Ursodiol
Ursodiol
Generic Name
Ursodiol
Mechanism
- Cholesterol solubilization: Ursodiol replaces hydrophobic bile acids in the bile, increasing the aqueous solubility of cholesterol and preventing stone precipitation.
- Reduction of bile acid pool: By decreasing the ileal reabsorption of endogenous bile acids, it lowers the cholesterol saturation index of bile.
- Anti‑inflammatory and cytoprotective effects: Modulates hepatic cell membrane stability and reduces hepatic inflammation via activation of liver X receptors (LXRs) and nuclear factor‑κB inhibition.
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Pharmacokinetics
| Parameter | Details |
| Absorption | Oral tablets; ~60–70 % bioavailability; best taken on an empty stomach or with a low‑fat meal. |
| Distribution | 50–60 % protein‑bound; penetrates bile ducts (~10–30 % of dose). |
| Metabolism | Minor hepatic biotransformation (CYP2C9) → glucuronide conjugates. |
| Elimination | Primarily biliary excretion; renal clearance contributes ~10 %. |
| Half‑life | 30–36 h (dose‑dependent); steady‑state achieved in ~7–10 days. |
| Special populations | Clearance reduced in severe hepatic impairment; dose adjustment may be needed in chronic kidney disease. |
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Indications
- Cholesterol gallstone dissolution in patients with single, <15 mm gallstones and a small gallbladder volume.
- Pre‑ and post‑operative prophylaxis for gallbladder and bile duct stones (e.g., after cholecystectomy).
- Primary biliary cholangitis (PBC) and other cholestatic liver disorders (e.g., autoimmune cholangitis, metabolic liver disease).
- Biliary dyskinesia secondary to low‑caffeine, low‑fat diet for symptom relief.
- Certain metabolic conditions (e.g., Smith–Lemli–Opitz syndrome) to reduce cholesterol burden.
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Contraindications
- Severe hepatic dysfunction (e.g., acute liver failure, decompensated cirrhosis).
- Choledocholithiasis with obstructive jaundice – urso does not solve mechanical obstruction.
- Gallbladder removal or suspected perforation – not effective.
- Known hypersensitivity to urso or bile acids.
- Pregnancy – not recommended; no definitive safety data.
- Concurrent use with cytochrome P450 inhibitors → possible elevations of serum urso.
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Dosing
| Condition | Typical Adult Dose | Frequency | Notes |
| Gallstone dissolution | 12.5–25 mg/kg/day | Divided q8–12 h | Total ≤ 600 mg/day. |
| PBC/Cholestasis | 10–15 mg/kg/day | Divided q48 h | Usually 6 mths if risk persists. |
| Children (≥1 yr) | 12.5–25 mg/kg/day | Divided q8–12 h | Weight‑based; max 60 mg/kg/day. |
• Administration: Oral tablets; may be crushed if swallowing difficulty.
• Take on an empty stomach (2 h before or 1 h after meals) to maximize absorption.
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Adverse Effects
| Category | Common (≤ 10 %) | Serious (≤ 1 %) | Action |
| GI | Nausea, diarrhea, abdominal pain | Severe, persistent GI upset → treat supportively | Antiemetics / laxatives |
| Hepatic | Mild hepatotoxicity (↑AST/ALT) | Acute liver injury | Monitor LFTs every 6 weeks; discontinue if >5× ULN |
| Dermatologic | Pruritus | Rash, photosensitivity | Hydrocortisone topical, photoprotection |
| Allergic | Rare rash | Anaphylaxis | Stop immediately, treat with epinephrine |
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Monitoring
- Baseline & periodic LFTs (AST, ALT, bilirubin) – every 4–6 weeks during first 3 months.
- Imaging (ultrasound) to assess stone dissolution every 3–6 months.
- Serum cholesterol if used for cholesterol gallstone prophylaxis.
- Medication adherence – counsel on consistent dosing schedule.
- Pregnancy test in women of childbearing age before initiation.
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Clinical Pearls
- Surgical prophylaxis: Even in routine cholecystectomy, a 6‑month course of 10–15 mg/kg/day lowers the risk of postoperative bile duct stones in high‑risk patients.
- High‑dose “pulsed” therapy (e.g., 100 mg q12 h for 4 weeks) may accelerate gallstone dissolution in selected cases.
- Drug interactions: Ursodiol is minimally bound to CYP enzymes but may enhance the effects of other cholestatic drugs (e.g., cholestyramine) by competing for bile acid receptors.
- Long‑term safety: No evidence of carcinogenicity up to 10 years of use in cholestatic liver disease.
- Pregnancy & lactation: Animal studies show no teratogenicity, but human data are limited; use only if benefits outweigh risks.
- Rebound effect: Discontinuation after rapid taper can lead to a “steroid‑like” rebound of cholestasis; taper over 4 weeks when possible.
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• Sources: UpToDate, KDIGO, FDA prescribing information, 2023 American Association for the Study of Liver Diseases (AASLD) guidelines.