Maralixibat

Maralixibat
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Tejasvi Aryaputra

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Overview

Maralixibat is an ileal bile acid transporter inhibitor that is FDA approved for the treatment of cholestatic pruritus associated with Alagille syndrome. Common adverse reactions include liver test abnormalities, abdominal pain, fat-soluble vitamin deficiency, diarrhea, bone fractures, and gastrointestinal bleeding.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

• 380 mcg/kg once daily, taken 30 minutes before the first meal of the day orally is recommended dosage in patients.
• 190 mcg/kg once daily is the recommended starting dosage for one week upon starting treatment of Maralixibat. After one week, increase dosage to recommended dosage of 380 mcg/kg.
• 3 mL per day is the maximum dosage in patients weighing above 70kg.

Table 1 shows Dosage of Maralixibat based on Patient’s Weight.

Insert Table 1

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Maralixibat in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Maralixibat in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding Maralixibat FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Maralixibat in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Maralixibat in pediatric patients.

Contraindications

There are no contraindications associated with Maralixibat.

Warnings

Liver Test Abnormalities

• Trial studies show patients experiencing abnormal liver tests at the baseline.
• Comparing baseline liver test data in patients, liver tests worsened in some patients when taking Maralixibat.
• Patients also showed increases in AST, ALT, or T/DB.
• Increase in ALT lead to patients having dose interruptions (n=2), permanent discontinuation (n=2), or dose modifications (n=1) as shown from clinical studies.
• Increased TB above the baseline found in clinical trials can cause a patient to discontinue treatment with Maralixibat.
• Monitor patients liver function through liver tests when taking Maralixibat.
• Liver-related adverse reactions and elevations in liver tests should be cautioned to patients taking Maralixibat.
• Advise patients to discontinue Maralixibat if signs of portal hypertension persist in patients.

Gastrointestinal Adverse Reactions

• Abdominal pain, vomiting, and diarrhea was reported in patients who take Maralixibat.
• 3% of patients in clinical studies who experienced vomiting required hospitalization.
• Reduce or interrupt dosages of Maralixibat in patients experiencing abdominal pain, vomiting, and diarrhea.
• Monitor patients hydration levels if they display vomiting and diarrhea when taking Maralixibat.
• Reduce the dosage from 380 mcg/kg back to 190 mcg/kg/day and slowly increase after abdominal pain, vomiting, or diarrhea in patients has been resolved.
• Permanently discontinue use of Maralixibat if abdominal pain, vomiting, or diarrhea continue to be a persist in patients after resolution.

Fat-Soluble Vitamin (FSV) Deficiency

• Fat-soluble vitamins (vitamin A, D, E, and K) absorption may be affected by use of Maralixibat.
• Fat-soluble vitamins deficiency can occur in ALGS patients.
• Trial 1 clinical studies show 10% of patients reporting fat-soluble vitamins deficiency
• Monitor patients fat-soluble vitamins levels and supplement fat-soluble vitamins when deficiency occurs when taking Maralixibat.
• Permanently discontinue use of Maralixibat if fat-soluble vitamins levels do not improve after fat-soluble vitamins supplementation.

Adverse Reactions

Clinical Trials Experience

Clinical Trial Experience

• Because clinical trials are conducted under widely varying conditions and durations of follow up, 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.

Alagille syndrome clinical development program

• This program was comprised of 5 clinical studies that looked into the adverse reactions in 86 patients being treated by Maralixibat. Patients received up to 760 mcg/kg per day of Maralixibat with the program that had a median duration of 32.3 months. 4-week placebo control period occurred in Trial 1 studies after 18 weeks of Maralixibat treatment. 13 weeks of placebo-controlled treatment occurred two long-term, open-label extension studies which specifically looked into patients receiving less than 380 mcg/kg/day dosages of Maralixibat. Dosage reductions and interruptions occurred 6% of patients that displayed vomiting, diarrhea, or abdominal pain in the studies conducted.

Table 2 shows Adverse Reactions (≥5%) caused by Maralixibat in ALGS patients.

Insert Table 2

Liver Test Abnormalities

• Pooled analysis of ALGS patients showed ALT increases with treatment of Maralixibat.
• ALT increases due to Maralixibat led to discontinuation (8.1%), and decreased dosage or dosage interruptions (3.5%) in patients.
• Cases of elevations was resolved through dosage modifications, dosage interruptions or no changes in dosage of Maralixibat
• 24% of patients showed increases to more than three times the baseline in ALT when using Maralixibat.
• 2% of patients showed increases to more than five times the baseline in ALT when using Maralixibat.
• 14% of patients showed AST increases to more than three times the baseline when using Maralixibat.
• 4.6% of patients showed bilirubin increases above baseline.

Postmarketing Experience

There is limited information about "Postmarketing Experiance" in the drug label.

Drug Interactions

Effects of Other Drugs on Maralixibat

Bile acid binding resins

• In the gut, Maralixibat may bind to bile acid binding resins.
• 4 hours before or 4 hours use of Maralixibat may have bile acid binding resins in the gut.

