Levocetirizine in the Treatment of Persistent Allergic Rhinitis – The Xyzal Persistent Allergic Rhinitis Study

The Xyzal Persistent Allergic Rhinitis (XPERT) study group investigated the efficacy of levocetirizine 5mg once daily in 551 adult outpatients with PER in a six-month, randomised, double-blind, parallel-group, multicentre trial.²⁴ In this study the change of HRQL scores and Total 5- Symptoms Scores (T5SS) compared with baseline were analysed as primary efficacy end-points. Over the first four weeks of therapy both total scores were significantly improved in the levocetirizine group compared with placebo (see RQLQ score, Figure 1). Four of the five individual T5SS (sneezing, rhinorrhoea, nasal pruritus and ocular pruritus) were improved, while the fifth symptom of the T5SS, nasal congestion, revealed significant improvements in levocetirizine versus placebo controls from three months until the end of the study at six months. However, all seven individual HRQL domains improved significantly after four weeks of therapy (see Figure 2). In addition, a significantly higher amount of rescue medication (p=0.002) was needed in the placebo group compared with levocetirizine-treated patients over the first four weeks of XPERT.






Furthermore, the general health status (SF-36) of the patients as another secondary efficacy end-point was incorporated into the study at the design stage. All eight domains of the SF-36 health-status assessment revealed significant improvements in both mental and physical components (p<0.05, see Figure 3). Interestingly, the ‘physical role’ or ‘emotional role’ domains revealed significantly high efficacy (p<0.001). An exploratory analysis of the XPERT data demonstrated that the number of patients with allergic asthma experienced significantly fewer acute asthma attacks compared with the placebo group during the sixmonth treatment period.²⁵ Taken together, these data suggest that long-term treatment with levocetirizine causes sustained improvement in HRQL and reduces disease burden in PER patients. Another piece of important information that XPERT provides for physicians is a link between symptoms (including congestion) and quality of life, as measured by the RQLQ.

Absorption, Pharmacokinetics and Side Effects

Pharmacokinetic trials revealed fast and high gastrointestinal absorption.²⁶ The metabolic pathways involved in levocetirizine’s metabolism are oxidation (hydroxylation, O-dealkylation, N-oxidation and N-dealkylation), glucuroconjugation, taurine conjugation and glutathione conjugation with formation of the mercapturic acids. The metabolic products are mostly excreted in the urine, but the need for dose adjustment in patients with moderate or severe renal insufficiency is suggested.²⁷ So far, specific guidelines are not available. However, based on data for racemic cetirizine, a 50% reduction in the dose of levocetirizine should be considered in patients with severe renal dysfunction.²⁸ The side effect profile of levocetirizine is mild. Importantly, levocetirizine does not produce any deleterious effect on psychometric or cognitive functions.²⁹ However, headaches, dizziness, fatigue and rashes have been reported.³⁰