Does ursodiol (ursodeoxycholic acid) tend to cause constipation?

From the Guidelines

Ursodiol does not typically cause constipation, and its mechanism of action tends to promote bowel movements rather than slow them down. The most common side effects associated with ursodiol include diarrhea, nausea, vomiting, and abdominal discomfort, rather than constipation 1. Ursodiol works by decreasing the production of cholesterol and increasing bile flow in the liver, which helps dissolve gallstones and improve liver function in conditions like primary biliary cholangitis.

Key Points

• The medication's mechanism of action actually tends to promote bowel movements rather than slow them down.
• Standard dosing for ursodiol varies by condition, typically ranging from 8-15 mg/kg/day divided into 2-3 doses for gallstone dissolution, or 13-15 mg/kg/day for primary biliary cholangitis.
• If a patient experiences constipation while taking ursodiol, it's likely due to other factors such as diet, hydration, other medications, or underlying conditions rather than the ursodiol itself.

Evidence Summary

Studies have shown that ursodiol improves liver biochemistry, but there is no evidence that it improves outcome and may be harmful in high doses 1. A large, multicentre study of high-dose UDCA (28–30 mg/kg) in 150 patients with PSC was terminated early after results showed higher rates of serious adverse events and primary endpoints of death, liver transplantation and development of varices in the UDCA-treated group 1.

Clinical Implications

Given the potential risks and lack of benefit, it is recommended that UDCA is not used for the routine treatment of newly diagnosed PSC (strength of recommendation: STRONG; quality of evidence: GOOD) 1. For patients already established on UDCA therapy, there may be evidence of harm in patients taking high dose UDCA 28–30 mg/kg/day (strength of recommendation: WEAK; quality of evidence: LOW) 1.

From the FDA Drug Label

Digestive System Abdominal Pain Cholecystitis Constipation Diarrhea Dyspepsia Flatulence Gastrointestinal Disorder Nausea Vomiting 67 8 15 42 26 12 6 22 15 (43.2) (5.2) (9.7) (27.1) (16.8) (7.7) (3.9) (14.2) (9.7) 70 7 14 34 18 12 8 27 11 (44.0) (4.4) (8.8) (21.4) (11.3) (7.5) (5.0) (17.0) (6. 9)

Constipation is reported as an adverse reaction in the ursodiol drug label, with an incidence of 9.7% in the gallstone dissolution group and 8.8% and 26.4% in the gallstone prevention group for ursodiol and 4.4% and 22.2% for placebo, respectively 2.

• The incidence of constipation is higher in the ursodiol group compared to the placebo group in the gallstone prevention study.
• Therefore, ursodiol tends to cause constipation.

From the Research

Ursodiol and Constipation

• There is no direct evidence in the provided studies that ursodiol tends to cause constipation 3, 4, 5, 6.
• However, the studies do mention the effects of ursodeoxycholic acid on the gastrointestinal system, including its role as a choleretic agent and its potential to cause diarrhea in a small proportion of patients 5.
• The provided studies focus on the pharmacology, clinical implications, and potential therapeutic targets of ursodeoxycholic acid, but do not specifically address its effects on bowel movements or constipation 3, 4, 5, 6.
• One study mentions that ursodeoxycholic acid is generally well tolerated, with rare adverse effects including diarrhea, but does not mention constipation as a potential side effect 5.