LIVMARLI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LIVMARLI (LIVMARLI).
LIVMARLI (maralixibat) is an ileal sodium/bile acid cotransporter (IBAT) inhibitor. It reduces bile acid reabsorption in the terminal ileum, increasing fecal bile acid excretion and decreasing systemic bile acid levels, thereby reducing pruritus and cholestatic liver injury.
| Metabolism | Metabolized primarily by UGT1A3 and CYP3A4 to a lesser extent; also undergoes biliary excretion. |
| Excretion | Primarily hepatobiliary (~90% as unchanged drug in feces); renal excretion of unchanged drug is negligible (<1%). |
| Half-life | 28-32 hours in healthy subjects; supports once-daily dosing. |
| Protein binding | >99% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | 0.1-0.3 L/kg, indicating limited extravascular distribution. |
| Bioavailability | Approximately 60% (oral); not administered IV. |
| Onset of Action | Oral: ~2-4 hours based on reduction in serum bile acid levels. |
| Duration of Action | Approximately 24 hours; trough serum bile acid levels maintained below baseline. |
LIVMARLI (maralixibat) is administered orally at a dose of 185 mg (5 mL) once daily, preferably in the morning with a meal. For patients with severe pruritus not adequately controlled, the dose may be increased to 370 mg (10 mL) once daily. Maximum daily dose is 370 mg.
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment is required for mild to moderate renal impairment (eGFR ≥30 mL/min/1.73 m2). There are no data in severe renal impairment (eGFR <30 mL/min/1.73 m2) or end-stage renal disease; use is not recommended. |
| Liver impairment | No dose adjustment is required for mild hepatic impairment (Child-Pugh A). For moderate to severe hepatic impairment (Child-Pugh B or C), the recommended dose is 185 mg (5 mL) once daily; increase to 370 mg (10 mL) once daily only if tolerated and needed. Maximum daily dose is 370 mg. |
| Pediatric use | Approved for pediatric patients 3 months and older weighing at least 5 kg. Dose is weight-based: For patients 5 kg to <12 kg: 185 mg (5 mL) once daily; for ≥12 kg: 185 mg (5 mL) once daily, may increase to 370 mg (10 mL) if needed. Administer with a meal. |
| Geriatric use | No specific dose adjustment is recommended based on age alone. However, consider renal and hepatic function, as elderly patients may have decreased organ function. Use the standard adult dosing with monitoring for adverse effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LIVMARLI (LIVMARLI).
| Breastfeeding | It is unknown whether maralixibat or its metabolites are excreted in human milk. In lactating rats, maralixibat was detected in milk at concentrations similar to maternal plasma. The M/P ratio is not established in humans. Because of the potential for adverse reactions in nursing infants, breastfeeding is not recommended during treatment and for 14 days after the last dose. |
| Teratogenic Risk | LIVMARLI (maralixibat) is an IBAT inhibitor. Limited human data; in animal studies, no evidence of teratogenicity in rats or rabbits at exposures up to 2.7 times the human AUC at the maximum recommended human dose. Risk during pregnancy cannot be completely excluded; first trimester exposure should be avoided unless benefit outweighs risk. Animal studies showed no fetal malformations, but there may be an increased risk of spontaneous abortion. Second and third trimester effects unknown; potential for fetal bile salt accumulation due to IBAT inhibition. Use only if clearly needed. |
■ FDA Black Box Warning
None.
| Serious Effects |
["History of hypersensitivity to maralixibat or any excipients.","Bowel obstruction or significant gastrointestinal motility disorder."]
| Precautions | ["Liver test abnormalities: Monitor ALT, AST, bilirubin, and GGT; dose reduction or interruption may be needed for persistent elevations.","Gastrointestinal adverse reactions: Diarrhea, abdominal pain, vomiting; manage with supportive care.","Fat-soluble vitamin deficiency: Monitor vitamin A, D, E, K levels and supplement as needed.","Hepatobiliary events: Rare cases of liver decompensation; discontinue if severe hepatobiliary injury occurs."] |
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| Fetal Monitoring | Monitor for signs of liver toxicity (elevated liver enzymes, bilirubin), gastrointestinal adverse effects (diarrhea, abdominal pain), and fat-soluble vitamin deficiencies. In pregnancy, monitor fetal growth and amniotic fluid index via ultrasound. Check maternal liver function tests, vitamin A, D, E, K levels periodically. Assess for drug-induced liver injury. |
| Fertility Effects | In animal studies, no effects on male or female fertility were observed at exposures up to 2.7 times the human AUC. Human fertility effects unknown. No specific fertility monitoring required, but consider potential impact of malabsorption on hormonal status. |