Maralixibat
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):
There is no FDA guidance on usage of Maralixibat in women who are pregnant.
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
There is no FDA guidance on the use of Maralixibat in women who are nursing.
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
- 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
There is limited information regarding Maralixibat Monitoring in the drug label.
IV Compatibility
There is limited information regarding the compatibility of Maralixibat and IV administrations.
Overdosage
There is limited information regarding Maralixibat overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
There is limited information regarding Maralixibat Pharmacology in the drug label.
Mechanism of Action
There is limited information regarding Maralixibat Mechanism of Action in the drug label.
Structure
There is limited information regarding Maralixibat Structure in the drug label.
Pharmacodynamics
There is limited information regarding Maralixibat Pharmacodynamics in the drug label.
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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Package and Label Display Panel
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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.