December 2002

From Ketchum

World's first head-to-head data on latest antihistamines has implications for hay fever management

Study using the recognised Environmental Exposure Unit (EEU) technology demonstrates that Xyzal® is more effective than NeoClarityn™

Harrogate, UK (4 December 2002). First head-to-head data on the two latest antihistamines presented for the first time at the Annual Meeting of the British Society for Immunology (BSI) and the British Society for Allergy & Clinical Immunology (BSACI) today, indicates that Xyzal® (levocetirizine) is more effective than NeoClaritynTM(desloratadine) in treating subjects with seasonal allergic rhinitis (hay fever). Results also showed that Xyzal has a more rapid (1 hour versus 3 hours, respectively) and longer duration of action than desloratadine. Xyzal further showed significant superiority in alleviating nasal congestion after the first drug intake.

Xyzal and NeoClarityn are the newest non-sedating antihistamines to have been launched in the UK. However, no head-to-head data has been available until now - the results of this study may therefore have a significant impact on the management of hay fever. Hay fever affects about 15% of adults in the UK 1.

Study Design

The double-blind, randomised, placebo controlled trial, involving 373 subjects, looked to compare the efficacy of the two treatments in controlling the symptoms of seasonal allergic rhinitis in sensitive subjects exposed to ragweed pollen challenge for 2 days in the Environmental Exposure Unit (EEU). The EEU is a recognised indoor pollen challenge system to test anti-allergic medication. This method was selected because it ensures a controlled environment, allows up to 160 subjects per session, has year round capacity. Its use is recommended to study onset of action and efficacy of antihistamines and has demonstrated clinical relevance. The objectives were to compare the onset of action, duration of action and changes from baseline in symptom scores and nasal obstruction in the different groups.

Subjects with qualifying symptom scores were randomised to once daily treatment with 5 mg of either Xyzal or desloratadine or placebo and exposed to ragweed pollen in the EEU - for 7 hours on the first day and 6 hours on the second. The symptoms of allergic rhinitis were evaluated at 30-minute intervals. Major symptoms were defined as runny nose, sniffles, itchy nose, nose blows, sneezes and watery eyes. Other symptoms measured: itchy eyes and ears, itchy throat, cough, postnasal drip and nasal congestion.

Results

Efficacy

  • The results showed that Xyzal was significantly more effective than desloratadine in relieving the major symptoms of hay feverin all time periods studied. Both treatments were significantly more effective than placebo.

  • With regards to onset of action, the improvement started to be statistically significant 1 hour after the first intake of Xyzal compared to placebo, compared to 3 hours after the desloratadine intake. The duration of action was also significantly longer with Xyzal than desloratadine.

  • The Xyzal response was superior to placebo throughout the study period for runny nose, itchy nose, sniffles, nose blows, sneezes, watery eyes, itchy eyes and ears and postnasal drip, while desloratadine only achieved significance over placebo for the duration of the study for nose blows and sneezes.

  • In the past antihistamines have generally been recognised as having little effect on nasal congestion. In this study, after the first intake, Xyzal alleviated nasal congestion to a significantly greater extent than desloratadine which in turn was not different to placebo.

Safety and Tolerability

There were no major differences in safety between the two treatment groups or placebo. The incidence of fatigue or somnolence was 3.3% with placebo, 3.5% in the Xyzal group and 5.7% in the desloratadine group.

The lead study investigator, Professor James H. Day, Professor of Medicine, Queen's University and Head of the Division of Allergy and Immunology, Kingston General Hospital, Ontario, Canada said: "This study indicates that levocetirizine is more effective than desloratadine in the treatment of seasonal allergic rhinitis under conditions of prolonged pollen exposure showing a more rapid onset and longer duration of action, coupled with the ability to control nasal congestion without causing sedation. This will be reassuring to physicians who are looking for a highly effective and very well tolerated treatment for their hay feverpatients''.

Dr Richard Powell, Consultant Allergist and Clinical Immunologist, Queen's Medical Centre, Nottingham, explained, "This large, well controlled study has produced the type of data that UK doctors have been waiting for. Levocetirizine and desloratadine have been made available in the last two years and we now have robust evidence on their comparative efficacy and tolerability in seasonal allergic rhinitis. Clinicians will undoubtedly find these results useful in determining their treatment strategies for patients with hay fever in 2003".

Allergic rhinitis represents a global health problem, affecting about 10%-25% of the population and its prevalence is increasing 1,3. Although it is not usually a severe disease, it alters the social life of patients and affects school performance and work productivity. Moreover, the costs incurred by allergic rhinitis are substantial. Importantly, asthma and rhinitis commonly occur together (co-morbidity), and ultimately clinicians should consider a combined strategy to treat co-existent upper and lower airway disease, as optimal management of rhinitis may improve co-existing asthma as is clearly defined by the ARIA guidelines 3.

