Pharmacotherapeutic group: Antihistamines for systemic use, piperazine derivatives,
ATC code: R06AE09.
Mechanism of action
Levocetirizine, the (R)-enantiomer of cetirizine, is a potent and selective antagonist of peripheral H1-receptors.
Binding studies have demonstrated that levocetirizine has a marked affinity for human H1-receptors (Ki = 3.2 nmol/l). Levocetirizine has twice the affinity of cetirizine (Ki = 6.3 nmol/l).
Levocetirizine dissociates from H1-receptors with a half-life of 115 ± 38 min.
Following a single dose, levocetirizine achieves 90% receptor occupancy at 4 hours and 57% at 24 hours.
Pharmacodynamic studies in healthy volunteers have shown that, at half the dose, levocetirizine produces an effect comparable to that of cetirizine on both skin and nasal responses.
Pharmacodynamic effects
The pharmacodynamic activity of levocetirizine has been investigated in the following randomised, controlled studies:
In a study comparing the effects of levocetirizine 5 mg, desloratadine 5 mg and placebo on histamine-induced wheal and flare, treatment with levocetirizine produced a statistically significant reduction (p < 0.001) compared with placebo and desloratadine; this effect was greatest within the first 12 hours and was maintained over 24 hours.
In placebo-controlled studies using an allergen-exposure chamber model, the onset of action of levocetirizine 5 mg on pollen-induced symptoms was observed one hour after dosing.
In vitro studies (Boyden chamber and tissue cultures) have shown that levocetirizine inhibits eotaxin-induced transendothelial migration of eosinophils across both dermal and pulmonary cells.
An in vivo pharmacodynamic experimental study (skin chamber method) demonstrated, compared with placebo, three principal inhibitory mechanisms in 14 adult patients (inhibition of VCAM-1 release, modulation of vascular permeability and reduced eosinophil recruitment) on the pollen-induced response within the first 6 hours after administration of levocetirizine 5 mg.
Clinical efficacy and safety
The efficacy and safety of levocetirizine have been demonstrated in a series of double-blind, placebo-controlled clinical trials in adult patients with seasonal, perennial and persistent allergic rhinitis. Several studies have shown that levocetirizine markedly improves the symptoms of allergic rhinitis, including nasal obstruction.
A six-month clinical study in 551 adult patients (276 of whom received levocetirizine) with persistent allergic rhinitis (symptoms present 4 days a week for at least four consecutive weeks) and sensitivity to house-dust mites and grass pollen demonstrated that levocetirizine 5 mg was clinically and statistically significantly more effective than placebo in reducing the overall allergic rhinitis symptom score throughout the study, with no evidence of tachyphylaxis. Throughout the study, levocetirizine significantly improved patients' quality of life.
In a placebo-controlled clinical study including 166 patients with chronic idiopathic urticaria, 85 patients received placebo and 81 received levocetirizine 5 mg once daily for more than 6 weeks. Treatment with levocetirizine produced a significant reduction in the severity of pruritus during the first week and throughout the treatment period compared with placebo. Levocetirizine also resulted in a greater improvement in health-related quality of life than placebo, as assessed by the Dermatology Life Quality Index.
Chronic idiopathic urticaria has been studied as a model for urticarial conditions. Since histamine release is a causal factor in urticarial diseases, levocetirizine is expected to provide effective symptomatic relief not only in chronic idiopathic urticaria but also in other urticarial conditions.
Levocetirizine has no clinically significant effect on the QT interval on the ECG.
Paediatric population
The safety and efficacy of levocetirizine tablets in children have been studied in two placebo-controlled clinical trials including patients aged 6 to 12 years with seasonal and perennial allergic rhinitis. In both studies, levocetirizine significantly improved symptoms and increased patients' health-related quality of life.
In children under 6 years of age, clinical safety has been established from several short- and long-term studies:
one clinical study in which 29 children aged 2 to 6 years with allergic rhinitis received levocetirizine 1.25 mg twice daily for 4 weeks
one clinical study in which 114 children aged 1 to 5 years with allergic rhinitis or chronic idiopathic urticaria received levocetirizine 1.25 mg twice daily for 2 weeks
one clinical study in which 45 children aged 6 to 11 months with allergic rhinitis or chronic idiopathic urticaria received levocetirizine 1.25 mg once daily for 2 weeks
one long-term (18-month) clinical study in 255 atopic subjects treated with levocetirizine, aged 12 to 24 months at enrolment.
The safety profile was similar to that observed in the short-term studies in children aged 1 to 5 years.
⚠️ Warnings
Caution is advised with concomitant intake of alcohol (see section 4.5).
Caution is advised in patients with predisposing factors for urinary retention (e.g. spinal cord lesions, prostatic hyperplasia), as levocetirizine may increase the risk of urinary retention.
Caution is advised in patients with epilepsy or at risk of seizures, as levocetirizine may cause exacerbation of seizures.
The response to allergy skin testing is suppressed by antihistamines, and a wash-out period (3 days) is required before such testing is performed.
Pruritus may occur upon discontinuation of levocetirizine, even if the symptom was not present prior to initiation of treatment. The symptom may resolve spontaneously. In some cases, the symptom may be intense and may require reinstatement of treatment. The symptom should resolve once treatment is reinstated.
Paediatric population
The use of film-coated tablets in children under 6 years of age is not recommended, as this dosage form does not allow for appropriate dose adjustment. The paediatric formulation of levocetirizine is recommended.
Warning regarding excipients with known effects
This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
