What is the role of gabapentin (Neurontin) in treating hyperphosphatemia-induced pruritus in a patient with End-Stage Renal Disease (ESRD)?

Gabapentin for Hyperphosphatemia-Associated Pruritus in ESRD

Gabapentin 100-300 mg administered after each dialysis session (three times weekly) is the most effective medication for treating uremic pruritus in ESRD patients, with significantly lower doses required than in non-ESRD populations due to reduced renal clearance. 1, 2, 3

Dosing Algorithm for ESRD Patients

Start with gabapentin 100 mg after each dialysis session (three times weekly). 1, 2, 4, 5 This minimal effective dose showed good response rates in a multicentre, double-blind, placebo-controlled trial, with visual analogue ratings falling in excess of 50% compared to placebo. 1

• If inadequate response after 2-4 weeks, titrate gradually up to 300 mg after each dialysis session. 1, 4
• The frequency of using the lowest dose (100 mg three times weekly) is significantly higher than other doses and should be the maintenance target. 4
• Expect clinical improvement within 3-8 weeks, with VAS scores decreasing by an absolute 5.7 to 9.4 points on average. 5
• Overall response rate is 66-88.9% for gabapentin in uremic pruritus. 4, 6

Critical Pre-Treatment Optimization

Before initiating gabapentin, optimize dialysis parameters and metabolic control, as these foundational interventions may reduce pruritus independently. 1, 2, 3

• Ensure adequate dialysis with target Kt/V of approximately 1.6, as pruritus is more common in underdialyzed patients. 1, 2, 3
• Normalize calcium-phosphate balance and control parathyroid hormone levels, as secondary and tertiary hyperparathyroidism often accompany ESRD and contribute to pruritus. 1, 2, 3
• Correct anemia with erythropoietin if present. 1, 2, 3
• Provide emollients regularly to address xerosis (dry skin), which is the most common cutaneous finding in dialysis patients and lowers the threshold for itch. 2, 3

Important Safety Considerations

Gabapentin causes mild drowsiness in a significant proportion of patients, but side effects are generally tolerable. 1, 4

• Side effects occur in approximately 37-47% of patients, with somnolence, dizziness, and fatigue being most common. 7, 8, 5
• Only 17% of patients discontinue gabapentin due to intolerability. 8, 5
• Conservatively managed CKD patients (not on dialysis) experience more side effects (47.1%) compared to hemodialysis patients (14.3%), though higher doses do not appear to be a factor associated with side effects. 8
• If gabapentin is not tolerated, pregabalin 25 mg after dialysis or daily can be substituted, with 81% response rate in gabapentin-intolerant patients. 6

Critical Pitfalls to Avoid

Do not use cetirizine for uremic pruritus—it is specifically ineffective for this condition despite efficacy in other pruritic disorders. 1, 2, 3

Avoid long-term sedating antihistamines (diphenhydramine, hydroxyzine) except in palliative care, as they may predispose to dementia. 1, 2, 3 While one study showed hydroxyzine 25 mg daily was as effective as gabapentin for pruritus control 7, the British Association of Dermatologists guidelines explicitly recommend against long-term sedating antihistamines due to dementia risk. 1

Alternative and Adjunctive Treatments

If gabapentin provides insufficient relief or cannot be tolerated:

• Topical capsaicin 0.025% cream applied four times daily is highly effective, with 14 out of 17 patients reporting marked relief and 5 achieving complete remission. 1, 2, 3, 9 Capsaicin depletes neuropeptides including substance P in peripheral sensory neurons. 1
• Broad-band UVB phototherapy is effective for many patients with uremic pruritus. 2, 3
• Topical calcipotriol can be considered for localized areas. 1, 3

Renal transplantation remains the only definitive treatment for uremic pruritus. 1, 3

Monitoring Response

• Use visual analogue scale (VAS) or 5-D pruritus scale to objectively measure treatment response. 4, 5
• Gabapentin also improves depression and sleep disturbances associated with pruritus in dialysis patients. 1
• If pruritus persists despite optimized gabapentin dosing and adequate dialysis, reassess for other contributing factors or consider combination therapy with topical capsaicin. 1, 3