Identification
- Summary
Odevixibat is an ileal sodium/bile acid cotransporter inhibitor indicated in the treatment of pruritus in patients with progressive familial intrahepatic cholestasis.
- Brand Names
- Bylvay
- Generic Name
- Odevixibat
- DrugBank Accession Number
- DB16261
- Background
Odevixibat, or A4250, is an ileal sodium/bile acid cotransporter inhibitor indicated for the treatment of pruritus in patients older than 3 months, with progressive familial intrahepatic cholestasis (PFIC).1,5 Odevixibat is the first approved non-surgical treatment option for PFIC.7 Previous therapies for PFIC included a bile acid sequestrant such as ursodeoxycholic acid.1
Odevixibat was granted FDA and Health Canada approval on 20 July 2021 and 13 November 2023 respectively.5,11
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Odevixibat (DB16261)
- Weight
- Average: 740.93
Monoisotopic: 740.29135687 - Chemical Formula
- C37H48N4O8S2
- Synonyms
- Odevixibat
- External IDs
- A-4250
- A4250
- AR-H064974
- AZD-8294
- AZD8294
- WHO 10706
Pharmacology
- Indication
Odevixibat is indicated for the treatment of pruritus in patients older than 3 months and 6 months with progressive familial intrahepatic cholestasis (PFIC) by the FDA and Health Canada respectively.9,10 It is also indicated for the treatment of cholestatic pruritus in patients 12 months of age and older with Alagille Syndrome.9 Odevixibat may not be effective in patients with PFIC type 2 with ABCB11 variants since these patients lack a functional bile salt export pump.5
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Cholestatic pruritus •••••••••••• •••••••• •••••••• •••••••• •••••• Treatment of Pruritus •••••••••••• •••••• Treatment of Pruritus •••••••••••• ••••••••••• •••••••• •••••••••••• ••••••••••• •••••• •••••••• •••••• - Contraindications & Blackbox Warnings
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Odevixibat, or A4250, is an ileal sodium/bile acid cotransporter inhibitor indicated for the treatment of pruritus in patients older than 3 months, with progressive familiar intrahepatic cholestasis (PFIC).1,5 It has a moderate duration of action as it is given once daily.5 Odevixibat has a wide therapeutic index as patients were given single doses up to 10 mg while the maximum therapeutic dose is 6 mg daily.1,5 Patients should be counselled regarding the risks of elevated liver function tests, diarrhea, and fat soluble vitamin defiencies.5
- Mechanism of action
Progressive familiar intrahepatic cholestasis (PFIC) is a group of autosomal recessive disorders leading to cholestasis, fibrosis, and eventually a need for liver transplantation.2 Patients with PFIC require liver transplants or develop hepatocellular carcinomas in their first few years of life.2 Many of these patients experience severe pruritus.2 The exact mechanism of pruritus is PFIC is not known, but lower concentrations of bile acids have been shown to reduce pruritus.3,4,5 Patients with certain forms of PFIC type 2, associated with a non-functional or absent bile salt export pump, are not expected to benefit from odevixibat treatment.5
The ileal sodium/bile acid cotransporter is a transport glycoprotein responsible for reabsorption of 95% of bile acids in the distal ileum.1 Odevixibat is a reversible inhibitor of the ileal sodium/bile acid contransporter.1,5 Patients taking odevixibat for a week experienced a 56% reduction in bile acid area under the curve with a 3 mg once daily dose.1 A 1.5 mg daily dose lead to a 43% reduction in bile acid area under the curve.1
The decreased reabsorption of bile acids, leads to reduced stimulation of FXR, which reduces expression of FGF19, reducing binding of FGF19 to FGF4R, decreasing inhibition of bile acid synthesis.1 Further synthesis of bile acids that will not be reabsorbed in the intestine contributes to lowering low density lipoprotein levels.1
Target Actions Organism AIleal sodium/bile acid cotransporter inhibitorHumans - Absorption
