What are the oral medication options for treating chronic pruritus?

Oral Medications for Chronic Pruritus

For chronic pruritus, start with non-sedating second-generation antihistamines (loratadine 10 mg daily or fexofenadine 180 mg daily), escalate to gabapentin (900-3600 mg daily) or pregabalin (25-150 mg daily) for refractory cases, and consider doxepin (10 mg twice daily) or SSRIs (paroxetine or sertraline) as alternative second-line agents, with specific modifications based on the underlying etiology. 1

Stepwise Oral Treatment Algorithm

First-Line: Antihistamines

Daytime Management:

• Non-sedating second-generation antihistamines are the initial oral therapy 1
• Loratadine 10 mg daily or fexofenadine 180 mg daily 1
• High-dose monotherapy (desloratadine 20 mg daily or fexofenadine 360 mg daily) may achieve 76.9-89% pruritus reduction in refractory cases 2

Nighttime Management:

• First-generation sedating antihistamines for nocturnal pruritus 1
• Diphenhydramine 25-50 mg or hydroxyzine 25-50 mg at bedtime 1, 3
• FDA-approved hydroxyzine dosing for pruritus: adults 25 mg three to four times daily 3

Critical Caveat: Long-term sedative antihistamines should be avoided except in palliative care due to dementia risk in elderly patients 1

Second-Line: Neuropathic Agents

When antihistamines fail after 2 weeks, advance to neuropathic agents 1:

• Gabapentin: 900-3600 mg daily in divided doses 1, 4
• Pregabalin: 25-150 mg daily 1, 4
• These agents are particularly effective for neuropathic or mixed etiology pruritus 4

Alternative Second-Line: Antidepressants

Doxepin (Dual H1/H2 Antagonist):

• 10 mg orally twice daily 1
• Achieves complete resolution in 58% of uremic pruritus patients (vs 8% placebo) 1
• Overall improvement rate of 87.5% 1
• Drowsiness occurs in 50% but typically resolves within 2 days 1
• First-line for uremic pruritus, second-line for generalized pruritus of unknown origin 1

SSRIs:

• Paroxetine or sertraline for refractory cases 1, 5
• Particularly effective for cholestatic and paraneoplastic pruritus 5

Etiology-Specific Modifications

Opioid-Induced Pruritus

• Naltrexone is first choice if opioid cessation impossible 1
• Alternatives: methylnaltrexone, ondansetron, mirtazapine, or gabapentin 1

Hepatic/Cholestatic Pruritus

• Rifampicin as first-line 1
• Cholestyramine as second-line 1
• Sertraline as third-line 1
• Avoid gabapentin in hepatic pruritus despite efficacy elsewhere 1

Uremic Pruritus (Dialysis Patients)

• Doxepin 10 mg twice daily as preferred agent 1
• Gabapentin as alternative 1
• Avoid long-term sedative antihistamines except palliative care 1

Pruritus of Unknown Origin

• Start with non-sedative antihistamines (fexofenadine 180 mg or loratadine 10 mg) 1
• Advance to gabapentin or doxepin if no response after 2 weeks 1

Quality of Life Considerations

Chronic pruritus affects approximately 22% of people in their lifetime and causes significant morbidity including impaired sleep, depression, and reduced quality of life 4. Approximately 10% of patients do not respond to first-line topical and oral antihistamine therapies, necessitating systemic treatments 4. The inflammatory etiology accounts for 60% of cases, neuropathic/mixed for 25%, and systemic/other causes for 15% 4.

Critical Pitfalls to Avoid

• Never use gabapentin for hepatic pruritus despite its broad efficacy 1
• Sedative antihistamines carry dementia risk with chronic use in elderly patients 1
• Reassess diagnosis if no improvement after 2 weeks of appropriate therapy 1
• Consider combination H1 and H2 antagonists only in truly refractory cases 1
• High-dose antihistamine monotherapy is preferable to combinations due to unknown drug interactions 2