What is Xyzal (levocetirizine)?

What is Xyzal (Levocetirizine)?

Xyzal is the brand name for levocetirizine, a second-generation oral antihistamine that selectively blocks histamine H1 receptors and is FDA-approved for treating allergic rhinitis (both seasonal and persistent) and chronic idiopathic urticaria. 1

Mechanism and Clinical Profile

Levocetirizine is the R-enantiomer of cetirizine, meaning it is the active component isolated from the racemic mixture. 2, 3 This gives it several pharmacological advantages:

• High receptor affinity and selectivity for H1 receptors with rapid onset and 24-hour duration of action 4, 2
• Minimal hepatic metabolism with primarily renal excretion unchanged, reducing drug interaction potential 5, 3
• High bioavailability and rapid absorption allowing for once-daily dosing at 5 mg 2, 6

FDA-Approved Indications

The medication is licensed for two primary conditions:

• Allergic rhinitis (seasonal and persistent): Relieves sneezing, runny nose, itchy nose/throat, and itchy/watery eyes 4, 1
• Chronic idiopathic urticaria: First-line therapy with well-established efficacy 4, 2

Clinical Efficacy Evidence

Levocetirizine demonstrates superior efficacy in persistent allergic rhinitis based on the landmark XPERT trial, which studied 551 patients over 6 months and showed significant improvement in nasal symptoms starting from week 1, with sustained benefit throughout the study period. 7, 8 Key findings include:

• Significant improvement in quality of life measures (RQLQ scores) compared to placebo (P <0.001) 8
• Relief of nasal congestion after 6 weeks of continuous treatment 7
• Reduction in comorbidities including asthma with prolonged 6-month therapy 5, 4
• Substantial cost savings to employers and society 7, 8

Allergen challenge studies suggest levocetirizine may have better efficacy than desloratadine, loratadine, or fexofenadine, though head-to-head long-term trials are needed. 2

Critical Safety Considerations and Contraindications

Absolute Contraindications (FDA Label)

Do not use levocetirizine if you have kidney disease or have ever had an allergic reaction to levocetirizine, cetirizine, or any ingredient in the product. 1

Renal Impairment Dosing Algorithm

This is a critical pitfall area requiring careful attention:

• Moderate renal impairment (CrCl 10-20 mL/min): Reduce dose by half 9, 5, 4
• Severe renal impairment (CrCl <10 mL/min): Avoid completely 9, 5, 4

Pregnancy and Lactation

All antihistamines, including levocetirizine, should ideally be avoided during pregnancy, especially in the first trimester, despite being FDA Pregnancy Category B (no evidence of fetal harm in animal studies but limited human data). 5, 10, 4 This represents a conservative approach given the lack of well-controlled human studies.

Sedation Risk

While levocetirizine is a second-generation antihistamine with less sedation than first-generation agents, patients should still be counseled about potential drowsiness and its impact on driving and operating machinery. 5, 10 The sedation risk is lower than cetirizine's 13.7% rate but not negligible. 5

Pediatric Considerations

• Excellent safety profile in children ≥6 years with appropriate dosing 5
• Attention to dosing and scheduling is important in school-age children as sedation may affect school performance 10
• Patients with low body mass may experience elevated drug levels with standard age-based dosing 5

Alternative Treatment Options

When levocetirizine is not suitable, consider:

• Other second-generation oral antihistamines: Desloratadine, fexofenadine, loratadine (similar efficacy profiles) 10
• Intranasal antihistamines: Azelastine or olopatadine for allergic rhinitis (onset 15-30 minutes) 9, 10

Anti-inflammatory Properties

Beyond H1 receptor blockade, levocetirizine demonstrates anti-inflammatory effects at clinically relevant concentrations, including effects on mast cell mediator release, which may enhance therapeutic benefit beyond simple antihistamine action. 3, 6

Long-term Use

Levocetirizine is increasingly used as long-term maintenance therapy rather than just acute symptom relief, particularly for persistent allergic rhinitis, with the XPERT trial demonstrating sustained efficacy and safety over 6 months. 7, 8, 6