What medications help with itching due to hyperbilirubinemia?

Management of Pruritus Associated with Elevated Bilirubin

Rifampicin should be considered as first-line treatment for pruritus in patients with hyperbilirubinemia, starting at 150 mg daily with monitoring of liver tests, which may be increased to a maximum of 600 mg daily. 1, 2

First-Line Treatment Options

Rifampicin

• Start at 150 mg daily with liver function monitoring
• May increase to maximum 600 mg daily if needed
• Strong evidence base for effectiveness 2
• Ongoing efficacy reported for up to 2 years of treatment
• Important monitoring:
  • Monitor liver function tests before dose escalation
  • Drug-induced hepatitis can occur in up to 12% of cholestatic patients after 2-3 months 2
  • Body secretions may be discolored during treatment

Bezafibrate (Alternative First-Line)

• Recently shown to be effective for moderate to severe cholestatic pruritus in the FITCH trial 2
• Particularly effective when combined with UDCA for patients with primary sclerosing cholangitis (PSC) or primary biliary cholangitis (PBC)
• Exerts strong anticholestatic effects in addition to antipruritic effects

Second-Line Treatment Options

Cholestyramine

• Traditional first-line agent in older guidelines 2
• Dosage: 4 g up to four times daily 2
• Binds bile salts in the gut lumen, preventing absorption 1
• Administration considerations:
  • Poor tolerance due to taste (can be improved by flavoring with fruit juice)
  • Must be spaced at least 4 hours apart from other medications (especially UDCA) to prevent binding 2
  • Less evidence for effectiveness in sclerosing cholangitis compared to PBC 2

Third-Line Treatment Options

Naltrexone (Oral Opiate Antagonist)

• Start at low dose (12.5-25 mg) to avoid opiate withdrawal-like reaction 2
• May increase to 50 mg daily 2
• Consider only after proven lack of efficacy or intolerance to rifampicin and cholestyramine 2

Sertraline

• Fourth-line treatment option 2
• Dosage: 25-75 mg daily 2
• Mechanism of action for pruritus relief remains unclear 2
• Clinical experience has been disappointing for many clinicians 2

Special Considerations

For Severe Refractory Cases

• Consider referral to specialized centers for more invasive approaches 2:
  • Extracorporeal albumin dialysis
  • Plasmapheresis
  • Bile duct drainage
  • Liver transplantation (effective but should only be considered when all other interventions have failed) 2

Non-Pharmacological Measures

• Use emollients to prevent skin dryness
• Avoid hot baths or showers
• Use cooling gels (e.g., menthol) for affected skin areas
• Keep nails shortened to minimize damage from scratching 2

Medications to Avoid

• Gabapentin is not recommended for hepatic pruritus 2, 1
• Sedative antihistamines have limited efficacy for cholestatic pruritus 2
• Ondansetron has insufficient evidence to support its routine use 1

Monitoring Response

• Use visual analogue scale to help assess response to interventions 2
• Expect improvement within 1-2 weeks of starting effective therapy
• Adjust therapy based on response and tolerability

The pathogenesis of cholestatic pruritus is complex and not fully understood, but potential contributors include lysophospholipids, sulfated progesterone metabolites, and dysregulation of the opioid system, rather than simply bile acid or bilirubin conjugates 3. This explains why multiple medication classes may be effective for different patients.