First-Line Medication for Pruritus in Jaundiced Patients
Rifampicin is the first-line pharmacological treatment for hepatic pruritus in patients with jaundice, starting at 150 mg twice daily and titrating up to 600 mg twice daily as needed. 1, 2
Treatment Algorithm
Initial Assessment and Non-Pharmacological Management
- Exclude biliary obstruction first - imaging studies (ultrasound/MRCP) should be performed to rule out mechanical obstruction requiring endoscopic or surgical intervention, as relieving obstruction often resolves pruritus promptly 1
- Implement supportive skin care measures - use emollients to prevent skin dryness, avoid hot baths/showers, apply cooling menthol gels to affected areas, and keep nails shortened 1, 3
Pharmacological Treatment Hierarchy
First-Line: Rifampicin
- Start at 150 mg twice daily, increase to 600 mg twice daily based on clinical response 1, 2, 4
- Strongest evidence base - supported by two meta-analyses of RCTs showing efficacy without increased side effects compared to placebo, unlike opioid antagonists 1, 2
- Monitor hepatotoxicity closely - drug-induced hepatitis occurs in up to 12% of cholestatic patients after 4-12 weeks of treatment, though the first 2 weeks are considered safe 1, 2
- Warn patients about discoloration - body secretions (urine, tears, sweat) will turn orange-red 1, 4
- High response rate - over 90% of patients with chronic cholestasis and severe refractory itching respond to rifampicin 4
Second-Line: Cholestyramine (Context-Dependent)
- Use 9 g daily orally if rifampicin is contraindicated or not tolerated 1
- Important limitation - only effective with incomplete biliary obstruction; must be administered separately from other medications (especially UDCA) as it impairs absorption 1, 5
- Evidence is weaker - limited effectiveness in sclerosing cholangitis compared to primary biliary cholangitis; meta-analyses show heterogeneous data 1
- Mechanism - binds bile salts in the gut lumen, preventing absorption in the terminal ileum 1, 5
Third-Line: Sertraline
- Dose: 75-100 mg daily 1, 3, 2
- Well-tolerated option - one small RCT demonstrates efficacy with fewer side effects than opioid antagonists 1, 2
- Consider as second-line if rifampicin is contraindicated or causes hepatotoxicity 2
Fourth-Line: Naltrexone
- Start at very low dose: 12.5 mg daily, titrate slowly to 50 mg daily 1, 3
- Critical pitfall to avoid - rapid initiation causes severe opioid withdrawal-like symptoms; slow titration is mandatory 1, 2
- More side effects than rifampicin and cholestyramine, which limits clinical utility 1
Emerging First-Line Option for Specific Populations
- Bezafibrate is recommended as first-line for moderate to severe pruritus specifically in primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) based on the FITCH trial 1
- This represents a shift in guidelines for cholestatic liver disease - the 2022 EASL guidelines for sclerosing cholangitis now favor bezafibrate over traditional agents 1
Critical Divergence in Guidelines
There is important evolution in recommendations between 2018 and 2022:
- The 2018 British Association of Dermatologists guidelines recommend rifampicin as first-line for all hepatic pruritus (Strength A, Level 1+) 1
- The 2022 EASL guidelines specifically for sclerosing cholangitis recommend bezafibrate as first-line for PSC/PBC, with rifampicin as an alternative 1
- For general hepatic pruritus without specified etiology, rifampicin remains the evidence-based first choice 1, 2
Medications to Avoid
- Do NOT use gabapentin for hepatic pruritus - it is ineffective in this context (though effective for uremic pruritus) 1, 3
- Ondansetron is not supported - two recent RCTs showed no benefit despite earlier positive trials 1, 2
- Avoid prolonged antihistamines - they are ineffective for cholestatic pruritus and may predispose to dementia with long-term use 3