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Azelastine, a phthalazinone compound, is a second generation histamine H1 receptor antagonist which has shown clinical efficacy in relieving the symptoms of allergic rhinitis when administered as either an oral or intranasal formulation. It is thought to improve both the early and late phase symptoms of rhinitis through a combination of antihistaminic, antiallergic and anti-inflammatory mechanisms. Symptom improvements are evident as early as 30 minutes after intranasal administration of azelastine [2 puffs per nostril (0.56mg)] and are apparent for up to 12 hours in patients with seasonal allergic rhinitis (SAR). The effect on nasal blockage is variable: in some studies objective and/or subjective assessment showed a reduction in blockage, whereas in other studies there was no improvement.
Intranasal azelastine 1 puff per nostril twice daily is generally as effective as standard doses of other antihistamine agents including intranasal levocabastine and oral cetirizine, ebastine, loratadine and terfenadine at reducing the overall symptoms of rhinitis. The relative efficacies of azelastine and intranasal corticosteroids (beclomethasone and budesonide) remain unclear. However, overall, the corticosteroids tended to improve rhinitis symptoms to a greater extent than the antihistamine.
Azelastine was well tolerated in clinical trials and postmarketing surveys. The most frequently reported adverse events were bitter taste, application site irritation and rhinitis. The incidence of sedation did not differ significantly between azelastine and placebo recipients and a preliminary report showed cardiovascular parameters were not significantly altered in patients with perennial allergic rhinitis (PAR).
Rationale for the Development of Intranasal Azelastine
Antihistamine compounds have been in use for the management of allergic rhinitis since the 1940s. The clinical value of the first generation histamine H1 receptor antagonists, however, was marred by their ability to cross the blood-brain barrier and cause, among other adverse events, sedation. The second generation histamine H1 receptor antagonists, which include ketotifen, cetirizine, terfenadine, loratadine, ebastine and azelastine, are generally less sedative and have fewer nonspecific effects.
Azelastine is a phthalazinone derivative which binds preferentially to peripheral rather than central receptors; the drug has been used orally to manage the symptoms of bronchial and allergic asthma and allergic rhinitis. Local administration via intranasal inhalation serves to further confine the activity of the drug and reduce possible adverse effects brought about by systemic exposure.
Sneezing caused by histamine nasal challenge was significantly reduced within 1 hour after initial application of azelastine 0.56mg (2 puffs per nostril) in patients and volunteers and it remained so for 10 to 12 hours thereafter. However, the effects of the drug on nasal blockage were varied: some studies showed improvements in either subjectively or objectively assessed nasal blockage, whereas others failed to show any improvements.
After allergen-specific nasal challenge, compared with baseline, single or repeated (twice daily for 2 weeks) administration of azelastine 1 puff per nostril significantly reduced objectively assessed nasal airway resistance (NAR) and increased nasal inspiration peak flowmeter values in patients with seasonal allergic rhinitis (SAR). The effects of azelastine compared with placebo on NAR, however, were varied. In a study which showed single-dose azelastine to have a significant effect compared with placebo, the mean time to onset of this effect was 135 minutes. Both the early (EPR) and late phase reaction (LPR) symptoms of allergen-induced rhinitis were significantly reduced (by up to 30%) in azelastine compared with placebo recipients. Azelastine significantly reduced allergen-induced sneezing within 15 minutes and was active for up to 10 hours.
In addition to its antihistamine and antiallergic effects, azelastine also has anti-inflammatory properties. It reduces EPR and LPR nasal mucosal infiltration of eosinophils and neutrophils by up to 49% after allergen-specific nasal challenge. Levels of a variety of inflammatory mediators were also reduced by azelastine, including nasal eosinophil cationic protein, myeloperoxidase, tryptase and intercellular adhesion molecule-1.
In vitro in human neutrophils, azelastine significantly and concentration-dependently inhibited arachidonic acid release and leukotriene B4 production. In neutrophils or eosinophils from nonallergic volunteers, stimulated generation of Superoxide, a reactive oxygen species, was decreased. Furthermore, azelastine significantly reduced the mobilisation of intracellular calcium in N-formyl-methionyl-leucyl-phenylalanine (FMLP)-stimulated neutrophils, a process that precedes Superoxide generation.
