What is the treatment for pruritis (itching) from obstructive jaundice?

Treatment of Pruritus from Obstructive Jaundice

First-line treatment is biliary drainage to relieve the obstruction, followed by cholestyramine 4-16 g/day as the primary pharmacological agent, with rifampicin 300-600 mg/day as second-line therapy if cholestyramine fails or is not tolerated. 1, 2, 3

Initial Management: Address the Obstruction

Before initiating any pharmacological therapy, exclude and treat mechanical bile duct obstruction as the underlying cause. 1, 2 In patients with large duct obstruction (such as from malignancy or strictures), endoscopic intervention with balloon dilation or stenting provides the most effective relief of pruritus. 1, 4 Surgical or endoscopic biliary drainage relieves pruritus in approximately 88-92% of cases and represents the definitive treatment when obstruction is present. 4, 5

Pharmacological Treatment Algorithm

First-Line: Cholestyramine

Cholestyramine is the recommended first-line pharmacological treatment for cholestatic pruritus due to its favorable safety profile. 1, 2, 3

• Dosing: Start with 4 g/day and titrate up to 8-16 g/day in divided doses as tolerated. 1, 3 Most patients achieve maximal benefit at 8-12 g/day with limited additional improvement beyond this dose. 1

• Administration: Must be given 2-4 hours before or after ursodeoxycholic acid (UDCA) if both are used, to prevent binding and loss of UDCA efficacy. 1 Give at breakfast time (an hour before or after eating) if the gallbladder is in situ. 1

• Palatability tip: Mixing with orange squash and refrigerating overnight improves taste. 1

• Side effects: The primary limitation is gastrointestinal symptoms, particularly constipation. 1, 3 Pharmacy consultation is needed to avoid interactions with concomitant medications. 1

Second-Line: Rifampicin

If cholestyramine fails or is not tolerated, rifampicin 300-600 mg/day is the recommended second-line agent. 1, 2

• Dosing: Start at 150 mg once to twice daily, then titrate upward based on symptoms and liver function test monitoring, with a maximum of 600 mg daily. 1

• Critical monitoring: Check liver function tests in 2-4 weeks after initiation. 1 Rifampicin carries a significant risk of drug-induced hepatitis in up to 12% of cholestatic patients after 4-12 weeks of treatment. 1, 2

• Caution: Use with particular care in advanced liver disease. 1 Consider vitamin K supplementation if the patient is icteric. 1

Alternative First-Line Option: Bezafibrate

In sclerosing cholangitis specifically, bezafibrate or rifampicin are recommended as first-line pharmacological treatments for moderate to severe pruritus. 1, 2 Bezafibrate has a favorable safety profile with no major side effects in short- or long-term treatment, though it requires monitoring for mild serum creatinine increases, myalgia, and rarely elevated transaminases. 2

Third-Line: Naltrexone

If first-line agents fail, naltrexone (an opioid antagonist) should be considered. 1, 2

• Dosing: Start at 12.5 mg/day and titrate slowly to a maximum of 50 mg/day to avoid opiate withdrawal-like reactions. 1

• Important warning: Some patients require an intravenous induction stage. 1 Long-term tolerability can be problematic, with ongoing withdrawal-like reactions or reduced pain threshold. 1

Fourth-Line: Sertraline

Sertraline (SSRI) 100 mg/day can be used as third- or fourth-line treatment. 1, 2

• Dosing: Titrate to symptoms and as tolerated. 1

• Side effects: Warn patients about dry mouth. 1

• Coordination: Requires interaction at the primary/secondary care interface if changing from an alternative antidepressant. 1

Adjunctive Therapy: Ursodeoxycholic Acid (UDCA)

UDCA 10-15 mg/kg/day may improve pruritus in 30-60% of cases, particularly in primary biliary cholangitis and intrahepatic cholestasis of pregnancy. 1, 6, 7 While UDCA is not specifically indicated for obstructive jaundice, it can be considered as adjunctive therapy once obstruction is relieved. 1 Pruritus improvement typically occurs within 1-2 weeks, and the dose can be titrated to a maximum of 21 mg/kg/day if needed. 1

Non-Pharmacological Measures

All patients should implement supportive measures regardless of pharmacological therapy: 1, 2

• Use emollients to prevent skin dryness 1, 2
• Avoid hot baths or showers 1, 2
• Apply cooling gels (e.g., menthol creams) to affected areas 1, 2
• Keep nails short to minimize excoriation 2

Note: Antihistamines (diphenhydramine, hydroxyzine) have limited benefit for cholestatic pruritus and work primarily through sedation rather than specific antipruritic effects. 1 They may be useful adjuncts for nighttime symptom control but are not recommended as primary therapy. 1

Common Pitfalls

• Failing to address the underlying obstruction: Pharmacological therapy alone is inadequate when mechanical obstruction persists. 1, 2, 5
• Incorrect timing of cholestyramine with UDCA: This leads to binding and loss of UDCA efficacy—maintain a 2-4 hour separation. 1
• Starting rifampicin without hepatotoxicity monitoring: Up to 12% develop drug-induced hepatitis, making early LFT monitoring essential. 1, 2
• Rapid naltrexone initiation: Starting at full dose causes severe withdrawal-like symptoms—always start low and titrate slowly. 1

Refractory Cases

For intractable pruritus unresponsive to all medical therapies, liver transplantation provides rapid and highly effective relief, often within 24 hours. 1, 2 Experimental approaches including UV light therapy, plasmapheresis, or albumin exchange may provide temporary relief in extreme situations while awaiting transplantation. 1