A 7.2 mg single oral dose of odevixibat in adults reaches a Cmax of 0.47 ng/mL, with an AUC0-24h of 2.19 h*ng/mL.5 The majority of adult and pediatric patients, given a therapeutic dose, do not have detectable plasma concentrations of odevixibat.1,5
- Volume of distribution
The majority of adult and pediatric patients, given a therapeutic dose, do not have detectable plasma concentrations of odevixibat.1,5 Therefore, a volume of distribution has not been calculated.1,5
- Protein binding
Due to the low systemic abosrption of odevixibat, plasma protein binding studies could not be performed in vivo.5 Odevixibat is >99% protein bound in vitro.5
- Metabolism
Odevixibat is largely unmetabolized, however a small amount is metabolized in vitro by mono-hydroxylation.5 The exact structure of the metabolite has not been characterized as a primary endpoint of the clinical trial was to characterize the structure of metabolites accounting for >10% of the dose in plasma, urine, or feces.6 No metabolites have been identified at such a high concentration.5
- Route of elimination
Odevixibat is 82.9% recovered in the feces and <0.002% recovered in the urine.5 The dose recovered in the feces is 97% unchanged parent compound.5
- Half-life
A 7.2 mg oral dose of odevixibat has a mean half life of 2.36 hours in adults.5
- Clearance
The majority of adult and pediatric patients, given a therapeutic dose, do not have detectable plasma concentrations of odevixibat.1,5 Therefore, the clearance has not been calculated.1,5
- Adverse Effects
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Data regarding overdoses of odevixibat are not readily available, due to the low systemic absorption of the drug.5 If patients experience an overdose, initiate treatment with symptomatic and supportive measures.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareCholestyramine The therapeutic efficacy of Odevixibat can be decreased when used in combination with Cholestyramine. Colesevelam The therapeutic efficacy of Odevixibat can be decreased when used in combination with Colesevelam. Colestipol The therapeutic efficacy of Odevixibat can be decreased when used in combination with Colestipol. Sevelamer The therapeutic efficacy of Odevixibat can be decreased when used in combination with Sevelamer. - Food Interactions
- Take with a high fat meal. The effect of food is not clinically significant.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- International/Other Brands
- Bylvay (Albireo Pharma, Inc.)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Bylvay Capsule 1200 mcg Oral Medison Pharma Canada Inc. Not applicable Not applicable Canada 
Bylvay Capsule 200 mcg Oral Medison Pharma Canada Inc. Not applicable Not applicable Canada Bylvay Capsule, coated pellets 400 ug/1 Oral Albireo Pharma, Inc. 2021-07-20 Not applicable US 
Bylvay Capsule 1200 µg Oral Albireo 2021-10-06 Not applicable EU 
Bylvay Capsule 200 µg Oral Albireo 2021-10-06 Not applicable EU
Categories
- ATC Codes
- A05AX05 — Odevixibat
- Drug Categories
- Classification
- Not classified
- Affected organisms
- Humans
Chemical Identifiers
- UNII
- 2W150K0UUC
- CAS number
- 501692-44-0
- InChI Key
- XULSCZPZVQIMFM-IPZQJPLYSA-N
- InChI
- InChI=1S/C37H48N4O8S2/c1-5-8-19-37(20-9-6-2)24-41(26-13-11-10-12-14-26)29-21-31(50-4)30(22-32(29)51(47,48)40-37)49-23-33(43)39-34(25-15-17-27(42)18-16-25)35(44)38-28(7-3)36(45)46/h10-18,21-22,28,34,40,42H,5-9,19-20,23-24H2,1-4H3,(H,38,44)(H,39,43)(H,45,46)/t28-,34+/m0/s1
- IUPAC Name
- (2S)-2-[(2R)-2-(2-{[3,3-dibutyl-7-(methylsulfanyl)-1,1-dioxo-5-phenyl-2,3,4,5-tetrahydro-1lambda6,2,5-benzothiadiazepin-8-yl]oxy}acetamido)-2-(4-hydroxyphenyl)acetamido]butanoic acid
- SMILES
- CCCCC1(CCCC)CN(C2=CC=CC=C2)C2=CC(SC)=C(OCC(=O)N[C@@H](C(=O)N[C@@H](CC)C(O)=O)C3=CC=C(O)C=C3)C=C2S(=O)(=O)N1
References
- General References
- Graffner H, Gillberg PG, Rikner L, Marschall HU: The ileal bile acid transporter inhibitor A4250 decreases serum bile acids by interrupting the enterohepatic circulation. Aliment Pharmacol Ther. 2016 Jan;43(2):303-10. doi: 10.1111/apt.13457. Epub 2015 Nov 2. [Article]
- Davit-Spraul A, Gonzales E, Baussan C, Jacquemin E: Progressive familial intrahepatic cholestasis. Orphanet J Rare Dis. 2009 Jan 8;4:1. doi: 10.1186/1750-1172-4-1. [Article]
