Generic Name

Urso Forte

Mechanism

Urso Forte exerts its therapeutic effects by:
• Replacing hydrophobic, cytotoxic bile acids in the bile pool, thereby decreasing detergent injury to cholangiocytes.
• Increasing the solubility of cholesterol in bile, which reduces cholesterol crystallization and gallstone formation.
• Enhancing hepatocyte protection through up‑regulation of antioxidant defenses and inhibition of apoptosis.
• Stimulating bile flow (choleresis) via modulation of bile acid transporters (NTCP, BSEP).

These actions lower serum bilirubin and improve cholestatic liver enzyme abnormalities.

Pharmacokinetics

• Absorption: Oral tablets are absorbed in the proximal small intestine; bioavailability ≈ 70 %.
• Distribution: Widely distributed; highly protein‑bound (~ 70 %).
• Metabolism: Minimal hepatic metabolism; primarily excreted unchanged.
• Excretion: Biliary (≈ 80 %) and fecal; small renal component.
• Half‑life: 6–8 hours; steady state reached in 3–5 days.
• Special populations:
• *Elderly:* Slightly longer half‑life; dose adjustment may be required.
• *Renal impairment:* Minimal impact; no dose change necessary.
• *Hepatic impairment:* Contraindicated in severe cirrhosis (Child‑Pugh C).

Indications

• Primary Biliary Cholangitis (PBC) – first‑line therapy to delay progression to cirrhosis.
• Gallstone management – prevention of symptomatic cholesterol gallstones in high‑risk patients.
• Drug‑induced cholestatic liver injury – supportive therapy to alleviate cholestasis.
• Cholestasis of pregnancy – safe adjunct to relieve pruritus and prevent liver failure.
• Extrahepatic bile duct obstruction – as adjunct to biliary drainage when stones cannot be cleared immediately.

Contraindications

• Contraindications
• Severe hepatic insufficiency (Child‑Pugh C).
• Known hypersensitivity to UDCA or any excipients.
• Warnings
• Gallstone risk: Chronic therapy can reduce cholesterol saturation; however, abrupt discontinuation may precipitate stone formation.
• Drug interactions: May alter the pharmacokinetics of drugs requiring bile‑acid transport for excretion; monitor for changes in serum levels.
• Pregnancy: Considered safe; category B.
• Lactation: Excreted in breast milk; infant monitoring may be warranted.

Dosing

• PBC: 28 mg/kg/day split q12h (max 600 mg/day).
• Gallstones (prevention): 1 mg/kg/day in two divided doses (max 600 mg/day).
• Drug‑induced cholestasis: 0.5–1 mg/kg/day until bilirubin normalizes.
• Administration: Oral tablets with or without food; ensure complete swallowing to avoid dose loss.

Re‑titration: If improvement is inadequate after 6 months, consider increasing dose by 25‑50 % (max 600 mg/day).

Adverse Effects

• Common
• Diarrhea or loose stools
• Nausea, abdominal discomfort
• Rash or itching (rare)
• Mild flushing
• Serious
• Hypersensitivity reactions (angioedema, anaphylaxis)
• Severe liver injury (unlikely but must monitor LFTs)
• Acute cholecystitis precipitated by stone formation

Monitoring

Clinical Pearls

• PBC first‑line: Ursodiol slows histologic progression by > 50 % after 24 months; patients with a > 25 % rise in ALP over 12 months should be considered for second‑line agents (e.g., obeticholic acid).
• Start low‑dose in frail elderly: A starting dose of 15 mg/kg/day mitigates GI upset while still achieving therapeutic effect once dose titration is confirmed.
• Preventing gallstones in high‑risk dysmotility: In patients with chronic pancreatitis or after pancreaticoduodenectomy, adding Ursodiol to a low‑fat diet reduces stone incidence twofold.
• Pregnancy safety: While considered safe, monitoring maternal LFTs ensures early detection of cholestasis of pregnancy; ursodiol reduces pruritus and improves bilirubin but has no proven fetal impact.
• Drug–drug interaction caution: Ursodiol may alter the hepatobiliary excretion of statins and certain antimicrobials; adjust dosing or monitor drug levels as needed.

Key Takeaway: Urso Forte remains the cornerstone of management for cholestatic liver diseases and gallstone prevention—its hydrophilic nature, safety profile, and robust evidence for disease modification make it indispensable in hepatology and gastroenterology practice.