Results from trials in rodent mast cell preparations suggest that azelastine may also interfere with protein kinase C activity and the release of tumour necrosis factor-α.
In animal models, azelastine has poor access to the CNS. In addition, studies in patients with SAR found that intranasal azelastine generally increased vigilance during the medication period. Intranasal but not oral azelastine reduced the circadian variation in vigilance.
Pharmacokinetic data for intranasal azelastine are scarce. Maximum plasma concentrations of azelastine were achieved approximately 2.5 hours after intranasal administration. After daily intranasal azelastine 0.56mg, mean steady-state plasma concentrations of the drug were about 0.26 μg/L in healthy volunteers and about 0.65 μg/L in patients; the estimated systemic exposure to the drug was 6-to 8-fold lower than that with oral azelastine 4.4mg. The systemic bioavailability after intranasal administration was approximately 40%. Azelastine is metabolised by the cytochrome P450 enzyme system to its major active metabolite desmethylazelastine. At steady state, the plasma metabolite concentration accounted for 20 to 50% of the azelastine concentration.
In adults and children aged ≥5 years with SAR or perennial allergic rhinitis (PAR), azelastine 1 or 2 puffs per nostril (0.28 or 0.56mg) twice daily over periods of 30 hours to ≥6 months, compared with baseline or placebo, significantly improved rhinitis symptoms including rhinorrhoea, itchy nose, sneezing, watery eyes, itchy eyes, ears or throat and postnasal drip. Compared with placebo, azelastine (2 puffs per nostril) significantly improved baseline rhinitis symptoms as early as 3 hours after drug administration in patients with SAR; significant improvement was apparent for up to 12 hours after initial use. Patient and physician global assessment of treatment with azelastine (1 or 2 puffs per nostril twice daily) of at least ‘good’ was similar and ranged from 75 to 86%.
Azelastine had varied effects on nasal blockage in clinical trials; some studies showed a significant improvement in azelastine compared with placebo recipients, whereas others found no significant effects.
In children (aged ≤12 years) with allergic rhinitis, azelastine 1 puff per nostril twice daily compared with placebo for up to 6 weeks significantly improved rhinitis symptoms. In a postmarketing survey in children aged 3 to 12 years, 85% of physicians evaluated the efficacy of azelastine as ‘good’ /‘very good’. Rhinoscopic evaluation in children (aged 7 to 16 years) with PAR revealed significant improvement in nasal secretion, oedema and inflammation after 6 weeks’ therapy with intranasal azelastine (0.6 mg/day); these symptoms were further improved in the 62 children who completed 6 months’ treatment.
Intranasal azelastine as an adjunct to oral azelastine therapy further improves rhinitis symptoms compared with the effects of oral therapy alone in patients with SAR.
In comparative studies, azelastine 1 puff per nostril twice daily was generally as effective at reducing the overall symptoms of rhinitis as the standard doses of other antihistamine agents including intranasal levocabastine and oral cetirizine, ebastine, loratadine and terfenadine.
Symptom relief within 30 minutes of initial drug administration occurred in similar numbers of patients receiving azelastine (1 puff per nostril) or levocabastine (2 puffs per nostril); the effect was maintained for up to 8 hours after initial drug administration in both groups. Each drug improved nasal congestion by about 48% and ocular symptoms by about 66% from baseline after 1 week of twice-daily administration.
Results from studies that compared the effects of azelastine 1 puff per nostril twice daily and intranasal corticosteroids on the symptoms of rhinitis were varied, but overall, the corticosteroids appeared more effective. A significantly more rapid overall symptom relief was achieved in azelastine compared with beclo-methasone recipients in 1 study, but after 2 weeks’ therapy, improvements in overall symptom scores were significantly greater in the beclomethasone recipients. Both beclomethasone and budesonide were superior to azelastine at reducing the nasal symptoms of rhinitis in some studies, whereas others found no statistically significant difference between treatments. Budesonide was associated with greater improvements in nasal blockage than azelastine, although these did not reach statistical significance. In addition, patients’ global assessments of ‘substantial’ or ‘total’ control of symptoms were significantly more common with budesonide (0.256mg once daily) than with azelastine (0.28mg twice daily) in a double-blind study (70.4 vs 44.7%).
