Version May 2024
Cholestatic pruritus due to Alagille syndrome: Oral solution (9.5 mg/mL): Oral: Initial: 0.19 mg/kg/dose (maximum: 14.25 mg/dose) once daily for 7 days, then increase to target dose of 0.38 mg/kg/dose (maximum: 28.5 mg/dose) once daily. Maximum daily dose: 28.5 mg/day.
Missed dose: If <12 hours from usual time, administer missed dose as soon as possible and return to original dosing schedule; if >12 hours have elapsed, omit dose and resume dosing at original dosing schedule.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Baseline hepatic impairment: There are no dosage adjustments provided in the manufacturer's labeling; patients with Alagille syndrome may have elevated liver enzymes as part of disease state; clinical trials included patients with baseline LFT elevations. Has not been studied in patients with significant portal hypertension or decompensated cirrhosis.
Hepatic impairment during therapy:
New-onset liver test abnormalities (eg, ALT, AST, bilirubin [direct/total], INR): Hold maralixibat therapy. If liver test abnormalities return to baseline or stabilize at a new baseline value (and no signs/symptoms of hepatitis or decompensation are present), may consider restarting at 0.19 mg/kg/dose (maximum: 14.25 mg/dose) once daily and increase as tolerated to 0.38 mg/kg/dose (maximum: 28.5 mg/dose) once daily. If liver test abnormalities recur, consider permanent discontinuation.
Hepatic decompensation (eg, variceal hemorrhage, ascites, hepatic encephalopathy, symptoms consistent with clinical hepatitis): Discontinue permanently.
Portal hypertension: Discontinue permanently.
Diarrhea (persistent or accompanied by bloody stools), vomiting, dehydration requiring treatment, or fever: Hold maralixibat. Once diarrhea, abdominal pain, and/or vomiting resolve, restart at 0.19 mg/kg/dose (maximum: 14.25 mg/dose) once daily and increase as tolerated to 0.38 mg/kg/dose (maximum: 28.5 mg/dose) once daily. If symptoms recur, consider discontinuation of maralixibat therapy.
Vitamin deficiency (fat soluble): If fat-soluble vitamin deficiency worsens or persists despite supplementation, consider discontinuation of maralixibat therapy.
(For additional information see "Maralixibat: Pediatric drug information")
Cholestatic pruritus due to Alagille syndrome:
Infants ≥3 months, Children, and Adolescents: Oral solution (9.5 mg/mL): Oral: Initial: 0.19 mg/kg/dose once daily for 7 days (maximum initial daily dose: 14.25 mg/day) then increase to target dose of 0.38 mg/kg/dose once daily. Maximum maintenance daily dose: 28.5 mg/day.
Dosage adjustment for toxicity:
GI toxicity:
Persistent diarrhea or diarrhea accompanied by bloody stools, vomiting, dehydration requiring treatment, or fever: Hold maralixibat. Once diarrhea, abdominal pain, and/or vomiting resolve, restart at 0.19 mg/kg/dose once daily and increase as tolerated to 0.38 mg/kg/dose once daily. If recurs, consider discontinuation of maralixibat therapy.
Other toxicity:
Fat-soluble vitamin deficiency: If occurs, supplement with deficient vitamin as appropriate. If deficiency worsens or persists despite adequate supplementation, consider discontinuation of maralixibat therapy.
There are no dosing adjustments provided in the manufacturer's labeling (has not been studied).
Infants ≥3 months, Children, and Adolescents: Oral:
Baseline hepatic impairment: There are no dosing adjustments provided in the manufacturer's labeling; patients with Alagille syndrome may have elevated liver enzymes as part of disease state; clinical trials included patients with baseline LFT elevations. Has not been studied in patients with significant portal hypertension or decompensated cirrhosis.
Hepatic impairment during therapy:
New-onset liver test abnormalities (eg, ALT, AST, bilirubin [direct/total], INR): Hold maralixibat therapy until return to baseline or stabilized at a new baseline value. Consider restarting at 0.19 mg/kg/dose once daily and increase as tolerated to 0.38 mg/kg/dose. If liver test abnormalities recur, consider permanent discontinuation.
Hepatic decompensation (eg, variceal hemorrhage, ascites, hepatic encephalopathy, symptoms consistent with clinical hepatitis): Discontinue permanently.
Portal hypertension: Discontinue permanently.
Elevations of liver functions tests (LFTs) or worsening of LFTs may commonly occur. Hepatic abnormalities may include increased serum alanine aminotransferase, increased serum aspartate aminotransferase, and increased serum bilirubin.
