daily, as tolerated.

For patients who weigh ≥60 kg, the maximum daily dose volume is 2 mL or 38 mg per day.

Use oral solution containing 19 mg of maralixibat per mL for treatment of cholestatic pruritus in progressive familial intrahepatic cholestasis. Individual dose volumes by patient weight are described in Table 2.

Adults

Cholestatic Pruritus in Alagille Syndrome

Oral

Initially, 190 mcg/kg once daily in the morning for one week, then increase dosage to 380 mcg/kg once daily, as tolerated.

For patients who weigh ≥70 kg, the maximum daily dose volume is 3 mL or 28.5 mg per day.

Use oral solution containing 9.5 mg of maralixibat per mL for treatment of cholestatic pruritus in Alagille syndrome. Individual dose volumes by patient weight are described in Table 1.

Cholestatic Pruritus in Progressive Familial Intrahepatic Cholestasis

Oral

Initially, 285 mcg/kg once daily in the morning. Then increase dose to 285 mcg/kg twice daily, 428 mcg/kg twice daily, and then 570 mcg/kg twice daily, as tolerated.

For patients who weigh ≥60 kg, the maximum daily dose volume is 2 mL or 38 mg per day.

Use oral solution containing 19 mg of maralixibat per mL for treatment of cholestatic pruritus in progressive familial intrahepatic cholestasis. Individual dose volumes by patient weight are described in Table 2.

Dosage Modification for Toxicity

Hepatotoxicity

If new onset liver abnormalities occur without other etiology, reduce dosage or interrupt maralixibat therapy. When laboratory values stabilize or return to baseline, consider resuming maralixibat at last tolerated dose and increase as tolerated. If liver function abnormalities persist or recur or clinical symptoms of hepatitis occur, consider permanently discontinuing therapy.

Permanently discontinue drug if hepatic decompensation occurs (e.g., variceal hemorrhage, ascites, hepatic encephalopathy).

GI Effects

If adverse GI effects (e.g., persistent diarrhea or abdominal pain, diarrhea with bloody stool, vomiting, dehydration requiring treatment, or fever) occur, consider reducing dose of maralixibat or temporarily withholding therapy. If diarrhea or abdominal pain persists without other etiology, consider discontinuing therapy.

When diarrhea or abdominal pain resolves, resume maralixibat at last tolerated dose and increase dosage, as tolerated. If adverse GI effect recurs upon rechallenge, consider discontinuing drug.

Special Populations

Hepatic Impairment

No specific dosage recommendations.

If liver abnormalities occur during therapy with maralixibat and no other etiology is identified, consider reducing the dosage of maralixibat or temporarily interrupting therapy.

Contraindicated in patients with prior or active hepatic decompensation.

Renal Impairment

No specific dosage recommendations for patients with renal impairment, including those with end-stage renal disease (ESRD) and those receiving hemodialysis.

Geriatric Patients

No specific dosage recommendations.

Cautions for Maralixibat

Contraindications

• Prior or active hepatic decompensation events.

Warnings/Precautions

Hepatotoxicity

Potentially associated with drug-induced liver injury. New or worsening elevations of liver function tests observed during therapy. Most common abnormalities include elevations in ALT, AST, and/or total bilirubin/direct bilirubin.

Obtain liver function values at baseline and monitor frequently for initial 6 to 8 months of therapy and as clinically indicated thereafter. Consider dosage reduction or treatment interruption if liver test abnormalities or signs of clinical hepatitis occur in the absence of other etiology.

Permanently discontinue maralixibat if persistent or recurrent liver test abnormalities, signs and symptoms consistent with clinical hepatitis occur upon rechallenge, or a hepatic decompensation event occur(s). Efficacy and safety not established in patients with decompensated cirrhosis. Monitor patients with compensated cirrhosis frequently and discontinue therapy if hepatic decompensation occurs. Therapy contraindicated in patients with prior or active hepatic decompensation.

GI Adverse Effects

Most common adverse GI effects are diarrhea and abdominal pain.

