Xyzal - Drug Monograph

Introduction

Xyzal (levocetirizine dihydrochloride) is a second-generation antihistamine medication approved by the FDA in 2007. It is the active enantiomer of cetirizine and represents an advancement in antihistamine therapy with improved selectivity for H1 receptors and reduced sedative effects compared to first-generation antihistamines. Xyzal is commonly prescribed for the management of allergic conditions.

Mechanism of Action

Levocetirizine is a potent, selective antagonist of peripheral H1 receptors. It competitively inhibits histamine binding at H1 receptors, preventing the downstream effects of histamine release including vasodilation, increased vascular permeability, and smooth muscle contraction. Unlike first-generation antihistamines, levocetirizine has minimal affinity for muscarinic, serotonin, or alpha-adrenergic receptors, resulting in reduced anticholinergic effects and improved safety profile.

Indications

• Perennial allergic rhinitis
• Seasonal allergic rhinitis
• Chronic idiopathic urticaria
• Other allergic skin conditions (off-label)

Dosage and Administration

• CrCl 50-80 mL/min: 2.5 mg daily
• CrCl 30-50 mL/min: 2.5 mg every other day
• CrCl 10-30 mL/min: 2.5 mg twice weekly
• CrCl <10 mL/min: Contraindicated

Pharmacokinetics

Contraindications

• End-stage renal disease (CrCl <10 mL/min)
• Hypersensitivity to levocetirizine, cetirizine, or any component of the formulation
• History of hypersensitivity reaction to hydroxyzine

Warnings and Precautions

• Renal impairment: Dose adjustment required
• Sedation: May cause drowsiness; caution when operating machinery
• Urinary retention: Use with caution in patients with prostatic hyperplasia
• Pregnancy: Category B - use only if clearly needed
• Lactation: Excreted in breast milk; use with caution
• Pediatric use: Safety established for children ≥6 years
• Geriatric use: Increased risk of adverse effects; consider renal function

Drug Interactions

• CNS depressants: Enhanced sedative effects with alcohol, benzodiazepines, opioids
• Theophylline: May decrease clearance of levocetirizine
• Ritonavir: Potential increased levocetirizine concentrations
• Anticholinergics: Additive anticholinergic effects

Adverse Effects

• Somnolence (6-14%)
• Fatigue (5-6%)
• Dry mouth (2-5%)
• Pharyngitis (3%)

• Anaphylaxis
• Angioedema
• Seizures
• Hepatitis
• Thrombocytopenia

Monitoring Parameters

• Efficacy assessment: Symptom control in allergic conditions
• Safety monitoring: Renal function (serum creatinine, CrCl)
• Adverse effects: Sedation, cognitive function
• Periodic assessment: Need for continued therapy

Patient Education

• Take medication in evening to minimize daytime drowsiness
• Avoid alcohol and other CNS depressants
• Report severe drowsiness, difficulty urinating, or palpitations
• Do not crush or chew tablets
• Store at room temperature (15-30°C)
• Seek immediate medical attention for signs of allergic reaction
• Inform healthcare providers of all medications being taken

References

1. FDA Prescribing Information: Xyzal (levocetirizine dihydrochloride) 2. Devillier P, Roche N, Faisy C. Clinical efficacy of levocetirizine in allergic rhinitis. Expert Opin Pharmacother. 2008;9(5):805-815. 3. Potter PC; LATIN Study Investigators. Levocetirizine is effective for symptom relief including nasal congestion in adolescent and adult (PAR) and chronic idiopathic urticaria. Allergol Immunopathol (Madr). 2010;38(5):246-252. 4. Simons FE, Simons KJ. Levocetirizine: pharmacokinetics and pharmacodynamics in children. Pediatr Allergy Immunol. 2011;22(3):282-288. 5. Church MK, Maurer M, Simons FE, et al. Risk of first-generation H(1)-antihistamines: a GA(2)LEN position paper. Allergy. 2010;65(4):459-466. 6. Zuberbier T, Oanta A, Bogacka E, et al. Comparison of the efficacy and safety of bilastine 20 mg vs levocetirizine 5 mg for the treatment of chronic idiopathic urticaria: a multi-centre, double-blind, randomized, placebo-controlled study. Allergy. 2010;65(4):516-528.