Results from postmarketing surveys in 7682 patients aged 3 to 85 years with allergic rhinitis who received azelastine 1 puff per nostril twice daily for up to 1 month showed the drug to be generally well tolerated. When azelastine was given alone, approximately 8% of patients reported adverse events; when it was given in combination with other antihistamines and/or topical corticosteroids the incidence of adverse events was approximately 20%. Bitter taste and rhinitis were the most frequently reported adverse events.
Where stated in clinical trials, physician and/or patient global assessment of tolerability was at least ‘good’ in more than 70% of patients (adults and children aged ≥7 years) receiving azelastine (typically 1 puff per nostril twice daily). Indeed, >90% of 35 azelastine recipients assessed tolerability as at least ‘good’ during a 21-month period of medication.
The most frequently reported adverse events were mild, transient bitter taste (associated with the taste of the drug) and application site irritation. Sedation did not differ significantly in azelastine or placebo recipients. Indeed, some study reports remarked on its absence and 1 trial reported an improvement in overall vigilance during a 2-week medication period.
Treatment withdrawal because of drug-related adverse events was rare (1 to 3 patients per study; ≤7%); reasons for withdrawal included mild increased nasal pruritus, nasal congestion, nausea and vomiting, dizziness and increased blood pressure.
No significant changes in PR, QS, QT or QTc intervals were observed in patients with PAR who were randomised to receive azelastine (2 puffs per nostril) or placebo twice daily for 8 weeks. In addition, there were no changes in mean heart rate or blood pressure in any patient.
Dosage and Administration
The US prescribing recommendations specify 2 puffs per nostril of azelastine nasal spray twice daily for adults and children aged ≥12 years; each puff delivers approximately 0.14mg of the drug. In the UK and a number of other European countries, azelastine is approved as 1 puff per nostril twice daily for adults and children aged ≥6 years.
Although somnolence is rare, the US prescribing information carries a caution regarding use of the medication and driving or operating potentially dangerous machinery. Concurrent use of alcohol and/or other CNS suppressants should be avoided.
- Rimmer S, Church MK. The pharmacology and mechanisms of action of histamine H1†-antagonists. Clin Exp Allergy 1990; 20 Suppl. 2: 3–17 CrossRef
- Simons FER, Simons KJ. Second-generation H1-receptor antagonists. Ann Allergy 1991 Jan; 66: 5–21
- McTavish D, Sorkin EM. Azelastine: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential. Drugs 1989 Nov; 38: 778–800 CrossRef
- Thomas KE, Ollier S, Ferguson H, et al. The effect of intranasal azelastine, Rhinolast (Rm), on nasal airways obstruction and sneezing following provocation testing with histamine and allergen. Clin Exp Allergy 1992 Jun; 22: 642–7 CrossRef
- Greiff L, Andersson M, Svensson C, et al. Topical azelastine has a 12-hour duration of action as assessed by histamine challenge-induced exudation of α2-macroglobulin into human nasal airways. Clin Exp Allergy 1997 Apr; 27: 438–44 CrossRef
- Spaeth J, Schultze V, Klimek L, et al. Azelastine reduces histamine-induced swelling of nasal mucosa. J Otorhinolaryngol Relat Spec 1996 May–Jun; 58: 157–63 CrossRef
- Horak F, Jäger S, Toth J, et al. Azelastine in pollen-induced allergic rhinitis: a pharmacodynamic study of onset of action and efficacy. Drug Invest 1994 Jan; 7: 34–40 CrossRef
