Livmarli

The following dosing information is available for LIVMARLI (maralixibat chloride):

Dosing
Administration
LIVMARLI
Generic

No enhanced Dosing information available for this drug.

Maralixibat is administered orally as a solution. The 9.5 mg of maralixibat per mL solution should be used for treatment of Alagille syndrome and the 19 mg of maralixibat per mL solution should be used for treatment of progressive familial intrahepatic cholestasis.

The 2 strengths of maralixibat should not be substituted for one another. Clinicians should carefully calculate the maralixibat dose volume. For patients <5 years of age this is especially important as maralixibat oral solution contains propylene glycol (364.5 mg/mL).

Administer maralixibat oral solution 30 minutes before a meal in the morning, using the provided calibrated measuring device (0.5 mL, 1 mL, or 3 mL oral dispenser). If a once daily dose is missed, the missed dose should be taken as soon as possible within 12 hours of the time it is usually taken, and then resume the normal dosing schedule. If the dose is missed by more than 12 hours, skip the missed dose and take the next dose at the regularly scheduled time.

If a twice daily dose is missed, the missed dose should be taken as soon as possible within 6 hours of the time it is usually taken, and then resume the normal dosing schedule. If the dose is missed by more than 6 hours, skip the missed dose and take the next dose at the regularly scheduled time. Store unopened maralixibat oral solution at 20-25degreesC (excursions permitted between 15-30degreesC).

After opening the bottle of maralixibat oral solution, store at <30degreesC. Discard any remaining solution 100 days after the first opening of the bottle. Maralixibat should be administered at least 4 hours before or after administration of bile acid sequestrants.

Dosing information for LIVMARLI
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
LIVMARLI 9.5 MG/ML ORAL SOLN	Maintenance	Adults take 380 mcg/kg (up to max 28.5 mg) by oral route once daily
LIVMARLI 19 MG/ML ORAL SOLN	Maintenance	Adults take 570 mcg/kg (up to max 19 mg) by oral route 2 times per day
LIVMARLI 10 MG TABLET	Maintenance	Adults take 1 tablet (10 mg) by oral route once daily in the morning, at least 30 minutes before a meal
LIVMARLI 15 MG TABLET	Maintenance	Adults take 1 tablet (15 mg) by oral route once daily in the morning, at least 30 minutes before a meal
LIVMARLI 20 MG TABLET	Maintenance	Adults take 1 tablet (20 mg) by oral route once daily in the morning, at least 30 minutes before a meal
LIVMARLI 30 MG TABLET	Maintenance	Adults take 1 tablet (30 mg) by oral route once daily in the morning, at least 30 minutes before a meal

No generic dosing information available.

The following drug interaction information is available for LIVMARLI (maralixibat chloride):

Contraindicated
Severe
Moderate

There are 0 contraindications.

There are 0 severe interactions.

There are 1 moderate interactions. The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.

Drug Interaction	Drug Names
Maralixibat; Odevixibat/Bile Acid Sequestrants SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Bile acid sequestrants may bind to maralixibat and odevixibat in the gut, resulting in decreased absorption of maralixibat or odevixibat.(1,2) CLINICAL EFFECTS: Coadministration of bile acid sequestrants with maralixibat or odevixibat may cause reduced efficacy of maralixibat or odevixibat.(1,2) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturers states to administer bile acid sequestrants (cholestyramine, colesevelam, and colestipol) at least 4 hours before or 4 hours after administration of maralixibat or odevixibat.(1,2) DISCUSSION: Bile acid sequestrants are known to bind to drugs when given concurrently. Administration with maralixibat or odevixibat may result in decreased systemic absorption.(1,2)	CHOLESTYRAMINE, CHOLESTYRAMINE LIGHT, CHOLESTYRAMINE RESIN, COLESEVELAM HCL, COLESTID, COLESTIPOL HCL, PREVALITE, QUESTRAN, QUESTRAN LIGHT, WELCHOL

Drug Interaction

Drug Names

Maralixibat; Odevixibat/Bile Acid Sequestrants

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Bile acid sequestrants may bind to maralixibat and odevixibat in the gut, resulting in decreased absorption of maralixibat or odevixibat.(1,2)

CLINICAL EFFECTS: Coadministration of bile acid sequestrants with maralixibat or odevixibat may cause reduced efficacy of maralixibat or odevixibat.(1,2)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturers states to administer bile acid sequestrants (cholestyramine, colesevelam, and colestipol) at least 4 hours before or 4 hours after administration of maralixibat or odevixibat.(1,2)

DISCUSSION: Bile acid sequestrants are known to bind to drugs when given concurrently. Administration with maralixibat or odevixibat may result in decreased systemic absorption.(1,2)

CHOLESTYRAMINE, CHOLESTYRAMINE LIGHT, CHOLESTYRAMINE RESIN, COLESEVELAM HCL, COLESTID, COLESTIPOL HCL, PREVALITE, QUESTRAN, QUESTRAN LIGHT, WELCHOL

The following contraindication information is available for LIVMARLI (maralixibat chloride):

Overview
Contraindicated
Severe
Moderate

Drug contraindication overview.

