Actigall (Ursodiol) vs Alternative Gallstone Treatments: A Detailed Comparison

Stephen Roberts 26 October 2025 3 Comments

If you or someone you know has been diagnosed with cholesterol gallstones or primary biliary cholangitis, you’ve probably heard the name Actigall. The big question is whether this bile‑acid medication is the best choice or if other options might work better for your specific situation. Below we break down how Actigall works, compare it side‑by‑side with the most common alternatives, and give you practical tips for making an informed decision.

What is Actigall (Ursodiol) and How Does It Work?

Actigall (Ursodiol) is a synthetic form of the naturally occurring bile acid ursodeoxycholic acid. It reduces the cholesterol saturation of bile, progressively dissolving cholesterol‑rich stones and improving liver enzyme profiles in cholestatic diseases. FDA‑approved in 1995, the typical oral dose for gallstone dissolution is 8-10 mg/kg daily, taken in two divided doses with meals.

Why Look at Alternatives?

While Actigall is effective for many patients, it isn’t a one‑size‑fits‑all solution. Some people can’t tolerate the drug’s side effects, others have stones that are too large, and a subset prefers a procedural approach that offers quicker relief. Understanding the strengths and limits of each option helps you avoid unnecessary trial‑and‑error.

Key Alternatives to Consider

Obeticholic acid is a semi‑synthetic bile acid that activates the farnesoid X receptor (FXR) more potently than ursodiol. It’s approved for primary biliary cholangitis patients who have an inadequate response to ursodiol alone.

Chenodeoxycholic acid (CDCA) was one of the first bile‑acid drugs used to dissolve gallstones. Its higher litholytic activity can be useful, but the risk of hepatotoxicity limits long‑term use.

Surgical cholecystectomy remains the gold standard for symptomatic gallstones. Laparoscopic removal offers a 95 % success rate with a short recovery period, though it involves anesthesia and a small incision.

Endoscopic retrograde cholangiopancreatography (ERCP) with stone extraction lets physicians retrieve stones directly from the bile duct without removing the gallbladder. It’s ideal for patients with choledocholithiasis who are poor surgical candidates.

Lithotripsy uses focused shock waves to fragment stones in situ. While less common in the United States, it can avoid surgery for stones larger than 3 cm that are resistant to medication.

Doctor explaining three gallstone treatments: surgery, medication, and lithotripsy in manga panels.

Side‑by‑Side Comparison

Key attributes of Actigall and its main alternatives
Attribute	Actigall (Ursodiol)	Obeticholic acid	Chenodeoxycholic acid	Laparoscopic cholecystectomy	ERCP with stone extraction	Lithotripsy
Mechanism	Reduces cholesterol saturation in bile	FXR agonist - increases bile flow	Directly solubilizes cholesterol crystals	Physical removal of gallbladder	Mechanical retrieval via endoscope	Acoustic fragmentation of stones
Primary indication	Cholesterol gallstones, primary biliary cholangitis	Primary biliary cholangitis (non‑responders)	Gallstone dissolution (historical)	Symptomatic gallstones, cholecystitis	Choledocholithiasis, biliary pancreatitis	Large or multiple stones unsuitable for meds
Typical dose	8-10 mg/kg/day (split BID)	5-10 mg daily	10-15 mg/kg/day	One‑time surgical procedure	Single endoscopic session	Multiple sessions as needed
FDA approval year	1995	2016 (for PBC)	1970s (withdrawn in US)	1992 (laparoscopic technique)	1996 (ERCP widespread)	2006 (experimental)
Common side effects	Diarrhea, abdominal pain, nausea	Pruritus, fatigue, liver enzyme rise	Hepatotoxicity, diarrhea	Incision pain, infection, retained stone	Pankreatitis, bleeding, infection	Skin bruising, temporary pain
Approximate monthly cost (US)	$150‑$250	$200‑$350	$120‑$200 (if obtainable)	$4,000‑$6,000 (incl. hospital stay)	$2,000‑$3,500 per procedure	$3,000‑$5,000 per series

