Azelastine Systematic (IUPAC) name (RS)-4-[(4-chlorophenyl)methyl]-2- (1-methylazepan-4-yl)-phthalazin-1-one Clinical data Trade names Optivar AHFS/Drugs.com MedlinePlus Pregnancy cat. C(US) Legal status Rx Only (US) Routes intranasal, ocular Pharmacokinetic data Bioavailability 40% (intranasal) Half-life 22 hours Identifiers CAS number ATC code R01 R06, S01 PubChem DrugBank ChemSpider UNII KEGG ChEBI ChEMBL Chemical data Formula C22H24ClN3O Mol. mass 381.898 g/mol SMILES & (what is this?)
Azelastine is a potent, second-generation, selective, histamine antagonist (histamine-H1-receptor antagonist) manufactured by MedaPharma. According to the Allergic Rhinitis and its Impact on Asthma (ARIA) treatment guidelines, intranasal anti-histamines are recommended for the first line therapy of mild intermittent, moderate/severe intermittent and mild persistent rhinitis (new classification system for rhinitis).
The chemical nomenclature of azelastine is (±)-1-(2H)-phthalazinone, 4-[(4-chlorophenyl) methyl]-2-(hexahydro-1-methyl-1H-azepin-4-yl)-monohydrochloride. It is white, almost odorless with a bitter taste.
Azelastine has been formulated both as a nasal spray (0.1% and 0.15% solutions) and as eye drops (0.05% solution). The nasal spray has been approved in over 60 countries and is marketed under various brand names including Allergodil in mainland Europe, Rhinolast in the UK, Astelin/Astepro in the US, and Azep in Australia. The eye drops have been launched in over 30 countries including the UK (Optilast) and the USA (Optivar). The nasal spray and eye drops are available over the counter in some countries.
- 1 Indications
- 2 Dosage
- 3 Pharmacokinetics and metabolism
- 4 Mode of action
- 5 Clinical efficacy
- 6 Safety and tolerability
- 7 References
- 8 External links
Azelastine nasal spray is indicated for the local treatment of the symptoms of seasonal allergic rhinitis and perennial allergic rhinitis, such as rhinorrhea, sneezing and nasal pruritis in adults and children 5 years of age and older. In some countries, it is also indicated for the treatment of vasomotor rhinitis in adults and children ≥ 12 years old. Azelastine eyes drops are indicated for the local treatment of seasonal and perennial allergic conjunctivitis.
Azelastine nasal spray
Azelastine nasal spray offers both flexibility of dose and dosage. For adults and children ≥ 12 years the recommend dosage is 1 or 2 sprays/nostril twice daily. One spray/nostril twice daily is effective and has an improved tolerability profile compared with the two spray regimen in patients with moderate-to-severe seasonal allergic rhinitis. For children aged between 5 and 11 years 1 spray/nostril twice daily is the recommended dosage. Because azelastine starts working within 15 minutes, it can be used on an as-needed basis, as and when symptoms arise (on-demand). On-demand use of azelastine nasal spray results in acceptable clinical control of rhinitis symptoms, although it does not significantly reduce allergic inflammation as observed at fixed doses of 0.28 and 0.56 mg/day.
Azelastine eye drops
Pharmacokinetics and metabolism
The systemic bioavailability of azelastine is approximately 40% when administered intranasally. Maximum plasma concentrations (Cmax) are observed within 2–3 hours. The elimination half life, steady-state volume of distribution and plasma clearance are 22 h, 14.5 l/kg and 0.5 l/h/kg respectively (based on intravenous and oral administration data). Azelastine is oxidatively metabolized by the cytochrome P450 family into its active metabolite, desmethylazelastine, and two inactive carboxylic acid metabolites. Approximately 75% of an oral dose is excreted in feces. Pharmacokinetics of orally administered azelastine are not affected by age, gender or hepatic impairment.
Mode of action
Azelastine has a triple mode of action:
- Anti-histamine effect,
- Mast-cell stabilizing effect and
- Anti-inflammatory effect.
Azelastine nasal spray
The clinical efficacy of azelastine nasal spray has been confirmed for the treatment of allergic, mixed and vasomotor rhinitis. Data from 4364 patients revealed that after 2 weeks sole treatment with azelastine nasal spray 78% of vasomotor rhinitis patients reported some or complete control of the symptom of post-nasal drip and 90% of patients with seasonal allergic rhinitis reported some or complete control of their sneezing. Additionally, more than 85% of patients reported improvements in sleeping patterns as well as reduction in impairment of daytime activities. Both doses of azelastine nasal spray currently available (0.1% and 0.15%) have been shown to significantly improve the nasal symptoms associated with seasonal allergic rhinitis.
