What is the initial treatment for pruritus (itching) due to cirrhosis?

Treatment of Pruritus in Cirrhosis

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

First-Line Treatment: Rifampicin

The British Association of Dermatologists guidelines (2018) explicitly recommend rifampicin as first-line therapy with the highest strength of recommendation (Grade A, Level 1+), based on meta-analyses of randomized controlled trials demonstrating efficacy without increased side effects compared to placebo. 1 This represents a shift from traditional practice, as rifampicin was historically considered second-line after cholestyramine. 1

Dosing and titration:

• Start at 150 mg twice daily 1, 3
• Increase stepwise to maximum 600 mg twice daily if needed 1, 3
• Clinical response typically occurs within the first month 4
• Efficacy is maintained over prolonged periods up to 2 years 2

Critical monitoring requirements:

• Monitor liver function tests before each dose escalation - drug-induced hepatitis occurs in up to 12% of cholestatic patients after 2-3 months of treatment 2, 3, 5
• Hepatotoxicity can be severe enough to require liver transplantation in rare cases 5
• Warn patients that body secretions (urine, tears, sweat) will turn orange-red in color 1, 3

Second-Line Treatment: Cholestyramine

If rifampicin is contraindicated, not tolerated, or ineffective, cholestyramine becomes the second-line option. 1 The EASL guidelines (2009) and older protocols traditionally placed cholestyramine first, but newer evidence supports rifampicin's superiority. 1

Dosing:

• 4 g up to four times daily 1, 6
• Must be spaced at least 4 hours away from UDCA and other medications to avoid binding interactions 1, 6
• Monitor fat-soluble vitamins (A, D, E, K) during long-term use 1

Limitations:

• Evidence is limited and heterogeneous - meta-analyses show data too varied to pool reliably 1
• Poor palatability and gastrointestinal side effects limit tolerability 1

Third-Line Treatment: Sertraline

Sertraline 75-100 mg daily is recommended as third-line therapy when rifampicin and cholestyramine have failed or are not tolerated. 1, 2

• A small randomized controlled trial demonstrated efficacy with good tolerance 1, 2
• Fewer side effects than opioid antagonists 1, 2
• Warn patients about dry mouth as a common side effect 1
• Mechanism likely involves altering central neurotransmitter concentrations 1, 7

Fourth-Line Treatment: Opioid Antagonists

Naltrexone 50 mg daily or nalmefene are fourth-line options. 1

Critical pitfall to avoid:

• Never start at full dose - initiate at 25 mg and titrate slowly to avoid severe opiate withdrawal-like reactions (anxiety, pain, confusion) 1, 2
• Consider IV naloxone induction phase with rapid escalation before converting to oral therapy 1
• Significantly more side effects than rifampicin or cholestyramine, limiting clinical utility 1
• Reduced pain threshold is an ongoing problem during treatment 1

Treatments to Avoid

Do NOT use gabapentin for hepatic pruritus - specific guideline recommendation (Grade A) based on failed placebo-controlled trials. 1, 2, 8

Do NOT routinely use ondansetron - two recent randomized controlled trials showed no benefit, contradicting earlier positive studies. 1, 2

Antihistamines are not recommended as specific therapy, though they may provide non-specific benefit through sedation in select patients. 1, 8

Refractory Cases

For pruritus unresponsive to all medical therapies:

• Consider experimental approaches: UV light therapy, nasobiliary drainage, plasmapheresis, or albumin dialysis 1, 9
• Liver transplantation is highly effective (relief often within 24 hours) but should only be considered when all other interventions have failed 1, 2
• Transplantation for pruritus alone raises significant ethical questions about organ allocation 1, 2

Treatment Algorithm Summary

1. First-line: Rifampicin 150 mg BID → titrate to 600 mg BID (monitor LFTs) 1, 2
2. Second-line: Cholestyramine 4 g QID (space from other meds) 1
3. Third-line: Sertraline 75-100 mg daily 1, 2
4. Fourth-line: Naltrexone 25-50 mg daily (start low, titrate slowly) 1
5. Refractory: Experimental therapies or transplant evaluation 1, 2