What is the treatment for pruritus in cholestatic jaundice?

Treatment of Pruritus in Cholestatic Jaundice

Bezafibrate (400 mg/day) is the first-line pharmacological treatment for moderate to severe pruritus in cholestatic jaundice, with rifampicin (150-300 mg/day) recommended as an effective second-line therapy. 1, 2

Initial Approach to Management

Step 1: Rule Out Mechanical Causes

• Exclude relevant bile duct strictures in large duct sclerosing cholangitis as the cause of progressive pruritus
• If strictures are present and reachable, treat with endoscopic balloon dilation or stenting 1

Step 2: Non-Pharmacological Measures

• Use emollients to prevent skin dryness
• Avoid hot baths or showers which can exacerbate pruritus
• Apply cooling gels (e.g., menthol gels) to affected skin areas
• Keep nails short to minimize skin damage from scratching 1

Pharmacological Treatment Algorithm

First-Line Therapy:

• Bezafibrate (400 mg/day)
  • Demonstrated clear benefit vs placebo in the FITCH trial for moderate to severe cholestatic pruritus
  • Has additional anticholestatic effects when combined with UDCA
  • Monitor for potential side effects:
    • Mild increase in serum creatinine
    • Myalgia/myopathies (uncommon)
    • Increased serum transaminases (rare) 1, 2

Second-Line Therapy:

• Rifampicin (150-300 mg/day)
  • Effective for cholestatic pruritus but with important safety considerations
  • Risk of drug-induced hepatitis in up to 12% of cholestatic patients after 4-12 weeks
  • First 2 weeks considered relatively safe
  • Requires monitoring of liver function after 2-4 weeks of treatment and periodically thereafter 1, 2

Third-Line Therapy:

• Naltrexone (starting at 12.5 mg, up to 50 mg daily)
  • Opioid antagonist that may help with pruritus
  • Start at very low doses (12.5 mg) to avoid side effects resembling opioid withdrawal
  • Monitor for potential reduction in pain threshold with long-term use 1, 2

Alternative/Historical Approaches:

• Cholestyramine (4-16 g/day)
  • Previously considered first-line but evidence for efficacy in sclerosing cholangitis is limited
  • If used, must be administered separately from other medications (especially UDCA) to avoid interaction
  • Can impair absorption of various medications
  • Monitor for constipation as a side effect 1, 3, 4

Refractory Cases

For patients with severe, intractable pruritus not responding to pharmacological therapy:

1. Experimental Therapies:

   • Nasobiliary drainage (provides temporary relief but technically complicated)
   • Molecular absorbance recirculating system (MARS)
   • Ultraviolet light therapy
   • Charcoal hemoperfusion (temporary improvement in 69% of patients in one study, but benefits not sustained) 1, 5

2. Last Resort:

   • Liver transplantation for persistent and intractable pruritus (highly effective with rapid reduction in pruritus severity, often within 24 hours) 1

Monitoring and Follow-up

• Evaluate response to treatment after 2-4 weeks
• For patients on rifampicin, monitor liver function regularly due to potential hepatotoxicity
• Consider supplementation with vitamin K if the patient is jaundiced during rifampicin use 2

Special Considerations

• In cholestasis of pregnancy, ursodeoxycholic acid (10-20 mg/kg per day) is the first-line treatment 1
• Ondansetron has shown anecdotal success in treating pruritus associated with cholestasis in some case reports 6

Pitfalls and Caveats

• Cholestyramine can significantly reduce serum levels of UDCA by 60% when administered simultaneously; administer at different times of day (at least 5 hours apart) 4
• Rifampicin can cause drug-induced hepatitis; monitor liver function closely
• Start naltrexone at very low doses to avoid withdrawal-like reactions
• Bezafibrate may cause mild increase in serum creatinine and rarely myopathy