Overview
11 DESCRIPTION LIVMARLI (maralixibat) is an ileal bile acid transporter (IBAT) inhibitor. Maralixibat is present as a chloride salt with the chemical name 1-[[4-[[4-[(4 R ,5 R )-3,3-dibutyl-7-(dimethylamino)-2,3,4,5-tetrahydro-4-hydroxy-1,1-dioxido-1-benzothiepin-5-yl]phenoxy]methyl]phenyl]methyl]-4-aza-1-azoniabicyclo[2.2.2]octane chloride.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Maralixibat is a reversible inhibitor of the ileal bile acid transporter (IBAT). It decreases the reabsorption of bile acids (primarily the salt forms) from the terminal ileum . Pruritus is a common symptom in patients with ALGS or PFIC and the pathophysiology of pruritus in patients with ALGS or PFIC is not completely understood. Although the complete mechanism by which maralixibat improves pruritus in ALGS or PFIC patients is unknown, it may involve inhibition of the IBAT, which results in decreased reuptake of bile salts, as observed by a decrease in serum bile acids [see Clinical Pharmacology (12.2) ] . 12.
Indications
- 1 INDICATIONS AND USAGE LIVMARLI is an ileal bile acid transporter (IBAT) inhibitor indicated for: • the treatment of cholestatic pruritus in patients 3 months of age and older with Alagille syndrome (ALGS). ( 1.1 ) • the treatment of cholestatic pruritus in patients 12 months of age and older with progressive familial intrahepatic cholestasis (PFIC). ( 1.2 ) o Limitations of Use: LIVMARLI is not recommended in a subgroup of PFIC type 2 patients with specific ABCB11 variants resulting in non-functional or complete absence of bile salt export pump (BSEP) protein. ( 14.2 ) 1.
Common Doses
- 9.5 mg
- 19 mg
- 380 mcg
- 190 mcg
Dosage
2 DOSAGE AND ADMINISTRATION • Use LIVMARLI Oral Solution 9.5 mg/mL for treatment of ALGS. ( 2.1 ) • Use LIVMARLI Oral Solution 19 mg/mL for treatment of PFIC. ( 2.1 ) • LIVMARLI Tablets can be used for treatment of both ALGS and PFIC in patients weighing 25 kg and above who can swallow tablets. ( 2.1 ) ALGS: ○ The recommended dosage is 380 mcg/kg once daily, taken 30 minutes before a meal in the morning. ○ Starting dose is 190 mcg/kg orally once daily,and should be increased to 380 mcg/kg daily after one week, as tolerated and not to exceed a maximum daily dose of 28.
Contraindications
- 4 CONTRAINDICATIONS LIVMARLI is contraindicated in patients with prior or active hepatic decompensation events (e.g., variceal hemorrhage, ascites, hepatic encephalopathy) [see Warnings and Precautions (5.1) ] . Patients with prior or active hepatic decompensation events (e.g., variceal hemorrhage, ascites, hepatic encephalopathy). ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in labeling: • Hepatotoxicity [see Warnings and Precautions (5.1) ] • Gastrointestinal Adverse Reactions [see Warnings and Precautions (5.2) ] • Fat Soluble Vitamin (FSV) Deficiency [see Warnings and Precautions (5.3) ] Most common adverse reactions (≥5%) are: • ALGS: diarrhea, abdominal pain, vomiting, fat-soluble vitamin deficiency, liver test abnormalities, and bone fractures. ( 6.
Interactions
- 7 DRUG INTERACTIONS • Bile Acid Sequestrants: Modify LIVMARLI administration schedule. ( 7.1 ) 7.1 Effects of Other Drugs on LIVMARLI Bile Acid Binding Resins Bile acid binding resins may bind to maralixibat in the gut. Administer LIVMARLI at least 4 hours before or 4 hours after administration of bile acid binding resins (e.g., cholestyramine, colesevelam, or colestipol). 7.2 Effects of LIVMARLI on Other Drugs OATP2B1 substrates Maralixibat is an OATP2B1 inhibitor based on in vitro studies. A decrease in the oral absorption of OATP2B1 substrates (e.g.