What are the next steps for managing chronic itching uncontrolled on cetirizine (Cetirizine) and Xyzal (Levocetirizine)?

Management of Chronic Itching Uncontrolled on Cetirizine and Levocetirizine

For patients with chronic itching unresponsive to cetirizine and levocetirizine, the next step should be to add an H2 antihistamine such as cimetidine, consider higher doses of non-sedating antihistamines, or switch to alternative agents such as doxepin, gabapentin, or mirtazapine depending on the underlying cause of pruritus. 1

Diagnostic Considerations

Before escalating therapy, consider these important factors:

• Determine if there is an underlying dermatosis or systemic cause for the pruritus 1
• Consider referral to secondary care if there is diagnostic uncertainty or poor response to first-line treatments 1
• Evaluate for specific causes of generalized pruritus such as:
  • Renal disease (uremic pruritus) 1
  • Liver disease (hepatic pruritus) 1
  • Hematologic disorders (iron deficiency, polycythemia vera) 1
  • Malignancy (lymphoma, solid tumors) 1
  • Drug-induced pruritus 1
  • Neuropathic pruritus 1

Next Treatment Steps

Step 1: Optimize Current Antihistamine Therapy

• Consider increasing the dose of non-sedating antihistamines above standard recommendations when benefits outweigh risks 1
• Adjust timing of medication to ensure highest drug levels when itching is most severe 1

Step 2: Add Second-Line Agents

• Add H2 antihistamine:

  • Combine H1 antihistamine with H2 antagonist (e.g., cimetidine) which may provide better control than H1 antihistamine alone 1

• Consider topical treatments:

  • Topical doxepin (limit to 8 days, 10% of body surface area, and 12g daily) 1
  • Menthol-containing preparations or clobetasone butyrate 1
  • Cooling antipruritic lotions such as calamine or 1% menthol in aqueous cream 1

Step 3: Alternative Systemic Therapies

• For generalized pruritus of unknown origin (GPUO):

  • Paroxetine, fluvoxamine, mirtazapine, naltrexone, gabapentin, pregabalin, ondansetron, or aprepitant 1
  • Sedative antihistamines only for short-term use or in palliative settings 1

• For specific causes:

  • Uremic pruritus: Gabapentin, capsaicin cream, or topical calcipotriol (note: cetirizine is not effective) 1
  • Hepatic pruritus: Rifampicin (first-line), cholestyramine (second-line), sertraline (third-line) 1
  • Neuropathic pruritus: Refer to relevant specialist 1
  • Lymphoma-associated: Cimetidine, carbamazepine, gabapentin, or mirtazapine 1

Step 4: Consider Phototherapy

• Broadband UVB (BB-UVB) is effective for many patients with uremic pruritus 1
• Narrowband UVB (NB-UVB) may benefit patients with psychogenic pruritus 1

Special Considerations

For Elderly Patients

• Avoid sedating antihistamines due to risk of dementia with long-term use 1
• Consider gabapentin for pruritus in elderly skin 1
• Use moisturizers with high lipid content 1

For Drug-Induced Pruritus

• If medication-related, consider trial of cessation if risk-benefit analysis is acceptable 1
• For opioid-induced pruritus: naltrexone, methylnaltrexone, ondansetron, droperidol, mirtazapine, or gabapentin 1

Common Pitfalls to Avoid

• Don't continue ineffective treatments: If both cetirizine and levocetirizine have failed, switching to another second-generation antihistamine is unlikely to be beneficial as they have similar mechanisms of action 2, 3
• Don't use crotamiton cream for generalized pruritus of unknown origin 1
• Don't use gabapentin in hepatic pruritus 1
• Don't use long-term sedating antihistamines except in palliative care settings due to dementia risk 1
• Don't overlook psychological factors which may require behavioral interventions, relaxation techniques, or psychiatric referral 1

Monitoring and Follow-up

• Reassess if symptoms don't improve with second-line treatments 1
• Consider referral to dermatology if pruritus remains uncontrolled despite multiple interventions 1
• Monitor for medication side effects, particularly sedation with certain antihistamines 1