Adis Drug Evaluation


, Volume 66, Issue 7, pp 973-996

First online:


A Review of its Use in the Management of Allergic Rhinitis and Skin Allergies
  • Philip I. HairAffiliated withAdis International Limited Email author 
  • , Lesley J. ScottAffiliated withAdis International Limited

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Levocetirizine (Xyzal®) is a selective, potent, oral histamine Hi receptor antagonist of the latest generation that is licensed for the symptomatic treatment of allergic rhinitis (including persistent allergic rhinitis [PER]) and chronic idiopathic urticaria (CIU).

Large, well designed trials indicate that levocetirizine is effective and generally well tolerated in the treatment of allergic rhinitis and CIU. Its pharmacological profile offers many positive aspects: a rapid onset and long duration of antihis-taminic effect; rapid absorption and high bioavailability; a low potential for drug interactions; a low volume of distribution; and a lack of effect on cognition, psychomotor function and the cardiovascular system. Allergen challenge chamber studies suggest that levocetirizine has better efficacy than desloratadine, loratadine or fexofenadine. Well controlled, long-term studies with other later-generation H1 receptor antagonists are required to fully define its clinical profile relative to other agents in this class. Overall, levocetirizine is a valuable addition to the oral H1 receptor antagonists available for the treatment of allergic rhinitis and as first-line therapy in patients with CIU.

Pharmacological Properties

Levocetirizine, the R-enantiomer of racemic cetirizine, exhibits a higher in vitro affinity for the H1 receptor than racemic cetirizine or the S-enantiomer, dextroce-tirizine, with the antihistaminic properties of racemic cetirizine residing in the R- rather than the S-enantiomer. Levocetirizine has a more rapid onset and longer duration of action than other antihistamines, with maximal inhibition of histamine-induced wheal in healthy volunteers occurring 2–4 hours after drug administration. In several double-blind studies, histamine-induced wheal and/or flare responses were generally inhibited to a greater extent with single or multiple doses of levocetirizine 5mg than with therapeutic doses of other antihistamines (including loratadine, desloratadine, fexofenadine, ebastine and mizolastine) in healthy adult volunteers and atopic adult patients. Levocetirizine also exerts anti-inflammatory effects in patients with allergic disorders. The drug has no clinically relevant effect on cognitive function, psychomotor function or cardiovascular parameters.

After single milligram-equivalent doses, the pharmacokinetic profile of levocetirizine did not differ regardless of whether it was given as the individual enantiomer or as a component of racemic cetirizine; however, levocetirizine exhibited a lower volume of distribution (suggesting a more limited distribution into tissues) and a lower renal clearance than dextrocetirizine. In healthy adult volunteers, levocetirizine is rapidly absorbed, with maximum plasma concentrations attained within 1 hour and steady-state concentrations after 2 days. The apparent volume of distribution of levocetirizine was low compared with that of other antihistamines (e.g. cetirizine, mizolastine, fexofenadine and desloratadine). The drug appears to have a high absolute oral bioavailability and exhibits a high level of plasma protein binding (≥87%). It undergoes minimal metabolism and is primarily excreted as unchanged drug in the urine, with 95% of the radiolabelled dose excreted over the first 48 hours. No conversion of radiolabelled levoce-tirizine to dextrocetirizine was detected. Pharmacokinetic parameters of levoce-tirizine 5mg in paediatric patients aged ≥6 years were similar to those in healthy adults. In patients with end-stage renal impairment, total body clearance of levocetirizine was ≈80% lower than that in subjects with normal renal function, with dosage adjustment recommended in patients with renal impairment. Levocetirizine appears to have a low potential for drug interactions, although no in vivo drug-interaction studies have been conducted to date.

Therapeutic Efficacy

Several well designed, placebo-controlled, short-term studies have shown oral levocetirizine 5mg once daily to be effective in alleviating symptoms in adult and/ or adolescent patients with seasonal allergic rhinitis (SAR), perennial allergic rhinitis (PAR), PER, CIU and other skin allergies, and in children (aged 6–12 years) with SAR and PAR. Levocetirizine also improved health-related quality of life in adults with PER and CIU and children with SAR and PAR. These data are supported by 2-day allergen challenge chamber studies and noncomparative, multicentre studies in the primary care setting, including a large noncomparative study in 17 638 patients with allergic disorders. Data from small (n < 50 patients), short-term studies and/or from 2-day allergen challenge chamber studies suggest that levocetirizine may be more effective than desloratadine, loratadine and fexofenadine in alleviating symptoms of SAR and has similar efficacy to cetirizine in CIU.

In Addition, the longer-term efficacy of levocetirizine was demonstrated in adult patients with PER in XPERT (Xyzal® in Persistent Rhinitis Trial), a 6-month, double-blind, multicentre trial. Levocetirizine significantly improved health-related quality of life and the Total 5 Symptoms Score over the first 4 weeks of treatment in adult patients with PER (co-primary endpoints), with these benefits sustained over the 6-month treatment period. Furthermore, the proportion of patients who experienced an asthma event during the 6-month treatment period was significantly lower in the levocetirizine than in the placebo group, as was the mean number of asthma events requiring medication per patient.


Levocetirizine was generally well tolerated in adults, adolescents and children with allergic conditions participating in clinical trials and in the clinical practice setting, based on a pooled analysis of therapeutic trials, a large study in the primary care setting and a large postmarketing surveillance study. In the pooled analysis of therapeutic studies in adults and adolescents (12–71 years of age), 11.3% of 935 levocetirizine recipients experienced at least one adverse event, with the most common being somnolence (5.2%), dry mouth (2.6%) and fatigue (2.5%). The vast majority (91.6%) of these treatment-emergent adverse events were of mild to moderate severity, with very few levocetirizine recipients (1%) discontinuing treatment because of an adverse event. In the postmarketing surveillance study, <0.1% of patients discontinued levocetirizine treatment because of drowsiness/sedation.