Ursodeoxycholic Acid

A05A - Bile therapy ATC A05AA02 Small molecule approved 1987 Oral Natural product

JFDA label: URSA Tab

Mechanism of Action

Agonist of Bile acid receptor — Bile acid receptor FXR agonist

Target	Action	Gene / class
Bile acid receptor efficacy	AGONIST	NR1H4

Indications

Approved

Gallstones (capsules only)
Primary biliary cirrhosis (tablets only)

Contraindications

Source: Lexicomp

Aadditional contraindications (not in US labeling): Complete biliary obstruction of extrahepatic origin Absolute
Hypersensitivity to ursodiol or any component of the formulation Absolute
allergy to bile acids Absolute
not to be used with calcified cholesterol stones, radiopaque stones, or radiolucent bile pigment stones Absolute
patients with unremitting acute cholecystitis, cholangitis, biliary obstruction, gallstone pancreatitis, or biliary-gastrointestinal fistula Absolute
widespread intrahepatic obstruction Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Nervous system disorders (2)

Very Common dizziness · Headache

Hepatobiliary disorders (1)

Common Cholecystitis

Renal and urinary disorders (2)

Common Increased serum creatinine · Urinary tract infection

Blood and lymphatic system disorders (2)

Common Leukopenia · thrombocytopenia

Immune system disorders (1)

Common Hypersensitivity reaction

Metabolism and nutrition disorders (1)

Common Hyperglycemia

Gastrointestinal disorders (6)

Very Common constipation · Diarrhea · dyspepsia · nausea

Common peptic ulcer · Vomiting

Skin and subcutaneous tissue disorders (2)

Common Alopecia · skin rash

Musculoskeletal and connective tissue disorders (3)

Very Common Back pain

Common Arthritis · musculoskeletal pain

Infections and infestations (1)

Common Viral infection

Respiratory, thoracic and mediastinal disorders (5)

Very Common Upper respiratory tract infection

Common bronchitis · cough · flu-like symptoms · Pharyngitis

Dosing

Source: Lexicomp

Gallstone dissolution (Actigall): Oral: 8-10 mg/kg/day in 2-3 divided doses; use beyond 24 months is not established Gallstone prevention (Actigall): Oral: 300 mg twice daily Primary biliary cirrhosis (Urso, Urso Forte): Oral: 13-15 mg/kg/day in 2-4 divided doses (with food)

Refer to adult dosing.

There are no dosage adjustments provided in the manufacturer’s labeling.

Warnings & Precautions

Source: Lexicomp

Biliary obstruction

Maintain bile flow during therapy to prevent biliary obstruction. Disease-related concerns:

Hepatic effects

Use with caution in patients with chronic liver disease; monitor liver function tests monthly for the first 3 months, and every 6 months thereafter or as clinically necessary. Discontinuation of therapy may be necessary with significant elevations in liver function tests. Other warnings/precautions:

Appropriate use

Gallbladder stone dissolution may take several months of therapy; complete dissolution may not occur and recurrence of stones within 5 years has been observed in up to 50% of patients. Patients should be cautiously selected for therapy, consider alternative treatments. Specific treatments should be initiated in patients with ascites, hepatic encephalopathy, variceal bleeding, or if an urgent liver transplant is necessary.

Nonvisualizing gallbladder

Use with caution in patients with a nonvisualizing gallbladder; therapy should be discontinued if gallbladder nonvisualization occurs during treatment.

Pregnancy & Lactation

Pregnancy

FDA category B

Adverse events have not been observed in animal reproduction studies. Ursodiol (ursodeoxycholic acid) is the treatment of choice for intrahepatic cholestasis of pregnancy (Kremer, 2011).

Lactation

It is not known if ursodiol is excreted in breast milk. The manufacturer recommends that caution be exercised when administering ursodiol to nursing women.

Monitoring

Clinical pearl	Gallstone disease: ALT, AST, sonogram Hepatic disease: Monitor liver function tests (GGT, AST, ALT, bilirubin, and alkaline phosphatase) monthly for the first 3 months and every 6 months thereafter or as clinically necessary.

Chemistry & Properties

Formula	C24H40O4
Molecular weight	392.58 g/mol
IUPAC name	(4R)-4-[(3R,5S,7S,8R,9S,10S,13R,14S,17R)-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoic acid
CAS	128-13-2
PubChem CID	31401
InChIKey	`RUDATBOHQWOJDD-UZVSRGJWSA-N`
logP	4.48 (XLogP 4.9)
Polar surface area	77.76 Å²
H-bond acceptors / donors	3 / 3
Drug-likeness (QED)	0.66
Lipinski violations	0

SMILES

C[C@H](CCC(=O)O)[C@H]1CC[C@H]2[C@@H]3[C@@H](O)C[C@@H]4C[C@H](O)CC[C@]4(C)[C@H]3CC[C@]12C

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	10.0%
Half-life	1.824 h
Volume of distribution	0.306 L/kg
Protein binding	90.5%
BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP2B6	Inhibitor	—
CYP2C8	Inhibitor	—
CYP3A4	Substrate	—

Receptor binding (top 1)

Target	Action	Affinity
Sodium/bile acid and sulphated solute cotransporter 1 (SLC10A1)	Inhibitor	pIC50 5.4

Transporters

ASBT (Inhibitor)BCRP (Inhibitor)BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MDR1 (Inhibitor)MRP1 (Inhibitor)MRP2 (Inhibitor)MRP4 (Inhibitor)NTCP (Inhibitor)OAT (Inhibitor)OATP (Inhibitor)OATP1A2 (Inhibitor)OATP1B1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)OAT (Substrate)OATP1A2 (Substrate)OATP1B1 (Substrate)OATP1B3 (Substrate)P-gp (Substrate)

Drug–drug interactions (3, DDInter)

Interacting drug	Severity	Management
Aluminum hydroxide	minor
Cyclosporine	minor
Magaldrate	minor

Registered Products (2)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
URSA Tab	Tablet 100 mg	100 tab	IBN CINA DRUG STORE	9.070
Ursa	Capsule 250 mg	60 cap	IBN CINA DRUG STORE	16.890