Dosing & Uses
Dosage Forms & Strengths
oral solution
- 9.5mg/mL
Cholestatic Pruritus
Indicated for cholestatic pruritus in patients with Alagille syndrome
Days 1-7: 190 mcg/kg PO qDay
Beginning Day 8: Increase to 380 mcg/kg PO qDay, as tolerated; not to exceed 28.5 mg/day for patients weighing >70 kg
Administer 30 minutes before first meal of the day
Dosage Modifications
Gastrointestinal adverse effects
- Diarrhea, abdominal pain, and/or vomiting: Consider reducing or interrupting dose
- Persistent diarrhea or severe (accompanied by bloody stool, vomiting, dehydration, fever): Consider interrupting dose
- When resolved, restart at 190 mcg/kg/day and increase dose as tolerated
- If symptoms recur upon rechallenge, consider discontinuing
Hepatic decompensation
- Interrupt dosing if new-onset liver test abnormalities occur in absence of other causes
- Once liver test abnormalities either return to baseline values or stabilize at a new baseline value, consider restarting at 190 mcg/kg, and increase to 380 mcg/kg as tolerated
- Consider discontinuing permanently if liver test abnormalities recur or symptoms consistent with clinical hepatitis are observed
- Not studied in patients with hepatic decompensation; discontinue permanently if hepatic decompensation event occurs (eg, variceal hemorrhage, ascites, hepatic encephalopathy)
Hepatic impairment
- Clinical studies included patients with impaired hepatic function at baseline
- Efficacy and safety in patients with clinically significant portal hypertension or decompensated cirrhosis have not been established
Renal impairment
- Minimally excreted in urine
- Pharmacokinetics were not studied in patients with impaired renal function, including those with ESRD or those on hemodialysis
Dosing Considerations
Monitoring
- Establish baseline pattern of variability of liver tests before initiating to identify potential signs of liver injury
- Monitor liver tests (eg, ALT, AST, total bilirubin, direct bilirubin) and INR during treatment
- Monitor for fat-soluble vitamin deficiency at baseline and periodically
Dosage Forms & Strengths
oral solution
- 9.5mg/mL
Cholestatic Pruritus
Indicated for cholestatic pruritus in patients aged ≥3 months with Alagille syndrome
Days 1-7: 190 mcg/kg PO qDay
Beginning Day 8: Increase to 380 mcg/kg PO qDay, as tolerated; not to exceed 28.5 mg/day for patients weighing >70 kg
Administer 30 minutes before first meal of the day
Dosage Modifications
Gastrointestinal adverse effects
- Diarrhea, abdominal pain, and/or vomiting: Consider reducing or interrupting dose
- Persistent diarrhea or severe (accompanied by bloody stool, vomiting, dehydration, fever): Consider interrupting dose
- When resolved, restart at 190 mcg/kg/day and increase dose as tolerated
- If symptoms recur upon rechallenge, consider discontinuing
Hepatic decompensation
- Interrupt dosing if new-onset liver test abnormalities occur in absence of other causes
- Once liver test abnormalities either return to baseline values or stabilize at a new baseline value, consider restarting at 190 mcg/kg, and increase to 380 mcg/kg as tolerated
- Consider discontinuing permanently if liver test abnormalities recur or symptoms consistent with clinical hepatitis are observed
- Not studied in patients with hepatic decompensation; discontinue permanently if hepatic decompensation event occurs (eg, variceal hemorrhage, ascites, hepatic encephalopathy)
Hepatic impairment
- Clinical studies included patients with impaired hepatic function at baseline
- Efficacy and safety in patients with clinically significant portal hypertension or decompensated cirrhosis have not been established
Renal impairment
- Minimally excreted in urine
- Pharmacokinetics were not studied in patients with impaired renal function, including those with ESRD or those on hemodialysis
Dosing Considerations
Monitoring
- Establish baseline pattern of variability of liver tests before initiating to identify potential signs of liver injury
- Monitor liver tests (eg, ALT, AST, total bilirubin, direct bilirubin) and INR during treatment
- Monitor for fat-soluble vitamin deficiency at baseline and periodically