*Prior or active hepatic decompensation events.

There are 0 contraindications.

There are 7 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Ascites
Bleeding esophageal varices
Hepatic encephalopathy
Vitamin A deficiency
Vitamin D deficiency
Vitamin E deficiency
Vitamin K deficiency

There are 1 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Disease of liver

The following adverse reaction information is available for LIVMARLI (maralixibat chloride):

Overview
Severe
Less Severe

Adverse reaction overview.

The most common adverse reactions (>=5%) reported with maralixibat in clinical studies for Alagille syndrome were diarrhea, abdominal pain, vomiting, fat-soluble vitamin deficiency, liver test abnormalities, and bone fractures. The most common adverse reactions (>=5%) reported with maralixibat in clinical studies for progressive familial intrahepatic cholestasis were diarrhea, fat-soluble vitamin deficiency, abdominal pain, liver test abnormalities, hematochezia, and bone fractures.

There are 5 severe adverse reactions.

More Frequent	Less Frequent
Abnormal hepatic function tests Fracture Gastrointestinal hemorrhage	Hyperbilirubinemia

Rare/Very Rare
Intracranial bleeding

There are 10 less severe adverse reactions.

More Frequent	Less Frequent
Acute abdominal pain Diarrhea Vitamin A deficiency Vitamin D deficiency Vitamin E deficiency Vitamin K deficiency Vomiting	Nausea

Rare/Very Rare
Bloody vomit Gamma-glutamyl transferase raised

The following precautions are available for LIVMARLI (maralixibat chloride):

Pediatric
Pregnant
Lactation
Geriatric

Safety and efficacy of maralixibat for the treatment of cholestatic pruritus in pediatric patients with Alagille syndrome have been established in the ICONIC study, which included 31 patients 1-15 years of age. Use of maralixibat in patients 3 to <12 months of age is supported by an open label, multicenter study which demonstrated similar safety, tolerability, and pharmacokinetic parameters compared with patients with Alagille syndrome >=12 months of age. Additional safety information was obtained from 4 studies in 55 patients up to 21 years of age.

Safety and efficacy of maralixibat have not been established in patients with Alagille syndrome <3 months of age. Safety and efficacy of maralixibat for the treatment of cholestatic pruritus in pediatric patients >=12 months of age with progressive familial intrahepatic cholestasis have been established. Clinicians should use the 19 mg/mL formulation of maralixibat in patients with this condition in order to minimize exposure to propylene glycol. Safety and efficacy of maralixibat have not been established in patients with progressive familial intrahepatic cholestasis <12 months of age.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None

Administration of maralixibat during pregnancy is not expected to result in measurable fetal exposure because the drug is minimally absorbed following oral administration. In animal reproduction studies, no developmental effects were observed. Maralixibat may inhibit the absorption of fat-soluble vitamins. Increased supplementation of fat-soluble vitamins may be necessary during pregnancy.

Maralixibat is minimally absorbed following oral administration; therefore, breast-feeding is not expected to result in exposure of the infant to the drug at the recommended dosage. It is not known whether maralixibat is distributed into human milk. The effects of the drug on breast-fed infants or on the production of milk also are unknown.

Consider the developmental and health benefits of breast-feeding along with the mother's need for maralixibat and any potential adverse effects on the breast-fed infant from the drug or underlying maternal condition. Patients with Alagille syndrome or progressive familial intrahepatic cholestasis may have concomitant fat-soluble vitamin deficiency. Because maralixibat may further reduce absorption of fat-soluble vitamins, levels of these vitamins should be monitored and supplementation should be provided if a deficiency is diagnosed during lactation.

Safety and efficacy of maralixibat for the treatment of pruritus in patients with Alagille syndrome or progressive familial intrahepatic cholestasis have not been established in patients >=65 years of age.

Cholestatic pruritus in patients with alagille syndrome
L29.8	Other pruritus
L29.81	Cholestatic pruritus
Q44.71	Alagille syndrome
Pruritus in progressive familial intrahepat. cholestasis
K83.1	Obstruction of bile duct