- Wang D, Clement P, Smitz J, et al. The activity of recent antiallergic drugs in the treatment of seasonal allergic rhinitis. Acta Otorhinolaryngol Belg 1996; 50: 25–32
- Pronzato C, Ricca V, Varese P, et al. Evaluation of antiallergic activity of azelastine nasal spray [abstract]. Allergy 1995; 50 Suppl. 26: 69
- Ciprandi G, Pronzato C, Passalacqua G, et al. Topical azelastine reduces eosinophil activation and intercellular adhesion molecule-1 expression on nasal epithelial cells: an antiallergic activity. J Allergy Clin Immunol 1996 Dec; 98 (Pt 1): 1088–96 CrossRef
- Roger Reig A, Roger Barri JM. The effect of topical azelastine and N-acetyl aspartyl-glutamate (NAAGA) on allergen nasal provocation test (NPT) [abstract]. Allergy 1995; 50 Suppl. 26: 196
- Bähre M, Klimek L, Mölich J, et al. Azelastine reduces release of eosinophil cationic protein (ECP) [abstract]. Allergy 1995; 50 Suppl. 26: 102
- Mösges R, Klimek L, Bähre M, et al. Azelastine reduces mediators of nasal inflammation in patients with nasal polyposis [abstract]. Allergy 1997; 52 Suppl. 37: 204
- Taniguchi K, Masuda Y, Takanaka K. Action sites of antiallergic drugs on human neutrophils. Jpn J Pharmacol 1990 Jan; 52: 101–8 CrossRef
- Busse W, Randlev B, Sedgwick J. The effect of azelastine on neutrophil and eosinophil generation of Superoxide. J Allergy Clin Immunol 1989 Feb; 83 (2 Pt 1): 400–5 CrossRef
- Akamatsu H, Miyachi Y, Asada Y, et al. Effects of azelastine on neutrophil chemotaxis, phagocytosis and oxygen radical generation. Jpn J Pharmacol 1991 Dec; 57: 583–9 CrossRef
- Umeki S. Effects of anti-allergic drugs on human neutrophil superoxide-generating NADPH oxidase. Biochem Pharmacol 1992 Mar 3; 43: 1109–17 CrossRef
- Kurosawa M, Hanawa K, Kobayashi S, et al. Inhibitory effects of azelastine on Superoxide anion generation from activated inflammatory cells measured by a simple chemiluminescence method. Arzneimittel Forschung 1990 Jul; 40: 767–70
- Hojo M, Hamasaki Y, Fujita I, et al. Effects of anti-allergy drugs on fMet-Leu-Phe-stimulated Superoxide generation in human neutrophils. Ann Allergy 1994 Jul; 73: 21–6
- Renesto P, Balloy V, Vargaftig BB, et al. Interference of anti-inflammatory and anti-asthmatic drugs with neutrophil-mediated platelet activation: singularity of azelastine. Br J Pharmacol 1991 Jun; 103: 1435–40 CrossRef
- Ventura MT, Bruno LM, Iacobelli A, et al. Eosinophil chemotactic activity in parietaria allergic patients: in. vitro and in vivo azelastine modulation [abstract]. Allergy 1997; 52 Suppl. 37: 111
- Morita M, Ohshima Y, Akutagawa H, et al. Inhibitory effects of azelastine hydrochloride on Ca2+ influx, actin polymerization and release of eosinophil cationic protein of an eosinophilic leukaemia cell line EoL-1. Curr Med Res Opin 1993; 13(3): 163–74 CrossRef
- Kamei C, Tasaka K. Participation of histamine in the step-through active avoidance response and its inhibition by H1-blockers. Jpn J Pharmacol 1991 Dec; 57: 473–82 CrossRef
- Guinnepain MT, Macquin-Mavier I, Verrière JL. Histamine skin prick tests during azelastine nasal spray treatment in healthy adults [abstract]. Allergy 1995; 50 Suppl. 26: 102
- Baumgarten CR, Petzold U, Dokic D, et al. Modification of allergen-induced symptoms and mediator release by intranasal azelastine. Pharmacol Ther 1994 Feb; 3: 43–51
- Meltzer EO. The pharmacological basis for the treatment of perennial allergic rhinitis and non-allergic rhinitis with topical corticosteroids. Allergy 1997; 52 Suppl. 36: 33–40 CrossRef
