URSO 250
Clinical safety rating: caution
Comprehensive clinical and safety monograph for URSO 250 (URSO 250).
Ursodeoxycholic acid (UDCA) reduces endogenous bile acid synthesis and secretion by inhibiting cholesterol absorption and decreasing bile acid hydrophobicity. It also displaces toxic endogenous bile acids from the enterohepatic circulation and exerts cytoprotective, anti-apoptotic, and immunomodulatory effects on hepatocytes and cholangiocytes.
| Metabolism | Conjugation with glycine and taurine in the liver; undergoes enterohepatic circulation with eventual renal excretion as conjugates. Minor metabolism via dehydroxylation by gut bacteria to lithocholic acid. |
| Excretion | Primarily fecal excretion (biliary) as unchanged drug; minimal renal excretion (<1%). Enterohepatic circulation occurs, with small amounts eliminated in bile. |
| Half-life | Terminal elimination half-life is approximately 3.5 to 5.8 days in patients with cholestatic liver disease, reflecting extensive enterohepatic recycling; in healthy individuals, half-life may be shorter. |
| Protein binding | Approximately 70% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | 0.1-0.3 L/kg; small volume indicating limited extravascular distribution, consistent with predominant confinement to the enterohepatic circulation and bile. |
| Bioavailability | Oral bioavailability is low, approximately 20-30% due to extensive first-pass hepatic extraction; however, absorption is enhanced in the presence of bile acids. |
| Onset of Action | Oral: Onset of action is gradual; clinical effects on biliary cholesterol saturation may be observed within 1 to 4 weeks, but maximal therapeutic benefit in primary biliary cholangitis may require 1 to 3 months. |
| Duration of Action | Duration of action is prolonged due to enterohepatic circulation, with effects persisting for days after discontinuation; clinical improvement in liver biochemistries may take months. |
13-15 mg/kg/day orally in 2-4 divided doses for primary biliary cholangitis; 300 mg twice daily for gallstone dissolution.
| Dosage form | TABLET |
| Renal impairment | No specific dose adjustment required for renal impairment; use with caution in severe impairment (eGFR <30 mL/min) due to limited data. |
| Liver impairment | Child-Pugh A/B: No adjustment. Child-Pugh C: Avoid use or reduce dose to 10 mg/kg/day based on tolerability. |
| Pediatric use | 5-10 mg/kg/day orally in 2-3 divided doses for cholestatic liver disease; not established for gallstones. |
| Geriatric use | Initiate at lower end of dosing range (10-13 mg/kg/day) due to age-related reduced hepatic function; monitor liver function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for URSO 250 (URSO 250).
| Breastfeeding | UDCA is excreted into breast milk in low amounts. M/P ratio not established. No adverse effects reported in breastfed infants. Considered compatible with breastfeeding; use caution in preterm or jaundiced infants. |
| Teratogenic Risk | Ursodeoxycholic acid (UDCA) is not known to be teratogenic. Data from prospective studies in women with intrahepatic cholestasis of pregnancy (ICP) show no increased risk of congenital malformations. First trimester exposure: no evidence of teratogenicity. Second and third trimester exposure: used therapeutically for ICP, no fetal harm reported. |
■ FDA Black Box Warning
None
| Serious Effects |
Absolute: Complete biliary obstruction, calcified or radiopaque gallstones, non-functioning gallbladder, acute cholecystitis, hypersensitivity to any component. Relative: Chronic liver disease with decompensated cirrhosis, pregnancy (though not contraindicated, benefit must outweigh risk).
| Precautions | Monitor liver function tests (LFTs) and bilirubin levels; discontinue if LFTs worsen or signs of cholestasis develop. May unmask or exacerbate hepatic decompensation in patients with cirrhosis. Use with caution in patients with chronic liver disease, pregnancy (Category B), or known hypersensitivity to bile acids. |
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| Fetal Monitoring |
| Monitor liver function tests (ALT, AST, GGT, bilirubin) and bile acids. In pregnancy, monitor fetal well-being with non-stress tests and biophysical profiles due to underlying ICP. |
| Fertility Effects | No known adverse effects on fertility. UDCA is used to improve bile flow and may benefit patients with primary biliary cholangitis, potentially improving fertility outcomes by reducing cholestasis-related hormonal disturbances. |