**4.2.1 Levocabastine**

72 Otolaryngology

et al, 1995) and loratadine (Boner et al, 1989) to first-generation antihistamines, with no

Various studies were identified which examined the efficacy of newer antihistamines among children with perennial AR (Baelde & Dupont, 1992; Jobst et al, 1994; Charpin et al, 1995; Pearlman et al, 1997; Sienra-Monge et al, 1999; Ciprandi et al, 2001; Yang et al, 2001; Lai et al, 2002; Wahn et al, 2003; Ciprandi et al, 2004; Hsieh et al, 2004). In three studies with active controls, cetirizine improved symptoms compared with placebo arms and compared with ketotifen and oxatomide (Lai et al, 2002). Cetirizine was comparable to montelukast in one study (Hsieh et al, 2004), but similar in efficacy in another (Chen et al, 2006). Three fairquality, placebo-controlled studies (Baelde & Dupont, 1992; Jobst et al, 1994; Ciprandi et al, 2001) found cetirizine efficacious for nasal symptoms, particularly at a dosage of 10 mg daily

Up until the late 80s, antihistamines had not yet been developed for local application. In the last 20 years, several clinical trials have been carried out on local application of various new

Azelastine hydrochloride was initially researched for use in bronchial asthma, and is currently used in the symptomatic treatment of seasonal AR and for acute exacerbations of perennial AR. It is administered in an aqueous solution as a nasal spray, and was initially

Clinical evaluation of its efficacy and side effects were carried out in several multicentre studies (Weiler & Meltzer, 1997). It does not affect driving ability or handling of machinery,

One of the first studies with azelastine was published by Dorow, who performed two studies with pollen-allergic patients. The first study compared azelastine with a doubleblind placebo in 16 patients over one week. Significant improvement was noted in the group using the drug, with a decrease in sneezing (*P*<.01) and nasal pruritus (*P*<.01). There were no significant improvements in nasal congestion and hydrorrhoea (Dorow et al, 1993).

The second study was a double-blind comparison of 36 patients treated with either azelastine or budesonide for 15 days. There were no significant differences between the

Weiler studied the effects of pre-treatment with azelastine in nasal provocation with grass pollens. Mean percent improvements in the total symptom complex severity scores for azelastine were statistically significant (*P*≤.05) or showed a trend toward statistical significance (*P*<.05 or *P*≤.10) versus placebo from the second through the first ten hours after the initial dose and for each of the last five hours of the second day, demonstrating a rapid onset of action and sustained efficacy over the 2-day study period (Weiler & Meltzer, 1997). Grossman performed a double-blind study of 199 patients with perennial AR for 8 weeks, obtaining significant improvement when compared to placebo (Grossman et al, 1994). Other

(either at bed time or divided doses twice daily) for children 6 to 12 years.

generation antihistamines. Their marketing and use started almost 15 years ago.

but may occasionally irritate the mucous membrane and cause epistaxis.

significant differences between groups.

**4.2 Topical (intranasal) antihistamines** 

**4.2.1 Azelastine** 

administered orally.

groups.

The first antihistamine developed for nasal application, levocabastine is a highly selective histamine antagonist of the H1 receptor, and acts immediately (Janssens et al, 1991). Since it is eliminated through the kidneys, it should be used with caution in renal patients. It does not sedate or boost the effects of alcohol. The dose is 2 applications of 0.5 mg each every 12 hours in each nostril. It is more powerful than chlorpheniramine (Dechant & Goa, 1991) and similar to other oral antihistamines [loratadine (Swedish GP Allergy Team, 1994) and terfenadine (The Livostin Study Group, 1993)] and disodium cromoglycate (Fisher, 1994).

In 1995, a study was published on 21 patients with AR sensitised to mites. The patients were treated with topical levocabastine, and a reduction of inflammatory mediators and nasal hyperreactivity was observed. The authors concluded that it was an effective antagonistic of H1 receptors, with immediate clinical response and few anti-inflammatory properties (de Graaf-in´t Veld et al, 1995). Previously in 1991, other spanish authors showed the efficacy of levocabastine in seasonal AR using a double-blind study (Palma-Carlos et al, 1991).