- Ciprandi G, Ricca V, Passalacqua G, et al. Seasonal rhinitis and azelastine: long- or short-term treatment? J Allergy Clin Immunol 1997 Mar; 99: 301–7 CrossRef
- Ford-Hutchinson AW, Bray MA, Doig MV, et al. Leukotriene B, a potent chemokinetic and aggregating substance released from polymorphonuclear leukocytes. Nature 1980 Jul 17; 286: 264–5 CrossRef
- Busse WW The role of leukotrienes in asthma and allergic rhinitis. Clin Exp Allergy 1996 Aug; 26: 868–79 CrossRef
- Palmblad J, Malmsten CL, Uden AM, et al. Leukotriene B4 is a potent and stereospecific stimulator of neutrophil chemotaxis and adherence. Blood 1981 Sep; 58(3): 658–61
- Curnutte JT. Activation of human neutrophil nicotinamide adenine dinucleotide phosphate, reduced (triphosphopyridine nucleotide, reduced) oxidase by arachidonic acid in a cell-free system. J Clin Invest 1985 May; 75: 1740–3 CrossRef
- McPhail LC, Shirley PS, Clayton CC, et al. Activation of the respiratory burst enzyme from human neutrophils in a cell-free system: evidence for a soluble cofactor. J Clin Invest 1985 May; 75: 1735–9 CrossRef
- Rasmussen H, Kojima I, Kojima K, et al. Calcium as intracellular messenger: sensitivity modulation, C-kinase pathway, and sustained cellular response. Adv Cyclic Nucleotide Protein Phosphorylation Res 1984; 18: 159–93
- Amos WMG. Hypersensitivity and autoimmunity. In: Basic Immunology. 1st ed. London:, 1981: 133–51
- Kurosawa M. Inhibitory effects of azelastine on protein kinase C and diphosphoinositide kinase in rat mast cells. Arzneimittel Forschung 1990 Feb; 40: 162–5
- Fanous K, Garay RP. Azelastine and allergen transduction signal in MC9 mast cells. Naunyn Schmiedebergs Arch Pharmacol 1993 Nov; 348: 515–9 CrossRef
- Middleton Jr E, Ferriola P, Drzewiecki G, et al. The effect of azelastine and some other antiasthmatic and antiallergic drugs on calmodulin and protein kinase C. Agents Actions 1989 Aug; 28: 9–15 CrossRef
- Hide I, Toriu N, Nuibe T, et al. Suppression of TNF-α secretion by azelastine in a rat mast (RBL-2H3) cell line: evidence for differential regulation of TNF-α release, transcription, and degranulation. J Immunol 1997 Sep 15; 159: 2932–40
- Hindmarch I. Psychometric aspects of antihistamines. Allergy 1995; 50 Suppl. 24: 48–54 CrossRef
- Spaeth J, Klimek L, Mösges R. Sedation in allergic rhinitis is caused by the condition and not by antihistamine treatment. Allergy 1996 Dec; 51: 893–906
- Kaneko T, Kitahara A, Ozaki S, et al. Effects of azelastine hydrochloride, a novel anti-allergic drug, on the central nervous system. Arzneimittel Forschung 1981; 31: 1206–12
- Wallace Laboratories. Azelastine hydrochloride nasal spray prescribing information. New Jersey, USA, 1997
- ASTA medica AG. Azelastine product monograph. Frankfurt am Main, Germany, May 1997
- Kisicki JC, Howard JR, Riethmuller-Winzen H, et al. Azelastine nasal spray — twenty-nine day tolerability and safety study in healthy subjects. Asta Pharma AG / Carter-Wallace Ltd. CP-90-254; Jul 02 1990 (Data on file)
- Weliky I, Howard JR, Wichmann JK. Absolute bioavailability (AB) and pharmacokinetics (PK) of azelastine (AZ) [abstract]. Pharm Res 1990 Sep; 7 Suppl.: S247 CrossRef
- Riethmüller-Winzen H, Peter G, Büker KM, et al. Tolerability, pharmacokinetics and dose linearity of azelastine hydrochloride in healthy subjects. Arzneimittel Forschung 1994 Oct; 44: 1136–40
- Kisicki JC, Herman R, Niebch G, et al. Amendment No. 1 to the report: azelastine nasal spray — twenty-nine day tolerability and safety study in healthy subjects. Asta Pharma AG / Carter-Wallace Ltd. CP-90-254; Apr 23 1993 (Data on file)
