Uses of Ursodeoxycholic Acid and Rifaximin in Liver Disorders
Ursodeoxycholic acid (UDCA) is the established first-line treatment for primary biliary cirrhosis at doses of 13-15 mg/kg/day, while rifaximin is primarily used for hepatic encephalopathy in patients with liver cirrhosis. 1
Ursodeoxycholic Acid (UDCA)
Primary Biliary Cirrhosis (PBC)
- UDCA at 13-15 mg/kg/day is the established first-line therapy for PBC based on multiple placebo-controlled trials 1
- UDCA significantly decreases serum bilirubin, alkaline phosphatase, cholesterol, and immunoglobulin M levels in PBC patients 1
- Long-term UDCA treatment delays histological progression of PBC when started at an early stage of the disease 1
- UDCA treatment is associated with significant reduction in liver transplantation or death in patients with moderate to severe PBC 1
- The optimum dose of 900 mg/day (equivalent to 13.5 mg/kg/day) has been established for early-stage PBC 2
Primary Sclerosing Cholangitis (PSC)
- The American Association for the Study of Liver Diseases does not recommend routine use of UDCA for PSC 1
- The British Society of Gastroenterology recommends against routine use of UDCA for newly diagnosed PSC due to limited efficacy 1
- High-dose UDCA (>20 mg/kg/day) has been associated with worse outcomes in PSC and should be avoided 3
Other Cholestatic Disorders
- UDCA has beneficial effects in intrahepatic cholestasis of pregnancy at doses of 10-15 mg/kg/day 1, 4
- UDCA is effective in liver disease associated with cystic fibrosis 4
- UDCA improves total parenteral nutrition-associated cholestasis 4, 5
Mechanism of Action of UDCA
- UDCA has cytoprotective, anti-apoptotic, membrane stabilizing, anti-oxidative and immunomodulatory effects 4
- UDCA protects injured cholangiocytes against toxic effects of bile acids 6
- UDCA stimulates impaired biliary secretion and detoxification of hydrophobic bile acids 6
- UDCA inhibits apoptosis of hepatocytes 6
Safety Profile of UDCA
- UDCA therapy has not been associated with liver damage 7
- UDCA is generally well tolerated, although nausea and mild dizziness may occur in up to 25% of patients 1
- UDCA is considered safe during pregnancy and breastfeeding 1
- Drug interactions may occur with bile acid sequestering agents (cholestyramine, colestipol), aluminum-based antacids, estrogens, oral contraceptives, and lipid-lowering drugs 7
Rifaximin
Hepatic Encephalopathy
- Rifaximin is effective for the treatment of pruritus in primary biliary cirrhosis 8
- Rifaximin is used for hepatic encephalopathy in patients with liver cirrhosis 9
- Mean rifaximin exposure in patients with a history of hepatic encephalopathy is approximately 12-fold higher than in healthy subjects 9
- Among patients with hepatic encephalopathy, those with Child-Pugh Class C hepatic impairment have 2-fold higher exposure than patients with Child-Pugh Class A impairment 9
Pharmacokinetics in Liver Disease
- The systemic exposure of rifaximin is markedly elevated in patients with hepatic impairment compared to healthy subjects 9
- Mean AUC in patients with hepatic impairment of Child-Pugh Class A, B, and C is 10-, 14-, and 21-fold higher, respectively, compared to healthy subjects 9
- Rifaximin is not suitable for treating systemic bacterial infections due to limited systemic exposure after oral administration 9
Drug Interactions
- Rifaximin is a substrate of P-glycoprotein, OATP1A2, OATP1B1, and OATP1B3 9
- Co-administration with cyclosporine significantly increases rifaximin exposure 9
Monitoring and Follow-up
- Regular monitoring of liver biochemistry is essential to assess treatment response to UDCA 1
- AMA-positive individuals with normal liver tests should undergo annual reassessment of biochemical markers of cholestasis 1
- For patients on rifaximin with hepatic impairment, careful monitoring is necessary due to increased drug exposure 9
- UDCA has not demonstrated significant effects on symptoms like fatigue or pruritus in PBC, so additional treatments may be needed for symptom management 1