What is the recommended treatment for pruritus in a patient with liver failure?

Treatment of Pruritus in Liver Failure

Rifampicin is the first-line treatment for hepatic pruritus, starting at 150 mg orally twice daily and titrating up to 600 mg twice daily based on response. 1, 2

First-Line Therapy: Rifampicin

• Rifampicin has the strongest evidence base with two meta-analyses of randomized controlled trials demonstrating superior efficacy (Strength A, Level 1+) and achieves meaningful relief in more than 90% of patients with chronic cholestasis and severe refractory itching. 1, 2

• Dosing protocol: Begin with 150 mg orally twice daily; increase gradually to a maximum of 600 mg twice daily if pruritus remains uncontrolled. 1, 2

• Critical monitoring requirement: Check liver enzymes regularly, particularly after 4–12 weeks, as drug-induced hepatitis occurs in up to 12% of cholestatic patients; the first 2 weeks are generally safe. 2

• Patient counseling: Warn patients that rifampicin causes harmless orange-red discoloration of urine, tears, and sweat. 1, 2

Second-Line Therapy: Cholestyramine

• Use cholestyramine only when rifampicin is contraindicated, ineffective, or not tolerated—it has weaker evidence with heterogeneous trial results. 1, 2

• Dosing: 9 g orally once daily (FDA label also describes 4 g up to four times daily). 1, 3

• Mandatory separation rule: Administer cholestyramine at least 4 hours apart from all other oral medications to prevent binding and loss of efficacy. 2

• Efficacy limitation: Cholestyramine is effective mainly when biliary obstruction is incomplete and has limited efficacy in cirrhosis. 2, 3

• Monitor fat-soluble vitamin status during prolonged therapy. 2

Third-Line Therapy: Sertraline

• Dosing: 75–100 mg orally once daily. 1, 2

• Evidence: Small randomized controlled trials show significant itch reduction with fewer adverse effects compared with opioid antagonists, making it a well-tolerated alternative. 1, 2

Fourth-Line Therapy: Naltrexone

• Initiate at 12.5–25 mg daily and titrate slowly to a maximum of 50 mg daily. 1, 2

• Critical safety warning: Rapid dose escalation can precipitate severe opioid-withdrawal-like symptoms (pain, confusion); gradual titration is mandatory. 1, 2

• Higher adverse event rates relative to rifampicin or cholestyramine limit routine use. 1, 2

Disease-Specific Consideration: Bezafibrate

• For primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC), the 2024 EASL guidelines recommend bezafibrate as first-line for moderate-to-severe pruritus based on the FITCH trial, with rifampicin listed as an alternative. 1, 2

Treatments to Avoid

• Gabapentin is ineffective for hepatic pruritus—it works only for uremic pruritus. 1, 2, 4

• Antihistamines do not relieve cholestatic pruritus and may increase the risk of dementia with long-term use, especially in elderly patients; avoid except in palliative care. 1, 2, 4

• Ondansetron: Two recent RCTs showed no benefit for cholestatic itch. 2

Common Pitfalls

• Do not use cholestyramine as first-line therapy—rifampicin has superior evidence and should be prioritized. 1, 2

• Do not forget the 4-hour separation rule for cholestyramine to prevent drug-binding interactions. 2

• Do not rapidly escalate naltrexone—this precipitates withdrawal-like symptoms. 1, 2

Refractory Cases

• Refer to specialized hepatology centers for experimental physical modalities such as extracorporeal albumin dialysis, plasmapheresis, bile-duct drainage, or ultraviolet phototherapy when medical options have failed. 1, 2

• Liver transplantation provides definitive relief for intractable pruritus unresponsive to all medical options, though this has become an extremely rare therapeutic strategy. 2, 5