indication

For the symptomatic treatment of seasonal allergic rhinitis and non-allergic rhinitis, as well as symptomatic relief of ocular itching associated with allergic conjunctivitis.

pharmacology

Azelastine is a relatively selective histamine H1 antagonist, which inhibits the release of histamine and other mediators from cells (e.g. mast cells) involved in the allergic response. It has some affinity to H2 receptors. Based on in vitro studies using human cell lines, inhibition of other mediators involved in allergic reactions (e.g. leukotrienes and PAF) has been demonstrated with azelastine. Azelastine may also inhibit the accumulation and degranulation of eosinophils at the site of allergic inflammation.

mechanism of action

Azelastine competes with histamine for the H1-receptor sites on effector cells and acts as an antagonist by inhibiting the release of histamine and other mediators involved in the allergic response.

biotransformation

Azelastine hydrochloride is oxidatively metabolized to the principal metabolite, N-desmethylazelastine, by the cytochrome P450 enzyme system, however the exact cytochrome P450 isoenzyme involved has not been determined. The major metabolite, desmethylazelastine, also has H1-receptor antagonist activity.

absorption

Absorption of azelastine following ocular administration was relatively low. Systemic bioavailability is approximately 40% after nasal administration.

half life

Elimination half-life (based on intravenous and oral administration) is 22 hours. Elimination half-life of the active metabolite, desmethylazelastine, is 54 hours (after oral administration of azelastine).

route of elimination

Approximately 75% of an oral dose of radiolabeled azelastine hydrochloride was excreted in the feces with less than 10% as unchanged azelastine. Azelastine hydrochloride is oxidatively metabolized to the principal metabolite, N-desmethylazelastine, by the cytochrome P450 enzyme system.

drug interactions

Tacrine: The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Azelastine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.

Trimethobenzamide: Trimethobenzamide and Azelastine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.

Triprolidine: Concomitant therapy with triprolidine and azelastine, two anticholinergics and CNS depressants, may result in additive adverse/toxic effects. Monitor for enhanced anticholinergic and CNS depressant effects during concomitant therapy.

Trospium: Trospium and Azelastine, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.