What medication is used to treat pruritus associated with jaundice?

Treatment of Pruritus Associated with Jaundice

Bezafibrate or rifampicin should be used as first-line pharmacological treatment for moderate to severe pruritus associated with jaundice. 1

Understanding Cholestatic Pruritus

Pruritus (itching) is a common and debilitating symptom in patients with jaundice, particularly when caused by cholestatic liver diseases. It can significantly impair quality of life and in severe cases may even lead to suicidal ideations.

Pathophysiology

The exact mechanism of cholestatic pruritus is not fully understood, but recent evidence points to several mediators:

• Lysophosphatidic acid (LPA) and its enzyme autotaxin (ATX) correlate with symptom intensity 2
• Bile acids accumulation in skin
• Endogenous opioids
• Serotonin

Treatment Algorithm for Jaundice-Associated Pruritus

First-line Treatments:

1. Bezafibrate (PPAR agonist)

   • Dosage: Not specified in guidelines but typically 200-400 mg daily
   • Evidence: The FITCH trial demonstrated clear benefit for moderate to severe cholestatic pruritus 1
   • Safety: Generally well-tolerated with minimal side effects in short-term treatment
   • Monitoring: Serum creatinine may increase mildly; monitor for myalgia

2. Rifampicin (equally recommended as first-line)

   • Dosage: 150-300 mg daily, can be increased to 600 mg daily 1
   • Evidence: Multiple meta-analyses support its efficacy 1
   • Caution: Monitor for hepatotoxicity; can induce drug-induced hepatitis in up to 12% of cholestatic patients after 4-12 weeks 1
   • Side effects: Discoloration of secretions

Second-line Treatment:

1. Cholestyramine (bile acid sequestrant)
   • Dosage: 4-16 g/day 1
   • Administration: Take separately from other medications (minimum 4 hours apart) 1
   • Mechanism: Binds bile salts in the gut lumen, preventing reabsorption 1
   • Limitations: Limited evidence for efficacy in sclerosing cholangitis compared to PBC 1
   • Note: Previously considered first-line but now second-line due to stronger evidence for bezafibrate and rifampicin

Third-line Treatment:

1. Sertraline (SSRI)
   • Dosage: 75-100 mg daily 1
   • Evidence: Limited but has shown benefit in small studies 1
   • Safety: Generally well-tolerated

Fourth-line Treatments:

1. Naltrexone (opioid antagonist)
   • Dosage: Start at very low dose (12.5 mg) and titrate up to 50 mg daily 1
   • Caution: May cause opioid withdrawal-like syndrome; significant side effects compared to other options 1
   • Alternative opioid antagonists: Nalmefene (0.25-1 mg/kg/day IV) 1

Fifth-line Options:

• Systemic dronabinol
• Phenobarbital
• Propofol
• Topical tacrolimus ointment 1

Non-Pharmacological Approaches

General Measures:

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

Invasive Approaches (for refractory cases):

• Extracorporeal albumin dialysis
• Plasmapheresis
• Bile duct drainage
• Liver transplantation (highly effective but reserved for intractable cases) 1

Important Clinical Considerations

1. Address underlying cause: If biliary obstruction is present, restoration of biliary drainage should be prioritized 1

2. Monitoring:

   • For rifampicin: Monitor liver function tests regularly
   • For bezafibrate: Monitor serum creatinine and watch for myalgia

3. Contraindications:

   • Gabapentin is not recommended for hepatic pruritus 1
   • Cholestyramine can impair absorption of various medications including UDCA 1

4. Special populations:

   • In children with cholestatic disorders, a similar stepwise approach is used with appropriate dose adjustments 3, 4

The management of jaundice-associated pruritus requires a systematic approach, often with sequential trials of different medications to find the most effective option for each patient.