Xyzal is a new antihistamine indicated for the treatment of symptoms associated with seasonal allergic rhinitis, perennial allergic rhinitis and chronic idiopathic urticaria. With a recommended dose of 5mg once daily, Xyzal is licensed for adults, adolescents and children aged 6-12 years 4.

Xyzal (levocetirizine), being the potent single isomer of cetirizine, binds twice as strongly to histaminic H1 receptors in vitro and has a highly consistent and predictable antihistamine action in vivo 4. In trials, the incidence of adverse events in excess of placebo was 3%, while the discontinuation rate was less than 1% and not different to placebo. Xyzal has been shown not to impair mental alertness, reaction times or the ability to drive 5, 6.

With a basic NHS cost of £7.45 for 5mg x 30 film-coated tablets, Xyzal competitively priced compared with other new antihistamines.

Notes to the Editor:
Please contact Vanessa Leon for background fact sheets on Allergic Rhinitis (hay fever) and treatment options.

References:

1. Scadding G.K., Richards D.H., Price M.J. Patient and physician perspectives on the impact and management of perennial and seasonal allergic rhinitis. Clinical Otolaryngology and Allied Sciences 2000; 25 (6): 551-557.
2. Professor James H Day et al. Comparative Efficacy of Levocetirizine 5 mg and Desloratadine 5 mg in subjects suffering from seasonal allergic rhinitis. Poster presented at the annual BSI / BASCI congress, Harrogate, UK (4 December 2002).
3. Allergic Rhinitis and its Impact on Asthma: A Pocket Guide for Physicians and Nurses, 2001. Based on the Allergic Rhinitis and its Impact on Asthma Workshop Report in collaboration with the World Health Organisation.
4. Xyzal Summary of Product Characteristics.
5. Verster et al. Driving ability after acute and subchronic administration of levocetirizine and diphenhydramines. Poster presented at EAACI 2002.
6. Volkerts et al. Acute and subchronic effects of levocetirizine and diphenhydramine on memory functioning, psychomotor performance and mood. Poster presented at EAACI 2002.
NeoClaritynTM is a trademark of Schering-Plough Corporation

XYZALTM TABLETS t ABBREVIATED PRESCRIBING INFORMATION:

Presentation: XYZAL (levocetirizine) 5mg film-coated tablets. Uses: Xyzal is indicated in adults, adolescents and children aged 6-12 years, for the treatment of the symptoms associated with seasonal allergic rhinitis, perennial allergic rhinitis and chronic idiopathic urticaria. Dosage: One 5mg tablet once daily. Dosage modification is only required in the presence of moderate to severe renal impairment. Please refer to the Summary of Product Characteristics for full details.

Contra-indications: Hypersensitivity to levocetirizine, piperazine derivatives or any of the constituents. Severe renal impairment. Precautions: Patients with galactose intolerance, lactase deficiency or glucose-galactose malabsorption should not take Xyzal. Caution is recommended with the intake of alcohol. There is no evidence, at the recommended dose, that levocetirizine impairs mental alertness, reactivity or the ability to drive. However, patients intending to drive should not exceed the recommended dose and should take their responses into account.

Pregnancy and Lactation: Data on a limited number of exposed pregnancies indicate no adverse effects of cetirizine on pregnancy or on the health of the fetus/new born child. For levocetirizine no data on exposed human pregnancies is available. However, animal studies indicate that there are no direct or indirect harmful effects with respect to pregnancy, embryonic/fetal development, parturition or post natal development. Use of levocetirizine in lactating women is not recommended, as it is expected to be excreted in breast milk. Side effects: In therapeutic trials withdrawal due to adverse drug reactions was 0.7% with levocetirizine against 0.8% with placebo. At the therapeutic dose, the incidence of undesirable effect reports in excess of placebo was 3.4%. These were mild to moderate. Those reported in excess of placebo were somnolence (<5%), dry mouth, fatigue (<2%), rhinitis and migraine (<0.5%). Overdose: Substantial overdose may result in somnolence. Levocetirizine is not effectively removed by haemodialysis. Presentation: Xyzal is supplied in aluminium foil blister packs containing 30 film-coated tablets. Basis NHS price: £7.45. Marketing Authorisation Number: PL 08972/0036. Marketing Authorisation Holder: UCB Pharma Ltd. UCB House, 3 George Street, Watford, Herts WD18 0UH. Legal category: POM. Date of preparation: December 2002.











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