Can Ursodiol Cause Diarrhea?
Yes, ursodiol can cause diarrhea, though it occurs in a minority of patients and is typically mild and transient.
Evidence from FDA Drug Label
The FDA-approved drug label for ursodiol clearly documents diarrhea as a recognized adverse effect 1. In clinical trials for gallstone dissolution, diarrhea occurred in 27.1% of patients taking ursodiol compared to 21.4% on placebo 1. For gallstone prevention studies, the incidence was 25.2% with ursodiol versus 20.9% with placebo 1.
In the extracorporeal shock-wave lithotripsy trial, 32.6% of patients on ursodiol experienced diarrhea compared to 24.7% on placebo (P < 0.04), representing a statistically significant difference 2.
Clinical Significance and Management
The diarrhea associated with ursodiol is generally:
- Dose-related: Higher doses (particularly above 20 mg/kg/day) may increase the risk
- Self-limiting: Most cases are transient and do not require discontinuation
- Mild in severity: Less than 1% of patients discontinue therapy due to diarrhea 3
One documented case in a primary sclerosing cholangitis trial required withdrawal specifically due to "UDCA-related diarrhea" 4, demonstrating that while uncommon, it can occasionally be severe enough to warrant stopping the medication.
Mechanism
The diarrhea likely results from ursodiol's choleretic effect (increased bile flow) and its impact on colonic water and electrolyte transport. The most severe manifestation of ursodiol overdose would predictably be diarrhea, which should be treated symptomatically 1.
Clinical Recommendation
When prescribing ursodiol, counsel patients that diarrhea may occur in approximately 1 in 4 patients, but it is usually mild and self-resolving. If diarrhea develops, assess severity before discontinuing therapy, as most cases do not require stopping the medication. Consider dose reduction if diarrhea is problematic but the medication is otherwise beneficial 5, 3.