URSODIOL
Clinical safety rating: safe
Animal studies have demonstrated safety
Ursodiol is a hydrophilic bile acid that reduces the concentration of hydrophobic bile acids, thereby decreasing cholesterol secretion into bile and promoting dissolution of cholesterol gallstones. It also exerts cytoprotective effects on hepatocytes by stabilizing cell membranes and reducing apoptosis in cholestatic liver diseases.
| Metabolism | Undergoes enterohepatic circulation; conjugated with glycine or taurine in the liver and secreted into bile; small fraction is deconjugated by intestinal bacteria and converted to lithocholic acid, which is sulfated and excreted. |
| Excretion | Primarily fecal (biliary excretion of unchanged drug and metabolites); minimal renal excretion (<1% unchanged in urine). |
| Half-life | Terminal elimination half-life: 3.5–5.8 days for endogenous bile acids; for exogenous ursodiol, half-life is approximately 4–6 days, reflecting slow turnover of bile acid pool. |
| Protein binding | Approximately 96–98% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution: 0.3–0.5 L/kg; indicates distribution largely within extracellular fluid and bile; low Vd consistent with high protein binding and limited tissue penetration. |
| Bioavailability | Oral bioavailability: Approximately 30–60% after oral administration due to extensive first-pass hepatic clearance; absorption occurs in the small intestine, and absorbed drug is efficiently extracted by the liver. |
| Onset of Action | Oral: Clinical effects (e.g., improvement in liver enzymes, gallstone dissolution) observed after several weeks (4–8 weeks); maximal effect may take 6–24 months for gallstone dissolution. |
| Duration of Action | Duration of action: Not well defined due to long-term therapy; effect persists as long as drug is taken; after discontinuation, bile acid composition returns to pretreatment levels over several weeks. |
| Molecular Weight | 392.57 |
13-15 mg/kg/day orally divided into 2-4 doses for cholesterol gallstones; 13-15 mg/kg/day orally divided into 2-4 doses for primary biliary cholangitis.
| Dosage form | CAPSULE |
| Renal impairment | No specific dose adjustment recommended; use caution in severe renal impairment (eGFR <30 mL/min) due to limited data. |
| Liver impairment | Child-Pugh Class A: No adjustment. Child-Pugh Class B or C: Not recommended; consider alternative therapy. |
| Pediatric use | For cholestatic liver disease: 10-15 mg/kg/day orally divided into 2-3 doses; maximum 15 mg/kg/day. |
| Geriatric use | No specific adjustment required; monitor renal function and for adverse effects. |
| 1st trimester | No evidence of harm in animal studies; human data limited. Generally considered safe if clinically indicated. |
| 2nd trimester | Safe for use in intrahepatic cholestasis of pregnancy. No known teratogenicity. |
| 3rd trimester | Safe for use in intrahepatic cholestasis of pregnancy. May improve bile acid levels. |
Clinical note
Aluminum-based antacids and cholestyramine may reduce absorption Generally well-tolerated with diarrhea being the most common side effect.
| Placental transfer | Crosses placenta; fetal concentrations similar to maternal. |
| Breastfeeding | Excreted into breast milk in low levels; not expected to cause adverse effects in infants. Considered compatible with breastfeeding. |
| Lactation Rating |
■ FDA Black Box Warning
None.
| Common Effects | primary biliary cholangitis |
| Serious Effects |
Hypersensitivity to ursodiol or any componentComplete biliary obstructionSclerosing cholangitis without patency of bile ducts
| Precautions | May cause diarrhea, constipation, nausea, vomiting, dyspepsia; use with caution in patients with pre-existing liver disease or biliary obstruction; not recommended for calcified gallstones or radiopaque stones; monitor liver function tests periodically. |
| Food/Dietary | Take with food or milk to enhance absorption. Avoid high-cholesterol foods as they may counteract the drug's effect on gallstone dissolution. No specific food restrictions, but a low-fat diet may be beneficial. |
Loading safety data…
| L2 (Safer) |
| Teratogenic Risk | Ursodiol is not associated with an increased risk of major congenital malformations based on human data. In animal studies, no teratogenicity was observed at clinically relevant doses. Fetal risk in all trimesters is considered low. |
| Fetal Monitoring | Monitor maternal liver function tests (ALT, AST, GGT, bilirubin) and pruritus severity. In pregnancy, fetal monitoring with ultrasound may be considered if intrahepatic cholestasis of pregnancy is being treated; assess fetal well-being with biophysical profiles or nonstress tests as clinically indicated. |
| Fertility Effects | Ursodiol does not impair fertility in animal studies. In humans, no significant adverse effects on fertility have been reported. |
| Clinical Pearls | Ursodiol is a hydrophilic bile acid that reduces cholesterol saturation in bile and promotes gallstone dissolution. It is also used to treat primary biliary cholangitis (PBC). For gallstone dissolution, patients must have radiolucent, non-calcified gallstones <20 mm in diameter with a functioning gallbladder. Efficacy is limited for stones >15 mm. Treatment may take up to 2 years; monitor with ultrasound every 6-12 months. In PBC, monitor liver function tests; dose adjustment may be needed in severe hepatic impairment. |
| Patient Advice | Take ursodiol with food or milk to improve absorption and reduce GI side effects. · Do not skip doses; take exactly as prescribed. Do not stop without consulting your doctor. · Report persistent diarrhea, severe abdominal pain, or worsening jaundice to your healthcare provider. · For gallstones: treatment may take months to years; stones may not dissolve completely. · Store at room temperature, away from moisture and heat. |