What is the best medication for a patient with pruritus (itching) associated with cirrhosis (liver disease)?

Best Medication for Pruritus in Cirrhosis

Rifampicin is the first-line treatment for pruritus associated with cirrhosis, starting at 150 mg twice daily and titrating up to 600 mg twice daily as needed. 1, 2

Treatment Algorithm

First-Line: Rifampicin

• Start rifampicin at 150 mg twice daily, increasing progressively to a maximum of 600 mg twice daily if necessary 1, 3, 2
• Meta-analyses of randomized controlled trials demonstrate superior efficacy compared to placebo, with 8 of 9 patients preferring rifampicin over placebo in controlled trials 1, 4
• More than 90% of patients with chronic cholestasis achieve complete or partial response 3
• Pruritus improvement typically occurs within the first week of treatment 4
• Mandatory liver function monitoring is required due to risk of rifampicin-induced hepatitis in up to 12% of cholestatic patients after 4-12 weeks of treatment 3, 5
• Warn patients that rifampicin changes body secretions (urine, tears, sweat) to orange-red color 1, 3

Second-Line: Cholestyramine

• Use cholestyramine 4-16 g per day in divided doses if rifampicin is ineffective, not tolerated, or contraindicated 1, 2, 6
• Works by binding bile salts in the gut lumen, preventing absorption in the terminal ileum 1, 7
• Must be administered separately from other medications by at least 4 hours to prevent binding and loss of efficacy of other drugs 2, 6
• Has favorable safety profile despite limited evidence of efficacy 2, 6

Third-Line: Sertraline

• Sertraline 75-100 mg daily orally acts on central nervous system neurotransmitters 1, 2
• Demonstrated efficacy in controlled trials for cholestatic pruritus 2
• Warn patients about dry mouth as a side effect 2

Fourth-Line: Opioid Antagonists

• Naltrexone 50 mg daily orally or nalmefene (0.25-1 mg/kg per day) 1, 2
• Demonstrated efficacy in randomized controlled trials but associated with significantly more side effects than rifampicin or cholestyramine, which may limit use 1, 2

Fifth-Line: Experimental Options

• Consider dronabinol, phenobarbital, propofol, or topical tacrolimus ointment for refractory cases 1, 2
• UVB phototherapy is effective for many patients with cholestatic pruritus 2
• Plasmapheresis or albumin exchange provides temporary relief in extreme situations 2

Critical Pitfalls to Avoid

• Do not use gabapentin for hepatic pruritus - controlled trials showed no benefit compared to placebo 1, 2, 6
• Antihistamines have limited efficacy for cholestatic pruritus, though may provide non-specific sedative relief 2, 6
• Long-term use of sedating antihistamines may predispose to dementia and should be avoided except in palliative care 2
• Ondansetron has shown inconsistent results in clinical trials and is not routinely recommended 6

Special Considerations

Primary Biliary Cirrhosis

• Ursodeoxycholic acid (10-20 mg/kg/day) may improve pruritus in 67-80% of patients but is not considered first-line treatment 2
• High doses of ursodeoxycholic acid (28-30 mg/kg/day) are contraindicated 2

Primary Sclerosing Cholangitis

• Exclude significant bile duct stenoses as cause of progressive pruritus and treat with balloon dilation if present and accessible 2
• Bezafibrate or rifampicin recommended for moderate to severe pruritus 2

Monitoring and Refractory Cases

• Use visual analogue scales to assess response to interventions 6
• Evaluate for dominant biliary strictures in patients with worsening pruritus, increasing bilirubin, or progressive bile duct dilation 6
• Liver transplantation is highly effective with rapid reduction of pruritus (often within first 24 hours) and is indicated for persistent and refractory pruritus after all therapeutic trials have failed 2, 6