Effects of LIVMARLI on Other Drugs

OATP2B1 substrates

• In vitro studies, Maralixibat can be an OATP2B1 inhibitor.
• OATP2B1 inhibition may cause a decrease in the oral absorption of OATP2B1 substrates.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): Clinical studies shows the systematic absorption of Maralixibat in the fetus is low for pregnant women taking the recommended dosage of Maralixibat orally. Fat-soluble vitamins absorption may be inhibited by use of Maralixibat. Studies done on pregnant rats, who received 1000 mg/kg/day of Maralixibat orally, and pregnant rabbits, who received 1000 mg/kg/day of Maralixibat orally, showed no effects were done to embryo development when using Maralixibat during a period of organogenesis. In female rats studies, Maralixibat had no effect on postnatal development when they received 750 mg/kg/day during organogenesis through lactation.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Maralixibat in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Maralixibat during labor and delivery.

Nursing Mothers

At recommended dosages, use of MAralixibat should not be exposed to the fetus during lactation. No current data has been done on the effects of Maralixibat on the breastfed infant and the effects on milk production in women when treated with Maralixibat. Monitor patients during lactation for fat-soluble vitamins deficiency.

Pediatric Use

Safety and effectiveness of pediatric patients with cholestatic pruritus using Maralixibat has been established in a study. This study included patients ranging from 1 year of age to 15 years of age. There was 18 weeks of open-label treatment that was followed up by a 4 week period of placebo-controlled randomized withdrawal and an immediate open-label treatment period that lasted 26 weeks. 4 studies have provided safety information of patients up to 21 years of age using Maralixibat.

Geriatic Use

The safety and effectiveness of the use of Maralixibat in ALGS patients who are 65 years and older in age for the treatment of pruritus has not been established.

Gender

There is no FDA guidance on the use of Maralixibat with respect to specific gender populations.

Race

There is no FDA guidance on the use of Maralixibat with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Maralixibat in patients with renal impairment.

Hepatic Impairment

Impaired hepatic function at baseline has been reported in ALGS patients treated with Maralixibat. Clinical studies on safety and effectiveness in both patients who have decompensated cirrhosis and portal hypertension have not been established.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Maralixibat in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance on the use of Maralixibat with respect to immunocompromised populations.

Administration and Monitoring

Administration

• Take recommended dosage as prescribed by the doctor 30 minutes before the first meal of the day.
• Patients should use calibrated measuring device from the pharmacy to measure Maralixibat dosage.
• If patients are taking a bile acid binding resin, do not take Maralixibat until at least 4 hours before or 4 hours after of the taking of bile acid binding resin.
• If a dosage is missed less than 12 hours of scheduled time, take dosage as soon as possible.
• If a dosage is missed by more than 12 hours, then skip dosage and take next dosage at scheduled time.

Monitoring

• Monitor patients liver tests throughout treatment with MAralixibat and compare the results to the baseline.
• Monitor patients TB, AST, and International Normalized Ratio levels when taking Maralixibat.
• Any liver test abnormalities should lead to interruption in Maralixibat dosage.
• If liver test abnormalities become stabilized, start patients with 190 mcg/kg of Maralixibat and work dosage back up to 380 mcg/kg if tolerated by patients.
• Hepatic decompensation events in patients should lead to permanent discontinuation of Maralixibat treatment.

IV Compatibility

There is limited information regarding the compatibility of Maralixibat and IV administrations.

Overdosage

• 500 mg, approximately 18-fold higher than the recommended dose, of Maralixibat in a single dose regimen has showed no indications of meaningful increase in adverse reactions in patients when compared to reactions occurring in lower dosage amounts.
• Monitor patients signs and symptoms when overdosed on Maralixibat.
• Propylene glycol (364.5 mg/mL) is found in Maralixibat.
• 50 mg/kg/day and 500 mg/kg/day of propylene glycol are considered safe in the body.
• CNS, hyperosmolality, cardiovascular, and/or respiratory effects may be present in patients who overdose on propylene glycol found in Maralixibat.

Pharmacology

There is limited information regarding Maralixibat Pharmacology in the drug label.

Mechanism of Action

• Maralixibat is a reversible inhibitor of the ileal bile acid transporter.
• In the terminal ileum, the reabsorption of bile acids is decreased in the presence of Maralixibat.
• Inhibition of the ileal bile acid transporter inhibitor may occur in the presence of Maralixibat which can decrease bile salts re-uptake.

Structure

• Maralixibat is an ileal bile acid transporter inhibitor for oral administration. It has an empirical formula of C40H56ClN3O4S and a molecular weight of 710.42 g/mol.

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Pharmacodynamics

• Trial 1 studies looked into serum bile acids levels in pediatric patients taking Maralixibat.
• Pediatric patients with ALGS started an initial 5-week dose-escalation period which was followed by open-label treatment for 13 weeks of 380 mcg/kg of a single daily dosage of Maralixibat.
• Patients in the study had serum bile acids levels that ranged from 20 to 749 µmol/L for the baseline.
• The mean of serum bile acid level was 283 (210.6) µmol/L of pediatric patients at baseline.
• As early as Week 12, patients reported decreases in serum bile acid levels when compared to the baseline.

Pharmacokinetics

There is limited information regarding Maralixibat Pharmacokinetics in the drug label.

Nonclinical Toxicology

There is limited information regarding Maralixibat Nonclinical Toxicology in the drug label.

Clinical Studies

There is limited information regarding Maralixibat Clinical Studies in the drug label.

How Supplied

There is limited information regarding Maralixibat How Supplied in the drug label.

Storage

There is limited information regarding Maralixibat Storage in the drug label.

Images

Drug Images

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Patient Counseling Information

There is limited information regarding Maralixibat Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Maralixibat interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Maralixibat Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Maralixibat Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.