Levocetirizine - Drug Monograph

Introduction

Levocetirizine is a third-generation, non-sedating antihistamine and the active enantiomer of cetirizine. As a selective H1-receptor antagonist, it is widely used for the management of allergic conditions. Approved by the FDA in 2007, levocetirizine offers improved receptor binding affinity and reduced side effect profile compared to its racemic parent compound.

Mechanism of Action

Levocetirizine competitively inhibits histamine H1 receptors, preventing the binding of endogenous histamine to these receptors. This action blocks the downstream effects of histamine-mediated allergic responses, including vasodilation, increased vascular permeability, smooth muscle contraction, and sensory nerve stimulation. The drug demonstrates 2-fold greater affinity for H1 receptors compared to cetirizine, with minimal anticholinergic or antiserotonergic effects.

Indications

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

Dosage and Administration

• CrCl 30-49 mL/min: 2.5 mg once daily
• CrCl 10-29 mL/min: 2.5 mg every other day
• CrCl <10 mL/min: Contraindicated

Pharmacokinetics

Contraindications

• Hypersensitivity to levocetirizine, cetirizine, hydroxyzine, or any component of the formulation
• End-stage renal disease (CrCl <10 mL/min)
• Children under 2 years of age

Warnings and Precautions

• Renal impairment: Requires dosage adjustment
• Sedation: Although less sedating than first-generation antihistamines, somnolence may occur
• Driving/operating machinery: Caution advised until individual response is established
• Pregnancy: Category B - use only if clearly needed
• Lactation: Excreted in breast milk; use with caution
• Elderly: Increased risk of adverse effects due to possible decreased renal function

Drug Interactions

• CNS depressants: Additive sedative effects with alcohol, benzodiazepines, opioids
• Theophylline: May slightly decrease levocetirizine clearance
• Ritonavir: Increases levocetirizine exposure (clinical significance unknown)
• P-glycoprotein inhibitors: Potential for increased levocetirizine concentrations

Adverse Effects

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

• Headache
• Dizziness
• Nausea
• Abdominal pain

• Hypersensitivity reactions
• Seizures
• Severe dizziness
• Tachycardia

Monitoring Parameters

• Efficacy of allergic symptom control
• Signs of sedation or cognitive impairment
• Renal function in patients with renal impairment
• Adverse effects, particularly in elderly patients
• Patient adherence to therapy

Patient Education

• Take medication as prescribed, usually once daily
• May be taken with or without food
• Be aware of potential sedative effects, especially when starting therapy
• Avoid alcohol and other CNS depressants
• Report any severe dizziness, rapid heartbeat, or difficulty breathing
• Keep medication out of reach of children
• Do not crush or chew tablets; swallow whole
• Inform healthcare providers of all medications being taken

References

1. Patel P, D'Andrea C, Sacks HJ. Levocetirizine: an update. Curr Med Chem. 2015;22(11):1344-1355. 2. Day JH, Briscoe MP, Rafeiro E, et al. Comparative clinical efficacy, onset and duration of action of levocetirizine and desloratadine for symptoms of seasonal allergic rhinitis in subjects evaluated in the Environmental Exposure Unit (EEU). Int J Clin Pract. 2004;58(2):109-118. 3. Xyzal® (levocetirizine) [package insert]. UCB, Inc.; 2021. 4. Bachert C, van Cauwenberge P, Khaltaev N. Allergic rhinitis and its impact on asthma (ARIA). Allergy. 2002;57(9):841-855. 5. Simons FE. Advances in H1-antihistamines. N Engl J Med. 2004;351(21):2203-2217. 6. Zuberbier T, Asero R, Bindslev-Jensen C, et al. EAACI/GA²LEN/EDF/WAO guideline: management of urticaria. Allergy. 2009;64(10):1427-1443.