Indications and Contraindications of Rifaximin and Ursodeoxycholic Acid
Ursodeoxycholic Acid (UDCA)
Indications
UDCA is the first-line treatment for primary biliary cirrhosis at 13-15 mg/kg/day, where it significantly improves biochemical markers and delays disease progression. 1
Cholestatic Liver Diseases
- Primary biliary cirrhosis: UDCA at 13-15 mg/kg/day decreases serum bilirubin, alkaline phosphatase, cholesterol, and immunoglobulin M levels, with long-term treatment delaying histological progression when started early 1
- Primary biliary cirrhosis (advanced): Associated with significant reduction in liver transplantation or death in moderate to severe disease 1
- Primary sclerosing cholangitis: Routine use is NOT recommended by the British Society of Gastroenterology due to limited efficacy, and high-dose UDCA (>20 mg/kg/day) should be avoided as it has been associated with worse outcomes 1
- Intrahepatic cholestasis of pregnancy (ICP): UDCA at 10-15 mg/kg/day should be offered for maternal pruritus treatment and in women with serum bile acids >40 μmol/L to reduce spontaneous preterm birth risk and potentially protect against stillbirth 2
- Pre-existing cholestatic diseases in pregnancy: UDCA should be continued during pregnancy in primary biliary cholangitis as it is safe in pregnancy and breastfeeding 2
Gallstone Disease
- Radiolucent, noncalcified gallbladder stones <20 mm: For patients with increased surgical risk due to systemic disease, advanced age, idiosyncratic reaction to general anesthesia, or those who refuse surgery 3
- Prevention of gallstone formation: In obese patients experiencing rapid weight loss 3
- Optimal response: Success rate increases to approximately 80% with stringent selection criteria including non-calcified floating cholesterol stones <10-15 mm diameter 4
Other Cholestatic Conditions
- Chronic graft versus host disease, total parenteral nutrition-associated cholestasis, and various pediatric cholestatic liver diseases: UDCA has beneficial effects 5
Contraindications
UDCA will not dissolve calcified cholesterol stones, radiopaque stones, or radiolucent bile pigment stones—these patients are not candidates for therapy. 3
Absolute Contraindications
- Calcified cholesterol stones, radiopaque stones, or radiolucent bile pigment stones 3
- Allergy to bile acids 3
- Compelling indications for cholecystectomy: Including unremitting acute cholecystitis, cholangitis, biliary obstruction, gallstone pancreatitis, or biliary-gastrointestinal fistula 3
Relative Contraindications/Cautions
- Obeticholic acid (not UDCA itself): Not recommended in pregnancy or lactation in women with primary biliary cholangitis or primary sclerosing cholangitis due to lack of safety data 2
- End-stage primary biliary cirrhosis: Rare cases of decompensation of liver cirrhosis reported after UDCA administration 6
Important Monitoring and Adverse Effects
- Generally well tolerated: Nausea and mild dizziness may occur in up to 25% of patients 1
- Diarrhea: Occurs in only a small proportion of patients 6
- Drug interactions: Absorption impaired by cholestyramine, colestimide, colestipol, aluminum hydroxide, and smectite; metabolic interactions with cytochrome P4503A substrates (ciclosporin, nitrendipine, dapsone) 6
- Monitoring: Regular liver biochemistry assessment essential to evaluate treatment response 1
- Safety in pregnancy: UDCA is considered safe during pregnancy and breastfeeding 1
Rifaximin
Indications
Rifaximin is FDA-approved for reduction in risk of recurrent hepatic encephalopathy in patients with advanced liver disease at 550 mg twice daily. 7
FDA-Approved Indications
- Prevention of recurrent hepatic encephalopathy: 550 mg orally twice daily for 6 months reduces breakthrough HE episodes (22% vs 46% placebo, P<0.001) and hospitalizations involving HE (13.6% vs 22.6% placebo, P=0.01) 7
Off-Label/Guideline-Supported Indications
- Pruritus in primary biliary cirrhosis: Effective for treatment 1
- Pruritus in intrahepatic cholestasis of pregnancy: May be considered as additional therapy, though current evidence is limited (300-600 mg daily) 2
- Pruritus in pre-existing cholestatic diseases during pregnancy: For de novo or worsening pruritus (300-600 mg daily) 2
- Irritable bowel syndrome (non-constipated): Improved IBS symptom management in 9% more patients than placebo (40.8% vs 31.7%, P<0.001) 7
Emerging Indications
- Clostridium difficile infection: Efficacy reported for refractory or recurrent CDI in small studies, but optimal dosing and duration unclear 7
Contraindications
Rifaximin is contraindicated in patients with hypersensitivity to rifaximin, any rifamycin antimicrobial agents, or any components in the formulation. 8
Absolute Contraindications
- Hypersensitivity to rifaximin or any rifamycin antimicrobial agents: Including reactions such as exfoliative dermatitis, angioneurotic edema, and anaphylaxis 8
- Hypersensitivity to any components in rifaximin formulation 8
Important Safety Considerations
- Safety profile comparable to placebo: In clinical trials for prevention of recurrent HE and nonconstipated IBS 7
- Common adverse events in HE trials (10-15%): Ascites, dizziness, fatigue, and peripheral edema 7
- Common adverse events in IBS trials (<10%): Abdominal pain, diarrhea, bad taste, headache, and upper respiratory tract infection 7
- Minimal systemic absorption: Acts locally in gastrointestinal tract with minimal systemic adverse effects 7
Critical Caveat for Pregnancy Use
When using rifaximin for cholestatic pruritus in pregnancy, vitamin K deficiency related to cholestasis and/or use of rifampicin should be corrected. 2 This is particularly important as rifampicin (rifaximin is related) can exacerbate vitamin K deficiency, increasing bleeding risk during delivery.