What non-sedating antihistamine can be given to a patient with a uticaria (hives) allergy to levofloxacin (Levaquin) who has an E. coli urinary tract infection (UTI) and is being treated with ciprofloxacin (Cipro) and Benadryl (diphenhydramine)?

Non-Sedating Antihistamine for Fluoroquinolone-Induced Urticaria

Add loratadine 10 mg once daily or fexofenadine as your non-sedating antihistamine alongside the Benadryl, as these are completely non-sedating second-generation H1 antihistamines recommended for urticaria management. 1, 2

Understanding the Clinical Context

Your patient has urticaria from levofloxacin but is now receiving ciprofloxacin for E. coli UTI. This is reasonable because:

• Cross-reactivity between fluoroquinolones is low and unpredictable 1, 3
• Studies show most ciprofloxacin-reactive patients (4/5) tolerate levofloxacin, and conversely, 3 of 4 levofloxacin-reactive patients tolerate ciprofloxacin 3
• A large multicenter study found only 6.3% reaction risk when challenging with ciprofloxacin after a different fluoroquinolone allergy 4
• The patient should be monitored in a controlled clinical setting where rapid treatment can be administered if an allergic reaction occurs 1

Optimal Non-Sedating Antihistamine Selection

First-line options (choose one):

• Loratadine 10 mg once daily - completely non-sedating at all doses and can be increased up to 40 mg daily if needed for better control 1, 2, 5
• Fexofenadine 180 mg once daily - completely non-sedating at all doses 2, 5
• Desloratadine 5 mg once daily - completely non-sedating with longest half-life (27 hours) 1, 2, 5

Avoid cetirizine as your non-sedating option because it may cause sedation in 13.7% of patients (vs 6.3% placebo), especially at higher doses, despite being classified as "second-generation" 1, 2

Why This Combination Strategy Works

• Combining a sedating antihistamine (Benadryl) at night with a non-sedating antihistamine during the day is explicitly supported by guidelines for urticaria management 1
• The British Journal of Dermatology notes that adding a sedating antihistamine at night (chlorphenamine 4-12 mg or hydroxyzine 10-50 mg) to a non-sedating antihistamine by day may help patients sleep better 1
• However, this combination probably has little additional clinical effect on urticaria if the H1 receptor is already saturated 1

Dose Escalation Strategy If Symptoms Persist

• Start with standard dosing and assess response after 2-4 weeks 2, 5
• If inadequate control, increase the non-sedating antihistamine dose up to 4-fold (e.g., loratadine up to 40 mg daily) before adding other therapies 1, 2, 5
• Higher doses demonstrate enhanced "antiallergic" effects on mast-cell mediator release 1, 2
• Allow 2-4 weeks at each dose level before escalating to properly assess response 2

Additional Adjunctive Measures

Consider adding an H2 antihistamine:

• Adding an H2 antihistamine (famotidine 20 mg) may provide better urticaria control than H1 antihistamine alone 1
• This is particularly helpful for dyspepsia that may accompany severe urticaria 1

Topical symptomatic relief:

• Cooling antipruritic lotions such as 1% menthol in aqueous cream provide soothing relief 1, 2, 6

Critical Pitfalls to Avoid

• Don't assume Benadryl alone is sufficient - first-generation antihistamines cause reduced concentration and performance, making them inappropriate as monotherapy 1
• Don't combine multiple first-generation antihistamines - they cause prolonged daytime drowsiness despite nighttime dosing 2
• Avoid NSAIDs and aspirin as they can worsen urticaria through cyclooxygenase inhibition 1, 2, 6, 7
• Minimize aggravating factors including overheating, stress, and alcohol 1, 2, 6

Monitoring for Fluoroquinolone Cross-Reactivity

Since your patient is receiving ciprofloxacin despite levofloxacin allergy:

• Monitor closely during the first dose and throughout treatment in a controlled clinical setting 1
• Have emergency medications immediately available including epinephrine, as anaphylaxis risk is 1.8-2.3 per 100 million treatment days 1
• If urticaria worsens or new symptoms develop (angioedema, respiratory symptoms, hypotension), stop ciprofloxacin immediately and treat as moderate-to-severe hypersensitivity reaction 1