Urso
Urso
Generic Name
Urso
Mechanism
- Inhibits gallstone formation by reducing the concentration of lithogenic bile components (cholesterol, saturated fatty acids).
- Protects hepatocytes through cholangiocyte membrane stabilization and enhancement of bile acid detoxification.
- Restores bile flow by promoting passive diffusion of bile acids across damaged cholangiocytes and stimulating intrinsic secretion.
- Reduces oxidative stress and inflammatory cytokine release within the liver.
> *Result*: Improved bile composition, decreased bilirubin levels, and decreased pruritus in cholestatic disorders.
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Pharmacokinetics
| Parameter | Typical Value | Comments |
| Absorption | 30–65 % oral | Variable; not bound to food (though dosing with meals improves tolerability). |
| Distribution | Large volume (~1.4 L/kg) | High tissue affinity; minimal plasma protein binding. |
| Metabolism | Hepatic conjugation (glucuronidation) | No active metabolites. |
| Half‑life | 7–9 h (t½) | Prolonged for effect due to enterohepatic circulation. |
| Excretion | Biliary (→ feces) | ~60 % fecal; ~30 % renal unchanged. |
| Drug‑Drug Interactions | Minimal; weak CYP3A4 inducer | Monitor for possible decreased efficacy of antiepileptics & statins. |
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Indications
- Primary Biliary Cholangitis (PBC)
- First‑line therapy; improves alkaline phosphatase (ALP), bilirubin, and fatigue.
- Cholestasis of Pregnancy / Neonatal Cholestasis
- Reduces serum total bile acids and improves liver function tests.
- Choledocholithiasis (Cholesterol Gallbladder Stones)
- Adjunct to lithotripsy or during conservative management.
- Drug‑induced Cholestasis (e.g., from anti‑epileptics, antibiotics)
- Symptomatic relief of pruritus and biochemical improvement.
- Non‑alcoholic Fatty Liver Disease (NAFLD) (off‑label, under investigation)
- Idiopathic Cholestasis
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Contraindications
- Absolute Contraindication:
- Known hypersensitivity to ursodeoxycholic acid or any excipients.
- Avoid in
- Severe hepatic failure (Child‑Pugh Class C).
- Pregnant or nursing women unless benefits outweigh risks.
- Warnings
- Gallbladder disease: May exacerbate gallbladder motility disorders.
- Surgical candidacy: Use cautiously when impending cholecystectomy; may alter gallstone composition.
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Dosing
| Condition | Dose | Frequency | Notes |
| PBC | 10–15 mg/kg/day (max 300–600 mg/day) | Divided doses | Start low; titrate up 2 weeks if well tolerated. |
| Gallstones | 10 mg/kg/day for 6–12 months | Once daily | Continue for 12 mo even if asymptomatic. |
| Neonatal cholestasis | 15 mg/kg/day | Divided dose | Requires close monitoring of bilirubin and hepatic enzymes. |
| Choledocholithiasis | 10–15 mg/kg daily | 3–6 months | Usually in combination with ERCP or lithotripsy. |
• Administration: Oral tablets; can be taken with a meal to reduce GI upset.
• Swallowing Difficulties: Crush and mix with 0.5 mL of water (if medically permissible and not contraindicated).
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Adverse Effects
- Common (≥5 %)
- Nausea, vomiting, diarrhea, abdominal discomfort.
- Skin rash, pruritus (especially with cholestasis).
- Headache, dizziness.
- Serious (≤1 %)
- Stevens–Johnson syndrome (rare hypersensitivity).
- Severe hepatic impairment (elevated transaminases).
- Renal dysfunction in patients with pre‑existing kidney issues.
> *Management*: Discontinue upon hypersensitivity; monitor liver enzymes and renal function periodically.
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Monitoring
| Parameter | Frequency | Rationale |
| Liver enzymes (ALT/AST, ALP, bilirubin) | Every 4–6 weeks (initially) | Efficacy & safety monitoring in cholestasis. |
| Kidney function (serum creatinine, BUN) | Every 3–6 months | Detectable accumulation in renal impairment. |
| Cholesterol | Baseline and every 12 months | Ursodeoxycholic acid can affect lipid profile. |
| Bile acid levels | 6 months, if available | Confirm therapeutic effect in cholestasis. |
| Clinical status | At each visit | Assess pruritus, fatigue, and gastrointestinal symptoms. |
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Clinical Pearls
- “Ursodeoxycholic acid is not a cholangiolytic drug” – Rather, it modulates bile acid composition, so it is ineffective in diseases where bile duct obstruction persists without mechanical clearance.
- Dose titration: Begin at 10‑15 mg/kg; increase every 2 weeks only if tolerated; avoid exceeding 600 mg/day to prevent GI upset.
- Enterohepatic circulation: Extends drug action; this explains why plasma levels plateau quickly yet the therapeutic effect can last weeks.
- Combination therapy: In PBC, co‑administering fluvastatin (to lower LDL) can counteract the mild hypercholesterolemic effect of Ursodeoxycholic acid.
- Pregnancy: While data are limited, the transplacental passage of ursodeoxycholic acid and its safety profile make it a reasonable choice for pruritic cholestasis when the benefits outweigh theoretical risks.
- Drug–Drug Interactions: As a weak CYP3A4 inducer, urso may lower the plasma concentration of certain anti‑epileptics (e.g., carbamazepine). Monitor seizure control and adjust doses accordingly.
- High‑yield mnemonic: U R A B –
- Ursodeoxycholic acid Reduce All bile acids (cholesterol, saturated fats) → Bile flow restored.
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• Key Takeaway
Urso (Ursodiol) remains an essential therapy for cholestatic liver diseases, acting through bile acid modulation. Proper titration, monitoring liver and renal function, and understanding its interaction profile ensure optimal efficacy and patient safety.