What is the mechanism of action (MOA) of azelastine hydrochloride?

From the Guidelines

Azelastine hydrochloride works primarily as a histamine H1-receptor antagonist with additional anti-inflammatory properties, making it effective for allergic rhinitis by blocking the allergic cascade and reducing underlying inflammation. The mechanism of action of azelastine hydrochloride involves competitively binding to H1 receptors, preventing histamine from attaching to these receptors and blocking the allergic cascade that leads to symptoms like sneezing, itching, and rhinorrhea 1. Unlike many antihistamines, azelastine also inhibits the release of inflammatory mediators such as leukotrienes, kinins, and platelet activating factor from mast cells and basophils, as well as reduces the production of pro-inflammatory cytokines and prevents the activation of eosinophils 1.

Key Points

• Azelastine hydrochloride is a histamine H1-receptor antagonist with anti-inflammatory properties
• It blocks the allergic cascade and reduces underlying inflammation, making it effective for allergic rhinitis
• The medication is typically administered as a nasal spray or eye drops, allowing for direct application to affected tissues with minimal systemic absorption
• Azelastine has been shown to be effective in reducing nasal symptoms, including congestion, and has been compared to other intranasal antihistamines such as olopatadine 1

Administration and Efficacy

Azelastine hydrochloride is formulated as a 0.1% aqueous solution and is recommended to be dosed at 2 sprays in each nostril twice daily for patients 12 years of age and older 1. The onset of action of nasal azelastine has been reported at 15 minutes, making it a rapid-acting treatment option for allergic rhinitis 1. In clinical trials, azelastine has been shown to significantly improve total nasal symptom score in patients with seasonal allergic rhinitis, and has been compared to other treatments such as fexofenadine 1.

Side Effects and Comparisons

Common side effects of azelastine hydrochloride include bitter taste and somnolence, although the rates of somnolence have been reported to be lower in more recent studies, ranging from 0.4% to 3% 1. Azelastine has been compared to other intranasal antihistamines, such as olopatadine, and has been shown to have equal efficacy in head-to-head, placebo-controlled comparison studies 1. Overall, azelastine hydrochloride is a effective and well-tolerated treatment option for allergic rhinitis, with a unique mechanism of action that makes it a valuable addition to the treatment arsenal.

From the FDA Drug Label

Azelastine hydrochloride, a phthalazinone derivative, exhibits histamine H1 -receptor antagonist activity in isolated tissues, animal models, and humans. The mechanism of action (MOA) of azelastine hydrochloride is as a histamine H1-receptor antagonist.

• The major metabolite, desmethylazelastine, also possesses H1-receptor antagonist activity 2.
• Azelastine hydrochloride works by blocking the action of histamine at the H1 receptor, which is involved in allergic reactions 2.

From the Research

Mechanism of Action of Azelastine Hydrochloride

• Azelastine hydrochloride is a fast-acting, efficacious, and well-tolerated H1-receptor antagonist for the treatment of rhinitis 3, 4, 5, 6, 7
• It has mast-cell stabilizing and anti-inflammatory properties, reducing the concentration of leukotrienes, kinins, and platelet activating factor in vitro and in vivo, as well as inflammatory cell migration in rhinitis patients 3, 6
• Azelastine also inhibits the production or release of many chemical mediators of the allergic response, such as leukotrienes, free radicals, and cytokines 4, 5
• It has a rapid onset of action, with benefits seen in about 2 hours, and a prolonged duration of activity (12 to 24 hours) 4, 6

Pharmacological Effects

• Azelastine has demonstrated a wide range of pharmacologic effects on chemical mediators of inflammation, including leukotrienes, kinins, and platelet activating factor in vitro and in vivo 6
• It downregulates intercellular adhesion molecule-1 expression and reduces inflammatory cell migration in patients with rhinitis 6
• Azelastine is a potent antiasthmatic agent, producing significant and long-lasting bronchodilation in patients with bronchial asthma 5

Clinical Efficacy

• Azelastine nasal spray improves nasal symptoms of rhinitis, including congestion and postnasal drip, and has a rapid onset of action 3, 6
• It is effective in alleviating nasal congestion, a particularly bothersome symptom for rhinitis sufferers, and is superior to oral antihistamines in this regard 3, 4
• Azelastine nasal spray has demonstrated greater efficacy when used in combination with fluticasone propionate nasal spray compared to either agent alone 3, 6