maralixibat (Rx)

Brand and Other Names:Livmarli
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Dosing & Uses

AdultPediatric

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 ≥1 year 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
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Interactions

Interaction Checker

and maralixibat

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    Contraindicated

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                    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%)

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                    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
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                    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

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                    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

                    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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                    Images

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                    Patient Handout

                    A Patient Handout is not currently available for this monograph.
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                    Formulary

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                    The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

                    Tier Description
                    1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
                    2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
                    3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
                    4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                    5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                    6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                    NC NOT COVERED – Drugs that are not covered by the plan.
                    Code Definition
                    PA Prior Authorization
                    Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
                    QL Quantity Limits
                    Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
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                    Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
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                    Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.