Hydroxyzine for Uremic Pruritus in ESRD Patients on Hemodialysis
Hydroxyzine should be avoided for uremic pruritus in elderly ESRD patients on hemodialysis; gabapentin 100-300 mg after each dialysis session (three times weekly) is the preferred first-line treatment. 1, 2
Why Hydroxyzine Is Not Recommended
Safety Concerns in Elderly ESRD Patients
- Long-term sedating antihistamines like hydroxyzine should be avoided except in palliative care settings, as they may predispose to dementia. 1, 2
- Hydroxyzine causes significant sedation and confusion in elderly patients, who should generally be started on low doses and observed closely due to increased sensitivity. 3
- The extent of renal excretion of hydroxyzine has not been determined, requiring cautious dose selection in patients with decreased renal function. 3
- Hydroxyzine carries risks of QT prolongation and Torsade de Pointes, particularly concerning in ESRD patients who often have electrolyte imbalances and cardiac comorbidities. 3
Limited Efficacy for Uremic Pruritus
- Antihistamines have limited efficacy specifically for uremic pruritus, despite effectiveness in other pruritic conditions. 2
- While one 2020 study showed hydroxyzine 25 mg/day reduced pruritus severity comparably to gabapentin, this contradicts current guideline recommendations that prioritize gabapentin as first-line therapy. 4
- The guideline evidence consistently emphasizes that cetirizine (another antihistamine) is ineffective for uremic pruritus, suggesting the mechanism of uremic itch is not histamine-mediated. 1, 2
Recommended Treatment Algorithm
First-Line: Optimize Dialysis Parameters
- Ensure adequate dialysis with target Kt/V of approximately 1.6, as pruritus is more common in underdialyzed patients. 1, 2
- Normalize calcium-phosphate balance and control parathyroid hormone levels to accepted ranges. 1, 2
- Correct anemia with erythropoietin if present. 1, 2
- Provide regular emollients for xerosis (dry skin), which lowers the threshold for itch. 2
First-Line Medication: Gabapentin
- Gabapentin 100-300 mg after each dialysis session (three times weekly) is the most effective medication for uremic pruritus in hemodialysis patients. 1, 2
- These doses are significantly lower than non-ESRD populations due to reduced renal clearance. 1
- Administer after hemodialysis sessions to avoid premature drug removal and facilitate adherence. 1
- Common side effects include mild drowsiness. 2
Alternative/Adjunctive Topical Treatment
- Topical capsaicin 0.025% cream applied four times daily to affected areas can provide marked relief, with 14 of 17 patients in trials reporting significant improvement. 1, 2
- Capsaicin works by depleting neuropeptides including substance P in peripheral sensory neurons. 2
Second-Line Options if Gabapentin Fails
- Broad-band UVB phototherapy is effective for many patients with uremic pruritus. 1, 2
- Topical doxepin may be considered for severe cases, but treatment must be strictly limited to 8 days, 10% of body surface area, and maximum 12 g daily. 2
Critical Pitfalls to Avoid
- Do not use hydroxyzine or other sedating antihistamines in elderly dialysis patients except in palliative care. 1, 2
- Avoid cetirizine and levocetirizine in severe renal impairment (CrCl <10 mL/min). 1
- Do not use calamine lotion or crotamiton cream, as there is no evidence supporting their use for uremic pruritus. 2, 5
- If hydroxyzine must be used for other indications, monitor closely for CNS depression, falls risk, and cardiac arrhythmias in this high-risk population. 3
Monitoring and Escalation
- If pruritus persists despite optimized dialysis parameters and gabapentin after 4-6 weeks, consider adding phototherapy or topical capsaicin. 2
- Renal transplantation remains the only definitive treatment for uremic pruritus but is not always feasible. 2
- Pruritus intensity can range from mild intermittent to severe sleep-disrupting, affecting quality of life significantly. 2, 6