- Slavetinsky C, Sturm E: Odevixibat and partial external biliary diversion showed equal improvement of cholestasis in a patient with progressive familial intrahepatic cholestasis. BMJ Case Rep. 2020 Jun 29;13(6). pii: 13/6/e234185. doi: 10.1136/bcr-2019-234185. [Article]
- Al-Dury S, Marschall HU: Ileal Bile Acid Transporter Inhibition for the Treatment of Chronic Constipation, Cholestatic Pruritus, and NASH. Front Pharmacol. 2018 Aug 21;9:931. doi: 10.3389/fphar.2018.00931. eCollection 2018. [Article]
- FDA Approved Drug Products: Bylvay (Odevixibat) Oral Capsule [Link]
- Clinical Trials: NCT03082937 [Link]
- Globe Newswire: Albireo Announces FDA Approval of Bylvay (odevixibat), the First Drug Treatment for Patients With Progressive Familial Intrahepatic Cholestasis (PFIC) [Link]
- FDA Approved Drug Products: Bylvay (Odevixibat) Oral Capsule (May 2023) [Link]
- FDA Approved Drug Products: Bylvay (Odevixibat) Oral Capsule (June 2023) [Link]
- Health Canada Approved Drug Proucts: BYLVAY (Odevixibat) capsule for oral use [Link]
- Ipsen and Medison Pharma Announce Health Canada Approval of Bylvay™ (odevixibat) for the treatment of pruritus due to Progressive Familial Intrahepatic Cholestasis (PFIC) [Link]
- External Links
- Human Metabolome Database
- HMDB0304842
- ChemSpider
- 8329135
- BindingDB
- 77040
- 2563966
- ChEMBL
- CHEMBL4297588
- PharmGKB
- PA166268805
- Wikipedia
- Odevixibat
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 3 Active Not Recruiting Treatment Alagille Syndrome 1 3 Active Not Recruiting Treatment Progressive Familial Intrahepatic Cholestasis (PFIC) 1 3 Completed Treatment Alagille Syndrome 1 3 Completed Treatment PFIC1 / PFIC2 1 3 Enrolling by Invitation Treatment Biliary Atresia 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Capsule Oral 1200 mcg Capsule Oral 1200 ug/1 Capsule Oral 1200 µg Capsule Oral 200 µg Capsule Oral 200 mcg Capsule Oral 400 ug/1 Capsule Oral 400 µg Capsule Oral 400 mcg Capsule Oral 600 µg Capsule Oral 600 mcg Capsule, coated pellets Oral 1200 ug/1 Capsule, coated pellets Oral 200 ug/1 Capsule, coated pellets Oral 400 ug/1 Capsule, coated pellets Oral 600 ug/1 - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US10487111 No 2019-11-26 2031-11-08 US US10981952 No 2021-04-20 2031-11-08 US US9694018 No 2017-07-04 2031-11-08 US US10011633 No 2018-07-03 2031-11-08 US US10093697 No 2018-10-09 2031-11-08 US US7132416 No 2006-11-07 2022-09-05 US US10975046 No 2021-04-13 2039-06-20 US US11365182 No 2019-06-20 2039-06-20 US US11583539 No 2021-11-12 2041-11-12 US US11732006 No 2011-11-08 2031-11-08 US US11801226 No 2019-06-20 2039-06-20 US US11802115 No 2019-06-20 2039-06-20 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.00115 mg/mL ALOGPS logP 4.44 ALOGPS logP 6.28 Chemaxon logS -5.8 ALOGPS pKa (Strongest Acidic) 3.4 Chemaxon pKa (Strongest Basic) -3.4 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 9 Chemaxon Hydrogen Donor Count 5 Chemaxon Polar Surface Area 174.37 Å2 Chemaxon Rotatable Bond Count 17 Chemaxon Refractivity 197.31 m3·mol-1 Chemaxon Polarizability 80.03 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Bile acid:sodium symporter activity
- Specific Function
- Plays a critical role in the sodium-dependent reabsorption of bile acids from the lumen of the small intestine. Plays a key role in cholesterol metabolism.
- Gene Name
- SLC10A2
- Uniprot ID
- Q12908
- Uniprot Name
- Ileal sodium/bile acid cotransporter
- Molecular Weight
- 37713.405 Da
References
- Karpen SJ, Kelly D, Mack C, Stein P: Ileal bile acid transporter inhibition as an anticholestatic therapeutic target in biliary atresia and other cholestatic disorders. Hepatol Int. 2020 Sep;14(5):677-689. doi: 10.1007/s12072-020-10070-w. Epub 2020 Jul 11. [Article]
- FDA Approved Drug Products: Bylvay (Odevixibat) Oral Capsule [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
References
- FDA Approved Drug Products: Bylvay (Odevixibat) Oral Capsule [Link]
Drug created at December 15, 2020 18:17 / Updated at January 10, 2024 06:22