odevixibat

Action and Spectrum

Actions and Spectrum:  

Regarding its spectrum, odevixibat has been shown to effectively reduce serum bile acid levels in patients with PFIC and Alagille syndrome. In clinical trials, odevixibat was found to significantly reduce pruritus (itching) and improve liver function in patients with PFIC. 

the action of odevixibat is to inhibit ileal bile acid transport and reduce the bile acid pool, which leads to improved symptoms and liver function in patients with certain liver disorders. Its spectrum of activity includes patients with PFIC and Alagille syndrome, as demonstrated by clinical trials. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Adults 

AST/ALT increased (12-21.1%) 

Vomiting (15.8-17.4%) 

Blood bilirubin increased (10.5-13%) 

Splenomegaly (4.8-10.5%) 

Abdominal pain (13-15.8%) 

FSV deficiency (7.1-15.8%) 

Diarrhea (21.1-39.1%)  

1-10% 

Adults 

Dehydration (2.4-5.3%) 

Fracture (4.3%) 

Cholelithiasis (2.4-5.3%) 

Black Box Warning

Black Box Warning:  

The black box warning for odevixibat highlights the potential risk of liver-related severe events, including hepatic decompensation and liver failure. In clinical trials, patients taking odevixibat were found to be at an increased risk of developing these serious liver-related adverse events compared to those receiving a placebo.

Additionally, odevixibat has been associated with an increased risk of bleeding and bruising, particularly in patients taking medications that affect blood clotting. 

Contraindication / Caution

Contraindication/Caution:   

The use of odevixibat is contraindicated in patients who have a history of cholangiocarcinoma, a type of bile duct cancer. Regarding its spectrum, odevixibat has been shown to effectively reduce serum bile acid levels in patients with PFIC and Alagille syndrome. 

Patients who have a known hypersensitivity to odevixibat or any of its components should also avoid taking this medication. 

odevixibat is not recommended for use in patients with severe hepatic impairment, as there is limited data on the safety and effectiveness of this medication in this patient population. 

Pregnancy / Lactation

Pregnancy warnings:     

Pregnancy category: N/A 

Lactation: Excreted 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 a 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 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

Pharmacology: 

odevixibat is a medication that belongs to the class of drugs known as ileal bile acid transport inhibitors. It works by selectively blocking the uptake of bile acids in the ileum, the last section of the small intestine. This leads to a decrease in the amount of bile acids that are released into the gastrointestinal tract and subsequently reduces the overall bile acid pool in the body. 

Pharmacodynamics: 

odevixibat exerts its pharmacodynamic effects by selectively inhibiting the ileal bile acid transporter (IBAT), which is responsible for the uptake of bile acids from the intestinal lumen into enterocytes in the ileum. By inhibiting this transporter, odevixibat reduces the reabsorption of bile acids in the ileum and thereby reduces the overall bile acid pool in the body. 

Mechanism of Action  

odevixibat works by selectively inhibiting the ileal bile acid transporter (IBAT), which is responsible for the uptake of bile acids from the intestinal lumen into enterocytes in the ileum, the last section of the small intestine. By inhibiting this transporter, odevixibat reduces the reabsorption of bile acids in the ileum and thereby reduces the overall bile acid pool in the body. 

Pharmacokinetics:  

Absorption 

odevixibat is taken orally and is rapidly absorbed from the gastrointestinal tract. The absolute bioavailability of odevixibat is approximately 20%. odevixibat is taken with food and the Cmax is increased by approximately 40% and the AUC is increased by approximately 70%. 

Distribution 

odevixibat is highly protein-bound (greater than 99%) and has a large volume of distribution. The mean steady-state volume of distribution is approximately 28 L. 

Metabolism 

odevixibat is primarily metabolized by the liver via cytochrome P450 (CYP) enzymes, specifically CYP3A4 and CYP2C8. The major metabolic pathway of odevixibat is oxidative metabolism, leading to the formation of two major metabolites. The metabolites are inactive and are excreted in the feces. 

Elimination and Excretion 

odevixibat and its metabolites are excreted primarily in the feces. Less than 1% of the administered dose is excreted in the urine. The elimination half-life of odevixibat is approximately 50 hours. 

Adminstartion

Administration:  

odevixibat is available in tablet form for oral administration. The recommended starting dose for patients with progressive familial intrahepatic cholestasis (PFIC) and Alagille syndrome is based on body weight and is as follows: 

For patients weighing less than 25 kg: 40 mg once daily 

For patients weighing 25 kg or more: 120 mg once daily 

odevixibat should be taken with food. Tablets should be swallowed whole with a glass of water and should not be crushed, chewed, or broken. 

If a dose of odevixibat is missed, it should be taken as soon as possible with food. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: odevixibat 

Why do we use odevixibat ?  

odevixibat is used to treat patients with certain liver disorders, specifically progressive familial intrahepatic cholestasis (PFIC) and Alagille syndrome. These disorders are characterized by impaired bile flow and the buildup of toxic levels of bile acids in the liver, leading to liver damage and other associated symptoms. 

odevixibat is a new medication and has been shown to be effective in clinical trials for the treatment of PFIC and Alagille syndrome.