What oral medications are recommended for a patient with generalized pruritus (itchiness all over the body) due to a systemic condition such as chronic kidney disease or liver disease, or a dermatological condition like eczema or psoriasis?

Oral Medications for Generalized Pruritus

For generalized itchiness without an obvious rash, start with non-sedating antihistamines like fexofenadine 180 mg or loratadine 10 mg daily, but recognize these work primarily for histamine-mediated conditions like urticaria—not for most systemic causes of itch. 1, 2

Initial Diagnostic Approach

Before prescribing oral medications, identify the underlying cause through targeted testing:

• Check complete blood count, comprehensive metabolic panel (including liver and kidney function), and ferritin levels in all patients with chronic generalized pruritus 1, 2
• Review all current medications as 20-30% of cases are drug-induced 2
• Look for specific clinical clues: aquagenic pruritus (itching after water contact) suggests polycythemia vera; nocturnal itch with weight loss and night sweats suggests lymphoma 1

Treatment Algorithm by Underlying Cause

Pruritus of Unknown Origin (After Negative Workup)

First-line oral therapy:

• Non-sedating antihistamines: fexofenadine 180 mg or loratadine 10 mg daily 1, 2
• Consider combining H1 and H2 antagonists (e.g., fexofenadine plus cimetidine) for enhanced effect 1
• Mildly sedating option: cetirizine 10 mg if nighttime sedation is desired 1

Second-line oral therapy (if antihistamines fail):

• Gabapentin or pregabalin for neuropathic components 1, 2
• SSRIs: paroxetine or fluvoxamine 1
• Mirtazapine (antidepressant with antipruritic properties) 1
• Naltrexone (opioid antagonist) 1

Uraemic Pruritus (Chronic Kidney Disease)

Critical warning: Cetirizine is NOT effective for uraemic pruritus 1

Oral medication options:

• Gabapentin is the recommended oral agent 1
• Avoid long-term sedating antihistamines (except in palliative care) due to dementia risk 1, 2

Hepatic/Cholestatic Pruritus

Follow this specific treatment hierarchy:

1. First-line: Rifampicin 150 mg twice daily, can increase to 600 mg twice daily 1, 3, 2

   • Monitor liver function tests for hepatotoxicity 3
   • Warn patients about orange discoloration of body secretions 3

2. Second-line: Cholestyramine 9 g daily if rifampicin fails or is not tolerated 1, 3, 2

3. Third-line: Sertraline 75-100 mg daily 1, 3, 2

4. Fourth-line: Naltrexone 50 mg daily or nalmefene 0.25-1 mg/kg/day 1, 3

   • Note: Opioid antagonists have significantly more adverse effects than rifampicin 3

Critical warning: Do NOT use gabapentin for hepatic pruritus—it is ineffective in this context 1, 3, 2

Lymphoma-Associated Pruritus

Oral medication options:

• Cimetidine, gabapentin, carbamazepine, or mirtazapine 1
• Oral corticosteroids for incurable lymphoma (palliative setting) 1

Polycythemia Vera-Associated Pruritus

Oral medication options:

• Aspirin 300 mg daily (often effective) 1
• SSRIs, cimetidine, or atenolol 1
• Interferon-alpha (also treats underlying PV but poorly tolerated) 1

Paraneoplastic Pruritus (Solid Tumors)

Oral medication options:

• Paroxetine, mirtazapine, granisetron, or aprepitant 1

Opioid-Induced Pruritus

First-choice: Naltrexone (if stopping opioid is impossible) 1, 2

Alternatives:

• Methylnaltrexone, ondansetron, droperidol, mirtazapine, or gabapentin 1

Critical Pitfalls to Avoid

• Never use sedating antihistamines long-term (except palliative care) due to increased dementia risk, especially in elderly patients 1, 2, 4
• Antihistamines have limited efficacy beyond urticaria and drug reactions—they don't work for most systemic causes 5, 6
• Cetirizine is ineffective for uraemic pruritus despite being effective for other conditions 1
• Gabapentin should NOT be used for hepatic/cholestatic pruritus 1, 3, 2
• Always correct underlying causes first: iron deficiency requires iron replacement (strength C), adequate dialysis for uraemia, optimize calcium-phosphate balance 1

Essential Complementary Measures

• Prescribe emollients liberally for all patients with generalized pruritus 1, 3, 2
• Advise keeping nails short to prevent scratch-induced skin damage 3
• Consider vitamin D supplementation as it may help some patients 1