maralixibat

Actions and Spectrum:

The action of maralixibat is as an IBAT inhibitor. By blocking IBAT, maralixibat reduces the amount of bile acids that are reabsorbed into the liver and intestine. This leads to a decrease in the concentration of bile acids in the body, which in turn reduces cholestasis (a buildup of bile acids in the liver) and its associated symptoms.

 

The spectrum of maralixibat is limited to its use in the treatment of cholestatic pruritus in children with Alagille syndrome. It is not used to treat other conditions or symptoms, and its effectiveness in other populations has not been established.

DRUG INTERACTION

Contraindicated  

Serious Use Alternative  

Monitor Closely  

Minor  

Frequency defined

>10%

Diarrhea (55.8%)

Abdominal pain (53.5%)

Vomiting (40.7%)

Fat-soluble vitamin deficiency (25.6%)

ALT/AST increased (18.6%)

Gastrointestinal bleeding (10.4%)

1-10%

Bone fractures (9.3%)

Nausea (8.1%)

Black Box Warning:

maralixibat does not currently have a black box warning

Contraindication/Caution:

 

Contraindication

Patients with a known hypersensitivity to maralixibat or any of its components should not take this medication.

 

Caution

maralixibat is not recommended for use in patients with severe liver disease, including cirrhosis.

Patients with a history of bowel obstruction or those at increased risk of bowel obstruction should use maralixibat with caution.

maralixibat has not been studied in pregnant or breastfeeding women, so caution should be exercised when using this medication in these populations.

maralixibat may interact with other medications, including bile acid sequestrants, cyclosporine, and some antifungal medications. Patients should inform their healthcare provider about all medications they are taking before starting maralixibat.

maralixibat may cause gastrointestinal side effects, including diarrhea, abdominal pain, and vomiting. Patients should be monitored for these side effects, and treatment should be adjusted if necessary.

maralixibat may also cause liver function abnormalities, so patients should have their liver function monitored during treatment.

Pregnancy consideration:

Pregnancy category: NA

Lactation: The excretion of drug into human milk is unknown

 

Pregnancy Categories:     

Category A: Studies that were well-controlled and met expectations revealed no risk to the fetus in either the first or second trimester.

Category B: There were lack of studies on pregnant women and no evidence of risk to the fetus in animal experiments.

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.

Category D: adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.

Category N: There is no data available for the drug under this category

Pharmacology:

maralixibat binds to the ileum’s IBAT protein and prevents the reabsorption of bile acids into the bloodstream. As a result, the amount of bile acid in the liver and intestine decreases, lowering the risk of cholestasis and its accompanying symptoms including pruritus (itching) and liver damage. maralixibat is predominantly eliminated in the faeces after being processed in the liver by cytochrome P450 enzymes.

Pharmacodynamics:

maralixibat lowers the amount of bile acids that are returned to the liver by blocking bile acid reabsorption in the ileum. As a result, the levels of bile acids in the liver and intestine are reduced, which reduces cholestasis and its accompanying symptoms. When compared to a placebo, clinical tests on children with Alagille syndrome showed that maralixibat lessens pruritus

Pharmacokinetics:

Absorption

maralixibat is administered orally and is rapidly absorbed after ingestion. The maximum concentration in the blood is reached within approximately 1 hour after dosing. The bioavailability of maralixibat is approximately 15%.

Distribution

maralixibat is extensively distributed throughout the body and is highly protein-bound (99.8%). The volume of distribution is approximately 20 L

Metabolism

Cytochrome P450 enzymes, mainly CYP3A4 and CYP2C9, predominantly metabolise maralixibat in the liver. M1, which is produced through oxidative metabolism, is the primary metabolite of maralixibat. M1 has a lower inhibitory potency for IBAT than the parent medication.

Elimination and Excretion

Only a small portion of maralixibat is excreted in the urine, with the majority being removed through the faeces. Maralixibat has a half-life of roughly 15 hours and a clearance rate of about 8 L/hour.

Administration:

maralixibat is a pill that must be swallowed to be taken by mouth. It is typically used once day, with or without food, and is available as a tablet.

Based on the patient’s body weight, maralixibat is prescribed at the following dosage for the treatment of Alagille syndrome-related pruritus: Individuals under 20 kg should receive 120 g/kg once daily, while those who weigh 20 kg or above should receive 10 mg once daily.

maralixibat pills should not be chewed or mashed; they should be ingested whole with a glass of water.

Patient information leaflet

Generic Name: maralixibat

Why do we use maralixibat?

The drug maralixibat is used to treat cholestatic pruritus in kids with Alagille syndrome. It functions by preventing the ileal bile acid transporter protein (IBAT), which lowers the levels of bile acids in the liver and gut and alleviates symptoms