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (0)
Monitor Closely (0)
Minor (0)
Adverse Effects
>10%
Diarrhea (55.8%)
Abdominal pain (53.5%)
Vomiting (40.7%)
Fat-soluble vitamin deficiency (25.6%)
ALT/AST increased (18.6%)
Gastrointestinal bleeding (10.4%)
1-10%
Bone fractures (9.3%)
Nausea (8.1%)
Warnings
Pregnancy
Maternal use at the recommended dose is not expected to result in measurable fetal exposure owing to low systemic absorption following oral administration
No developmental effects were observed in animal reproduction studies
Clinical considerations
- Maralixibat may inhibit fat-soluble vitamin absorption
- Monitor for deficiency and supplement as needed
- Increased supplementation of vitamins may be needed during pregnancy
Lactation
Low absorption following oral administration; breastfeeding is not expected to result in exposure to the infant at the recommended dose
Data are not available on presence of drug in human milk, effects on breastfed infants, or effects on milk production
As with pregnancy, consider supplementation with fat-soluble vitamins
Contraindications
None
Cautions
Diarrhea, abdominal pain, and vomiting were reported as the most common adverse reactions; dosage interruption and/or discontinuation may be necessary
Liver test abnormalities
- Patients with Alagille syndrome often present with jaundice or paucity of intrahepatic bile ducts
- Obtain baseline liver tests and monitor during treatment
- Consider dose reduction or treatment interruption if hepatic abnormalities occur in the absence of other causes
- For persistent or recurrent liver test abnormalities, consider treatment discontinuation
Drug interaction overview
-
Bile acid–resins
- Administer maralixibat and bile acid binding resins 4 hr apart
- Bile acid binding resins (eg, cholestyramine, colesevelam, colestipol) may bind to maralixibat in the gut
-
OATB2B1 substrates
- Monitor effects of OATP2B1 substrates as needed
- Maralixibat is an OATP2B1 inhibitor based on in vitro studies and may decrease oral absorption of OATP2B1 substrates (eg, statins) owing to OATP2B1 inhibition in the gastrointestinal tract
-
Fat-soluble vitamins
- Monitor for vitamin deficiency and supplement as needed
- Consider discontinuing maralixibat if deficiency persists or worsens despite adequate supplementation
- Maralixibat may affect absorption of fat-soluble vitamins (eg, vitamins A, D, E, K); patients with Alagille syndrome can have fat-soluble vitamin deficiency at baseline
Pharmacology
Mechanism of Action
Inhibitor of the ileal bile acid transporter (IBAT)
IBAT inhibitors act locally in the distal ileum to decrease reuptake of bile acids and increase clearance of bile acids through the colon, thereby, reducing bile acid serum concentration
Absorption
Minimally absorbed, and plasma concentration is typically below the limit of quantification
Pediatric patients
- Peak plasma time: 0.75
- Peak plasma concentration: 1.65 ng/mL
- AUC: 3.43 ng⋅h/mL
Effect of food
- High-fat meal decreased AUC and peak plasma concentration compared with fasted state, although changes of systemic exposure are not clinically significant since the mechanism of action takes place in the gut
Distribution
Protein bound: 91%
Metabolism
No maralixibat metabolites have been detected in plasma
Elimination
Half-life: 1.6 hr
Excretion: 73% feces (94% unchanged); 0.066% urine
Administration
Oral Administration
Administer with calibrated measuring device (0.5-mL, 1-mL, or 3-mL oral dosing dispenser) provided by the pharmacy to accurately measure and deliver prescribed dose
Administer at least 30 minutes before first meal of the day
Refer to prescribing information for choosing the correct dosing dispenser size
Missed dose
- Within 12 hr of missed dose: Take as soon as possible, then resume original dosing schedule
- >12 hr: Omit dose, then resume original dosing schedule
Patients taking bile acid–binding resins
- Take maralixibat at least 4 hr before or 4 hr after bile acid–binding resin
Storage
Store at 20-25ºC (68-77ºF)
Discard any remaining solution 45 days after first opening bottle
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Formulary
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