If adverse GI effects (e.g., persistent diarrhea or abdominal pain, diarrhea with bloody stool, vomiting, dehydration requiring treatment, or fever) occur, consider reducing dose or temporarily withholding therapy. If diarrhea or abdominal pain persists without other etiology, consider discontinuing therapy. Monitor patients for dehydration due to diarrhea and treat promptly. Maralixibat therapy not evaluated in patients with progressive familial intrahepatic cholestasis and chronic diarrhea requiring IV fluids.

When diarrhea or abdominal pain resolves, resume maralixibat at last tolerated dose and increase dosage, as tolerated. If adverse GI effect recurs upon rechallenge, consider discontinuing drug.

Fat-soluble Vitamin Deficiency

Patients with Alagille syndrome and progressive familial intrahepatic cholestasis can be fat-soluble vitamin-deficient (e.g., vitamins A, D, E, and K) at baseline and are frequently supplemented with fat-soluble vitamins; maralixibat may inhibit absorption of these vitamins.

Patients administered maralixibat experience more treatment-emergent bone fractures as compared to placebo-treated patients. If a fracture occurs, consider withholding therapy and supplement with fat-soluble vitamins. Once a fat-soluble vitamin deficiency is corrected and maintained at appropriate levels, maralixibat therapy may be resumed.

If bleeding occurs, withhold therapy. Maralixibat may be resumed after correction of fat-soluble vitamin deficiency and resolution of bleeding.

Obtain fat-soluble vitamin levels (e.g. vitamins A, D, E, and K [measured using INR levels]) prior to initiation of therapy and monitor periodically during therapy; supplement fat-soluble vitamins if a deficiency is diagnosed.

Consider discontinuing maralixibat if fat-soluble vitamin deficiency persists or worsens despite adequate supplementation.

Risk of Propylene Glycol Toxicity

Maralixibat contains propylene glycol, which may cause adverse events, particularly in patients <5 years of age. Consider total daily intake of propylene glycol from all sources when managing risk of propylene glycol toxicity.

Monitor patients for signs of propylene glycol toxicity (i.e., hemolysis, hyperosmolarity with anion gap metabolic acidosis, acute kidney injury, CNS toxicity). If propylene glycol toxicity is suspected, discontinue therapy.

Specific Populations

Pregnancy

Not expected to result in measurable fetal exposure. No developmental effects observed in animal studies.

Increased supplementation of fat-soluble vitamins may be necessary during pregnancy.

Lactation

Breast-feeding is not expected to result in exposure of the infant to maralixibat at the recommended dosage. Not known whether maralixibat is distributed into human milk. Effects of the drug on breast-fed infants or on milk production also unknown.

Consider developmental and health benefits of breast-feeding along with the mother's need for maralixibat and any potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.

Monitor fat-soluble vitamin levels and provide supplementation if a deficiency is diagnosed during lactation.

Pediatric Use

Safety and efficacy established in pediatric patients ≥3 months of age with Alagille syndrome.

Safety and efficacy established in pediatric patients ≥12 months of age with progressive familial intrahepatic cholestasis.

Geriatric Use

Safety and efficacy not established in patients ≥65 years of age.

Hepatic Impairment

Clinical studies included patients with Alagille syndrome and progressive familial intrahepatic cholestasis and hepatic impairment at baseline.

Safety and efficacy not established in patients with Alagille syndrome or progressive familial intrahepatic cholestasis and clinically significant portal hypertension or decompensated cirrhosis. Therapy contraindicated in patients with prior or active hepatic decompensation.

Renal Impairment

Pharmacokinetics not studied in patients with renal impairment, including those with end-stage renal disease (ESRD) and those receiving hemodialysis.

Common Adverse Effects

Most common adverse reactions (≥5%) for Alagille syndrome: diarrhea, abdominal pain, vomiting, fat-soluble vitamin deficiency, liver test abnormalities, bone fractures.

Most common adverse reactions (≥5%) for progressive familial intrahepatic cholestasis: diarrhea, fat-soluble vitamin deficiency, abdominal pain, liver test abnormalities, hematochezia, bone fractures.

