Levocetirizine: R-Enantiomer of Cetirizine, Second-Generation Antihistamine
Levocetirizine (Xyzal, Xusal) is the pharmacologically active R-enantiomer of cetirizine. It has twice the H1-binding affinity of cetirizine at half the dose, with a similar safety and tolerability profile.
Approved for seasonal and perennial allergic rhinitis, chronic idiopathic urticaria. Mild sedation is a distinguishing feature — more than fexofenadine, less than first-generation antihistamines.
Mechanism of Action
Potent, selective inverse agonist at peripheral H1 receptors. Has higher H1-receptor affinity (Ki ~3 nM) than cetirizine or loratadine. Minimal CNS penetration compared to first-generation antihistamines.
Indications & Use
Seasonal allergic rhinitis, perennial allergic rhinitis, chronic idiopathic urticaria (CIU). Approved from age 2 years. Once-daily dosing improves adherence.
Dosage
Adults and children ≥12 years: 5 mg once daily (evening preferred). Children 6–11 years: 5 mg once daily. Children 2–5 years: 1.25 mg (2.5 mL oral solution) twice daily. Dose reduction required in renal impairment (GFR-based).
Side Effects
Somnolence (more than fexofenadine, less than first-generation): ~6% in clinical trials. Dry mouth, fatigue, headache. No significant anticholinergic effects at standard doses.
Drug Interactions
CNS depressants (alcohol, sedatives): additive sedation — advise caution. Theophylline: slight increase in levocetirizine levels (minor). P-glycoprotein inhibitors may modestly increase CNS exposure.
Contraindications
Severe renal impairment (GFR <10 mL/min), hypersensitivity to cetirizine or levocetirizine. Caution in elderly (falls risk). Not recommended in end-stage renal disease.
Frequently Asked Questions
Is levocetirizine better than cetirizine?
Levocetirizine binds H1 receptors with twice the affinity at half the dose. Some patients tolerate levocetirizine better. In practice, clinical efficacy differences are modest and both are acceptable options.
Can levocetirizine be taken in the morning?
It is usually recommended in the evening because mild sedation can be used to advantage for night-time symptoms and sleep. However, for purely morning symptoms, morning dosing is acceptable for most patients.
Is levocetirizine safe during pregnancy?
Cetirizine/levocetirizine are among the preferred antihistamines in pregnancy (category B animal data). While no antihistamine is definitively proven safe in pregnancy, second-generation antihistamines are preferred over first-generation.
References
- EMA Xyzal SPC 2023
- EAACI Guideline Urticaria 2022
- Tillement JP et al. Clin Exp Allergy 2001
Medical Disclaimer: This information is for educational purposes only and does not replace professional medical advice.