What are alternative medications for pruritus in patients with liver cirrhosis who cannot take hydroxyzine?

Alternative Medications for Pruritus in Liver Cirrhosis

Rifampicin should be your first-line treatment for hepatic pruritus in cirrhotic patients who cannot take hydroxyzine, starting at 150 mg twice daily and titrating up to 600 mg twice daily based on response. 1, 2, 3

First-Line: Rifampicin

• Rifampicin is now the preferred first-line agent for cholestatic pruritus, supported by multiple meta-analyses of randomized controlled trials demonstrating superior efficacy compared to placebo with a strength of recommendation A (Level 1+ evidence). 1, 2, 3

• Start at 150 mg twice daily and increase progressively to a maximum of 600 mg twice daily if needed, based on symptom response. 1, 4, 2, 3

• Monitor liver function tests every 2-4 weeks because rifampicin causes significant hepatitis in approximately 7.3% of cholestatic patients, typically occurring 4-12 weeks after treatment initiation. 4, 3, 5

• Warn patients that rifampicin changes the color of bodily secretions (urine, tears, sweat) to orange-red. 1, 4, 2

• Clinical response is excellent: more than 90% of patients with chronic cholestasis achieve complete or partial relief of pruritus. 4, 6, 7, 8

Second-Line: Cholestyramine

• If rifampicin fails, causes hepatotoxicity, or is not tolerated, switch to cholestyramine 4 g daily, titrating up to a maximum of 16 g daily in divided doses. 1, 2, 3

• Administer cholestyramine 2-4 hours before or after all other medications to prevent binding interactions that reduce efficacy of other drugs. 2, 3

• Cholestyramine binds bile acids in the gut lumen, preventing their absorption in the terminal ileum and reducing pruritus through decreased bile acid deposition in dermal tissue. 1, 9

• Evidence for cholestyramine is weaker (Strength D, Level 4), but its favorable safety profile justifies frequent use as second-line therapy. 1, 2

Third-Line: Sertraline

• For patients who fail both rifampicin and cholestyramine, initiate sertraline 75-100 mg daily. 1, 2, 3

• Sertraline acts on central nervous system neurotransmitters and has demonstrated efficacy in controlled trials for cholestatic pruritus. 2

• Warn patients about dry mouth as a common side effect. 2

Fourth-Line: Opioid Antagonists

• Naltrexone 50 mg daily orally or nalmefene are reserved for refractory cases after sertraline failure. 1, 2, 3

• Opioid antagonists have significantly more side-effects than rifampicin or cholestyramine, which limits their use despite proven efficacy in meta-analyses. 1

Treatments to Avoid

• Do not use gabapentin for hepatic pruritus—controlled trials show no benefit compared to placebo (Strength D, Level 4 evidence). 1, 2, 3

• Avoid antihistamines like hydroxyzine as specific therapy for hepatic pruritus—they provide only non-specific relief through sedative properties, not antihistamine action. 2, 3

• Long-term use of sedating antihistamines may predispose to dementia and should be avoided except in palliative care. 2

• Ondansetron is not recommended due to lack of efficacy in recent randomized controlled trials. 1, 3

Special Considerations

• For primary biliary cirrhosis specifically, ursodeoxycholic acid (10-20 mg/kg/day) may improve pruritus in 67-80% of patients, though it is not generally considered first-line treatment. 2

• For primary sclerosing cholangitis, exclude significant bile duct stenoses as a cause of progressive pruritus and treat with balloon dilation if present and accessible. 2

• Bezafibrate is specifically recommended for sclerosing cholangitis and applicable to other cholestases as a fourth-line option. 2

Refractory Cases

• UVB phototherapy is effective for many patients with cholestatic pruritus who fail pharmacologic therapy. 2

• Liver transplantation is highly effective, with pruritus frequently resolving within 24 hours, and should be considered when all available interventions have failed. 2, 3