Azelastine vs oral antihistamines
Azelastine nasal spray has a more rapid onset of action and is more effective than oral antihistamines such as desloratadine or cetirizine  in the treatment of allergic rhinitis. It is also effective in those patients who previously failed to respond to oral antihistamine therapy. Azelastine alleviates the symptom of nasal congestion to a greater degree than oral anti-histamines, an important observation since this is a particularly bothersome symptom for many rhinitis sufferers, and second-generation anti-histamines have traditionally shown little decongestant activity.
Azelastine vs intranasal corticosteroids
Azelastine nasal spray has shown comparable efficacy to the intranasal corticosteroid fluticasone propionate in improving patients’ quality of life and rhinitis symptoms and is superior to intranasal budesonide in improving the symptom of rhinorrhea in patients with perennial allergic rhinitis. Additive effects have been reported when azelastine and fluticasone are co-administered. Although azelastine has a weaker anti-inflammatory effect compared to corticosteroids, it has a significantly more rapid onset of action. Intranasal corticosteroids require days or even weeks to produce maximum benefit.
Azelastine vs leukotriene receptor antagonists
A review comparing the efficacy of azelastine and the leukotriene receptor antagonist montelukast in the treatment of perennial allergic rhinitis showed that in terms of the Rhinitis Severity Score, azelastine has the greatest overall benefit in alleviating the symptoms of allergic rhinitis. Azelastine’s effect was greater than montelukast for reduction of rhinorrhea. However, systemic montelukast, as expected, provided better relief for symptoms distant from the nasal cavity such as ocular itching and throat/palate itching.
Azelastine vs other intranasal antihistamines
Azelastine nasal spray (1.12 mg, two sprays twice daily) was more effective than intranasal levocabastine (0.4 mg, two sprays twice daily) at reducing morning and evening nasal symptoms in patients with seasonal allergic rhinitis. Global efficacy, as rated by both patients and doctors, also favored azelastine over levocabastine nasal spray. Compared with newer intranasal antihistamines, the effects of azelastine (0.1%) were comparable to those of olopatadine (0.6%) in suppressing nasal symptoms in patients with seasonal allergic rhinitis; the mean reductions from baseline in reflective total nasal symptom score was 29.9% for azelastine and 26.8% for olopatadine. Olopatadine is not indicated for the treatment of vasomotor rhinitis. In a nasal allergen provocation model azelastine (0.1%) and olopatadine (0.1%) inhibited the release of lysozyme to a similar degree and at the higher concentration of 0.2%, olopatadine also inhibited histamine and albumin release. However, others have shown that on an equimolar basis, azelastine is a more potent inhibitor of proinflammatory mediator release (interleukin 6 and tryptase) from human mast cells.
Azelastine eye drops
Azelastine eye drops are effective and well-tolerated at a concentration of 0.05% for the treatment of the symptoms of seasonal allergic conjunctivitis, such as itching, lacrimation and conjunctival redness in both adults  and children (4–12 years old). The drops start working within 3 minutes, with the effect lasting at least 8–10 hours. Azelastine eye drops in combination with azelastine nasal spray is also safe and effective for the treatment of severe seasonal rhinoconjunctivitis. Twice daily topical azelastine (0.05%) was at least as effective as levocabastine eye drops or the mast cell stabilizing agent sodium cromoglycate (4 times daily) in improving itching and conjunctival redness in allergic conjunctivitis patients, but with a slightly quicker onset of effect. Results from a conjunctival allergen challenge model study reported that both olopatadine (0.1%) and azelastine (0.05%) were significantly more effective than placebo in reducing conjunctival itching.
Safety and tolerability
Azelastine is safe and well-tolerated in both adults and children (≥12 years) with allergic rhinitis. Bitter taste, headache, nasal burning and somnolence are the most frequently reported adverse events. US prescribing recommendations warn against the concurrent use of alcohol and/or other central nervous system depressants, but to date there have been no studies to assess the effects of azelastine nasal spray on the CNS in humans. More recent studies have shown similar degrees of somnolence (approx. 2%) compared with placebo treatment. The problem of bitter taste may be reduced by correct application of the nasal spray (i.e. slightly tipping the head forward and not inhaling the medication too deeply), or alternatively using the azelastine/sucralose formulation (Astepro).
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- Azelastine Information Website
- Official Astelin Website
- Official Astepro Website
- Official Optivar Website
- Astelin Official FDA Information, Side-effects and Uses
- Optivar Official FDA Information, Side-effects and Uses
- Rhinolast Nasal Spray Summary of Product Characteristics
- Optilast Eye Drops Summary of Product Characteristics
- Allergic Rhinitis and its Impact on Asthma (ARIA) Guidelines
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