What medications can help alleviate itching in a patient with End-Stage Renal Disease (ESRD)?

Medications for Itching in ESRD

Gabapentin 100-300 mg administered after each hemodialysis session (three times weekly) is the most effective first-line medication for uremic pruritus in ESRD patients, with the strongest evidence base and greatest reduction in itch scores. 1, 2, 3

First-Line Pharmacologic Treatment

Gabapentin (Preferred)

• Gabapentin demonstrates the greatest reduction in itch scores among all studied interventions for uremic pruritus, with high-certainty evidence showing a 4.95 cm reduction on the 10 cm Visual Analogue Scale compared to placebo. 3
• Dosing is dramatically lower than non-ESRD populations: 100-300 mg after each dialysis session (three times weekly), not daily dosing. 1, 2
• Pregabalin is an alternative gabapentinoid with similar efficacy. 3

Kappa-Opioid Agonists (Alternative First-Line)

• Nalfurafine reduces itch with high-certainty evidence, showing a 1.05 cm reduction on VAS compared to placebo, though this effect is more modest than gabapentin. 3, 4
• Available in Japan and some other countries for uremic pruritus. 4

Topical Therapy (Adjunctive or Localized Itch)

Capsaicin 0.025% Cream

• Apply four times daily to affected areas, with 14 of 17 patients in randomized trials reporting marked relief and 5 achieving complete remission. 1, 2
• Works by depleting substance P and other neuropeptides in peripheral sensory neurons. 1

Emollients

• Apply regularly to all patients, as xerosis (dry skin) affects 54-69% of dialysis patients and lowers the threshold for itch. 1, 5
• Should be used as baseline therapy regardless of other interventions. 6, 7

Second-Line Options

Oral Medications with Moderate Evidence

• Montelukast showed itch reduction in small studies. 3
• Turmeric demonstrated benefit but requires further investigation. 3
• Zinc sulfate reduced itch scores in limited trials. 3

Phototherapy

• Broad-band UVB phototherapy is effective for many patients and can be used as an escalation option if gabapentin fails after 2-4 weeks. 1, 2, 6, 7

Medications to AVOID

Antihistamines (Ineffective for Uremic Pruritus)

• Cetirizine and other antihistamines are specifically ineffective for uremic pruritus despite efficacy in other conditions. 1, 2
• Ondansetron showed little or no effect on itch scores (0.38 cm reduction on VAS, not clinically significant) with high-certainty evidence. 3
• First-generation sedating antihistamines (diphenhydramine, hydroxyzine) should be avoided except in palliative care due to increased risk of falls, sedation, and potential dementia risk. 2

Other Ineffective Topicals

• Calamine lotion has no literature supporting its use for uremic pruritus. 1
• Crotamiton cream has been shown ineffective compared to vehicle control. 1

Essential Concurrent Optimization

Dialysis Adequacy

• Ensure target Kt/V of approximately 1.6, as pruritus is more common in underdialyzed patients and higher dialysis efficacy reduces prevalence. 1, 2, 8

Metabolic Parameters

• Normalize calcium-phosphate balance to accepted ranges. 1, 2, 5
• Control parathyroid hormone levels. 1, 2, 5
• Correct anemia with erythropoietin if present. 1, 2

Treatment Algorithm

1. Start with emollients for all patients plus optimize dialysis adequacy and metabolic parameters. 1, 5
2. Add gabapentin 100-300 mg after each dialysis session as first-line systemic therapy. 1, 2, 3
3. For localized itch, add capsaicin 0.025% cream four times daily to affected areas. 1, 2
4. If inadequate response after 2-4 weeks, consider broad-band UVB phototherapy or switch to nalfurafine if available. 1, 3, 6
5. For refractory cases, consider μ-opioid receptor antagonists (naltrexone) or κ-opioid receptor agonists as experimental options. 6

Critical Pitfalls

• Do not prescribe antihistamines expecting benefit for uremic pruritus—they are ineffective for this specific indication. 1, 2, 3
• Do not use standard gabapentin dosing; ESRD patients require dramatically reduced doses (100-300 mg three times weekly, not daily). 1, 2
• Administer all oral medications after hemodialysis sessions to avoid premature drug removal. 2
• If localized itch spreads to become generalized, this indicates broader uremic pruritus requiring systemic therapy escalation. 1