Maralixibat

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). • the treatment of cholestatic pruritus in patients 12 months of age and older with progressive familial intrahepatic cholestasis (PFIC). 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.

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.

• Use LIVMARLI Oral Solution 9.5 mg/mL for treatment of ALGS. • Use LIVMARLI Oral Solution 19 mg/mL for treatment of PFIC. • LIVMARLI Tablets can be used for treatment of both ALGS and PFIC in patients weighing 25 kg and above who can swallow tablets. 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 28.5 mg per day for the oral solution and 30 mg per day for the tablets.

LIVMARLI is contraindicated in patients with prior or active hepatic decompensation events (e.g., variceal hemorrhage, ascites, hepatic encephalopathy). Patients with prior or active hepatic decompensation events (e.g., variceal hemorrhage, ascites, hepatic encephalopathy).

• Hepatotoxicity: Obtain baseline liver tests and monitor patients frequently for the first 6 to 8 months after starting therapy, and as clinically indicated thereafter during treatment. If liver test abnormalities or signs of clinical hepatitis occur, consider dose reduction or treatment interruption. For persistent or recurrent liver test abnormalities relative to baseline, discontinue LIVMARLI. Monitor patients with compensated cirrhosis frequently. Permanently discontinue LIVMARLI if hepatic decompensation event occurs. • Gastrointestinal Adverse Reactions: Consider reducing the dosage or interrupting LIVMARLI treatment if a patient experiences persistent diarrhea or abdominal pain, or has diarrhea with bloody stool, vomiting, dehydration requiring treatment, or fever. Consider stopping LIVMARLI treatment if diarrhea or abdominal pain persists and no alternate etiology is identified.

The following clinically significant adverse reactions are described elsewhere in labeling: • Hepatotoxicity • Gastrointestinal Adverse Reactions • Fat Soluble Vitamin (FSV) Deficiency Most common adverse reactions (≥5%) are: • ALGS: diarrhea, abdominal pain, vomiting, fat-soluble vitamin deficiency, liver test abnormalities, and bone fractures. • PFIC: diarrhea, fat soluble vitamin deficiency, abdominal pain, liver test abnormalities, hematochezia, and bone fractures.

• Bile Acid Sequestrants: Modify LIVMARLI administration schedule. 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).

Store unopened LIVMARLI oral solution and tablets between 20°C and 25°C (68°F and 77°F), excursion permitted between 15°C and 30°C (59°F and 86°F).