Are oral medications an option to treat cholelithiasis (gallstones)?

From the Guidelines

Oral medications, such as ursodeoxycholic acid, are a viable treatment option for certain patients with cholelithiasis, specifically those with small, cholesterol-rich stones, but they are not a replacement for surgery in most cases. The use of oral bile acids, like ursodeoxycholic acid, can dissolve cholesterol stones by increasing the cholesterol in bile, but this treatment is limited to patients with stones less than 1.5 cm in size and primarily composed of cholesterol, which accounts for only about 20% of cholecystectomy patients 1.

Key Considerations

• The effectiveness of oral medications in treating gallstones is generally lower compared to surgical interventions, with a success rate ranging from 30-60% and a recurrence rate of about 50% within 5 years after stopping treatment.
• Ursodeoxycholic acid works by decreasing cholesterol production in the liver and reducing cholesterol absorption in the intestines, which helps dissolve existing stones and prevent new ones.
• This treatment is typically reserved for patients who cannot undergo surgery due to medical conditions or who refuse surgery, as surgical removal of the gallbladder (cholecystectomy) is considered the definitive treatment with lower recurrence rates and the ability to prevent future complications such as gallbladder cancer.

Treatment Details

• The dosage of ursodeoxycholic acid for gallstone dissolution is typically in the range of 8-10 mg/kg/day, divided into two doses.
• Treatment duration can vary from 6 to 24 months, depending on the size and composition of the stones, as well as the patient's response to the medication.
• It's crucial for clinicians and patients to weigh the benefits and limitations of oral medication therapy against the risks and benefits of surgical intervention, considering factors such as the patient's overall health, the size and type of gallstones, and the potential for recurrence or development of complications.

From the FDA Drug Label

Although liver injury has not been associated with ursodiol therapy, a reduced capacity to sulfate may exist in some individuals, but such a deficiency has not yet been clearly demonstrated. Pharmacodynamics Ursodiol suppresses hepatic synthesis and secretion of cholesterol, and also inhibits intestinal absorption of cholesterol It appears to have little inhibitory effect on synthesis and secretion into bile of endogenous bile acids, and does not appear to affect secretion of phospholipids into bile. With repeated dosing, bile ursodeoxycholic acid concentrations reach a steady-state in about 3 weeks Although insoluble in aqueous media, cholesterol can be solubilized in at least two different ways in the presence of dihydroxy bile acids. In addition to solubilizing cholesterol in micelles, ursodiol acts by an apparently unique mechanism to cause dispersion of cholesterol as liquid crystals in aqueous media. Thus, even though administration of high doses (e.g., 15 mg/kg/day to 18 mg/kg/day) does not result in a concentration of ursodiol higher than 60% of the total bile acid pool, ursodiol-rich bile effectively solubilizes cholesterol. The overall effect of ursodiol is to increase the concentration level at which saturation of cholesterol occurs The various actions of ursodiol combine to change the bile of patients with gallstones from cholesterol-precipitating to cholesterol-solubilizing, thus resulting in bile conducive to cholesterol stone dissolution. Clinical Results Gallstone Dissolution On the basis of clinical trial results in a total of 868 patients with radiolucent gallstones treated in 8 studies (three in the U.S. involving 282 patients, one in the U. K. involving 130 patients, and four in Italy involving 456 patients) for periods ranging from 6 to 78 months with ursodiol doses ranging from about 5 mg/kg/day to 20 mg/kg/day, an ursodiol dose of about 8 mg/kg/day to 10 mg/kg/day appeared to be the best dose With an ursodiol dose of about 10 mg/kg/day, complete stone dissolution can be anticipated in about 30% of unselected patients with uncalcified gallstones < 20 mm in maximal diameter treated for up to 2 years

Oral medications are an option to treat cholelithiasis (gallstones).

• The medication ursodiol is effective in dissolving gallstones, particularly those that are uncalcified and less than 20 mm in diameter.
• The optimal dose of ursodiol for gallstone dissolution is approximately 8-10 mg/kg/day.
• Complete stone dissolution can be anticipated in about 30% of unselected patients with uncalcified gallstones < 20 mm in maximal diameter treated for up to 2 years 2

From the Research

Oral Medications for Cholelithiasis

Oral medications can be an option to treat cholelithiasis (gallstones) in selected patients. The following points highlight the key aspects of oral medication treatment:

• Oral bile acids, such as ursodeoxycholic acid (ursodiol) and chenodeoxycholic acid, can be effective in dissolving cholesterol gallstones 3, 4, 5, 6, 7.
• Patient selection is crucial, and ideal candidates have small, radiolucent stones (< 0.5 cm in diameter) and a functioning gallbladder 3, 4, 5.
• Oral bile acid therapy is most successful in patients with radiolucent gallstones that are < or = 0.5 cm in diameter or are shown by oral cholecystogram (OCG) to be floating 4.
• The treatment is generally safe, especially when ursodiol is given without the addition of chenodeoxycholic acid 4.
• Annual dissolution rates can be up to 75% for small stones (< 6 mm in diameter) treated with oral bile acids 5.

Treatment Considerations

The following considerations should be taken into account when using oral medications to treat cholelithiasis:

• Gallstones must be cholesterol-rich and radiolucent for medical treatment to be effective 5, 6.
• The cystic duct must be patent, as indicated by gallbladder opacification on oral cholecystography 5.
• Stone size is an important factor in choosing the treatment, with smaller stones being more suitable for oral bile acid therapy 4, 5.
• Combination therapy with extracorporeal shock-wave lithotripsy (ESWL) can be effective for single radiolucent gallstones that are not greater than 2 cm in diameter 4, 5.