- Peter G, Romeis P, Borbe HO, et al. Tolerability and pharmacokinetics of single and multiple doses of azelastine hydrochloride in elderly volunteers. Arzneimittel Forschung 1995 May; 45: 576–81
- Hirata-Dulas CAI, Awni WM, Weliky I, et al. Disposition of azelastine (AZ) and desmethylazelastine (DAZ) in patients with hepatic dysfunction (HEP) and renal insufficiency (RI) [abstract]. Pharm Res 1992 Oct; 9 Suppl.: S318
- Mackay IS. Classification and differential diagnosis of rhinitis. Eur Resp Rev 1994; 4(20): 245–7
- Kontou-Fili K. H1-receptor antagonists in the management of allergic rhinitis: a comparative review. Clin Immunother 1994 Nov; 2: 352–75 CrossRef
- Meltzer EO, Weiler JM, Dockhorn RJ, et al. Azelastine nasal spray in the management of seasonal allergic rhinitis. Ann Allergy 1994 Apr; 72: 354–9
- LaForce C, Dockhorn RJ, Prenner BM, et al. Safety and efficacy of azelastine nasal spray (Astelin NS) for seasonal allergic rhinitis: a 4-week comparative multicenter trial. Ann Allergy Asthma Immunol 1996 Feb; 76: 181–8 CrossRef
- Ratner PH, Findlay SR, Hampel Jr JF, et al. A double-blind, controlled trial to assess the safety and efficacy of azelastine nasal spray in seasonal allergic rhinitis. J Allergy Clin Immunol 1994 Nov; 94: 818–25 CrossRef
- Weiler JM, Meltzer EO, Benson PM, et al. A dose-ranging study of the efficacy and safety of azelastine nasal spray in the treatment of seasonal allergic rhinitis with an acute model. J Allergy Clin Immunol 1994 Dec; 94 (Pt 1): 972–80 CrossRef
- Weiler JM, Meltzer EO. Azelastine nasal spray as adjunctive therapy to azelastine tablets in the management of seasonal allergic rhinitis. Ann Allergy Asthma Immunol 1997 Oct; 79: 327–32 CrossRef
- LaForce CF. Study protocol on azelastine. Reply [letter]. Ann Allergy Asthma Immunol 1997 Feb; 78: 244 CrossRef
- Grossman J, Meltzer E, Pearlman D, et al. Onset of action and patient acceptance of azelastine in a nasal spray formulation (abstract no. 251). Presented at the XVIth International Conress of Allergy and Immunology, 1997 Oct 19–24; Cancun, Mexico
- Mösges R, Spaeth J, Conrad F, et al. Azelastine nasal spray in the allergological practice [in German]. Aktuel Neurol 1995; 3: 173–6
- Gastpar H, Dorow P, Aurich R et al. Investigation of long-term efficacy and tolerability of azelastine nasal spray in the treatment of perennial allergic rhinitis. Arzneimittel Forschung 1993 Jul; 43: 771–6
- Storms WW, Pearlman DS, Chervinsky P, et al. Effectiveness of azelastine nasal solution in seasonal allergic rhinitis. Ear Nose Throat J 1994 Jun; 73: 382–6, 390–4
- Cua-Lim F, Cua PE, Perez A, et al. The efficacy and safety of azelastine nasal spray in perennial allergic rhinitis in Pilipinos [abstract]. Allergy 1997; 52 Suppl. 37: 209
- Aun WT, Almeida CIR, Almeida WL, et al. Azelastine nasal spray in the treatment of perennial allergic rhinitis-Brazilian multicentric study [abstract]. Allergy 1997; 52 Suppl. 37: 201
- Wober W, Diez Crespo C, Bähre M. Evaluation of the drug monitoring programme of azelastine hydrochloride nasal spray in the treatment of allergic rhinitis in children under 13 years of age. Arzneimittel Forschung 1997 Jul; 47: 841–4
- Piggot PV. Expert reoprt on the clinical documentation azelastine nasal spray 0.1% for children. Asta Medica (Germany), 1996, project/report number A-05610/6800000013 (Data on file)
