Comparison of azelastine nasal spray and oral ebastine in
treating seasonal allergic rhinitis
Current Medical Research and Opinion (1995), 13, No. 6, 299
D. J. Conde Hernández, J. L. Palma Aqilar and
J. Delgado Romero
Servicio de Inmunoalergología,
Virgen de la Macarena, Avda.
Dr Fedriani 3, E-41071 Seville, Spain
Received: 9th May 1995
The efficacy and safety of the nasally administered histamine H1 receptor blocking drug azelastine was investigated in a randomized comparative trial with ebastine. Patients were treated for 14 days and efficacy was assessed by the physician using a rating scale measuring 10 nasal and ocular symptoms of seasonal rhinitis (0 = absent, 1 = mild, 2 = moderate, 3 = severe). Tolerability was measured on the basis of reported adverse events. Data from a total of 59 patients were included in the efficacy analysis. Both treatment groups had dramatic reductions in the physician's total symptom score following treatment. Mean scores in the azelastine group decreased from 12.4 pretreatment to 5.6, while the mean ebastine scores decreased from 13.6 to 6.6. There was no significant difference between the two groups ( p = 0.86). Changes in individual rhinitis symptoms showed no differences between the two groups. The majority of patients in both treatment groups reported an initial relief of symptoms within 1 h of dosing. For seven patients treated with azelastine, the initial effect was already seen after 10 min (ebastine: two patients). Eight adverse events were reported in each treatment group; all were mild except one report of sedation in an ebastine patient, which was of moderate severity. Three patients reported somnolence during treatment with ebastine. A bitter taste was mentioned by four patients in the azelastine group, but neither somnolence nor sedation was reported with azelastine. In conclusion, the results of the study suggest that both azelastine and ebastine are effective treatments of the symptoms of seasonal allergic rhinitis. Both drugs were well tolerated.
Key words: Seasonal allergic rhinitis - azelastine - ebastine - nasal spray - clinical study
Azelastine, a derivative of phthalazinone, is a selective histamine H1 antagonist (3,6) and is available as a nasal spray indicated for the treatment of seasonal and perennial allergic rhinitis. Azelastine has also been shown to inhibit the release or synthesis of a number of other chemical mediators of hypersensitivity such as the leukotrienes and platelet activating factor.(1) Clinical trials comparing azelastine with other commonly prescribed agents have demonstrated the excellent efficacy and tolerance of azelastine nasal spray.(5) Ebastine (Ebastel®) is a newly developed orally administered H1 receptor antagonist which has been studied in clinical trials in Spain and the United Kingdom. The results of studies in both seasonal and perennial allergic rhinitis suggest that ebastine is effective and free of sedative effects at the therapeutic dose of 10 mg once daily.(4)
The objectives of the present study were to compare the relative efficacy and tolerance of azelastine nasal spray given twice daily (0.56 mg/day) with ebastine tablets 10 mg once daily and also to study the efficacy of azelastine and ebastine against exposure to an unusual pollen, that from olive trees, which is one of the main causes of seasonal allergic rhinitis in Spain.
Patients and methods
Patients with a history of seasonal allergic rhinitis were entered into the study and randomly allocated to receive either azelastine nasal spray (one puff into each nostril morning and evening (0.56 mg/day)) or ebastine tablets (one tablet each evening (10 mg/day)) for a period of 14 days. Patients were assessed in clinic at the beginning and at the end of treatment. Assessment included a grading of the severity of the following 10 individual symptoms of rhinitis (absent = 0, mild = 1, moderate = 2 or severe = 3):
|nasal itching||flow of tears|
|stuffed nose||pharyngeal itching|
In order to be eligible for entry to the study patients required a total rhinitis score of at least 8 prior to treatment. The use of antihistamines, ketotifen, disodium cromoglycate and topical or inhaled corticosteroids was not permitted during the 2 weeks prior to the study.
Anterior rhinomanometry was performed before and after treatment and at the end of treatment a global assessment of efficacy and tolerance was performed by both the physician and the patient.
The primary criterion for the assessment of efficacy was the change in the total rhinitis score (sum of the scores of the 10 individual symptoms) from the start to the end of the treatment period. The change in the total rhinitis score was analysed using a two-sided t-test. Statistical significance throughout the study was fixed at the 5% level. The two treatment groups were compared with respect to changes in individual symptoms (classified as: worse, unchanged or improved) using Fisher's exact test. Rhinomanometry data were analysed using the two-sided t-test.
Criteria for the assessment of tolerance were the occurrence of adverse events and the physician's global assessment of tolerability at the end of the treatment period.
The study protocol was approved by the Ethics Committee of the University Hospital Virgen Macarena, Seville and the Spanish Ministry of Health. All patients gave informed witnessed consent prior to enrolment in the study.
