Pharmacology of Levocetirizine

Introduction

Levocetirizine is a second-generation antihistamine, serving as the pharmacologically active R-enantiomer of cetirizine. Commonly prescribed for chronic allergic rhinitis and chronic idiopathic urticaria, levocetirizine delivers high efficacy with a low risk of sedation, improving over first-generation antihistamines through minimisation of CNS side effects due to limited blood-brain barrier penetration.​

Chemical Structure & Classification

• Class: Piperazine-based, second-generation H1-antihistamine
• Structure: (R)-2-[2-[4-[(R)-(4-chlorophenyl)phenylmethyl]-1-piperazinyl]ethoxy] acetic acid
• Key Features: Carboxyl group (reduces CNS penetration), aromatic rings (enhance receptor affinity), R-enantiomer (higher potency).​

Mechanism of Action

Levocetirizine acts as a selective antagonist at peripheral H1-receptors, competitively inhibiting histamine binding in the respiratory tract, vasculature, and GI tract. This prevents classic allergy symptoms—vasodilation, increased permeability, pruritus, and wheal-and-flare skin reactions.​

• Receptor affinity: 2x greater than cetirizine racemate; 5x versus S-enantiomer
• Onset: ~1 hour; Duration: ≥24 hours, supporting once-daily dosing.​

Pharmacokinetics

Indications

• Perennial allergic rhinitis
• Chronic idiopathic urticaria
• Mild allergy symptoms OTC​

Adverse Effects

Levocetirizine is generally well tolerated, but notable side effects include:​

• Somnolence (low incidence)
• Fatigue
• Dry mouth (xerostomia)
• Nasopharyngitis, pharyngitis
• Headache, dizziness
• Serious: hypersensitivity, anaphylaxis, angioedema, seizures (rare)

In children: pyrexia, cough, epistaxis. Post-marketing: rare reports of aggression, visual disturbances, palpitations, hepatitis.

Contraindications & Precautions

• Hypersensitivity to levocetirizine or cetirizine
• End-stage renal disease
• Severe renal impairment in children <12 years
• Caution in patients predisposed to urinary retention​

Special Populations

• Pregnancy/Lactation: Use with caution; insufficient human data. Appears in animal breast milk—avoid if possible.​
• Geriatric/Renal impairment: Dose adjustment may be necessary.

Comparative Profile

Levocetirizine’s minimal CNS penetration and high receptor selectivity distinguish it from first-generation antihistamines (e.g., diphenhydramine) and make it one of the least sedating second-generation agents.​

Conclusion

Levocetirizine is a potent, selective antagonist of peripheral H1-receptors, optimised for once-daily use. Its high efficacy, low sedation risk, and favorable safety profile support its status as a preferred agent for allergic rhinitis and chronic urticaria. Drug interactions and hepatic metabolism are minimal, making it safe for most patients, with renal function as the primary consideration for dosing.​

References

• Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 13th ed.
• Katzung BG, Basic and Clinical Pharmacology, 15th ed.
• Rang & Dale’s Pharmacology, 8th ed.
• Simons FER, Simons KJ. H1 Antihistamines: Current Status and Future Directions. World Allergy Organ J. 2021;14(6):100534.
• Mayo Clinic: Levocetirizine (oral route) – Side effects & dosage
• DrugBank: Levocetirizine profile
• ScienceDirect: Levocetirizine—an overview
• FIP Monograph: Levocetirizine Dihydrochloride