- Bähre M, Gröger J, Roloff A. Assessment of the efficacy and safety of azelastine nasal spray in seasonal rhinitis in 6 to 12 years old children. Abstract at 4th International Conference on Pediatric ENT, Siena, Oct 1996
- Baehre M, Herman D, Le Gal M, et al. Azelastine nasal spray in children with perennial allergic rhinitis [abstract]. Allergy 1996; 51 Suppl. 31: 157–8
- Herman D, Garay R, Le Gal M. A randomized double-blind placebo controlled study of azelastine nasal spray in children with perennial rhinitis. Int J Pediatr Otorhinolaryngol 1997 Feb 14; 39: 1–8 CrossRef
- Marin Molina AM, Botey Sala J, Eseverri Asin JL, et al. Investigation of the efficacy and tolerance of azelastine nasal spray versus budesonide aqueous solution in the treatment of children with perennial allergic rhinitis. Allergol Immunopathol 1995; 24 Suppl. 1
- Santoro Jr M, Rosario Filho NA, Kovalhik L, et al. Evaluación de la eficacia y tolerancia del spray nasal de azelastina en niños con rinitis alérgica perenne. Pediatria Moderna 1996 Oct; 23(6): 691–6
- Boné Calvo J, Botey Sala J, Caballero Gómez L, et al. Long term safety and efficacy of azelastine HC1 nasal spray in the treatment of children with perennial allergic rhinitis. Acta Paediatr Espanola 1996; 54(10): 750–64
- Dechant KL, Goa KL. Levocabastine: a review of its pharmacological properties and therapeutic potential as a topical antihistamine in allergic rhinitis and conjunctivitis. Drugs 1991; 41(2): 202–24 CrossRef
- Klimek L, Bähre M, Conrad F, et al. Oral, nasal or combined treatment of seasonal allergic rhinitis? A double-blind comparative trial with azelastine nasal spray and azelastine tablets [abstract]. Allergy 1996; 51 Suppl. 31: 156
- Mösges R, Spaeth J, Klimek L. Efficacy and tolerability of levocabastine and azelastine nasal sprays for the treatment of allergic rhinitis. Mediators Inflamm 1995 May; 4 Suppl. 1: S11–5 CrossRef
- Charpin D, Godard P, Garay RP, et al. A multicenter clinical study of the efficacy and tolerability of azelastine nasal spray in the treatment of seasonal allergic rhinitis: a comparison with oral cetirizine. Eur Arch Otorhinolaryngol 1995 Dec; 252: 455–8 CrossRef
- Passali D, Piragine F. A comparison of azelastine nasal spray and cetirizine tablets in the treatment of allergic rhinitis. J Int Med Res 1994 Jan–Feb; 22: 17–23
- Conde Hernández DJ, Palma Aqilar JL, Delgada Romero J. Comparison of azelastine nasal spray and oral ebastine in treating seasonal allergic rhinitis. Curr Med Res Opin 1995; 13(6): 299–304 CrossRef
- Gambardella R. A comparison of the efficacy of azelastine nasal spray and loratidine tablets in the treatment of seasonal allergic rhinitis. J Int Med Res 1993 Sep–Oct; 21: 268–75
- Miniti A, Mello Jr JF. A comparison of efficacy and tolerability of azelastine nasal spray and loratadine tablets in patients with perennial allergic rhinitis [abstract]. Allergy 1997; 52 Suppl. 37: 201
- Mösges R, Dostal M, Grohmann E, et al. Ist bei der allergischen Rhinitis die Therapie mit Azelastin-Nasenspray wirkungs-äquivalent der systemischen Therapie mit Loratadin-Tabletten? Topische Therapie der allergischen Rhinitis; Referate und Vortrage des Aachener gesprache zur Allergologie 1993: 121–129
- Gastpar H, Nolte D, Aurich R, et al. Comparative efficacy of azelastine nasal spray and terfenadine in seasonal and perennial rhinitis. Allergy 1994 Mar; 49: 152–8 CrossRef
- Newson-Smith G, Powell M, Baehre M, et al. A placebo controlled study comparing the efficacy of intranasal azelastine and beclomethasone in the treatment of seasonal allergic rhinitis. Eur Arch Otorhinolaryngol 1997 May; 254: 236–41 CrossRef