Sixty-three patients were entered into the study during the spring and summer of 1993. All patients complied with the inclusion criteria; three (two azelastine, one ebastine) were lost to follow-up for reasons unrelated to the medication. Data from these three patients were not included in the per-protocol analysis but were included in the intent-to-treat analysis. Two further patients were withdrawn due to lack of efficacy (both in the ebastine group); data from these patients were included in both efficacy analyses. All evaluable patients were included in the tolerability analysis.
The two treatment groups were compared with respect to age (range 18-59 years, median 27 years), sex (27 males, 36 females), height, weight and duration of history of allergic rhinitis (range 2-50 years). The two groups were comparable for all these parameters. Nearly all patients were allergic to grass pollen and/or the pollen from the olive tree.
Total rhinitis symptom score
Both treatment groups showed a dramatic improvement in symptoms. Mean scores in the azelastine group decreased from 12.4 pretreatment to 5.6 at the end of treatment, the mean ebastine scores decreased from 13.6 to 6.6. There was no significant difference between the two groups (p = 0.86). Scores are summarized in Table I.
|Azelastine (n = 29)||Ebastine (n = 31)|
|Day 1||Day 15||Day 1||Day 15|
|Total symptom score||12.4||5.6||13.6||6.6|
|Pharyngeal itching and cough||2.0||0.7||1.7||0.9|
Changes in the individual rhinitis symptoms showed an improvement in all cases with no differences between the two treatment groups.
Measurements from the left and right nostril were summed. Both groups showed an improvement from baseline to post-treatment values. In the azelastine group the mean of the summed measurements of both nostrils decreased from 3.24 Pa s-1 ml-1 to 2.43; in the ebastine group the mean decreased from 2.76 to 1.77. This reduction in resistance was not markedly different between the two groups (p = 0.80).
Global assessment of efficacy
At the end of the study 14 out of 29 patients in the azelastine group and 15 out of 31 patients in the ebastine group judged the efficacy of their study medication as 'good' or 'very good'. Sixteen patients in the azelastine group recorded an initial relief of symptoms within 45 min of dosing compared to 15 patients in the ebastine group. For seven patients treated with azelastine an initial effect was already seen after 10 min (ebastine: two patients). The judgement of the physician was more positive: he judged efficacy to 'good' or 'very good' in 23 azelastine patients and 20 ebastine patients.
The tolerability was judged as 'good' or 'very good' by 29 patients in the azelastine group and by 31 patients in the ebastine group. Investigators rated tolerability as 'good' or 'very good' in 29 and 30 cases, respectively. Sixteen adverse events were reported during study treatment (azelastine eight, ebastine eight). These are summarized in Table II. All events were mild with the exception of one report of sedation in an ebastine patient, which was described as moderate. A bitter taste was mentioned by four patients in the azelastine group, three patients suffered pharyngeal or nasal itching following azelastine, and three patients reported somnolence during treatment with ebastine.
(n = 30)
(n = 32)
|Application site reaction||3||0|
Discussion and conclusions
The results of this study suggest that azelastine nasal spray given at a dose of 0.56 mg/day and ebastine tablets 10 mg/day are comparable and effective treatments of the nasal and ocular symptoms of seasonal allergic rhinitis. The onset of activity was more rapid in the azelastine-treated group: 24% of patients reported an improvement in their symptoms within the first 10 min after treatment compared to only 6% in the ebastine-treated group. Both treatments gave symptom relief within 1 h in the majority of patients. The more rapid onset of the action of azelastine is probably due to local application on the nasal membranes. Both drugs were well tolerated. Sedation, which is reported with the classical histamine H1 receptor blockers, was not observed in the azelastine group. Mild or moderate somnolence was reported in three of the ebastine-treated patients (10%). A bitter taste was reported in four of the azelastine-treated patients, which is in line with previous studies.(2) None of the adverse events led to withdrawal from the treatment.
1. Chand, N., (1986). Antagonism of histamine
and leukotrienes by azelastine in isolated guinea pig ileum.
Agents Actions, 19, 164-168.
2. Davies, R. J., Lund, V. J., and Harten-Ash, V. J., (1993). The effect of intranasal azelastine and beclomethasone on the symptoms and signs of nasal allergy in patients with perennial allergic rhinitis. Rhinology, 31, 159-164.
3. Diamantis, W., (1981). In vivo and in vitro H1 antagonist properties of azelastine. The Pharmacologist, 23, 149.
4. Ebastine: a novel H1-receptor antagonist, (1992). Drugs of Today, 28 (Suppl. B), 69-79.
5. Gastpar, H., Aurich, R., Petzold, U., and Virnkaes, C., (1993). Azelastine nasal spray for topical treatment of allergic rhinopathy. Atemw. Lungenkrkh. Jahrgang., 19, 148-154.
6. McTavish, D., and Sorkin, E. M., (1989). A review of the pharmacodynamic and pharmacokinetic properties and therapeutic potential. Drugs, 38, 778-800.