Drug Interactions

In vitro, does not induce CYP isoenzymes 1A2, 2B6, or 3A4, or inhibit CYP1A2, 2B6, 2C8, 2C9, 2C19, or 2D6 at clinically relevant concentrations. Inhibits CYP3A4 in vitro; however, clinically important pharmacokinetic interactions with CYP3A4 substrates unlikely.

In vitro, does not inhibit P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), organic anion transporter (OAT) 1, OAT3, organic anion transporting polypeptide (OATP) 1B1, OATP1B3, peptide transporter (PEPT) 1, organic cation transporter (OCT) 1, OCT2, OCT3, OCTN1, OCTN2, multidrug resistance protein (MRP) 2, multidrug and toxin extrusion (MATE) 1, or MATE2-K at clinically relevant concentrations. In vitro, inhibits OATP2B1, which can result in decreased absorption of drugs requiring OATP2B1-mediated uptake in the GI tract.

Not a substrate of P-gp, BCRP, OATP1B1, OATP1B3, or OATP2B2; therefore, concomitant therapy with drugs affecting these drug transporters are not expected to affect the pharmacokinetics of maralixibat.

Specific Drugs

Maralixibat Pharmacokinetics

Absorption

Bioavailability

Median time to peak plasma concentration was 0.75 hours following oral administration.

Systemic exposure is minimal. Following oral administration, plasma concentrations are below the limit of quantification in pediatric patients with Alagille syndrome or progressive familial intrahepatic cholestasis and healthy adults.

Systemic exposure increases in a dose-dependent manner over an oral dose range of 30–100 mg.

No accumulation observed following repeated oral administration of up to 100 mg daily in healthy adults.

Food

High-fat meal decreased total exposure and peak plasma concentrations by 64.8% and 85.8%, respectively, compared with administration in the fasting state.

Distribution

Extent

Not known whether distributed into human milk; however, drug is minimally absorbed following oral administration.

Plasma Protein Binding

91%.

Elimination

Metabolism

No metabolites detected in plasma. Three minor metabolites detected in feces following oral administration.

Elimination Route

Eliminated in feces (73%; 94% as unchanged drug) and urine (0.066%).

Half-life

1.6 hours in healthy adults.

Stability

Storage

Oral

Solution

Store at 20–25°C (excursions permitted between 15–30°C). After opening, store at <30°C. Discard any remaining solution 100 days after first opening of bottle.

Actions

• Reversible inhibitor of the ileal bile acid transporter (IBAT).

• Decreases reabsorption of bile acids (primarily the salt forms) from terminal ileum.

• Mechanism of action in patients with pruritus associated with Alagille syndrome not fully elucidated, but may involve inhibition of IBAT.

• Inhibition of IBAT decreases reuptake of bile salts.

Advice to Patients

• Advise the patient or their caregiver(s) to read the FDA-approved patient labeling.

• Advise patients to contact their healthcare provider if they experience new onset or worsening of GI adverse events (abdominal pain, vomiting, nausea, diarrhea, and dehydration).

• Advise patients that their healthcare provider will obtain liver tests before starting the drug and periodically during treatment. Advise patients to report any symptoms of liver problems (e.g., nausea, vomiting, skin or the whites of eyes turning yellow, dark or brown urine, pain on the right side of the abdomen, loss of appetite).

• Advise patients that their healthcare provider will obtain serum levels of vitamins A, D, E, and INR (for vitamin K) before starting and periodically during treatment to assess for worsening deficiency of these vitamins.

• Take maralixibat 30 minutes before a meal using a calibrated measuring device (0.5 mL, 1 mL or 3 mL oral dispenser) provided by the pharmacist to measure and deliver the prescribed dose accurately.

• Patients taking bile acid binding resins (e.g., cholestyramine, colesevelam, or colestipol) should take maralixibat at least 4 hours before or 4 hours after the bile acid binding resin.

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.

• Advise patients to inform their clinician if they are or plan to become pregnant or plan to breast-feed.

• Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Maralixibat can only be obtained through a designated specialty pharmacy. Contact the manufacturer or consult the Livmarli website for specific availability information.

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