What oral medication can be used to treat pruritis in someone allergic to Benadryl (diphenhydramine)?

Oral Medication for Pruritus in Patients Allergic to Benadryl

For patients allergic to diphenhydramine (Benadryl), use second-generation non-sedating antihistamines as first-line oral therapy, specifically loratadine 10 mg daily or fexofenadine 180 mg daily. 1, 2

First-Line Alternatives to Diphenhydramine

Second-Generation Antihistamines (Preferred)

• Loratadine 10 mg daily is recommended as the first choice for daytime pruritus management 1, 2
• Fexofenadine 180 mg daily is equally effective and non-sedating 1, 2
• Cetirizine 10 mg daily is a mildly sedative option that provides effective pruritus relief with minimal drowsiness 1, 3
  • Cetirizine can be increased up to 40 mg daily for refractory cases 3
  • It has proven efficacy in urticaria and atopic dermatitis-related pruritus 3
  • Recent evidence shows cetirizine is noninferior to diphenhydramine for acute urticaria with fewer adverse effects 4

Why These Are Superior to Diphenhydramine

• Second-generation antihistamines cause significantly less sedation and anticholinergic side effects 4
• They have longer duration of action, requiring only once-daily dosing 3, 4
• Patients spend less time in treatment centers and have lower return rates compared to diphenhydramine 4
• No impairment of driving performance or response time at standard doses 3

Alternative First-Generation Antihistamine

Hydroxyzine (If Second-Generation Fails)

• Hydroxyzine 25-50 mg daily can be used for nighttime pruritus due to sedative properties 1, 5
• FDA-approved dosing for pruritus: 25 mg three to four times daily in adults 5
• Important caveat: Hydroxyzine should only be used short-term or in palliative settings due to dementia risk with chronic use of sedating antihistamines 1, 2
• Hydroxyzine is chemically distinct from diphenhydramine, making cross-reactivity less likely, though caution is warranted

Second-Line Options for Refractory Pruritus

GABA Agonists

• Gabapentin 900-3600 mg daily is effective for antihistamine-resistant pruritus 1, 2
• Pregabalin 25-150 mg daily provides similar efficacy with potentially better tolerability 1, 2
• These work by reducing peripheral release of calcitonin gene-related peptide and central itch signaling 1

Antidepressants

• Doxepin 10 mg twice daily functions as both a tricyclic antidepressant and potent H1/H2 histamine antagonist 2
  • Achieves 87.5% overall improvement rate in uremic pruritus 2
  • Drowsiness occurs in 50% but typically resolves within 2 days 2
• Paroxetine, fluvoxamine, or mirtazapine can be considered for refractory cases 1, 2

Combination Therapy

• H1 + H2 antagonist combination (e.g., fexofenadine + cimetidine) may provide additional benefit for refractory pruritus 1
• This combination is particularly effective for acute urticaria 6

Critical Pitfalls to Avoid

• Never use long-term sedative antihistamines except in palliative care due to dementia risk 1, 2
• Avoid topical diphenhydramine as it can cause allergic contact dermatitis and has limited evidence for efficacy 1
• Do not use crotamiton cream as it lacks significant antipruritic effect compared to vehicle 1
• Avoid calamine lotion as there is no literature supporting its use 1
• Gabapentin should not be used in hepatic pruritus despite efficacy in other pruritus types 2

Practical Algorithm

1. Start with loratadine 10 mg or fexofenadine 180 mg daily for daytime pruritus 1, 2
2. Add cetirizine 10 mg at bedtime if nighttime pruritus persists 1, 3
3. If inadequate response after 2 weeks, add gabapentin 900-3600 mg daily or pregabalin 25-150 mg daily 1, 2
4. For persistent symptoms, consider doxepin 10 mg twice daily or combination H1/H2 antagonist therapy 1, 2
5. Ensure adequate emollient use throughout treatment as dry skin exacerbates pruritus 1, 2