Livmarli Generic Name & Formulations
Maralixibat 9.5mg/mL; oral soln; grape flavor.
Ileal bile acid transporter (IBAT) inhibitor.
Mechanism of Action
Maralixibat decreases the reabsorption of bile acids (primarily the salt forms) from the terminal ileum. The complete mechanism by which maralixibat improves pruritus in ALGS patients is unknown, but it may involve inhibition of the IBAT, which results in decreased reuptake of bile salts, as observed by a decrease in serum bile acids.
Treatment of cholestatic pruritus in Alagille syndrome (ALGS).
Livmarli Dosage and Administration
Adults and Children
<3mos: not established. Use a calibrated measuring device. Give at 30mins before a meal in the AM. ≥3mos: initially 190mcg/kg once daily; after 1 week, increase to 380mcg/kg once daily, as tolerated. Max daily dose (patients >70kg): 3mL or 28.5mg/day. For individual dose volume by weight, dose modification for adverse events: see full labeling.
Livmarli Boxed Warnings
Obtain baseline liver tests (eg, ALT, AST, total/direct bilirubin, INR) and monitor during therapy; consider dose reduction or interruption if abnormalities occur in the absence of other causes. Consider discontinuing if persistent or recurrent liver test abnormalities occur. ALGS with cirrhosis: monitor for liver elevations, liver-related adverse reactions; permanently discontinue if progresses to portal hypertension or a hepatic decompensation event (eg, variceal hemorrhage, ascites, hepatic encephalopathy). Consider dose reduction or interruption if GI reactions occur (diarrhea, abdominal pain, vomiting) and no alternate etiology is identified. Monitor for dehydration if diarrhea or vomiting occur. Consider dose interruption if persistent diarrhea or diarrhea accompanied with signs/symptoms occur; restart and adjust dose appropriately when resolves. Obtain serum fat-soluble vitamin (FSV) levels at baseline and monitor during therapy; consider discontinuing if FSV deficiency persists or worsens despite supplementation. Elderly (≥65yrs), ALGS with clinically significant portal hypertension or with decompensated cirrhosis: not established. Pregnancy. Nursing mothers.
Maralixibat is minimally absorbed and plasma concentrations are often below the limit of quantification (0.25 ng/mL) after single or multiple doses at recommended doses. Following a single oral administration of maralixibat 30, 45, and 100 mg liquid formulation under fasted condition, AUClast and Cmax increased in a dose-dependent manner with increase of 4.6-and 2.4-fold, respectively, following a 3.3-fold dose increase from 30–100 mg.
Effect of Food: Concomitant administration of a high-fat meal with a single oral dose of maralixibat decreased both the rate and extent of absorption. AUC and Cmax of maralixibat values in the fed state were 64.8% to 85.8% lower relative to oral administration of 30 mg in fasted conditions.
Plasma protein bound: 91%.
Fecal (73%), renal (0.066%). Half-life: 1.6 hours.
Administer bile acid binding resins (eg, cholestyramine, colesevelam, colestipol) at least 4hrs before or 4hrs after. Concomitant OATP2B1 substrates (eg, statins); monitor as needed.
Livmarli Adverse Reactions
Diarrhea, abdominal pain, vomiting, fat-soluble vitamin deficiency, liver test abnormalities, GI bleeding, bone fractures.
Livmarli Clinical Trials
Livmarli Patient Counseling