Onset: Delayed; in a clinical trial, serum alanine aminotransferase increased above baseline after >1 year of treatment (Ref).
Risk factors:
• History of persistent or recurrent LFT abnormalities
Diarrhea, abdominal pain, and vomiting may commonly occur, leading to dehydration hospitalization. Nausea has also been reported frequently.
Mechanism: Related to sequelae of bile acid malabsorption (Ref).
Onset: Delayed; in one clinical trial, the majority of events occurred within the first four weeks of treatment (Ref).
Fat-soluble vitamin (FSV) deficiency (including vitamin A deficiency, vitamin D deficiency, vitamin E deficiency, and vitamin K deficiency) may commonly occur.
Mechanism: Dose-related; related to the pharmacologic action (ie, decreased absorption of FSVs).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in children, adolescents, and young adults.
>10%:
Endocrine & metabolic: Vitamin deficiency (including vitamin A deficiency, vitamin D deficiency, vitamin E deficiency, vitamin K deficiency)
Gastrointestinal: Abdominal pain, diarrhea, vomiting
Hematologic & oncologic: Increased INR
Hepatic:Increased serum alanine aminotransferase, increased serum aspartate aminotransferase
1% to 10%:
Gastrointestinal: Gastrointestinal hemorrhage, nausea
Hepatic: Increased serum bilirubin
Neuromuscular & skeletal: Bone fracture
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to maralixibat or any component of the formulation.
Dosage form specific issues:
• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated with hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007). See manufacturer's labeling.
Some dosage forms may contain propylene glycol; in neonates, large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults including hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Shehab 2009).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Oral, as chloride:
Livmarli: 9.5 mg/mL (30 mL) [contains edetate (edta) disodium, propylene glycol]
No
Solution (Livmarli Oral)
9.5 mg/mL (per mL): $2,136.00
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Oral, as chloride:
Livmarli: 9.5 mg/mL (30 mL) [contains edetate (edta) disodium, propylene glycol]
Oral: Administer in the morning 30 minutes before a meal; patient should be seated upright or standing; patient should remain upright for a few minutes after administration. Administer using calibrated oral dosing syringe; do not use a household teaspoon or other dosing device; for dose volumes ≤0.5 mL, use a 0.5 mL syringe; for dose volumes 0.6 to ≤1 mL, use a 1 mL syringe; for dose volumes >1 mL, use 3 mL dosing syringe.
Oral: Administer 30 minutes before a meal in the morning; patient should be seated upright or standing and should remain upright for a few minutes after administration. Administer using calibrated oral dosing syringe; do not use a household teaspoon or other dosing device; for dose volumes ≤0.5 mL, use a 0.5 mL syringe; for dose volumes 0.6 to ≤1 mL, use a 1 mL syringe; for dose volumes >1 mL, use 3 mL dosing syringe.
Missed dose: If <12 hours from usual time, administer missed dose as soon as possible and return to original dosing schedule; if >12 hours have elapsed, omit dose and resume dosing at original dosing schedule.
Cholestatic pruritus due to Alagille syndrome: Treatment of cholestatic pruritus in patients with Alagille syndrome ≥3 months (US labeling) or ≥12 months (Canadian labeling) of age.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Bile Acid Sequestrants: May decrease the serum concentration of Maralixibat. Management: Bile acid sequestrants should be administered either at least 4 hours before, or 4 hours after, maralixibat. Risk D: Consider therapy modification
Adverse events were not observed in animal reproduction studies.
Due to low systemic absorption following oral administration, potential fetal exposure is expected to be limited. Maternal use of maralixibat may decrease the absorption of fat-soluble vitamins; supplementation may be needed.
It is not known if maralixibat is present in breast milk.
Due to low systemic absorption following oral maternal administration, exposure to an infant via breast milk is expected to be limited. Maternal use of maralixibat may decrease the absorption of fat-soluble vitamins; supplementation may be needed. According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
Monitor liver function (ALT, AST, bilirubin [total/direct], INR) (baseline, periodically), fat-soluble vitamin serum concentrations; GI symptoms (diarrhea, vomiting).
Reversibly inhibits the ileal bile acid transporter, decreasing the reabsorption of bile acids from the terminal ileum.
Absorption: Minimal systemic absorption.
Protein binding: 91%.
Half-life elimination: 1.6 hours.
Excretion: Feces (primary route; 94% as unchanged drug).
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