Decision‑Making Criteria

Stone size and composition: Small (<1 cm) cholesterol stones often dissolve with Actigall; mixed or pigment stones respond poorly.
Patient tolerance: Diarrhea or pruritus may push you toward a procedural route.
Underlying liver disease: For primary biliary cholangitis, adding Obeticholic acid can boost outcomes.
Comorbidities: Severe heart or lung disease may preclude surgery, making ERCP or lithotripsy preferable.
Cost and insurance coverage: Medications are generally cheaper long‑term, but failed medical therapy can end up costing more if surgery becomes necessary.

Pros and Cons of Each Option

Actigall (Ursodiol)

Pros: Non‑invasive, can preserve the gallbladder, well‑studied safety profile, useful for liver cholestasis.
Cons: Takes 6‑12 months to see stone reduction, ineffective for large or calcified stones, GI side effects.

Obeticholic acid

Pros: Strong FXR activation, improves liver biochemistry in PBC, can be combined with ursodiol.
Cons: Pruritus is common, higher price, not approved for gallstone dissolution.

Chenodeoxycholic acid

Pros: Faster stone dissolution in theory.
Cons: Higher liver toxicity, largely withdrawn from US market.

Laparoscopic cholecystectomy

Pros: Definitive solution, minimal recurrence risk.
Cons: Surgical risks, recovery time, possible bile duct injury.

ERCP with stone extraction

Pros: Avoids gallbladder removal, immediate stone clearance.
Cons: Procedure‑related pancreatitis risk, requires skilled endoscopist.

Lithotripsy

Pros: Non‑surgical, useful for large stones.
Cons: Limited availability, may need multiple sessions, risk of fragment migration.

Patient in kitchen holding water bottle and calendar, with small stone shown on ultrasound.

Practical Tips for Patients Starting Actigall

Take the dose with meals to improve absorption.
Monitor liver enzymes every 3‑4 months; report any persistent itching.
Maintain a low‑fat diet; high‑fat meals can overwhelm the reduced bile flow.
Stay hydrated; adequate fluid helps the medication work on stone particles.
If no stone size reduction after 6 months, discuss imaging follow‑up with your doctor to decide on next steps.

When to Switch or Add an Alternative

Switching isn’t a decision you make on a whim. Typical red flags include:

Persistent or worsening abdominal pain after 3 months of therapy.
Ultrasound showing no change or growth in stone size.
Elevated ALT/AST >2× ULN despite compliance.
Intolerable side effects (e.g., severe diarrhea >5 watery stools per day).

In those cases, talk to your hepatologist about adding Obeticholic acid, considering ERCP, or moving straight to surgery.

Frequently Asked Questions

How long does it take for Actigall to dissolve gallstones?

Most patients see a measurable reduction after 6‑12 months of consistent dosing. Larger stones may need up to 24 months, and some never fully resolve.

Can I combine Actigall with Obeticholic acid?

Yes, especially for primary biliary cholangitis patients who don’t achieve target liver enzymes with ursodiol alone. Combination therapy can improve outcomes but may increase pruritus.

What are the most common side effects of Actigall?

Diarrhea, mild abdominal cramping, nausea, and occasional fatigue. Most side effects lessen after the first few weeks.

Is surgery still necessary if I’m on medication?

If stones shrink enough and symptoms vanish, many avoid surgery. However, recurrent stones or complications like cholecystitis still warrant cholecystectomy.

How does lithotripsy compare cost‑wise to medication?

Lithotripsy typically costs $3,000‑$5,000 for a full treatment series, which can exceed a year’s supply of Actigall. Insurance coverage varies widely.

Can I take Actigall while pregnant?

Ursodiol is classified as pregnancy Category B; it’s considered relatively safe, but you should still discuss risks with your obstetrician.

What follow‑up imaging is recommended?

A baseline abdominal ultrasound before starting therapy, then repeat imaging at 6 months and again at 12 months to assess stone size changes.