- Davies RJ, Lund VJ, Harten-Ash VJ. The effect of intranasal azelastine and beclomethasone on the symptoms and signs of nasal allergy in patients with perennial allergic rhinitis. Rhinology 1993 Dec; 31: 159–64
- Pelucchi A, Chiapparino A, Mastropasqua B, et al. Effect of intranasal azelastine and beclomethasone dipropionate on nasal symptoms, nasal cytology, and bronchial responsiveness to methacholine in allergic rhinitis in response to grass pollens. J Allergy Clin Immunol 1995 Feb; 95: 515–23 CrossRef
- Gastpar H, Aurich R, Petzold U, et al. Intranasal treatment of perennial allergic rhinitis: comparison of azelastine nasal spray and budesonide nasal aerosol. Arzneimittel Forschung 1993 Apr; 43: 475–9
- Dorow P, Aurich R, Petzold U. Efficacy and tolerability of azelastine nasal spray in patients with allergic rhinitis compared to placebo and budesonide. Arzneimittel Forschung 1993 Aug; 43: 909–12. Summary in 2 parts (Pt B)
- Stern MA, Ridout S, Campbell LM. Budesonide (Rhinocort® Aqua) versus azelastine (Rhinolast®) in a placebo controlled efficacy study in perennial allergic rhinitis [abstract]. In: 1996 Annual Meeting American College of Allergy, Asthma & Immunology.:, 1996: 47
- Wober W, Diez Crespo C, Bähre M. Efficacy and tolerability of azelastine nasal spray in the treatment of allergic rhinitis: large scale experience in community practice. Curr Med Res Opin 1997; 13(10): 617–26 CrossRef
- MacMahon MT, Newson-Smith G, Garnham SP, et al. Intranasal azelastine in seasonal allergic rhinitis [abstract]. 95th Annual Meeting of the American Society for Clinical Pharmacology and Therapeutics New Orleans, Louisiana 1994 Mar 30–Apr 1: 184
- Lassig W, Wober W, Höflich C, et al. Topical therapy of allergic rhinitis in childhood: Allergodil nasal spray—non-sedating in children. Curr Med Res Opin 1996; 13(7): 391–5 CrossRef
- Lund VJ. Practical application of the International Consensus on the Management of Rhinitis. Clin Immunother 1995 Oct; 4: 270–8 CrossRef
- Wiseman LR, Faulds D. Ebastine: a review of its pharmacological properties and clinical efficacy in the treatment of allergic disorders. Drugs 1996 Feb; 51: 260–77 CrossRef
- Bronsky EA, Meltzer EO, Perhach JL, et al. Cardiac safety of azelastine following 8 weeks of intra-nasal administration [abstract]. J Allergy Clin Immunol 1997 Jan; 99 (Pt 2): S445
- Datapharm Publications Ltd. AB PI compendium of data sheets and summaries of product characteristics 1996–97 (p59-60). Rhinolast nasal spray, ASTA Medica Ltd, 1996
- Medicines Control Agency. Medically targeted abridged application PL 08336/0077 Name of product: Rhinolast Nasal Spray. Asta Medica Ltd (Cambridge, UK) 1996; UK Marketing Authorisation: PL 08336/0039 (Data on file)
- Spector SL. Overview of comorbid associations of allergic rhinitis. J Allergy Clin Immunol 1997 Feb; 99: S773–80 CrossRef
- Creticos PS. Allergic rhinitis. In: Busse WW, Holgate ST, editors. Asthma and rhinitis. first ed. Oxford: Blackwell Scientific Publications, 1995: 1394–403
- Parikh A, Scadding GK. Seasonal allergic rhinitis. BMJ 1997 May 10; 314: 1392–5 CrossRef
- Fornadley JA, Corey JP, Osguthorpe JD, et al. Allergic rhinitis: clinical practice guideline. Otolaryngol Head Neck Surg 1996 Jul; 115: 115–22 CrossRef
- Noble S, McTavish D. Levocabastine: an update of its pharmacology, clinical efficacy and tolerability in the topical treatment of allergic rhinitis and conjunctivitis. Drugs 1995 Dec; 50: 1032–49 CrossRef
- Intranasal Azelastine
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