What medications are used to treat pruritus associated with liver disease?

Treatment of Pruritus Associated with Liver Disease

Rifampicin is recommended as the first-line treatment for pruritus in liver disease due to its strong evidence base for effectiveness, starting at 150 mg daily with potential increase to a maximum of 600 mg daily. 1

Treatment Algorithm

First-Line Options:

1. Rifampicin

   • Starting dose: 150 mg daily
   • May increase to maximum 600 mg daily
   • Requires monitoring of liver function tests
   • Mechanism: Acts through PXR activation, detoxifying bile acids and other pruritogens
   • Efficacy: Moderate, with evidence of sustained effect for up to 2 years 2, 1
   • Caution: Can cause urine/tear discoloration and drug-induced hepatitis in up to 12% of cholestatic patients after 2-3 months 2

2. Cholestyramine

   • Traditional first-line agent (though less effective than rifampicin)
   • Dosage: 4-9 g daily
   • Mechanism: Binds bile salts in gut lumen, preventing absorption
   • Administration: Space at least 4 hours apart from other medications
   • Efficacy: Marginal 2, 1
   • FDA approved for pruritus associated with partial biliary obstruction 3
   • Limitations: Poor tolerance due to taste (can be improved with fruit juice) 2

Second-Line Options:

1. Naltrexone/Opioid Antagonists
   • Starting dose: 12.5-25 mg, may increase to 50 mg daily
   • Caution: May cause opiate withdrawal-like reaction on initiation
   • Consider IV naloxone induction phase to mitigate withdrawal symptoms 2, 1
   • Efficacy: Variable, with ongoing problems related to pain and confusion 2

Third-Line Options:

1. Sertraline
   • Dosage: 25-100 mg daily
   • Mechanism: Unclear for pruritus relief
   • Clinical experience: Often disappointing 2, 1

Fourth-Line/Experimental Options:

1. Ursodeoxycholic acid (UDCA)

   • Not generally considered first-line due to lack of evidence
   • Often tried early due to low risk profile
   • Mechanism: Changes bile acid composition from hydrophobic to hydrophilic
   • Efficacy: Low in FIC1 deficiency, variable in MDR3 deficiency 2
   • Note: Paradoxical worsening of itch has been reported anecdotally 2

2. Antihistamines

   • Efficacy: Marginal, primarily sedative effect
   • Limited utility in cholestatic pruritus 2, 1

Invasive Approaches (For Refractory Cases)

• Extracorporeal albumin dialysis
• Plasmapheresis
• Bile duct drainage
• Liver transplantation (when all other interventions have failed) 1

Symptomatic Relief

• Use emollients to prevent skin dryness
• Avoid hot baths/showers
• Apply cooling gels (e.g., menthol) to affected areas
• Keep nails shortened to minimize damage from scratching 1

Monitoring and Assessment

• Use visual analogue scale to assess response
• Expect improvement within 1-2 weeks of starting effective therapy
• Monitor liver function tests regularly, especially with rifampicin
• Rifampicin can cause significant hepatitis in 7.3% of patients treated for cholestatic liver disease 4

Clinical Pearls

• Pruritus often worsens in evenings and early night
• Commonly affects palms and soles but can be generalized
• Skin may become hyperpigmented and excoriated, particularly on hands and feet
• Pruritus with fatigue may indicate more aggressive liver disease 1
• The pathophysiology is multifactorial, involving bile salts accumulation, opioid system dysregulation, and histamine/progesterone metabolites 1, 5

Medications to Avoid

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